Upload
others
View
0
Download
0
Embed Size (px)
Citation preview
Asymmetries in unimanual and bimanual coordination: Evidence from
behavioural and transcranial magnetic stimulation studies.
Deborah Faulkner, B.Sc., B.A. (Honours)
This thesis is presented for the degree of Doctor of Philosophy and partial fulfilment of
Master of Psychology (Clinical Neuropsychology) of The University of Western
Australia
School of Psychology and Centre for Neuromuscular and Neurological Disorders, The
University of Western Australia
2009
iii
ABSTRACT
The issue of the laterality of control during unimanual and bimanual coordination was
addressed in this thesis. Two tasks were used throughout: a repetitive discrete response
task (finger tapping) and a continuous task (circle-drawing). Different mechanisms have
been implicated in the temporal control of repetitive discrete movements and continuous
movements. The tasks also differ in the degree of spatiotemporal coordination required
which might have important implications in the question of laterality of control.
The first section of the thesis examined between-hand differences in the dynamics of
performance during unimanual and bimanual coordination. During tapping, the
dominant hand was faster and less temporally variable than the nondominant hand.
During circle drawing the dominant hand was faster, more accurate, less temporally and
spatially variable, and produced smoother trajectories than the nondominant hand.
During bimanual coordination, several of these asymmetries were attenuated: the rate of
movement of the two hands became equivalent (the hands became temporally coupled),
the asymmetry in temporal variability during tapping was reduced, and the asymmetry
in trajectory smoothness during circle drawing was reduced.
The second section of the thesis examined the effects of disrupting motor processes with
transcranial magnetic stimulation (TMS) over the left or right primary motor cortex
(M1) on the ongoing performance of the hands. In the first study, TMS over left or right
M1 during unimanual tapping caused large disruptions to tapping with the contralateral
hand but had little effect on the ipsilateral hand. In contrast, for a subset of trials during
bimanual tapping, two lateralized effects of stimulation were seen: the effect of TMS on
the contralateral hand was greater after stimulation over left M1 than after stimulation
over right M1, and prolonged changes in inter-tap interval were observed in the left
hand regardless of the side of stimulation. In the second study, TMS over left M1 during
circle drawing decreased the accuracy of drawing with both the contralateral and
ipsilateral hand, whereas TMS over right M1 decreased accuracy of drawing only with
the contralateral hand. This lateralized effect was not limited to the bimanual case, but
was also apparent during unimanual drawing.
The final chapter addressed issues in bimanual motor control after unilateral stroke.
Performance of the affected limb was examined during unimanual and bimanual
coordination in a group of stroke patients with varying levels of impairment. The results
indicated an improvement in the performance of the affected limb for some patients
with mild to moderate, but not severe upper limb motor deficits during bimanual
movement. The improvements were limited to the patients who showed evidence of
temporal coupling between the hands.
These findings support the hypothesis that the dominant motor cortex has a role in the
control of both hands during bimanual coordination. In addition, the dominant
hemisphere appears to play a role in controlling both hands during unimanual
movements which require a greater degree of spatiotemporal coordination. The final
study suggests that temporal coupling between the limbs is crucial for the facilitation of
performance of the affected limb during bimanual coordination, which has both
theoretical and practical implications.
iv
v
CONTENTS
Abstract......................................................................................................................iii
Declaration of authorship.......................................................................................... ix
Chapter 1. Introduction.............................................................................................. 1
Neural substrates of interlimb coordination ....................................................................................... 2 Laterality of bimanual control ............................................................................................................. 6 Outline of thesis ................................................................................................................................ 10
Chapter 2. Unimanual and bimanual finger tapping. ............................................. 13
2.1 Method ............................................................................................................................................ 14 Participants........................................................................................................................................ 14 Procedure .......................................................................................................................................... 14 Data analysis...................................................................................................................................... 15
2.2 Results.............................................................................................................................................. 16 Comfortable-pace tapping................................................................................................................. 16 Rapid tapping..................................................................................................................................... 19
2.3 Discussion......................................................................................................................................... 22
Chapter 3. Unimanual and bimanual circle drawing. ............................................. 29
3.1 Method ............................................................................................................................................ 31 Participants........................................................................................................................................ 31 Procedure .......................................................................................................................................... 31 Data analysis...................................................................................................................................... 32
3.2 Results.............................................................................................................................................. 35 Accuracy of drawing .......................................................................................................................... 35 Rate of drawing ................................................................................................................................. 38 Spatial variability ............................................................................................................................... 40 Rate variability................................................................................................................................... 41 Smoothness of drawing..................................................................................................................... 43 Pressure............................................................................................................................................. 45
3.3 Discussion......................................................................................................................................... 46 Bimanual versus unimanual drawing ................................................................................................ 47 Large- versus small-circle drawing .................................................................................................... 49 Left-right asymmetries in performance ............................................................................................ 50
Chapter 4. TMS-induced disruption of motor performance................................... 55
Transient and Sustained Effects of TMS within M1........................................................................... 55 TMS-induced disruption of motor performance ............................................................................... 57
Chapter 5. TMS-induced disruption of unimanual and bimanual finger tapping . 67
5.1 Method ............................................................................................................................................ 69 Participants........................................................................................................................................ 69
TMS ................................................................................................................................................... 69 Procedure.......................................................................................................................................... 69 Data analysis ..................................................................................................................................... 71
5.2 Results ............................................................................................................................................. 73 Baseline (pre-TMS) performance...................................................................................................... 73 Motor threshold and silent period duration..................................................................................... 73 TMS-induced disruption to unimanual tapping ................................................................................ 74 TMS-induced disruption of bimanual tapping .................................................................................. 83
5.3 Discussion ........................................................................................................................................ 96 General effects of TMS on the contralateral hand ........................................................................... 96 Contralateral and ipsilateral effects of TMS during unimanual tapping........................................... 98 Contralateral and ipsilateral effects of TMS during bimanual tapping ............................................. 99
Chapter 6. Disruption of unimanual and bimanual circle drawing with TMS .... 105
6.1 Method .......................................................................................................................................... 108 Participants ..................................................................................................................................... 108 TMS ................................................................................................................................................. 109 Procedure........................................................................................................................................ 109 Data analysis ................................................................................................................................... 111
6.2 Results ........................................................................................................................................... 113 Baseline (pre-TMS) performance.................................................................................................... 113 TMS at 10% above threshold .......................................................................................................... 115 TMS at threshold............................................................................................................................. 130 TMS at 10% below threshold .......................................................................................................... 136
6.3 Discussion ...................................................................................................................................... 142
Chapter 7. Unimanual and bimanual performance after unilateral stroke.......... 151
7.1 Method .......................................................................................................................................... 156 Participants ..................................................................................................................................... 156 Procedure........................................................................................................................................ 157
7.2 Results ........................................................................................................................................... 159 Unimanual and bimanual tapping................................................................................................... 160 Unimanual and bimanual circle-drawing ........................................................................................ 165
7.3 Discussion ...................................................................................................................................... 177 Interlimb coupling........................................................................................................................... 180 Mechanisms of facilitation of performance with the impaired limb .............................................. 181
General Discussion.................................................................................................. 185
References ............................................................................................................... 195
Appendix A.............................................................................................................. 211
vi
vii
Acknowledgements
I extend a warm thank you to my supervisors Geoff Hammond, who provided
invaluable advice, astute insights, and kind criticisms, and Gary Thickbroom, who also
provided enormously useful advice, technical expertise, and encouragement just when it
was needed. Thank you both for your support and patience.
Michelle Byrnes supported me in accessing patients and provided technical expertise,
without which this thesis would not have been possible. A warm thank you also to all of
the patients and other participants who generously gave their time.
Many friends supported me throughout, and I especially want to thank Tim Perich who
was always there (despite moving to Japan then Sydney!) with an encouraging word or
motivational thought to lift my confidence; Tim Booth for his steady support, friends
and colleagues at CCRN for their support and patience, and my fellow PhD students,
who were inspirational.
Finally, my family. My dad, Bob Faulkner, who passed away suddenly in the middle of
all of this, my inspirational mum, my brother, and my step father; where would I be
without your faith in me?
viii
ix
DECLARATION OF AUTHORSHIP
1
CHAPTER 1. INTRODUCTION
Bimanual movements constitute the majority of our daily activities. Yet for the most
part, our ability to execute precisely coordinated actions with our hands goes unnoticed;
little (if any) conscious thought goes into tying shoelaces, pouring a glass of wine, using
a knife and fork. These tasks appear easy, even effortless, unless our motor system
becomes compromised by injury or disease at which time the importance of these
abilities is brought into sharp focus.
Despite the apparent effortlessness of the task of bimanual coordination, bimanual skills
are anything but a simple task for the central nervous system to execute; bimanual
coordination is the result of a finely tuned orchestration of activity within a widely
distributed network of brain areas (Debaere et al., 2001; Swinnen, 2002). However,
many aspects of this neural organization remain unclear. One aspect of motor control
which is largely unresolved is the issue of laterality in the control of bimanual
coordination, which forms the basis of the present thesis.
There is a natural tendency, when coordinating two different effectors, to move them
synchronously, so that when the two hands are used together, movements tend to be
coupled in time. Two patterns of bimanual synchronization are relatively easy to
produce: in-phase (symmetrical), and anti-phase (asymmetrical) movements. Of the two
modes, in-phase coordination is more stable, so that above a critical frequency of
tapping, there is a tendency to flip from an anti-phase to an in-phase mode (Kelso,
1984). The two hands also tend to be tightly temporally coupled when moving through
space, for example, initiation and termination of bimanual aiming movements occurs
almost simultaneously even when the two hands aim to targets at different distances
2
(Kelso, Southard, & Goodman, 1979). Tight temporal coupling is also observed during
other bimanual movements such as drawing circles or lines concurrently (Franz,
Zelaznik, & McCabe, 1991; Semjen, Summers, & Cattaert, 1995) and during more
natural goal-oriented behaviours such as opening a drawer and retrieving an object
(Kazennikov et al., 1994; Perrig, Kazennikov, & Wiesendanger, 1999) or pouring liquid
from a bottle into a glass (Weiss & Jeannerod, 1998).
Bimanual movements are coupled spatially as well as temporally. If two tasks which
differ in a spatial dimension are executed simultaneously, an integration of features of
the motor response of one limb into the motor response of the other limb is seen (e.g.
consider patting your head while rubbing your stomach). When aiming movements are
made with the two hands simultaneously to targets at different distances, each
movement becomes more like the other; the shorter amplitude movement tends to be
overshot, and the longer amplitude movement tends to be undershot (Marteniuk,
MacKenzie, & Baba, 1984; Sherwood, 1990). In more complex tasks, such as drawing
two different figures concurrently, the assimilation becomes more obvious. For
example, when drawing lines with one hand and circles with the other, both shapes take
on characteristics of the other and become elliptical (Franz, 1997; Franz, Zelaznik, &
McCabe, 1991).
Neural substrates of interlimb coordination
The emerging consensus is that bimanual coordination is the result of tightly
coordinated activity within a distributed network of brain areas (Debaere et al., 2001;
Swinnen, 2002). Neuroimaging, neurophysiological, and lesion studies with humans
and non-human primates have revealed the major areas responsible for interlimb
coordination include the supplementary motor area (SMA), primary motor cortex (M1),
3
premotor cortex, corpus callosum, and cerebellum (see Swinnen & Wenderoth, 2004 for
a recent review).
A series of studies on patients with callosal agenesis and patients who have undergone
callosal resection for intractable epilepsy highlights the importance of interhemispheric
transfer of motor information during bimanual coordination. After callosotomy,
temporal coupling between the limbs is preserved (Franz, Eliassen, Ivry, & Gazzaniga,
1996) or even enhanced (Tuller & Kelso, 1989) for tasks requiring production of
discrete bimanual movements whereas timing between the hands is decoupled in these
patients during a continuous bimanual oscillation task (Kennerley, Diedrichsen,
Hazeltine, Semjen, & Ivry, 2002). The finding that temporal coupling of the hands in a
discrete coordination task does not depend on interhemispheric transfer of information,
but coupling of the hands in a continuous task does depend on such transfer suggests a
different neural origin for the processes governing timing during repetitive discrete and
continuous bimanual movements (Zelaznik, Spencer, & Ivry, 2002; Zelaznik et al.,
2005). In contrast, patients with cerebellar lesion exhibit disruptions in the timing of
discrete but not continuous movements (Spencer, Zelaznik, Diedrichsen, & Ivry, 2003),
implicating this structure in the representation of explicit temporal information.
Split brain patients have an advantage in decoupling spatial aspects of movements, and
are able to produce two different shapes with little interference between the hands
(Franz, Eliassen, Ivry, & Gazzaniga, 1996). Similarly, force coupling between the limbs
is attenuated in individuals with callosal agenesis compared to normal controls
(Diedrichsen, Hazeltine, Nurss, & Ivry, 2003). These findings suggest that both spatial
coupling and force coupling observed during bimanual coordination is largely cortical
in origin, mediated by interhemispheric transfer of direction and force information.
4
Recent work by Carson and colleagues in unimpaired individuals (Carson, Smethurst,
Oytam, & de Rugy, 2007) suggests that corticomotor excitability is modulated by the
recruitment of muscles on the other side of the body and that this mediates interactions
between the limbs; furthermore, the authors concluded that modulation of excitability
occurs via interhemispheric interactions between motor cortices (Carson et al., 2004).
The SMA has long been considered important for bimanual motor control. The SMA
has interconnections via the corpus callosum, which makes it particularly well suited to
the task of interlimb coordination (Rouiller et al., 1994). Several lines of research
converge to implicate SMA in bimanual coordination; in non-human primates bimanual
movement is associated with SMA neural activity (Donchin, Gribova, Steinberg,
Bergman, & Vaadia, 1998; Tanji & Kurata, 1982), unilateral lesions to SMA in
monkeys leads to unwanted mirror movements during bimanual coordination (C.
Brinkman, 1984), repetitive transcranial magnetic stimulation over SMA degrades
bimanual coupling (Steyvers et al., 2003) and neuroimaging studies show activation of
SMA during bimanual coordination (Sadato, Yonekura, Waki, Yamada, & Ishii, 1997;
Stephan et al., 1999; Viviani, Perani, Grassi, Bettinardi, & Fazio, 1998). However, the
role of SMA as a coordinating structure specifically responsible for interlimb
coordination has been challenged. Contrary to Brinkman’s (1984) findings, Kazennikov
and colleagues reported that unilateral lesions in SMA in monkeys led to a delay in
movement initiation in the contralateral limb, but did not lead to deficits in bimanual
goal directed task performance (Kazennikov et al., 1998). Furthermore, equivalent SMA
activation has been found during repetitive unimanual and in-phase bimanual hand
movements, suggesting that SMA activity is not specific for bimanual movements
(Stephan, Binkofski, Posse, Seitz, & Freund, 1999). These authors found that SMA
activity increased during anti-phase bimanual movements, and concluded that activity in
5
SMA is related to temporal aspects of coordination and the complexity of a task rather
than its bimanual nature. Consistent with a role for SMA in complex coordination tasks
is the report of a large increase in SMA activation when musicians tapped a complex
polyrhythmic bimanual sequence compared to a simple in-phase bimanual sequence (W.
Lang, Obrig, Lindinger, Cheyne, & Deecke, 1990).
Recordings from neurons within SMA and M1 in monkeys suggest that each area plays
an important a role in interlimb coordination. Surprisingly, the proportion of “bimanual
neurons”1 in M1 is equivalent to the proportion in SMA (Kermadi, Liu, Tempini,
Calciati, & Rouiller, 1998), suggesting a crucial role for both areas in interlimb
coordination. Furthermore, Donchin and colleagues found bimanual-related activity in
M1 that was in addition to the neural activity seen during unimanual movements
(Donchin, Gribova, Steinberg, Bergman, & Vaadia, 1998). Similar to the results of the
previous study, the amount of bimanual-related activity in M1 was comparable to the
amount of bimanual-related activity in SMA, challenging the conventional view of M1
as a simple output area and SMA as the coordinating structure during bimanual
coordination. These results are consistent with the emerging view that M1 codes not
only for the dynamics of movement generation by the contralateral limb but also for
more complex aspects of movement control. For example, M1 neurons show
anticipatory activity for upcoming elements in a sequence of movements (Ben-Shaul et
al., 2004; Lu & Ashe, 2005). Neuroimaging results in humans also show an increase in
M1 and SMA activation during bimanual compared to unimanual coordination
(Toyokura, Muro, Komiya, & Obara, 1999) suggesting that both areas are critical for
the control of bimanual coordination.
1 Bimanual neurons were defined as those whose discharge patterns were specifically associated with bimanual movement during a sequential bimanual coordination task (not predicted from their discharge patterns during equivalent unimanual movements).
6
Laterality of bimanual control
The issue of laterality in bimanual motor control has been gaining support in recent
years. We have a natural asymmetry in motor control which is reflected in handedness,
characterized by the dominant hand being more adept at fast, precisely controlled
movements (Peters, 1976; Peters & Durding, 1979) and producing smoother movements
with more consistent temporal and spatial features (Phillips, Gallucci, & Bradshaw,
1999) than the nondominant hand. These performance asymmetries are also obvious
during bimanual coordination when the two hands perform the same task concurrently
(e.g.`, Byblow, Carson, & Goodman, 1994; Carson, Thomas, Summers, Walters, &
Semjen, 1997; Helmuth & Ivry, 1996), and in the natural roles adopted by each hand;
the nondominant hand usually performs a stabilizing and orienting role and the
dominant hand performs precise manipulations (Guiard, 1987).
Several lines of evidence point to a possible role of the dominant hemisphere in the
coordination of the hands during bimanual performance. Liepman (1908`, 1920`, cited
in Goble & Brown, 2008) was the first to suggest asymmetric processing for motor
control after observing that fine motor control was affected in both left and right upper
limb movements after left-sided lesions, but only in left limb movements after right-
sided lesions, a finding confirmed in subsequent studies (Wyke, 1971). Left parietal and
premotor areas are associated with planning complex sequences of movements
performed with either hand in normal controls (Haaland, Elsinger, Mayer, Durgerian, &
Rao, 2004). Lesion studies highlight the importance of the left hemisphere in
sequencing with both hands (Haaland & Harrington, 1994), preparation of movement
(Haaland & Harrington, 1989) and complex goal directed behaviour (Haaland,
Harrington, & Knight, 2000).
7
There is also evidence for the importance of the left hemisphere in control of interlimb
coordination. Some support for lateralized control of interlimb coordination comes from
behavioural data in normal individuals. Despite the abundance of evidence that the
motor system synchronizes the hands during bimanual coordination, the
synchronization is not perfect; the dominant hand usually leads the nondominant hand
by around 20 ms during continuous and discrete bimanual movements (Stucchi &
Viviani, 1993; Swinnen, Jardin, & Meulenbroek, 1996). This observation has led to the
hypothesis that some aspects of motor control are specified in the dominant hemisphere
and transferred to the nondominant hemisphere during bimanual coordination. An
important addendum to this finding is that the asynchrony is unlikely to reflect an
attentional bias towards the dominant hand since directing one’s attention towards the
dominant or nondominant hand modifies the magnitude of the asynchrony but does not
abolish it (Swinnen, Jardin, & Meulenbroek, 1996). It has been suggested that the
asynchrony between the hands reflects temporal control by the dominant hemisphere;
the lag resulting from the time for interhemispheric transfer of timing information from
the dominant to the nondominant hemisphere (Stucchi & Viviani, 1993; Viviani, Perani,
Grassi, Bettinardi, & Fazio, 1998). However, this idea is not without contention; the
hand that leads during bimanual coordination might depend in part on task
requirements. Although some studies on hand asynchrony during bimanual circle
drawing have found a right-hand lead during symmetrical and asymmetrical drawing
(Semjen, Summers, & Cattaert, 1995; Stucchi & Viviani, 1993), others have found that
mode of coordination affects which hand leads. During asymmetrical circle drawing,
Franz and colleagues found that in right-handers the right hand leads when both hands
circle in a clockwise direction, and the left hand leads when both hands circle in a
counter-clockwise direction (Franz, Rowse, & Ballantine, 2002). Nevertheless, at least
8
in the symmetrical mode of coordination, the finding that the dominant hand tends to
lead has been found in most studies.
Further behavioural evidence for dominant hemispheric control of bimanual
coordination comes from temporal and spatial interactions between the limbs during
bimanual coordination. Both spontaneous and intentional transitions from asymmetric
to symmetric modes of coordination are more often generated by the nondominant limb
falling into phase with the dominant limb than vice versa (Byblow, Carson, &
Goodman, 1994; de Poel, Peper, & Beek, 2006; de Poel, Peper, & Beek, 2007; Semjen,
Summers, & Cattaert, 1995). The tendency for these transitions to be initiated by
changes in the nondominant limb’s trajectory has been attributed to an asymmetry in
interlimb coupling strength (the dominant hemisphere exerts a stronger coupling
strength on the nondominant hemisphere than the reverse). It has been argued that phase
transitions from the asymmetric to the symmetric mode of bimanual coordination are
due to uncrossed (ipsilateral) descending pathways; individuals in whom ipsilateral
responses could be elicited after transcranial magnetic stimulation over M1 showed
greater spatial and temporal error than those for whom such responses could not be
elicited (Kagerer, Summers, & Semjen, 2003). Furthermore, larger ipsilateral responses
were elicited after stimulation over the dominant than the nondominant hemisphere,
which suggests a greater proportion of these fibres originate in the dominant than the
nondominant hemisphere. This could account for a greater instability in the
coordination of the nondominant than the dominant hand, and could explain the
tendency for phase transitions to be initiated by the nondominant hand. Transcallosal
motor connections may also be important; temporal coupling between the hands is
disrupted in callosotomy patients during continuous bimanual coordination (Kennerley,
Diedrichsen, Hazeltine, Semjen, & Ivry, 2002). Spatial interactions between the hands
9
are also asymmetric; the nondominant hand is more affected by the spatial trajectory of
the dominant hand than vice versa (Byblow, Lewis, Stinear, Austin, & Lynch, 2000;
Marteniuk, MacKenzie, & Baba, 1984; Sherwood, 1994), which also suggests left
hemispheric dominance of bimanual motor control.
Neuroimaging results, however, are equivocal with respect to a lateralized role of M1 in
interlimb coordination. Bimanual sequential finger-thumb movements were associated
with greater left than right hemisphere activation, although no distinction was made in
the report between M1 and premotor areas (Jäncke et al., 1998), and bimanual ellipse
drawing was associated with greater left than right hemisphere activation in both M1
and premotor areas (Viviani, Perani, Grassi, Bettinardi, & Fazio, 1998). However,
during a simpler bimanual task (in-phase finger tapping), similar loci of neuromagnetic
sources were seen in the left and right sensorimotor cortices suggesting that the neural
control of bimanual coordination is not lateralized for these movements (Pollok, Muller,
Aschersleben, Schnitzler, & Prinz, 2004). The authors speculated that task complexity
rather whether a task is bimanual may determine the amount of left hemispheric
involvement. However, in a study using a more complex anti-phase bimanual tapping
task, no asymmetry in M1 activation was observed (Toyokura, Muro, Komiya, &
Obara, 1999). Similarly, when the tapping rates required of each hand are different (one
hand tapping at double the pace of the other), levels of left and right sensorimotor cortex
activation during bimanual tapping were equivalent to the levels of activation during
unimanual tapping, although there was greater left than right SMA activation during
bimanual coordination (Jäncke et al., 2000).
Koeneke and colleagues (2004) also addressed the issue of task complexity. The authors
noted that most imaging studies of bimanual coordination have not used a unimanual
10
task that adequately controls for the level of difficulty of the bimanual task (bimanual
tasks usually require coordination of two effectors, whereas the comparison unimanual
task requires movement of a single effector). When a complex visuospatial tracking task
was performed by moving a cursor with either two fingers on different hands or two
adjacent fingers on the same hand, no asymmetry in M1 activation was observed during
the bimanual task. In fact, the authors reported less left M1 activation during the
bimanual tasks than during the left-hand unimanual task, and interpreted this as
evidence that the participants may have found the nondominant unimanual task more
difficult than the bimanual task. Furthermore, although greater left SMA activity was
observed during the bimanual task, a similar asymmetry in SMA activity was seen
during left and right unimanual tasks, and these authors also suggested that the degree
lateralized activation of motor areas depends on task difficulty rather than the bimanual
nature of a task.
An EEG coherence study during unimanual and bimanual cyclical flexion-extension
movements showed that whereas unimanual movements showed greater coherence from
the contralateral hemisphere, coupled bimanual movements were associated with greater
coherence from the dominant to the nondominant sensorimotor cortex, suggesting
greater drive from the dominant than nondominant hemisphere during bimanual
movements (Serrien, Cassidy, & Brown, 2003). The coherence decreased when the
bimanual movements became uncoupled by perturbation, suggesting that direct
transmission of drive between sensorimotor areas is responsible for bimanual coupling.
Outline of thesis
The physiological mechanisms underlying interlimb coordination remain unclear. In
this thesis, the question of the laterality of control during unimanual and bimanual
11
coordination is addressed. Two tasks were chosen: tapping, and circle-drawing. As
discussed earlier, there is evidence that these tasks represent two fundamentally
different types of bimanual coordination: different mechanisms have been implicated in
the temporal control of repetitive discrete events versus continuous coordination (Ivry &
Richardson, 2002). The first section of the thesis (Chapters 2 and 3) examine between-
hand differences in dynamics of performance during unimanual and bimanual
coordination.
The second section of the thesis examines the effects of disrupting cortical processing
with TMS over the left or right M1 on the ongoing coordination patterns between the
hands. Chapter 4 reviews the literature on the effects of TMS on unimanual and
bimanual performance. The studies reported in Chapters 5 and 6 used TMS to examine
the contribution of left and right M1 to the control of bimanual movements. The first
study examined the effects of TMS on unimanual and bimanual repetitive finger tapping
and the second study examined the effects of TMS on unimanual and bimanual circle
drawing. The circle-drawing task requires a larger degree of spatiotemporal
coordination than the repetitive tapping task. While both tasks are accomplished by the
sequential activation of different muscles, in the tapping task the raising and lowering of
the finger around a single joint is accomplished by of the reciprocal activation of flexor
and extensor muscles, whereas the circle-drawing task is a multi-joint coordination task,
which requires a more complex pattern of activation of multiple muscles in order to
produce the required trajectory with pen on paper. The differences in complexity of
sequential muscle activation between the tasks may have important consequences for
the issue of laterality of control (Pollok, Muller, Aschersleben, Schnitzler, & Prinz,
2004).
12
The final chapter addresses issues in bimanual motor control after unilateral stroke.
There is evidence that performance with the affected limb after stroke is enhanced
during bimanual coupling (Cunningham, Phillips Stoykov, & Walter, 2002; McCombe
Waller, Harris-Love, Liu, & Whitall, 2006). Neuroimaging data showed that, in stroke
patients, greater activation of the affected hemisphere was seen during bilateral
movement than during unilateral movement (Staines, McIlroy, Graham, & Black,
2001). In addition, rehabilitation strategies which emphasize the use of both hands have
been shown to have beneficial outcomes (Stewart, Cauraugh, & Summers, 2006;
Whitall, McCombe Waller, Silver, & Macko, 2000). In chapter 7, the performance of
the affected limb during bimanual and unimanual coordination are presented for three
groups of patients with varying levels of deficit.
13
CHAPTER 2. UNIMANUAL AND BIMANUAL FINGER TAPPING.
There is evidence that repetitive discrete, and continuous tasks represent two
fundamentally different types of bimanual coordination: different mechanisms have
been implicated in the temporal control of repetitive discrete events versus continuous
coordination (Ivry & Richardson, 2002; Kennerley, Diedrichsen, Hazeltine, Semjen, &
Ivry, 2002). Previous studies of the repetitive, discrete type of bimanual coordination
have examined inter-limb coordination during finger tapping or wrist flexion-extension.
These studies have usually employed either a synchronization task or a synchronization-
continuation task in which participants synchronize their taps to the beat of a
metronome, and continue this rhythm in the continuation phase, with both hands
moving either at the same rate (Drewing & Aschersleben, 2003; Glencross, Piek, &
Barrett, 1995; Helmuth & Ivry, 1996; Pollok, Muller, Aschersleben, Schnitzler, &
Prinz, 2004) or different rates (Peters, 1981, , 1985; Ullen, Forssberg, & Ehrsson, 2003).
It is assumed that in the continuation phase of the synchronization-continuation task the
timing of events is based on an internal representation of the temporal interval formed
in the synchronization phase, and response initiation is contingent on this internal
representation (Ivry & Richardson, 2002). The current study used a more naturalistic,
un-paced tapping task to measure speed and temporal regularity of unimanual and
bimanual tapping at two rates; at a comfortable (submaximal) rate or as rapidly as
possible, with either hand alone, or both hands together. This study extends previous
studies which have shown a bimanual advantage in temporal variability during
synchronization-continuation tasks (Helmuth & Ivry, 1996) to un-paced tapping.
14
2.1 Method
Participants
Ten right-handed adults, 6 females and 4 males, with ages ranging from 21 to 58 years
(median age 30 years) participated. Handedness, measured as the laterality quotient
from the Edinburgh Handedness Inventory (Oldfield, 1971) ranged from 70 to 100
(median 95). The procedure for this study (and all subsequent studies in this thesis) was
approved by The University of Western Australia’s Human Research Ethics Committee,
and informed consent was obtained from all participants.
Procedure
Participants sat comfortably with their elbows flexed at approximately 90 degrees and
both hands resting on a desk surface (palm down). Participants were instructed to tap at
a comfortable pace or at a rapid pace (as fast as possible) for ten seconds with their left
hand alone, with their right hand alone, or with both hands together, by extending and
flexing their index finger(s) around the metacarpal-phalangeal joint, keeping their hand
and other fingers flat on the table. Finger movement was measured with a miniature
accelerometer mounted in a resin block, attached over the index finger of each hand
(Figure 2.1). Output from the accelerometers was sampled from the audio input of a
computer at 44 kHz.
Figure 2.1. Participant set-up showing mounted accelerometer attached over right index finger.
15
Participants self-initiated each trial, and the timing of a trial began when the
accelerometer signal exceeded a predetermined threshold, indicating that the participant
had started tapping, and ended after ten seconds. Two blocks of 9 trials were performed
(one block at each tapping rate); each block consisted of three trials each of left
unimanual, right unimanual and bimanual tapping. The order of trials were determined
by Latin square.
Data analysis
Figure 2.2 shows 2.5 s of accelerometer output from a typical trial. Large vertical spikes
in accelerometer output indicate the sudden change in acceleration that occurred when
the participant’s finger contacted the table. The time of each contact was stored for later
analysis. Inter-tap intervals (ITIs) were determined as the time between successive
contacts. Asynchrony of left and right hand contacts was calculated (a positive
asynchrony indicated that the right hand led). Coefficients of variation (CV) of the ITIs
were calculated as a measure of tapping variability as the standard deviation of ITIs on
each trial divided by mean trial ITI and expressed as a percentage.
Time (ms)
Figure 2.2. Signal output from an accelerometer during tapping. Long vertical spikes in the signal indicate the rapid deceleration which occurred when the participant’s finger contacted the table. Inter-tap intervals (ITIs) were calculated as the time between successive contacts. The dashed horizontal line indicates the amplitude threshold for identifying a tap.
0 500 1000 1500 2000 2500
16
Autocorrelations of ITIs (correlations between ITIs within a trial) were calculated at
lags 1 to 8 for each hand during unimanual and bimanual tapping. Fisher’s r-to-z
transforms were applied to the correlation coefficients to allow averaging and statistical
analyses (Guilford, 1965). The correlation coefficients presented here are back-
transformed values.
Statistical analyses. ITIs and CV of ITIs were analysed using two-way repeated
measures ANOVAs with Hand (left and right) and Mode (unimanual and bimanual) as
within-subject factors. Systematically negative ITI autocorrelations at lag 1 (correlations
between adjacent intervals) were of particular interest (Wing & Kristofferson, 1973),
and significance of the difference of each z-transformed autocorrelation from zero were
calculated using t-tests.
2.2 Results
Comfortable-pace tapping
Table 2.1 shows mean ITI for the left and right hands during unimanual and bimanual
tapping at a comfortable rate. Mean ITI was approximately the same for the left and
right hands during both unimanual tapping and bimanual tapping. Tapping was slightly
slower with the right hand than the left hand during unimanual tapping, and equal for
the hands when tapping bimanually. The effect sizes for Hand (partial η2 = .28) and for
the interaction between Hand and Mode (partial η2 = .30) were fairly substantial
however neither effect was significant (F(1,9) = 3.57, p = .09 and F(1,9) = 3.85, p = .08,
respectively). There was no significant effect of Mode (F(1,9) = 0.12, p = .73, partial η2 =
.01).
17
Table 2.1.
Mean inter-tap-interval (ms) for each hand in unimanual and bimanual tapping at a comfortable rate. Standard deviations are in parentheses.
Mode Left Right Mean
Unimanual 411 (87) 421 (96) 416 (89) Bimanual 425 (72) 425 (72) 425 (70)
Mean 418 (79) 423 (84) 420 (79)
Table 2.2 shows mean CV for the left and right hands during unimanual and bimanual
tapping. Tapping was more variable with the left hand than the right hand during both
unimanual and bimanual tapping, and there was a significant effect of Hand (F(1,9) =
6.37, p = .03, partial η2 = .41). There was no marked difference between the variability
of each hand during unimanual and bimanual tapping, and no significant effect of
Mode (F(1,9) = 0.37, p = .56, partial η2 = .04) or interaction between Hand and Mode
(F(1,9) = 0.30, p = .60, partial η2 = .03).
Table 2.2.
Mean coefficient of variation for each hand during unimanual and bimanual tapping at a comfortable rate. Standard deviations are in parentheses.
Mode Left Right Mean
Unimanual 5.1 (1.6) 4.0 (0.6) 4.6 (1.3) Bimanual 5.2 (1.7) 4.3 (0.8) 4.7 (1.4)
Mean 5.2 (1.6) 4.2 (0.7) 4.7 (1.3)
The mean asynchrony between left and right hand taps during self-paced bimanual
tapping was 4.0 ms (SD = 4.7 ms). Examining the asynchrony data within each trial
revealed that for all participants, the hand which led was highly variable, even within a
single trial. All but one participant tended to lead with the right hand. With this
18
participant excluded, mean asynchrony was 5.2 ms (SD = 3.6 ms). For the participants
who tended to lead with their right hand, the mean proportion of taps in which the right
hand led was 0.66 (SD = 0.12), and for the participant who tended to lead with her left
hand, the proportion of taps in which the right hand led was 0.38.
Autocorrelations of ITIs at lags from 1 to 8 for each hand during unimanual and
bimanual tapping are shown in Figure 2.3. During unimanual tapping, autocorrelations
were close to zero for all lags, and there was no systematic difference between the
hands. Autocorrelations at lag 1 (correlations between adjacent inter-tap intervals) were
not significantly different from zero for either hand during unimanual tapping (left, t(9) =
0.68, p = .35; right, t(9) = 1.11, p = .29). During bimanual tapping, negative
autocorrelations were seen for both hands at lag 1 (a significant deviation from zero for
the left hand, t(9) = 2.79, p = .02, but not the right hand, t(9) = 1.81, p = .10) and
autocorrelations at all other lags were close to zero.
Figure 2.3. Mean ITI autocorrelations at lags 1 to 8 of inter-tap interval during unimanual and bimanual tapping at a comfortable pace with the left ( ) and right ( ) hands. Error bars are ± 1 standard error of the mean. Points of left and right data sets are slightly offset on the x-axis for clarity.
Unimanual Bimanual
Lag Lag
CO
RR
ELA
TIO
N C
OE
FF
ICIE
NT
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
0.4
0 2 4 6 8
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
0.4
0 2 4 6 8
19
Rapid tapping
Table 2.3 shows mean ITI for the two hands during unimanual and bimanual rapid
tapping. Tapping was faster with the right hand than the left hand during unimanual
tapping and during bimanual tapping the rates of the two hands were the same. There
was a significant effect of Hand (F(1,9) = 23.47, p = .001, partial η2 = .72), but no
significant effect of Mode (F(1,9) = 0.50, p = .83, partial η2 = .01). There was a
significant interaction between Hand and Mode (F(1,9) = 23.58, p = .001, partial η2 =
.72), reflecting the slower rate of the right hand during bimanual than unimanual
tapping and the faster rate of the left hand during bimanual than unimanual tapping.
Table 2.3.
Mean inter-tap-interval (ms) for each hand during unimanual and bimanual tapping at a rapid rate. Standard deviations are in parentheses.
Mode Left Right Mean
Unimanual 201 (27) 190 (27) 195 (27) Bimanual 196 (24) 196 (24) 196 (23)
Mean 198 (25) 193 (25) 196 (25)
Table 2.4 shows mean CV for the left and right hands during unimanual and bimanual
rapid tapping. Tapping was more variable with the left hand than the right hand during
both unimanual and bimanual tapping, reflected by a significant effect of Hand (F(1,9) =
4.85, p = .05, partial η2 = .35). Although tapping was less variable for both hands
during bimanual than unimanual tapping, the main effect of Mode was not significant
(F(1,9) = 1.28, p = .29, partial η2 = .12). The difference between unimanual and
bimanual tapping variability was greater fro the left hand than the right, and the effect
size for the interaction between Hand and Mode was .27, however this effect was not
significant (F(1,9) = 3.37, p = .10).
20
Table 2.4.
Mean coefficient of variation for each hand during rapid unimanual and bimanual tapping. Standard deviations are in parentheses.
Mode Left Right Mean
Unimanual 10.4 (5.1) 6.5 (3.8) 8.4 (4.8) Bimanual 7.4 (2.2) 6.4 (4.1) 6.9 (3.2)
Mean 8.9 (4.1) 6.4 (3.8) 7.7 (4.1)
The mean asynchrony between the left and right hand during rapid bimanual tapping
was 13.5 ms (SD = 16.5 ms). All but two participant tended to lead with the right hand
(as indicated by positive asynchronies). One led more often with his left hand and one
led inconsistently with either her left or right hand (mean asynchrony close to zero).
With these two participants excluded, the mean asynchrony was 19.2 ms (SD = 13.6).
For the participants who tended to lead with their right hand, the proportion of taps in
which the right hand led was fairly consistent (mean = 0.87, SD = 0.21). For the
participant who led with his left hand, the proportion of taps led by the right hand was
0.33, and for the participant who had an inconsistent lead-hand, the proportion of taps
led by the right hand was 0.56.
Autocorrelations of ITI at lags from 1 to 8 for each hand during unimanual and
bimanual tapping are shown in Figure 2.4. During unimanual tapping, small positive
autocorrelations were seen at all lags, and there was no systematic difference between
the hands. During bimanual tapping, a negative autocorrelation was seen for the left
hand and a positive autocorrelation for the right hand at lag 1, autocorrelations at most
other lags were close to zero. Autocorrelations at lag 1 were not significantly different
from zero for either hand during unimanual tapping (left, t(9) = 1.31, p = .22 right, t(9) =
1.47, p = .18), was significantly less than zero for the left hand (t(9) = 2.33, p = .04), and
greater than zero for the right hand (t(9) = 3.26, p = .01) during bimanual tapping.
21
Figure 2.4. Mean ITI autocorrelations at lags 1 to 8 of inter-tap interval during rapid unimanual and bimanual tapping with the left ( ) and right ( ) hands. Error bars are ± 1 standard error of the mean. Points of left and right data sets are slightly offset on the x-axis for clarity. Negative autocorrelations at lag 1 were due to a tendency to alternate between relatively
large and small ITIs whereas positive autocorrelations were due to a progressive
decrease (or increase) in ITI across a trial (Figure 2.5).
Figure 2.5. Illustrative trials from two participants showing the pattern of ITIs resulting in a negative autocorrelation at lag 1 (r = -.49; left panel) and positive autocorrelation at lag 1 (r = .49; right panel).
100
120
140
160
180
200
220
240
1 50
100
120
140
160
180
200
220
240
1 50
Lag Lag
ITI (
ms)
C
OR
RE
LAT
ION
CO
EF
FIC
IEN
T
Response number Response number
Unimanual Bimanual
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
0.4
0 2 4 6 8
-0.4
-0.3
-0.2
-0.1
0
0.1
0.2
0.3
0.4
0 2 4 6 8
22
2.3 Discussion
The main findings of this study were: 1) tapping was faster with the right than left hand
during fast but not comfortably paced unimanual tapping and tapping rates of the hands
equalized during bimanual tapping, 2) the right hand was less temporally variable than
the left hand at both paces and this asymmetry was maintained though attenuated
during bimanual tapping, 3) a trend to lower temporal variability during bimanual than
unimanual tapping was observed for the left but not right hand during rapid but not
during comfortably paced tapping, and 4) right hand taps preceded left hand taps
during fast bimanual tapping and less consistently during comfortably paced bimanual
tapping. These findings will be discussed in turn.
Tapping rates were faster with the right hand than the left hand during rapid unimanual
tapping and were equivalent during slow (comfortably paced) unimanual tapping. Not
surprisingly, the rates of tapping with two hands were identical during bimanual
tapping at either rate. The faster rate of the dominant hand during rapid unimanual
tapping is a replication of a consistently found performance asymmetry (Hammond,
Bolton, Plant, & Manning, 1988; Peters, 1980; Schmidt, Oliveira, Krahe, & Filgueiras,
2000; Todor & Kyprie, 1980). Peters (1980) demonstrated that this performance
difference between the hands is largely attributable to a faster and less variable
transition between movement directions by the dominant than nondominant hand and
suggested that this is due to a greater precision in specification of timing and
magnitude of excitatory outflow to muscles of the dominant hand than the
nondominant hand.
Tapping with the right hand was consistently less variable than tapping with the left
hand regardless of speed of performance. This is also a robust asymmetry between the
23
hands (Todor & Kyprie, 1980; Truman & Hammond, 1990), which persists, as in this
study, during bimanual tapping (Drewing & Aschersleben, 2003; Helmuth & Ivry,
1996). The greater precision of force modulation which was proposed as the source of
the dominant hand’s speed advantage during rapid tapping is also responsible for the
smaller variability in timing with the dominant than nondominant hand. Heuer (2007)
found greater co-contractions of antagonist muscles in the nondominant hand than in
the dominant hand during fast rhythmical finger oscillations. Heuer reported that
movements were characterized by faster and less variable cycle durations when
performed with the dominant hand than the nondominant hand, similar to the result
during rapid finger tapping in the current study. A critical finding was that activation
patterns in the dominant hand were characterized by sharply defined, non-overlapping
contractions of antagonist muscles, indicating a more precise control of their reciprocal
activation. Furthermore, the greater variability in timing of movement oscillations with
the non-dominant hand was associated with greater variability in the relative timing of
antagonist muscle activity. These findings suggest that a more precise control of
reciprocal activation in the dominant hand results in smaller variability in timing of
movements with the dominant hand.
Previous research has shown that the variability in both hands is reduced during
bimanual tapping compared to unimanual tapping (Drewing & Aschersleben, 2003;
Helmuth & Ivry, 1996; Yamanishi, Kawato, & Suzuki, 1980). In the current study, no
benefit of bimanual tapping on temporal variability was observed during slow tapping.
During rapid tapping, temporal variability was smaller for the left hand during the
bimanual task than during the unimanual task, although this difference was not
statistically significant. Helmuth and Ivry attributed the smaller variability during
bimanual tapping to the integration of the outputs of two separate timing mechanisms
24
(from each hemisphere), leading to reduced temporal variability in movements with
both hands. Drewing and Aschersleben showed that variability of both unimanual and
bimanual tapping was reduced by providing auditory feedback and attributed at least
part of the bimanual advantage (less variable tapping bimanually than unimanually) to
the additional sensory reafference associated with bimanual movements compared to
unimanual movements. Important methodological differences between this study and
prior research may explain the differences. Most research on temporal variability has
employed a synchronization-continuation task in which participants tap in synchrony
with an auditory timing stimulus for some time then attempt to continue to tap at the
same frequency in the absence of the auditory stimulus (performance variability is
assessed during the continuation period). In addition to the synchronization phase,
which establishes a consistent response, explicit instructions are given to maintain the
tapping pace during the continuation phase. In contrast, in the current study, which was
more naturalistic and less contrived, timing was not an explicit goal for the participants,
nor was consistency of tapping emphasised. This difference in methodology might
explain the differences between the current study and previous findings. Nevertheless,
the improvement in tapping variability with the left hand when paired with the right
hand during fast tapping requires an explanation. It is possible that during fast tapping,
the dominant hemisphere plays a role in controlling the left hand. This is consistent with
the finding that during rhythmical bimanual wrist movements there is greater
interhemispheric coherence from the dominant to the nondominant sensorimotor cortex
than vice versa, suggesting greater cortical drive from the dominant than from the
nondominant hemisphere during bimanual movements (Serrien, Cassidy, & Brown,
2003).
25
It has been argued that different timing mechanisms are responsible for temporal
precision of rapid and slow tapping (Peters, 1989). In particular, Peters proposed that
short intervals are produced as automatic movements and longer intervals as controlled
movements, the transition between automatic and controlled mechanisms occurring in
the range of 300 ms. Other evidence supports a distinction between two different
modes of tapping; preferred rates of tapping have been found to form a bimodal
distribution, with modes at 272 ms and 450 ms (Collyer, Broadbent, & Church, 1994).
The intervals produced during fast and comfortably paced tapping in the current study
clearly fell on either side of this division. Although Peters’ distinction originally
applied to synchronization tasks, two findings in the current study support a similar
distinction between slow and fast tapping in un-paced modes. Firstly, the trend to a
bimanual advantage (less variable bimanual than unimanual tapping) for the left hand
was seen during fast paced but not comfortably paced tapping. In addition, there was a
difference between the asynchrony data the two tapping rates. During bimanual
coordination, asynchronies in the timing of movements are commonly observed
between the limbs (Stucchi & Viviani, 1993; Swinnen, Jardin, & Meulenbroek, 1996).
In the current study, the asynchrony between the hands was inconsistent during slow
bimanual tapping (although 9/10 participants tended to lead with their right hand, the
right hand led in only 66% of taps, and the mean asynchrony was small, around 5 ms).
In contrast, the asynchrony during rapid tapping was more consistently associated with
a right-hand lead (in the 8/10 participants who showed a consistent right-hand lead, 87
percent of taps were led by the right hand). The magnitude of the mean asynchrony
during rapid tapping (19 ms) was comparable to that reported previously of around 20
to 25 ms (Viviani, Perani, Grassi, Bettinardi, & Fazio, 1998). As discussed in the
introduction, a proposed explanation for the asynchrony between the hands is that it
reflects temporal control of both hands by the dominant hemisphere; the lag is
26
proposed to result from the time for interhemispheric transfer of timing information
from the dominant to the non-dominant hemisphere. It is possible that during bimanual
tapping at the fast rate, which according to Peters’ distinction represents a type of
automatic movement, the asynchrony data is a good reflection of left hemispheric
control of the two hands. At longer intervals, other processes may be involved in
maintaining the tapping rate (such as attentional processes), which could add to the
variability of tapping with each hand, and might obscure the expression of
asymmetrical control through the asynchrony data.
A final note concerns the inconsistent patterns of autocorrelations seen during fast and
comfortably-paced tapping. The clock model of motor control proposed by Wing and
Kristofferson (1973) predicts that adjacent inter-tap intervals should be negatively
correlated (according to the model, a long delay for the completion of one inter-tap
interval will tend to shorten the next interval and vice versa) and that inter-response
intervals separated by one or more intervals should have correlations close to zero. In
the current study, correlations between adjacent inter-tap intervals (lag 1
autocorrelations) did not consistently reflect this prediction. The lack of a metronome
paced segment of each trial or explicit instructions to maintain a stable rhythm might
account for this negative finding, and the strong positive correlations between adjacent
taps which were sometimes observed indicate that there was drift in tapping rates
within trials. It was only during bimanual tapping that the lag 1 autocorrelations
significantly deviated from zero. It is possible that additional sensory reafference
associated with bimanual movements provided an additional “comparison” interval for
each hand in a similar way to the pacing by a metronome in other studies. However,
caution should be used in interpreting these findings because the total duration of
tapping in the current study was not long compared to previous work, and therefore
27
may not have provided a large enough sample of ITIs to make a reliable estimate of the
autocorrelations.
In summary, a superiority of the dominant hand in terms of speed and variability of
tapping was shown in the current study. In contrast to previous research, a bimanual
advantage for tapping variability with both hands was not seen, possibly due to the less
constrained nature of the current study. A bimanual advantage was seen for the left
hand during rapid tapping implicating the left hemisphere in control of bimanual
movements. Finally, several findings point to differences in the mechanisms of
movement control during slow-paced and rapid tapping.
28
29
CHAPTER 3. UNIMANUAL AND BIMANUAL CIRCLE DRAWING.
Naturally occurring bimanual movements typically require multi-joint coordination.
Whereas early work on bimanual coordination employed simple, single joint
coordination tasks such as finger tapping or wrist flexion-extension, a growing body of
research has employed multi-joint tasks; one such task is the continuous production of
circles. Previous work using this task has primarily focused on interactions between the
hands during two modes of bimanual coordination: symmetric coordination in which the
two hands cycle in different directions (one clockwise and one counter-clockwise)
which maintains symmetry with respect to the body mid-line, and asymmetric in which
the two hands cycle in the same direction, resulting in movements which are not
symmetrical with respect to the body mid-line. A major finding is that both modes of
coordination can be produced easily but symmetric coordination patterns are more
stable and produced more accurately than asymmetric patterns. The relative stability of
symmetric movements compared to asymmetric movements becomes obvious at high
frequencies of movement when transitions occur from the asymmetric to the symmetric
mode, but not in the reverse direction (Byblow, Lewis, Stinear, Austin, & Lynch, 2000;
Carson, Thomas, Summers, Walters, & Semjen, 1997; Semjen, Summers, & Cattaert,
1995). These transitions are mostly due to reversals in the direction of the non-preferred
hand, indicating an unequal interaction between the hands. Several possible
explanations for this finding have been forwarded including: conflict between
contralateral and ipsilateral descending pathways, interhemispheric interactions, and
attentional asymmetries during bimanual coordination.
30
There is evidence from the studies mentioned above that the dominant hand produces
more accurate and temporally consistent circles than the non-dominant hand, however,
because most previous work has focused on inter-limb dynamics there is little
information on the kinematic differences between the hands during unimanual and
bimanual circle-drawing. Phillips characterized differences between the hands in a
hand-writing task (the drawing of repetitive cursive letter ls and their mirror inverse)
and found that the dominant hand of right-handers produced faster, smoother
trajectories, of more consistent duration, length, and peak velocity than the non-
dominant hand (Phillips, Gallucci, & Bradshaw, 1999). The current study extends this
work to examine the kinematic profile of the left and right hand of right-handers during
unimanual and bimanual continuous circle-drawing. Furthermore, while previous work
has compared unimanual and bimanual drawing of large circles, this study extends the
comparison to the more dexterous task of drawing of small circles, which is arguably
more like the handwriting task employed by Phillips and colleagues than the large-circle
drawing tasks employed thus far. Biomechanical requirements are different for small-
and large-circle drawing; large circles are drawn with movements of proximal effectors
and small circles are drawn with proportionately greater involvement of distal effectors.
A series of recent studies by Buchanan and Ryu varied circle size to determine the
effect of joint amplitude on stability of drawing (Buchanan & Ryu, 2005; Ryu &
Buchanan, 2004). The authors found that spatial variability varied directly with circle
diameter. In these studies similar effectors were used to draw each circle size, whereas
in the current study two sizes of circles were used to encourage the use of distal and
proximal effectors in small and large circle drawing, respectively. Byblow and
colleagues studied interlimb coordination dynamics during circle-drawing with distal
and proximal musculature (Byblow, Lewis, Stinear, Austin, & Lynch, 2000).
Participants intentionally reversed the direction of drawing and the authors found that
31
unintentional disruptions in the contralateral limb trajectories were equivalent for distal
and proximal postures, and concluded that these disruptions are unlikely to arise from
ipsilateral pathways (if this was the case, the authors predicted greater disruption in the
proximal than distal posture because of greater ipsilateral control during proximal than
distal movements). The primary focus of the current study is to characterize the
kinematics of circle-production by the left and right hands during unimanual and
bimanual drawing with proximal and distal musculature. Given the predominantly
contralateral control of distal musculature and bilateral control of proximal musculature
(Kuypers, 1981), it was predicted that interlimb differences in accuracy of circle
production would be larger for the small circles (executed by distal musculature) than
the large circles (executed by proximal musculature).
3.1 Method
Participants
Thirty two right-handed subjects, 23 females and 9 males, with ages ranging from 20 to
69 years (median age 31.5 years) participated. Handedness, measured as the Laterality
Quotient from the Edinburgh Handedness Inventory (Oldfield, 1971) ranged from 60 to
100 (median 88).
Procedure
Participants traced the contours of two circles (either 15-mm or 70-mm diameter),
centres 120 mm apart, on a digitizing tablet (WACOM Intuos 2 Graphics Tablet, Model
No. XD-1212-U) continuously for 10 seconds, at a comfortable and individually
determined pace. Circles were drawn in the clockwise direction with the left hand and in
the counter-clockwise direction with the right hand to maintain biomechanical
equivalence. For the small circle targets, drawing was performed with the forearm
32
resting on the surface of the graphics tablet, which was the position adopted naturally by
participants using their right hand. Subjects were instructed to adopt this position with
the left hand to eliminate the tendency to use the whole arm during left-hand drawing,
thus limiting proximal movements and promoting distal movements, and ensuring task
equivalence across the hands. For the large circle targets, participants were free to adopt
a comfortable drawing position. Each trial began when force was detected from one pen
(for unimanual drawing) or two pens (for bimanual drawing) on the graphics tablet,
indicating that the subject had begun drawing. Each participant completed four trials of
three tasks: unimanual left, unimanual right, and bimanual circle-drawing, for each
circle size. Task order was partially counter-balanced across participants by Latin
square arrangement.
Data analysis
For each trial, time, X and Y coordinates of pen positions, and pen pressure on the
digitizing tablet were sampled at 100 Hz with a computer, and stored for later analysis.
The DC components of the X and Y waveforms were removed and the data were dual
band-pass filtered with the low cut-off frequency determined as half the average peak
frequency from the power spectra of X and Y waveforms and the high cut-off
determined using the method described by Winter (2005, p. 45). The purpose of the dual
filtering process (filtering once in the forward and once in the reverse direction) was to
correct the phase shift otherwise introduced by a single filtering process. The linear
excursion of the pen was calculated from consecutive X-Y coordinate pairs. The data
were separated into cycles, which were defined by every second zero crossing in the Y
dimension. Accuracy, rate, variability, and smoothness of drawing were assessed using
the following measures (calculated for each cycle):
33
Rate of drawing. Period (time to complete one cycle in seconds), mean linear speed, and
peak speed, for each cycle, calculated as the first derivative of linear distance with
respect to time, were calculated.
Accuracy. X- and Y-amplitude (calculated as the maximum minus minimum X- or Y-
value for each cycle), and circularity (defined below) were used to assess accuracy of
drawing. To enable comparison of accuracy in X- and Y-dimensions between different
target sizes, X-amplitude ratio and Y-amplitude ratio were calculated as the X- or Y-
amplitude of each cycle divided by the diameter of the template circle (15 mm or 70
mm). Because the shapes drawn in the present study were often more complex than
simple ellipses (e.g., small circles drawn with the left hand often took on a triangular
appearance; see Figure 3.1), a simple aspect ratio of minor to major axes would not
have sufficiently captured the complexity of the figures. The circularity ratio defined
below has been used in geography to describe the degree of “compactness” of complex
land regions (a circle being the most “compact” two-dimensional shape), and also more
recently in the bio-medical field to describe tumour shapes (Boyce & Clark, 1964;
Iwano, Nakamura, Kamioka, & Ishigaki, 2005).
Circularity was calculated:
drawnshapeofperimeterwithcircleofArea
drawnshapeofAreayCircularit =
2
4
Perimeter
Area⋅⋅= π
Circularity as defined above ranges from 0 to 1 (with a straight line scoring 0 and a
perfect circle scoring 1). Circularity can be calculated for any shape; as examples, an
equilateral triangle scores 0.60 and a square scores 0.79.
34
Variability. Spatial variability was measured by coefficient of variation (CV) of X- and
Y-diameters and temporal variability was measured by CV of period, CV of speed, and
CV of peak speed measured.
Smoothness of drawing. Number of cycles of acceleration-deceleration, and RMS jerk
were calculated as measures of drawing smoothness. The number of cycles of
acceleration and deceleration per drawing stroke has been used as a measure of drawing
efficiency; lower values indicate more efficient stroke production (Hogan & Flash,
1987). This measure has been used previously to quantify differences in efficiency
between the left and right hands (Phillips, Gallucci, & Bradshaw, 1999). Acceleration
was calculated as the second derivative of linear distance with respect to time. Number
of cycles of acceleration-deceleration were calculated by counting the number of Y-zero
crossings in the acceleration function during each cycle.
A related measure, jerk (change in acceleration), is also smaller in smooth movements
(Flash & Hogan, 1985), and has been shown to be larger in patients with Parkinson’s
disease than in normal controls (Teulings, Contreras-Vidal, Stelmach, & Adler, 1997).
Jerk was calculated as the third derivative of linear distance with respect to time.
Statistical analyses. All measures were analysed using three-way repeated-measures
ANOVAs with Hand (left and right), Mode (unimanual and bimanual), and Size (small
and large) as within-subject factors. An alpha-level of 0.05 was used for all statistical
tests. Partial eta squared (η2) values are presented as estimates of effect size.
35
3.2 Results
Figure 3.1 shows unimanual and bimanual tracings of small and large circles with the
left and right hands from a typical participant. Drawings made with the left hand appear
more spatially variable than those made with the right hand and this difference is
particularly noticeable for the small shapes. Small circles drawn with the left hand
appeared more “segmented” than those drawn with the right hand, often appearing
almost triangular (as is the case for this participant). Differences between the hands
were less obvious for large circles.
Accuracy of drawing
Figure 3.2 shows X-amplitude ratio (X-amplitude/ template diameter; panel A), Y-
amplitude ratio (Y-amplitude/template diameter; panel B), and circularity (panel C) of
shapes drawn with the left and right hands during unimanual and bimanual drawing of
small and large circles. Amplitude ratios were used to enable comparisons between
small and large circle-drawings. Table 3.1 shows the results of three-way repeated
measures ANOVAs for these measures with Hand (left and right), Mode (unimanual
and bimanual), and Size (large and small) as within-subjects factors.
A comparison of X- and Y-amplitude ratios (Figure 3.2, panels A and B, respectively)
shows that shapes were slightly elliptical; they were drawn with a smaller X amplitude
than Y amplitude for all conditions. Mean X-amplitudes were smaller than the template
diameter (the dashed line indicates equivalence of drawing and template diameters) and
mean Y-amplitudes were larger than the template diameter.
36
Figure 3.1. Example of a typical participant’s responses during unimanual and bimanual drawing of small (template diameter = 15 mm), and large (template diameter = 70 mm) circles. Mean circularity (Circ), period (Per; s), X-diameter (X; mm), Y-diameter (Y; mm) and number of cycles of acceleration/deceleration (Ac/Dec) are shown for each trial.
Right Hand Left Hand
Unimanual
Bimanual
10 mm
Small Circles
Large Circles
20 mm
Right Hand Left Hand
Unimanual
Bimanual
Circ: 0.90 Per: 0.60
X: 15.2 Y: 17.4
Ac/Dec: 2.8
Circ: 0.98 Per: 0.53
X: 13.8 Y: 14.3
Ac/Dec: 2.6
Circ: 0.92 Per: 0.53
X: 15.3 Y: 15.9
Ac/Dec: 2.4
Circ: 0.93 Per: 0.53
X: 11.4 Y: 13.3
Ac/Dec: 1.9
Circ: 0.94 Per: 1.89
X: 59.1 Y: 62.2
Ac/Dec: 5.5
Circ: 0.97 Per: 1.89
X: 64.1 Y: 62.4
Ac/Dec: 4.9
Circ: 0.98 Per: 1.19
X: 66.1 Y: 69.7
Ac/Dec: 3.3
Circ: 0.99 Per: 1.05
X: 69.1 Y: 67.5
Ac/Dec: 3.3
37
0.80
0.85
0.90
0.95
1.00
Table 3.1. Three-Way Repeated-Measures ANOVA for X-Amplitude Ratio, Y-Amplitude Ratio, and Circularity, with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.
X-Amplitude ratio Y-Amplitude ratio Circularity Source F p Partial η2 F p Partial η2 F p Partial η2
Hand (H) 10.72 .003 .26 22.13 <.001 .42 87.12 <.001 .74 Mode (M) 0.08 .782 <.01 0.01 .912 <.01 3.78 .061 .11 Size (S) 28.61 <.001 .48 50.91 <.001 .62 47.55 <.001 .61 H x M 3.06 .090 .09 4.44 .043 .12 0.54 .468 .02 H x S 8.49 .007 .22 11.82 .002 .18 41.17 <.001 .57 M x S 21.45 <.001 .41 3.56 .069 .10 0.92 .344 .03 H x M x S 2.26 .143 .07 2.67 .112 .08 0.60 .446 .02
Figure 3.2. Spatial measures: Mean X- and Y-amplitude ratios (A and B) and mean circularity (C) of small and large circles drawn with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual circle-drawing. X- and Y- amplitude ratios were calculated as the X- and Y-amplitude of the shape drawn divided by the diameter of the template circle. Dashed horizontal lines in panels A and B indicate accurate amplitude reproduction. Error bars are ±1 standard error of the mean.
0.7
0.8
0.9
1.0
1.1
1.2
1.3
Large Small Unimanual Unimanual Bimanual Bimanual
Large Small Unimanual Unimanual Bimanual Bimanual
A B
C
Circ
ular
ity
X-A
mpl
itude
rat
io
0.7
0.8
0.9
1.0
1.1
1.2
1.3
Y-A
mpl
itude
rat
io
38
Circles were slightly larger when drawn with the left hand than with the right hand, in
both the X-dimension and Y-dimension. The largest differences between the hands in
X- and Y-amplitude ratios were seen when drawing small circles.
Shapes were more circular when drawn with the right hand than with the left hand
(Figure 3.2, panel C). Mean circularities with the right hand were equivalent for small
and large circles. In contrast, with the left hand, circularity was smaller for small circles
than large circles. Mode of drawing had no effect on circularity; for each hand shapes
were equally circular when drawn in unimanual and bimanual modes.
Rate of drawing
Figure 3.3 shows mean period (panel A), speed (panel B), and peak speed (Panel C) of
the left and right hands during unimanual and bimanual drawing of small and large
circles. Table 3.2 shows the results of three-way repeated measures ANOVAs for these
measures with Hand (left and right), Mode (unimanual and bimanual), and Size (large
and small) as within-subjects factors.
The most obvious differences in period of circle drawing were between small- and
large-circle drawing (Figure 3.3, panel A). As expected, mean period of circle drawing
was longer for large circles than for small circles. Although period of circle drawing
was significantly shorter with the right hand than the left hand overall, this difference
was almost entirely due to a difference between the period of left and right hands when
they drew small circles in the unimanual mode (mean period with left hand 0.86, SD
0.26, and right hand 0.68, SD 0.20). During all other tasks, the period of circle drawing
was similar for the left and right hands. The significant Hand by Mode by Size
interaction (Table 3.2) reflected this observation.
39
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
0
50
100
150
200
250
0
50
100
150
200
250
300
Table 3.2. Three-Way Repeated-Measures ANOVA for Period (s) and Speed (mm.s-1), with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.
Period Speed Peak Speed Source F p Partial η2 F p Partial η2 F p Partial η2
Hand (H) 17.66 <.001 .36 0.01 .925 <.01 6.50 .016 .17Mode (M) 4.161 .050 .12 5.28 .029 .14 4.68 .038 .13Size (S) 155.41 <.001 .83 345.76 <.001 .92 355.48 <.001 .92H x M 16.70 <.001 .35 12.53 .001 .29 10.54 .003 .25H x S 22.81 <.001 .42 4.79 .036 .13 0.10 .756 >.01M x S 0.60 .446 .02 0.34 .564 .01 >0.01 .982 >.01H x M x S 22.44 <.001 .42 6.73 .014 .18 2.69 .111 .08
Figure 3.3. Mean period (A), speed (B), and peak speed (C) of drawing large and small shapes with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual circle-drawing. Error bars are ±1 standard error of the mean.
PE
RIO
D (
s)
Bimanual
Large Small Unimanual Unimanual Bimanual
PE
AK
SP
EE
D (
mm
.s-1
)
Large Small Unimanual Unimanual Bimanual Bimanual
SP
EE
D (
mm
.s-1
)
A
B C
L R L R
L R L R
L R L R
L R L R
40
Although it took less time to draw small circles than large circles (Figure 3.3, panel A),
mean linear speed was slower for small circles than for large circles (panel B). The left
hand was faster than the right hand (although the differences were not great) for all
conditions except when small circles were drawn in the unimanual mode; in this
condition, speed of drawing with the right hand was greater than speed of the left hand.
This is reflected in a significant Hand by Mode by Size interaction.
Peak speed was also slower for small circles than large circles (Figure 3.3, panel C).
The peak speed of drawing was faster with the left hand than with the right hand. The
largest difference in peak speed between the hands was observed in the bimanual mode,
reflected in a significant Hand by Mode interaction.
Spatial variability
Figure 3.4 shows mean between-cycle variability of X amplitude (CV of X-amplitude;
panel A) and Y-amplitude (CV of Y-amplitude; panel B) for the left and right hands
during unimanual and bimanual drawing of large and small circles. Table 3.3 shows the
results of three-way repeated measures ANOVAs for these measures with Hand (left
and right), Mode (unimanual and bimanual), and Size (large and small) as within-
subjects factors.
Amplitudes were more variable for small circles than large circles in the X-dimension
(Figure 3.4, panel A) and in the Y-dimension (panel B). Circles produced with left hand
were more variable than circles produced with the right hand in the X-dimension (panel
A), and in the Y-dimension (panel B), and the greatest differences between the hands in
spatial variability were seen when participants drew small circles; this was reflected in
significant interactions between Hand and Size in both the CV of X- and CV of Y-
41
0
2
4
6
8
10
12
0
2
4
6
8
10
12
amplitude data. Bimanual drawing was also associated with more variability in X- and
Y-amplitudes than unimanual drawing.
Table 3.3. Three-Way Repeated-Measures ANOVA for CV of X-Amplitude and CV of Y-Amplitude, with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.
CV of X-amplitude CV of Y-amplitude Source F p Partial η2 F p Partial η2
Hand (H) 19.63 <.001 .39 21.01 <.001 .40 Mode (M) 47.14 <.001 .60 25.29 <.001 .45 Size (S) 38.58 <.001 .55 66.77 <.001 .68 H x M 0.29 .592 .01 0.06 .811 <.01 H x S 14.34 .001 .32 13.58 .001 .30 M x S 3.40 .075 .10 2.06 .162 .06 H x M x S 0.92 .344 .03 2.67 .113 .08
Figure 3.4. Mean CV of X-amplitude (A) and mean CV of Y-amplitude (B) with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual drawing of small and large circles. Error bars are ±1 standard error of the mean.
Rate variability
Figure 3.5 shows mean between-cycle variability of period of drawing (CV of period,
panel A), speed (CV of speed, panel B) and peak speed (CV of peak speed, panel C) for
the left and right hands during unimanual and bimanual drawing of small and large
Bimanual
CV
X-A
mpl
itude
Large Small Unimanual Unimanual Bimanual Bimanual
CV
Y-A
mpl
itude
Large Small Unimanual Unimanual Bimanual
L R
L R
L R
L R
L R
L R
L R
L R
A B
42
0
1
2
3
4
5
6
7
8
0
2
4
6
8
10
12
0
2
4
6
8
10
12
14
circles. Table 3.4 shows the results of three-way repeated measures ANOVAs for these
measures.
Table 3.4. Three-Way Repeated-Measures ANOVA for CV of Period, CV of Speed and CV of Peak Speed, with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.
CV of Period CV of Speed CV of Peak Speed Source F p Partial η2 F p Partial η2 F p Partial η2
Hand (H) 0.36 .553 .01 1.08 .307 .03 12.56 .001 .29 Mode (M) 0.75 .393 .02 3.49 .071 .10 7.23 .011 .19 Size (S) 2.57 .119 .08 8.75 .006 .22 27.59 <.001 .47 H x M 2.24 .144 .07 0.04 .836 <.01 0.02 .887 <.01 H x S 5.40 .027 .15 12.60 .001 .29 15.29 <.001 .33 M x S 0.20 .655 .01 3.10 .088 .09 1.76 .195 .05 H x M x S 6.69 .015 .18 0.94 .341 .03 0.96 .334 .03
Figure 3.5. Mean CV of period (A), CV of speed (B), and CV of peak speed (C) with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual drawing of small and large circles. Error bars are ±1 standard error of the mean.
There was no systematic difference in the between-cycle variability of period between
the small and large circles (Figure 3.5, panel A). Neither was there a systematic
Bimanual
Large Small Unimanual Unimanual Bimanual Bimanual
Large Small Unimanual Unimanual Bimanual
CV
Spe
ed
CV
Pea
k S
peed
CV
Per
iod
A
B C
L R
L R
L R
L R
L R L R L R L R
43
difference between the hands in the variability of period. However, the variability of
period tended to be larger with the left hand than the right hand in all conditions except
when large circles were drawn in the unimanual mode; in this condition, CV of period
was larger with the right hand than the left hand. This is reflected in a significant Hand
by Mode by Size interaction.
Overall, small circles were drawn with more variable speed than large circles (Figure
3.5, panel B). When drawing small circles, the variability of speed was larger for the left
hand than the right hand. In contrast, when drawing large circles, the differences
between the hands were flipped; variability of speed was slightly larger for the right
hand than the left hand and this was reflected in a significant Hand by Size interaction.
There was no systematic difference between unimanual and bimanual modes of drawing
in variability of speed.
The variability of peak speed data (Figure 3.5, panel C) were similar to the variability of
speed data (panel B). Variability of peak speed was larger for the left hand than the right
hand when drawing small circles, and approximately equal for the left and right hands
when drawing large circles. Variability of peak drawing was slightly greater overall
during bimanual than unimanual drawing.
Smoothness of drawing
Figure 3.6 shows mean the mean number of cycles of acceleration-deceleration per
cycle (panel A) and RMS jerk (panel B) for the left and right hands during unimanual
and bimanual drawing of small and large circles. Table 3.5 shows the results of three-
way repeated measures ANOVAs for these measures.
44
0
1
2
3
4
5
0
200
400
600
800
1000
1200
1400
1600
1800
Table 3.5. Three-Way Repeated-Measures ANOVA for Cycles of Acceleration-Deceleration and RMS Jerk (mm.s-3), with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subject Factors. Values in Bold are Significant at p<.05.
Acceleration-Deceleration RMS Jerk (mm.s-3) Source F p Partial η2 F p Partial η2
Hand (H) 22.39 <.001 .42 84.96 <.001 .73 Mode (M) 2.20 .148 .07 1.05 .313 .03 Size (S) 10.99 .002 .26 33.53 <.001 .52 H x M 4.08 .052 .12 2.81 .104 .08 H x S 0.28 .602 .01 2.57 .119 .08 M x S 4.63 .039 .13 5.80 .022 .16 H x M x S 0.98 .330 .03 0.07 .794 <.01
Figure 3.6. Mean number of cycles of acceleration-deceleration per cycle (A) and RMS jerk (B) with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual drawing of small and large circles. Error bars are ±1 standard error of the mean.
There were fewer cycles of acceleration-deceleration per cycle with the right than the
left hand (panel A), indicating a smoother trajectory with the right hand than the left
hand. In addition, small circles were drawn with fewer cycles of acceleration-
deceleration than large circles. During small-circle drawing, the number of cycles of
acceleration-decelerations was larger for unimanual than bimanual drawing (indicating
smoother drawing in the bimanual mode). In contrast, during large-circle drawing, the
Bimanual
Large Small
Unimanual Unimanual Bimanual Bimanual
Large Small
Unimanual Unimanual Bimanual
RM
S J
erk
(mm
.s-3
)
Cyc
les
of A
c/D
ec
A
L R L R
L R
L R B
L R
L R
L R L R
45
number of cycles of acceleration-decelerations was larger for bimanual than unimanual
drawing (indicating smoother drawing in the unimanual mode).
RMS jerk (the third derivative of distance with respect to time) was smaller with the
right than the left hand (Figure 3.6, panel B). RMS jerk was also smaller during small-
circle drawing than large-circle drawing. Furthermore, during large-circle drawing,
RMS jerk was similar for unimanual and bimanual modes, but during small-circle
drawing, RMS jerk was smaller for the bimanual mode than the unimanual mode,
indicating smoother drawing with both hands during the unimanual mode.
Pressure
Figure 3.7 shows mean median pressure (in non-scaled pressure units) for the left and
right hands during unimanual and bimanual drawing of small and large circles. Table
3.6 shows the results of three-way repeated measures ANOVAs for pressure.
More pressure was used with the right hand than with the left hand during all drawing
conditions, which may be an indirect indicator of greater confidence of drawing with the
dominant than nondominant hand (LaRoque & Obrzut, 2006). Although significantly
more pressure was applied during unimanual than bimanual drawing, the difference was
small.
46
0
100
200
300
400
500
600
700
800
900
Table 3.6. Three-Way Repeated-Measures ANOVA for Pressure (in non-scaled pressure units), with Hand (left and right), Mode (unimanual and bimanual), and Size (small and large) as Within-Subjects Factors. Values in Bold are Significant at p<.05.
Source F-value p-value Partial η2
Hand (H) 47.618 <.001 .61 Mode (M) 7.178 .012 .19 Size (S) 1.76 .195 .05 H x M 0.21 .648 .01 H x S 0.01 .920 <.01 M x S 0.11 .742 <.01 H x M x S 1.42 .242 .04
Figure 3.7. Mean pressure (in non-scaled pressure units) with the left hand (light shading) and right hand (dark shading) during unimanual and bimanual drawing of small and large circles. Error bars are ±1 standard error of the mean
3.3 Discussion
The main findings of this study were: 1) circles drawn with the right hand were more
spatially accurate, less spatially variable, had smoother trajectories and were drawn with
more pressure than circles drawn with the left hand, 2) large circles were drawn more
accurately than small circles with the left hand, but not with the right hand (the
circularity of large and small circles was equivalent with the right hand), 3) small circles
were more spatially and temporally variable than large circles, but were associated with
Bimanual
Large Small
Unimanual Unimanual Bimanual
Pre
ssur
e
L R L R L R L R
47
smoother trajectories than large circles and 4) bimanual drawing was associated with
greater spatial variability but smoother trajectories than unimanual drawing, whereas
accuracy of drawing was similar in unimanual and bimanual modes.
Bimanual versus unimanual drawing
There were no differences between unimanual and bimanual drawing in the accuracy of
the shapes drawn; circularity was equivalent and there were no systematic X- or Y-
amplitude differences between shapes drawn unimanually and bimanually. Although
previous research has shown reduced accuracy in bimanual drawing than unimanual
drawing (Carson, Thomas, Summers, Walters, & Semjen, 1997), differences in
methodology may account for the difference between this finding and the current
results. Carson and colleagues used a paced circle-drawing task and found that as rate of
drawing increased, accuracy decreased. In the current study, no temporal constraints
were imposed; participants were free to draw at their preferred pace. Consequently,
speed of drawing was slower during bimanual than unimanual drawing, which suggests
that in a trade-off between speed and accuracy, participants slowed their drawing to
preserve accuracy during the more demanding task of bimanual drawing. However,
more spatial variability was seen during bimanual than unimanual drawing. Given that
this was not associated with a reduction in accuracy of drawing, this finding may reflect
a reduced capacity to allocate attention to each hand during bimanual drawing.
Participants were free to direct their attention wherever they wished, which probably
resulted in attention being focused on the responding hand during unimanual drawing,
whereas during bimanual drawing they may have adopted a strategy of alternating their
attention between the hands.
48
There was an attenuation of the asymmetry between the hands in smoothness of circle
drawing (cycles of acceleration/deceleration) during bimanual coordination. This was
only seen during small-circle drawing, and it represented an improvement in the
performance of the nondominant hand, with no apparent change in the performance of
the dominant hand, which suggests an integration of features of the movement trajectory
of the dominant limb into the trajectory of the nondominant limb. A second measure of
trajectory smoothness (RMS jerk) was smaller for both hands during bimanual than
unimanual small circle drawing (although the absolute asymmetry between the hands
was the same during unimanual and bimanual coordination). The apparent discrepancy
between the two measures of movement smoothness might be due to a faster rate of
circling with the dominant hand during unimanual than bimanual modes which could
have contributed to its smaller jerk when coupled with the nondominant hand (i.e. the
smaller jerk is secondary to a decreased rate of movement). The rate of drawing with the
nondominant hand did not change markedly from unimanual to bimanual drawing (if
anything its rate was slightly faster in the bimanual mode) so this cannot explain the
smoother trajectories with the nondominant hand during bimanual movements.
The greater smoothness with the nondominant hand during bimanual than unimanual
drawing in the current study was not associated with a reduction in between-cycle
temporal variability, indeed, between-cycle amplitude and temporal variability was
greater during bimanual than unimanual drawing. Rather, the greater smoothness during
bimanual than unimanual drawing occurred within each cycle, reflecting greater within-
cycle precision in the spatiotemporal specification of muscle activity. A tentative
explanation for these findings is that the features of the movement trajectories of the
dominant limb become integrated into the motor response of the nondominant limb.
This has been shown to occur at a coarser level during the attempt to draw circles with
49
one hand and lines with the other, although in this case, the resulting figures both hands
become more elliptical (Franz, 1997; Franz, Zelaznik, & McCabe, 1991). The substrate
for the interaction between trajectories of the two hands may be interhemispheric
connections via the corpus callosum since callosotomy patients are able to produce
shapes which have different trajectories with each hand concurrently (Franz, Eliassen,
Ivry, & Gazzaniga, 1996). In the current study this effect was unidirectional (at least for
the acceleration/deceleration measure of smoothness), which suggests that the dominant
hemisphere has a role in the control of the nondominant hand during bimanual
movements for the task used in the current study. That greater smoothness during
bimanual than unimanual drawing was seen for small circles but not large circles may
be related to differences in the control of distal and proximal musculature, which is
explored further below.
Large- versus small-circle drawing
Large circles were drawn with less spatial and temporal variability than small circles
with both hands and period of drawing was smaller for small than large circles
indicating less time was required to produce each cycle during small- than large-circle
drawing. Despite a more variable performance during the production of small circles
than large circles, drawing small circles required fewer cycles of acceleration-
deceleration and was associated with less jerk than drawing large circles. This
represents greater efficiency of stroke production during small- than large-circle
drawing, which may be related to different neural control during the two tasks.
Biomechanical requirements were different for small- and large-circle drawing; large
circles were drawn with movements of more proximal effectors and small circles were
drawn with movements of proportionately greater involvement of distal effectors.
Corticomotoneuronal connections to motoneurons innervating distal muscles have been
50
proposed as the neural substrate for fine finger movements. In monkeys, intrinsic hand
muscles receive strong input from the dorsolateral corticospinal tract and the activity of
corticomotoneuronal cells is related to fractionated activity in hand muscles (Bennett &
Lemon, 1996). Furthermore, corticomotoneuronal projections, which originate almost
entirely in the primary motor cortex, are more numerous to motoneurons of distal
muscles than proximal muscles (Kuypers, 1981), and comparisons across different
primates indicates that an increased density of these monosynaptic connexions is related
to an increased capacity to perform independent finger movements (Heffner &
Masterton, 1983). Transcranial magnetic stimulation suggests that the projection of the
corticomotoneuronal system to the upper limb in humans follows a similar pattern to
that in monkeys, with greater distal than proximal innervation (Palmer & Ashby, 1992).
The smoother trajectories during small-circle drawing than during large-circle drawing
reflect an ability to more precisely modulate the activity of agonist-antagonist muscles
for distal than proximal effectors, which is possibly at least partly related to the greater
number of monosynaptic projections of cortico-motoneuronal cells onto motoneurons
innervating distal than proximal muscles.
Left-right asymmetries in performance
Drawing was more accurate, less spatially variable, and smoother with the right hand
than the left hand. Similar left-right asymmetries were found in a study which compared
handwriting with the left hand and right hand in right-handers (Phillips, Gallucci, &
Bradshaw, 1999). The authors found that the right hand was faster than the left hand,
writing strokes drawn with the right hand were less variable in length, duration, and
peak velocity, and the right hand produced more efficient strokes than the left hand
(there were fewer cycles of acceleration-deceleration with the right than left hand). In
the present study, the size of the small circle template was comparable to that of the
51
handwriting study. In this task, the rate of drawing with the right hand was greater than
the rate of drawing with the left hand (during unimanual drawing), and the right hand
was less spatially variable, less variable in rate, less variable in peak speed, and
produced more efficient strokes than the left hand. These between-hand differences
were also seen during large-circle drawing for all measures except variability of rate and
peak speed. However, the magnitude of the asymmetry between the hands was smaller
when drawing large than small circles. The left-right asymmetry differences between
large and small drawing tasks are particularly noticeable in Figure 3.1; the performances
of the left and right hands are not markedly different when drawing large circles, but
considerable distortions in the shapes and more cycle-to-cycle variability is obvious in
small circles drawn by the left than the right hand. Obvious submovements in the
trajectories of small circles drawn with the left but not the right hand, as seen in the
illustrative example, were common, whereas submovements were never obvious in the
drawings of large circles. Submovements have been shown to be more prevalent in the
initial stages of motor skill acquisition and become fewer and more blended with skill
development (von Hofsten, 1991), a finding mirrored during recovery from stroke
(Rohrer et al., 2004). The presence of less well blended submovements in left- than
right-hand trajectories during small-circle drawing in the current study may reflect less
precise control of agonist and antagonist muscle activity in the left hand than the right
hand. Furthermore, submovements in the nondominant hand appeared to become more
blended during bimanual coordination which suggests, similar to the point made above,
that aspects of the trajectory of the dominant hand become integrated into the trajectory
of the nondominant hand. This further supports the hypothesis that the dominant
hemisphere plays a role in managing the nondominant limb during bimanual
coordination.
52
The biomechanical difference between the tasks discussed above, coupled with a natural
tendency to control movements of the left limb by controlling more proximal joints
(compared to control of the right limb), might explain the larger between-hand
differences during small-circle drawing than during large-circle drawing. Right-handers
naturally use more proximal movements for writing with their left hand, and more distal
movements for writing with their right hand (Mack, Gonzalez Rothi, & Heilman, 1993),
which is accomplished by a greater “locking” of the more distal joints in the left than in
the right limb (Newell & Van Emmerik, 1989). In the current study, biomechanical
differences between the hands during small-circle drawing were minimized by
encouraging participants to adopt a similar drawing position with the left and right
hands (using the position naturally adopted with the right hand for both), forcing the use
of distal joints with both hands.
The basis for the greater asymmetries during small-circle than large-circle drawing may
be related to a difference in the control of distal and proximal effectors; distal muscles
are controlled predominantly by projections from the contralateral hemisphere, whereas
proximal muscles are controlled from both hemispheres (J. Brinkman & Kuypers,
1972). From this observation, it may be expected that hemispheric differences in motor
control would be reflected more in tasks that require distal control than in tasks that
require proximal control. Hore and colleagues (1996) found that inaccuracies in
throwing with the left arm were the result of variability in the control of distal effectors
(the fingers). The authors reported greater variability with the left limb than the right
limb in both proximal and distal joint movements, however the asymmetry was more
marked for distal joints, and it was the less precise control of distal joint rotations which
accounted for most of the variability in throwing with the left limb.
53
Representations of the forelimb muscles in monkeys extend over large areas of M1
(Donoghue, Leibovic, & Sanes, 1992) and the representation of each small finger
muscle in M1 has multiple foci that overlap with representations of other muscles (Sato
& Tanji, 1989). This pattern of overlapping muscle representation in M1 has been
proposed to form the basis for the control of muscle synergies, and may also allow for a
dynamic reorganization of interconnections between different muscle representations
during the learning a new skill (Donoghue, Leibovic, & Sanes, 1992). Furthermore, the
areas of digit representation are more widely distributed in dominant than nondominant
M1 (Volkmann, Schnitzler, Witte, & Freund, 1998), possibly reflecting use-dependent
plastic changes. Greater neuropil volume in dominant than nondominant M1 suggests
more profuse intracortical connections in the dominant than nondominant hemisphere
(Amunts et al., 1996) providing a neural substrate for these plastic changes. On this
note, it is likely that practice contributed to the performance asymmetries in the current
study given the more extensive exposure to dexterous tasks received by the right hand
than the left hand. Extensive practice can reduce the magnitude of left-right
asymmetries in tapping speed (Peters, 1976). Practice is also associated with reductions
in the spatial variability of movement trajectories (Georgopoulos, Kalaska, & Massey,
1981) and a reduction in the variability of motor unit discharge rate (Kornatz, Christou,
& Enoka, 2005). The more accurate, less variable, and more efficient movement
trajectories with the right hand than the left hand in the current study could, at least
partly, be the result of differences between the hands in exposure to related tasks. The
greater practice, combined with a neural substrate to capitalize on that practice (the
greater interconnections between movement representations in the dominant than
nondominant hemisphere) could explain a more effective control of movement
synergies with the dominant than the nondominant hand, reflected in the more precise
54
spatiotemporal control of fine finger movements and blending of submovements seen in
the current study.
In summary, the right hand produced more accurate, less variable, and more efficient
trajectories than the left hand. Others have shown greater accuracy and smaller temporal
and spatial variability with the dominant than non-dominant hand using a large-circle
drawing task (Carson, Thomas, Summers, Walters, & Semjen, 1997). This study
extended the findings to small-circle drawing, and showed greater asymmetries between
the hands during this task. Furthermore, although accuracy was not different between
unimanual and bimanual modes of drawing, circle trajectories were smoother during
bimanual than unimanual drawing despite showing more cycle-to-cycle spatial
variability. This last finding was observed during the small circle task but not the large
circle task, and was asymmetric; the nondominant hand benefited from bimanual
coupling but the nondominant hand did not. This may reflect an integration of features
of the movement trajectories of the dominant hand into the motor response of the
nondominant limb and provides support for the hypothesis that the dominant
hemisphere has a role in managing the nondominant hand during bimanual
coordination.
55
CHAPTER 4. TMS-INDUCED DISRUPTION OF MOTOR PERFORMANCE
Transcranial magnetic stimulation (TMS) can be used to temporarily disrupt ongoing
neural processes during the performance of motor tasks. In its single-pulse mode, a brief
intense magnetic field generated by an insulated coil held over the scalp passes virtually
unattenuated through the skin and skull and induces an electrical current in the
underlying cortex resulting in neural depolarisation (Barker, Jalinous, & Freeston,
1985). The delivery of single-pulse TMS can be precisely timed, the magnetic field
generated by the coil is brief (less than 1 ms`, Walsh & Rushworth, 1999), and its
effects have been extensively studied, making this mode of TMS delivery an ideal tool
for examining processes of voluntary movement control. The review which follows
briefly outlines the physiological effects of single-pulse TMS within the cortex, the
behavioural effects of TMS on motor performance, and the proposed mechanisms of
disruption to motor control.
Transient and Sustained Effects of TMS within M1
The immediate effect of TMS is a transient, trans-synaptic excitation of corticospinal
neurons, resulting in their depolarisation. When TMS is delivered over the hand area of
M1 at a sufficiently high intensity, the resulting corticospinal volley excites spinal
motoneurons which results in a motor evoked potential (MEP) in hand muscles
contralateral to the side of delivery.
Although the area of electrical current induced by the TMS pulse is relatively focal, the
area of the brain affected by TMS extends to regions outside the stimulated area through
spread of activation. Increased regional neural activity in ipsilateral and contralateral
56
motor cortex after single-pulse TMS have been demonstrated using functional magnetic
resonance imaging (Bohning et al., 2000). Additionally, electroencephalographic
recordings after TMS over M1 have shown spread of activation to anatomically
connected regions within the same hemisphere within 5 to 10 ms, and to homologous
regions in the contralateral hemisphere within 20 ms (Ilmoniemi et al., 1997).
Sustained effects of single-pulse TMS result from the activation of inhibitory neurons.
These sustained effects are very powerful, and in active muscle, result in a complete or
partial interruption of the voluntary cortical drive to a target muscle which can be
observed as a silent period (SP) in the EMG activity immediately following the MEP
induced by TMS. The SP lasts up to 250 ms and increases with increasing TMS
intensity (Inghilleri, Berardelli, Cruccu, & Manfredi, 1993). While the first 50 ms of the
SP may be largely due to spinal mechanisms, the final stage is cortical in origin, and
reflects a reduced outflow from M1 (Fuhr, Agostino, & Hallett, 1991). The cortical
effect is thought to be due to the activation of inhibitory interneurons. Like the
immediate effects of TMS, the sustained effects are not limited to the site of TMS
application; silent periods in muscles ipsilateral to the side of delivery have been
reported with high intensity TMS (Chiappa et al., 1995).
The output of the motor cortex is a function of the interplay between excitatory and
inhibitory input to corticospinal tract neurons. Rapidly acting excitatory and inhibitory
circuits are thought to shape motor output by the excitation of relevant output cells and
inhibition of irrelevant output cells (Liepert, Classen, Cohen, & Hallett, 1998; Zoghi,
Pearce, & Nordstrom, 2003). The functional significance of long-lasting inhibitory
circuits is less well understood, but these circuits may modulate ongoing motor output
(Rosenkranz & Rothwell, 2003). Asymmetries in both short- and long-lasting inhibitory
57
circuits have been reported, with more excitable circuitry for both in the dominant than
non-dominant hemisphere (Hammond, Faulkner, Byrnes, Mastaglia, & Thickbroom,
2004; Hammond & Garvey, 2006; Matsunaga, Uozumi, Tsuji, & Murai, 1998),
implicating them in fine motor control.
TMS introduces a non-physiological form of neural “noise” into the organised pattern
of neural firing by disrupting both intracortical excitatory and inhibitory processes and
hence interferes with the organized output from M1. TMS provides a powerful tool to
disrupt cortical processing during motor control, analogous to the classical lesion
studies in examining cortical functions, with the advantages of being reversible, and
having greater temporal resolution.
TMS-induced disruption of motor performance
Unimanual motor performance. TMS can either facilitate or lengthen RT, depending on
the intensity of the stimulus, its timing relative to the response, and the site of
stimulation. At subthreshold intensities, TMS applied at around the time of the response
signal (i.e. early in the response latency) shortened both simple RT (Hashimoto, Inaba,
Matsumura, & Naito, 2004; Pascual-Leone, Brasil-Neto, Valls-Solé, Cohen, & Hallett,
1992) and go/no-go RT (Sawaki, Okita, Fujiwara, & Mizuno, 1999). These effects were
similar in the contralateral and ipsilateral hands. When applied later in the response
latency (within 120 ms of an expected movement), subthreshold TMS had no effect on
RT in the ipsilateral hand, and shortened RT in the contralateral hand (Hashimoto,
Inaba, Matsumura, & Naito, 2004; Sawaki, Okita, Fujiwara, & Mizuno, 1999).
The facilitation of RT by subthreshold TMS is likely to result from at least two different
cortical processes. The facilitation observed when a stimulus is applied early in the
58
response latency is probably due to non-specific intersensory facilitation (conferred by
the loud auditory click associated with TMS discharge), since sham TMS, subthreshold
TMS, and suprathreshold TMS applied at around the time of the response signal all
shorten RT to a similar extent (Ziemann, Tergau, Netz, & Homberg, 1997). This
facilitation is similar to the facilitation of RT observed when an accessory stimulus,
conveying no information pertinent to the response to be performed, is presented at
around the time of a response signal (Nickerson, 1970). The facilitation of contralateral
RT by subthreshold stimulation later in the response latency results from a different
mechanism, since neither sham TMS nor ipsilateral TMS applied at this time affect RT
(Hashimoto, Inaba, Matsumura, & Naito, 2004). M1 excitability (measured as MEP
amplitude to a fixed stimulus intensity) increases gradually in the period preceding a
movement, starting around 100 ms before a self-paced movement and 80 ms before a
RT movement (R. Chen, Yaseen, Cohen, & Hallett, 1998). This increase in M1
excitability parallels an increase in the firing rate of cells in M1 just prior to a voluntary
movement (Evarts, 1966), which continues until a threshold is reached for discharging
spinal motoneurons. Subthreshold TMS applied late in the response latency may shorten
RT by increasing the pre-movement M1 excitability, bringing the M1 discharge rate
closer to the threshold for spinal motoneuron discharge.
In contrast, suprathreshold TMS applied over M1 during a critical time window of
approximately 120 ms prior to movement onset delays contralateral RT by up to 150
ms, whereas suprathreshold TMS applied earlier than this has little effect (Romaiguère,
Possamai, & Hasbroucq, 1997), or facilitates RT as discussed above. Furthermore, the
closer the application of TMS to the next expected movement, the longer the delay (Day
et al., 1989). The delay in RT increases with increasing TMS intensity (Taylor,
Wagener, & Colebatch, 1995; Ziemann, Tergau, Netz, & Homberg, 1997). Similarly,
59
RT in the hand ipsilateral to stimulation can be delayed by a very high intensity
stimulus (up to 2.1 times threshold) applied late in the response latency (Meyer & Voss,
2000). At a lower intensity (1.2 times threshold), TMS over ipsilateral M1 has no effect
on RT (Foltys et al., 2001).
The critical time window during which TMS can delay RT corresponds to the time of
increased discharge rate of contralateral M1 neurons prior to the execution of a
movement (Evarts, 1966), and suggests that TMS acts at the final motor output stage.
The TMS-induced delays in RT appear to be cortical in origin, since during the RT
delay after TMS over contralateral M1, spinal motoneurons are still accessible to
descending input (Day et al., 1989). The delay does not seem to be related to the
immediate excitatory effect of TMS, since the delay in RT is not related to the size of
the MEP (Wilson, Thickbroom, & Mastaglia, 1993), suggesting a different neural origin
of the two phenomena. Several studies implicate inhibitory processes within M1 in the
delay of voluntary movement. Firstly, in a simple RT task, the onset of movement
following TMS over the contralateral M1 was delayed until the end of the SP (Wilson,
Lockwood, Thickbroom, & Mastaglia, 1993). Furthermore, RT delays have been shown
to correlate with SP durations both within and between subjects (Burle, Bonnet, Vidal,
Possamai, & Hasbroucq, 2002; Ziemann, Tergau, Netz, & Homberg, 1997) and the
delay in RT increases linearly (with a slope of 1) as the time between TMS and
expected response onset decreases (Day et al., 1989). These findings suggest that,
during a critical period of motor preparation, TMS induces a relatively fixed period of
disruption to M1 processing, halting motor output for a similarly fixed period regardless
of when TMS is applied during the critical period, after which neural processing
resumes.
60
Two lines of evidence suggest that the pre-movement processing in M1 is temporarily
halted by TMS, but not abolished. Firstly, the increase in M1 excitability that occurs in
the final stage before a movement is executed is maintained during the period after TMS
is delivered, suggesting that the processes responsible for the pre-movement increase in
excitation in M1 continue unabated despite the reduced output from M1 (Palmer,
Cafarelli, & Ashby, 1994). Secondly, Day and colleagues (1989) found that although a
TMS pulse delivered over M1 during the response latency delayed simple RT in the
contralateral hand, the pattern of agonist and antagonist EMG bursts in the delayed
movement was unchanged. These authors reasoned that because the movement was
executed in an intact form immediately following the SP, the motor commands must be
held in a temporary buffer, probably upstream of M1, and were executed after the
temporary block of M1 output had lifted. TMS over M1 during this critical period
therefore seems to affect motor cortex output, by delaying, but not abolishing, pre-
movement processing. After a fixed period of disrupted processing, the motor cortex
seems to resume processing from the state it was in prior to the TMS disruption.
Delays in ipsilateral RT caused by suprathreshold TMS applied close to the onset of
movement are shorter than those seen in the contralateral hand (40 ms compared with
up to 150 ms`, respectively`, Day et al., 1989; Meyer & Voss, 2000), and almost
identical to the duration of the SP evoked by ipsilateral stimulation (Aranyi & Rosler,
2002). The ipsilateral RT delays are likely to be the result of transcallosally mediated
inhibition (Meyer & Voss, 2000).
Single-pulse TMS applied over secondary motor cortices can also affect motor
performance. Suprathreshold TMS applied over premotor cortex or SMA late in the
response latency has no effect on simple RT (Taylor, Wagener, & Colebatch, 1995).
61
However, stimulation over premotor cortex early in the response latency delays choice
RT, reflecting the role of the premotor cortex in the preparation of movements
(Schluter, Rushworth, Passingham, & Mills, 1998), and the earlier critical time window
for disruption of motor control by stimulation of areas cortically upstream of M1. This
is consistent with the time course of the onset of neuronal firing in the premotor and
SMA cortical areas relative to firing in M1 (Tanji & Kurata, 1982).
TMS over M1 also disrupts the performance of ongoing rhythmical motor tasks. TMS
applied over M1 during a sequence of finger flexion/extensions affected only the first
element of the sequence in the contralateral hand, whereas TMS over premotor cortex
and SMA lengthened movement time for elements later in the sequence (Amassian,
Cracco, Maccabee, Bigland-Ritchie, & Cracco, 1991). The effect of TMS over SMA
and premotor cortex on elements later in the sequence of movements is consistent with
a role of these areas in the preparation of sequential finger movements. The disruption
to only the first element in the sequence after TMS over M1 suggests a similar
mechanism of interference to that postulated for the delays in RT; a period of inhibition
during which there is reduced output from M1, followed by a resumption of M1 output
in an unchanged form. However, a recent study indicated that TMS applied over M1
during a critical window of approximately 100 ms prior to movement onset had two
distinct effects on repetitive tapping: 1) an immediate delay in tapping with the
contralateral hand which lasted a single tapping cycle, and 2) the introduction of
“implementation noise” observed as an increase in variability of tapping rate in intervals
after TMS application (Verstynen, Konkle, & Ivry, 2006). Furthermore, others have
shown a more sustained effect of TMS over M1 on repetitive rhythmical movements
when the task required more complex two-joint synergies, with effects persisting for
several cycles of movement (Latash, Danion, & Bonnard, 2003). This finding is
62
consistent with the view that M1 is not exclusively an output area, but also contributes
to movement preparation; single-cell recordings in M1 of the monkey have shown
activity associated with future elements in a sequence of movements (Lu & Ashe,
2005).
Very few studies have attempted to compare the contributions of left M1 and right M1
to unimanual motor control using single-pulse TMS as a tool to disrupt M1 activity.
Stimulation over left and right M1 has equivalent effects on simple RT with the
contralateral hand (Schluter, Rushworth, Passingham, & Mills, 1998) suggesting that
neither hemisphere is dominant in the control of simple finger movements. Similarly,
these authors found no differential effect on simple RT with the ipsilateral hand after
stimulation over left and right M1. In right-handers performing a continuous finger-
tapping task, contralateral finger tapping was disrupted more by TMS over left M1 than
by TMS over right M1 (J. T. Chen et al., 2005), presumably reflecting either a greater
number of corticomotoneuronal projections from dominant M1 than from non-dominant
M1 during this task, or a greater excitability of dominant than non-dominant M1
corticomotoneuronal cells. There was a small disruption to ipsilateral tapping, but no
difference between left- and right-sided stimulation on the ipsilateral effect, suggesting
that, in simple unimanual movements such as repetitive finger tapping, there is no
lateralized contribution of dominant M1 to ipsilateral movement control.
Bimanual motor performance. Few studies have utilized single-pulse TMS to disrupt
ongoing M1 processing during bimanual performance. Foltys et al. (2001) found that
the effects of TMS over M1 on simple RT were similar during unimanual and bimanual
tasks; during both tasks the ipsilateral hand was facilitated by stimulation early in the
response latency and responses were progressively delayed by stimulation later in the
63
response latency, while the contralateral hand was slightly facilitated or unaffected by
stimulation early in the response latency, and responses were delayed to a greater degree
by stimulation later in the response period. These effects were similar regardless of
hemisphere of stimulation. The similarity of the effects during unimanual and bimanual
responding suggests similar M1 engagement in simple unimanual and bimanual
movements. Similarly, during a bimanual in-phase finger-tapping task, TMS caused a
larger disruption of tapping with the contralateral hand than with the ipsilateral hand,
with similar results after TMS over left and right M1 (J. T. Chen et al., 2005). In this
last study, the hand ipsilateral to the side of stimulation was more affected during
bimanual than unimanual tapping, which may reflect a greater contribution of ipsilateral
M1 in the control of bimanual movements. Alternatively, the greater disruption to
ipsilateral tapping during the bimanual task may have been a behavioural consequence
of the disruption to tapping with the contralateral hand, that is, after a disruption to the
tapping of the contralateral hand, the most parsimonious solution to attain
resynchronization of the hands may be to alter the tapping rates with both the
contralateral hand and the ipsilateral hand. These authors quantified changes in
performance after TMS as “resetting index”2, which limited any detailed analysis of the
evolving change in tapping after TMS or of a detailed analysis of the relationship
between disruptions in each hand following stimulation.
The absence of a lateralized effect in these studies suggests that the left hemisphere does
not have a special role in the control of simple bimanual movements such as simple RT
2 Tap onset was defined by EMG burst onset. Phase resetting was calculated by determining the mean baseline inter-tap-interval (aveI), the time between TMS and the last EMG burst before TMS (as a proportion of the aveI, denoted as %I), and the interval between predicted EMG bursts after TMS and actual EMG bursts after TMS (as a proportion of aveI) for five tapping intervals after TMS (d1/aveI to d5/aveI). Resetting index was then calculated as the mean slope of the regression lines of %I against d(n)/aveI (mean of the slopes of five regression lines). Thus, resetting index indicates the (proportional) increase in inter-tap-interval with increasing time of TMS application from last EMG burst. A limitation of this method is that any evolution of the change in tapping over the five intervals post-TMS will be missed because of the averaging procedure.
64
and simple in-phase repetitive finger tapping. In contrast, growing evidence indicates a
greater contribution from left motor areas than right motor areas in the control of
complex motor behaviour. Clinical evidence from patients with unilateral cortical
lesions indicate left hemispheric dominance for control of complex motor behaviour,
with left sided cortical lesions causing both contralateral and ipsilateral deficits whereas
right-sided lesions cause only contralateral deficits (Wyke, 1971). Similarly patients
with left sided lesions produce more sequencing errors with the ipsilateral hand than
patients with right sided lesions (Haaland & Harrington, 1994). Functional imaging
studies have shown greater ipsilateral activation with left hand than right hand
movements, although the results are equivocal concerning the lateralized contribution of
M1. Some have shown no difference in the amount of ipsilateral M1 activation during
simple unimanual hand movements (Volkmann, Schnitzler, Witte, & Freund, 1998) or
during finger-thumb opposition movements (Jäncke et al., 1998). Others have found
greater left sided ipsilateral activation in pre-motor cortex (Singh et al., 1998) and
parietal areas during complex unimanual hand movements (Haaland, Elsinger, Mayer,
Durgerian, & Rao, 2004), but no lateralized activity in M1. Others, however, have
shown greater ipsilateral left M1 activation than ipsilateral right M1 activation during
unimanual sequential finger movements (Kansaku et al., 2005) and during finger-thumb
opposition movements (Kawashima et al., 1993; Kim et al., 1993), suggesting a greater
contribution of left M1 than right M1 in the control of sequential movements of both
hands. Repetitive TMS has also been shown to induce more ipsilateral timing errors in
sequential finger movements when delivered over left M1 than over right M1 (R. Chen,
Gerloff, Hallett, & Cohen, 1997). Several imaging studies have shown greater left M1
than right M1 activation during bimanual motor tasks (Jäncke et al., 1998; Viviani,
Perani, Grassi, Bettinardi, & Fazio, 1998), although others have found no such
asymmetry (Toyokura, Muro, Komiya, & Obara, 1999). The results are therefore
65
equivocal with respect to a lateralized role of M1 in bimanual coordination, although
some evidence suggests that the degree of asymmetry between left and right M1
contribution to bimanual control may be related to task complexity (Koeneke, Lutz,
Wustenberg, & Jäncke, 2004). When an adequate unimanual control was used for the
multi-effector bimanual coordination tasks, Koeneke and colleagues found a similar
network of activation during unimanual and bimanual coordination, suggesting that task
difficulty was a better predictor of cortical activation than mode of coordination per se.
However, the unimanual task (controlling a cursor with two fingers of the same hand)
may have been more difficult to perform than the bimanual task (controlling a cursor
with the left and right index fingers), limiting the interpretation of the results.
The studies reported in the next two chapters used TMS to examine the contribution of
left and right M1 to the control of bimanual movements. TMS was used to manipulate
neurophysiological processes during unimanual and bimanual repetitive finger tapping
and circle drawing; for both tasks, the behavioural consequences of TMS over left and
right M1 were measured during unimanual and bimanual coordination. As discussed in
the introduction, there is evidence that these two tasks represent two fundamentally
different types of bimanual coordination; different mechanisms have been implicated in
the temporal control of repetitive discrete movements versus continuous coordination
(Ivry & Richardson, 2002). Furthermore, the circle-drawing task requires a larger
degree of spatiotemporal coordination than the repetitive tapping task. While both tasks
are accomplished by the sequential activation of different muscles, in the tapping task
the raising and lowering of the finger around a single joint is accomplished by of the
reciprocal activation of flexor and extensor muscles, whereas the circle-drawing task is
a multi-joint coordination task, which requires a more complex pattern of activation of
multiple muscles in order to produce the required trajectory with pen on paper. The
66
differences in complexity of sequential muscle activation between the tasks may have
important consequences for the issue of laterality of control.
67
CHAPTER 5. TMS-INDUCED DISRUPTION OF UNIMANUAL AND
BIMANUAL FINGER TAPPING
Left hemispheric dominance for control of bimanual movements in right-handers is
suggested from several lines of evidence including behavioural (Byblow, Lewis,
Stinear, Austin, & Lynch, 2000; Marteniuk, MacKenzie, & Baba, 1984; Stucchi &
Viviani, 1993) and imaging (Jäncke et al., 1998; Viviani, Perani, Grassi, Bettinardi, &
Fazio, 1998) studies. However, during simple bimanual tasks (in-phase finger tapping),
no lateralization of loci of neuromagnetic sources were seen in sensorimotor cortices
suggesting that the neural control of bimanual coordination is not lateralized (Pollok,
Muller, Aschersleben, Schnitzler, & Prinz, 2004). Similarly, in a study using a more
complex anti-phase bimanual tapping task, no asymmetry in M1 activation was
observed (Toyokura, Muro, Komiya, & Obara, 1999). Furthermore, the absence of a
lateralized effect of TMS on bimanual reaction time and bimanual tapping suggests that
the left hemisphere does not have a special role in the control of simple bimanual
movements (J. T. Chen et al., 2005; Foltys et al., 2001). Some authors have posited that
task complexity rather than whether a task is bimanual may determine the amount of left
hemispheric involvement. However, an EEG coherence study during simple unimanual
and bimanual cyclical wrist flexion-extension movements showed that whereas
unimanual movements are largely controlled by the contralateral hemisphere, coupled
bimanual movements were associated with greater drive from the dominant to the non-
dominant sensorimotor cortex, indicating predominant control by the dominant
hemisphere (Serrien, Cassidy, & Brown, 2003). The issue of dominant control of
bimanual coordination remains a topic of debate.
68
This study extends the findings of the study by Chen et al. (2005) which showed no
lateralized effects of TMS over M1 on bimanual tapping. As discussed in the
introduction to this section, in the study by Chen and colleagues, changes in tapping
rates after TMS were averaged over five taps after TMS application, which limited a
detailed analysis of the evolving change in ITI after TMS. In addition, the authors
equated response onset with onset of EMG. Although this technique is not uncommon
in motor control research, a recent study showed more sharply defined EMG bursts for
dominant than nondominant hand movements (Heuer, 2007), adding a confound to any
comparison of movement onset if EMG is used for this purpose. The current study
calculated an ITI difference score for each tap interval after TMS was applied over left
and right M1 to examine both the pattern of changes in ITI over time in each hand and
the relationship between these changes.
TMS was delivered over left and right M1 at various times within the inter-tap interval
during ongoing unimanual and bimanual tapping. Based on previous studies, discussed
in the previous section, which showed that TMS applied over M1 during a critical time
window (approximately 120 ms) prior to movement onset delays contralateral RT but
TMS applied earlier than this has little effect, TMS was applied at three intervals before
an expected response onset: short (40 ms), medium (90 ms), and long (140 ms)
intervals. Changes in inter-tap interval after TMS was delivered were examined. Based
on neuroimaging and TMS data it was predicted that the effects of TMS over left and
right M1 would be similar. Specifically, during unimanual tapping, TMS over either
hemisphere was expected to disrupt tapping with the contralateral, but not the ipsilateral
hand. Similarly, during bimanual tapping, TMS over either hemisphere was expected to
cause an immediate, transient disruption to tapping with the contralateral but not the
ipsilateral hand. Given the strong tendency to couple the timing of taps with each hand
69
during bimanual tapping, disruptions to tapping with one hand may result in changes to
the inter-tap-intervals with both hands. Given the previous results which have shown
contralateral control for simple repetitive movements, the effects were expected to be
equivalent after left- and right-sided stimulation.
5.1 Method
Participants
Ten right-handed participants, 6 females and 4 males, with ages ranging from 21 to 58
years (median age 30 years) participated. Handedness, measured as the laterality quotient
from the Edinburgh Handedness Inventory (Oldfield, 1971) ranged from 70 to 100
(median 95). A brief screening questionnaire was administered to exclude individuals
who had previous or current neurological conditions, aneurism clips, pace makers,
cochlear implants, or who were taking drugs with psychoactive effects (Appendix A). If
participants responded in the affirmative on any item they were excluded from the study.
TMS
Magnetic stimuli were generated with a Magstim 200 stimulator and delivered through
a figure-of-eight coil (70-mm diameter). The coil was held manually and was aligned in
the para-sagittal plane with the handle posterior to the coil. Scalp sites were identified
on a snugly fitting cap with pre-marked sites at 1-cm spacings.
Procedure
Electromyographic (EMG) activity was recorded from the extensor indicis and flexor
digitorum superficialis muscles in the forearm using surface electrodes placed
approximately 2 cm apart. The EMG signal was amplified (1000x), filtered (high-pass
70
100 Hz; low-pass 2 kHz), and digitized at a frequency of 2 kHz for 500 ms following
stimulation. The optimal site for eliciting an MEP from the extensor muscle was
determined by systematically delivering four stimuli over 1-cm spaced adjacent scalp
sites at an intensity sufficient to produce an MEP discernible above background EMG in
active muscle. The scalp site with the largest mean MEP amplitude was selected as the
optimal site for stimulation of the extensor muscle. The intensity chosen for stimulation
during testing was the minimum intensity which consistently elicited a silent period
duration of at least 100 ms in the slightly contracted finger extensor. The motor
threshold (minimum intensity at which three of four successive stimulations elicited an
MEP) was also recorded. During determination of optimal site, threshold, and silent
period duration, subjects maintained a slight contraction of the extensor muscles by
extending their index finger to emulate the level of extensor activation during finger
tapping.
Task. Participants sat comfortably with their elbows flexed at approximately 90 degrees
and both hands resting on a desk surface (palm down). Participants were instructed to
tap at a comfortably rapid pace for five seconds by extending and flexing their index
finger around the metacarpal-phalangeal joint, keeping their hand and other fingers flat
on the table. Finger movement was measured with a miniature accelerometer mounted
in a resin block, attached over the index finger of each hand. Prior to testing,
participants tapped for 2.5 seconds with the left and right hands and an amplitude
threshold for identifying taps on the accelerometer output was set (Figure 5.1). EMG
activity and output from the accelerometers were sampled at 1.5 kHz with a computer.
Participants self-initiated each trial, and the timing of a trial began when the
accelerometer signal exceeded a predetermined threshold, indicating that the participant
71
had begun tapping, and ended after five seconds. TMS was applied over left or right M1
during each trial. For each trial, a mean ITI was calculated from the first 2 seconds of
tapping and was used to determine the timing of TMS delivery. TMS was timed to
occur at short (40 ms), medium (90 ms), and long (140 ms) intervals prior to the first
expected tap (TMS-tap interval) after 2.5 s of tapping had occurred. For bimanual trials,
the TMS-tap interval was based on the timing of taps with the hand contralateral to the
side of TMS delivery. Two sessions (one for each side of TMS) consisting of four
blocks of 9 trials were performed; each block consisted of one trial each of left
unimanual, right unimanual, and bimanual tapping at each of the three TMS-tap
intervals. Left and right M1 stimulation were performed in separate sessions at least 24
hours apart. Each session lasted approximately 80 minutes.
Data analysis
Figure 5.1 shows 2.5 s of accelerometer output from a typical trial. Large vertical spikes
in accelerometer output indicate the sudden change in acceleration that occurred when
the participant’s finger contacted the table. ITIs were determined as the time between
successive contacts. For each trial, ITI was measured prior to and after TMS delivery. A
difference score for each ITI after TMS delivery was calculated as ITI minus the mean
of the ITIs in the first 2.5 seconds of tapping.
72
Time (ms)
Figure 5.1. Signal output from an accelerometer during tapping. Long vertical spikes in the signal indicate the rapid deceleration which occurred when the participant’s finger contacted the table. Inter-tap intervals (ITIs) were calculated as the time between successive contacts. The dashed horizontal line indicates the amplitude threshold for identifying a tap.
Statistical analyses. Baseline (pre-TMS) ITIs were analysed using a two-way repeated
measures ANOVA with Hand (left and right) and Task (unimanual and bimanual) as
within-subject factors.
Preliminary examination of the data indicated that the behavioural changes in tapping
occurred within six ITIs after TMS. Trend analyses were performed to identify any
systematic relationships between ITI and interval after TMS by performing one-way
repeated-measures ANOVAs with Interval (6 intervals post-TMS) as the within-subject
factor for each hand and each side of stimulation. To compare the effects of left- and
right-sided stimulation, two-way repeated-measures ANOVAs with Side of TMS and
Interval as within subject factors were conducted on ITI difference scores for ipsilateral
and contralateral hands separately. Linear, quadratic, and cubic trends are reported;
higher order trends are not reported. An alpha-level of 0.05 was used for all statistical
0 2500 500 1000 1500 2000
73
tests, and partial eta squared (η2) values are presented as estimates of effect size.
5.2 Results
Baseline (pre-TMS) performance
Table 5.1 shows mean ITI for the left and right hands during unimanual and bimanual
tapping prior to TMS. Mean inter-tap interval was longer with the left than with the
right hand during unimanual tapping and during bimanual tapping the inter-tap interval
of the two hands was approximately equal, with the left hand matching the speed of the
right hand. There was a significant effect of Hand (F(1,9) = 6.8, p = .03, partial η2 = .43)
and Task (F(1,9) = 9.0, p = .02, partial η2 = .50) and a significant interaction between
Hand and Task (F(1,9) = 5.3, p = .05, partial η2 = .37). The mean ITI in this study was
slightly longer than the mean ITI for rapid tapping in Chapter 2 because participants
were instructed to tap at a comfortably rapid pace for this task, whereas in the previous
study they were instructed to tap as rapidly as possible. However, the pattern of results
was similar in each study.
Table 5.1.
Mean inter-tap-interval (ms) for each hand in unimanual and bimanual tapping. Standard deviations are in parentheses.
Task Left Right Mean
Unimanual 212 (12) 206 (10) 209 (11) Bimanual 207 (10) 206 (10) 206 (10)
Mean 209 (11) 206 (10) 208 (10)
Motor threshold and silent period duration
Mean motor threshold was 45% of stimulator output (SD 12 %) for the left hemisphere
(right extensor) and 45% (SD 9%) for the right hemisphere (left extensor). Mean testing
74
intensity was 60% (SD 12%) for left M1 stimulation, which during a slight contraction
evoked a silent period duration of 123 ms (SD 17 ms) in the right extensor, and 59%
(SD 10%) for right M1 stimulation, which evoked a silent period duration of 138 ms
(SD 28 ms) in the left extensor.
TMS-induced disruption to unimanual tapping
Figures 5.2, 5.3, and 5.4 show the accelerometer output and EMG signals from the limb
contralateral to the side of TMS delivery in typical unimanual trials after TMS timed to
occur at short, medium, and long intervals before an expected tap, respectively.
At the short TMS-tap interval (Figure 5.2), in this example, TMS was delivered after the
conclusion of the EMG activity of the extensor muscle, towards the end of or after the
burst of flexor activity. There was a delay in the EMG activity of the extensor muscle
before the next burst of activity, which was followed by a return of EMG activity in the
flexor muscle. The ITI that contained the TMS (ITI1) was not prolonged and the interval
after TMS delivery (ITI2) was prolonged.
At the medium TMS-tap interval (Figure 5.3) TMS was delivered after the conclusion
of EMG activity in the extensor muscle, during a period of EMG activity in the flexor
muscle. A silent period was observed in the flexor EMG before a return of activity. The
ITI that contained the TMS (ITI1) was not prolonged and the interval after TMS
delivery (ITI2) was prolonged.
At the long TMS-tap interval (Figure 5.4), TMS was delivered during a period of EMG
activity in the extensor and flexor muscles, resulting in a silent period in each muscle
before simultaneous return of EMG in the two muscles. The ITI that contained the TMS
75
(ITI1) was prolonged relative to the mean baseline ITI.
Figure 5.5 shows mean ITI difference scores (ITI for each interval following TMS
minus the mean ITI from the first 2.5 s of tapping) for each hand after TMS over left
and right M1 at each TMS-tap interval. Trends (linear, quadratic and cubic) for these
data are presented in Table 5.2. The effects of TMS over left and right M1 on ITI were
compared using a two-way repeated measures ANOVA with Hand (left, right) and
Interval (1 to 5) as within subject variables (presented in Table 5.3).
76
1800 2000 2200 2400 2600 2800 3000
0.5 mV
A
B
C
ITI 2 ITI 1
Time (ms)
Figure 5.2. Unimanual tapping with the contralateral (left) hand before and after TMS delivered 40 ms before an expected tap in a typical participant: accelerometer signal (A), EMG activity in extensor (B), and EMG activity in flexor (C) muscles. The broken vertical line shows the time of TMS delivery and an MEP can be seen in both extensor and flexor activity after TMS delivery. The accelerometer signal shows no prolongation of the inter-tap interval that contained the TMS (ITI1) and a prolongation of the next interval (ITI2).
77
Figure 5.3. Unimanual tapping with the contralateral (left) hand before and after TMS delivered 90 ms before an expected tap in a typical participant: accelerometer signal (A), EMG activity in extensor (B), and EMG activity in flexor (C) muscles. The broken vertical line shows time of TMS delivery. The accelerometer signal shows no prolongation of the inter-tap interval that contained the TMS (ITI1) and a prolongation of the next interval (ITI2). A silent period (SP) is observed in the EMG of the flexor muscle.
0.5 mV
A
B
C
ITI 2 ITI 1
Time (ms)
SP
1800 2000 2200 2400 2600 2800 3000
78
Figure 5.4. Unimanual tapping with the contralateral (left) hand before and after TMS delivered 140 ms before an expected tap in a typical participant: accelerometer signal (A), EMG activity in extensor (B) and EMG activity in flexor (C) muscles. The broken vertical line shows time of TMS delivery. The accelerometer signal shows a prolongation of the inter-tap interval that contained the TMS (ITI1). A silent period (SP) is observed in the EMG activity of the extensor muscle.
1600 1800 2000 2200 2400 2600 2800
0.5 mV
A
B
C
ITI 2 ITI 1
Time (ms)
SP
79
At the short TMS-tap interval (Figure 5.5, top panel), there was no change in ITI for the
interval in which TMS was delivered after TMS over left and right M1. The greatest
change in ITI in the contralateral hand was seen in the following interval. TMS over left
and right M1 prolonged this interval in the contralateral hand to a similar extent. In the
ipsilateral hand, ITI difference scores were small after TMS over left and right M1,
although there were significant trends in the ipsilateral data for both hands (Table 5.2).
At the medium TMS-tap interval (Figure 5.5, middle panel), TMS over both left and
right M1 caused a small increase in ITI in the contralateral hand in the interval of TMS
delivery and a larger increase in the next interval. The magnitude of the change in ITI
difference scores was similar after TMS over left and right M1. ITI difference scores for
the ipsilateral hand were close to zero for all intervals after TMS over left and right M1.
At the long TMS-tap interval (Figure 5.5 bottom panel), TMS over both left M1 and
right M1 prolonged the ITI for the interval of TMS delivery in the contralateral hand.
The following ITI was also prolonged, although to a smaller extent. The magnitude of
the changes in contralateral ITI was similar after TMS over left and right M1. The
changes in ITI in the ipsilateral hand after TMS over left and right M1 were small.
The effects of TMS over left and right M1 during unimanual tapping were similar.
There were no significant effects of Side of TMS or interactions between Side of TMS
and Interval for either the contralateral or the ipsilateral hand at any of the TMS timings
(Table 5.3), indicating no lateralized effect of TMS on unimanual tapping.
80
-20
0
20
40
60
80
100
120
140
-20
0
20
40
60
80
100
120
140
1 2 3 4 5 6-20
0
20
40
60
80
100
120
140
1 2 3 4 5 6
Left M1 TMS Right M1 TMS
Interval
Figure 5.5. Mean difference in inter-tap interval (ITI difference) from baseline during unimanual tapping with the ipsilateral ( ) and contralateral ( ) hands after TMS to the left and right M1 at short, medium, and long TMS-expected tap intervals. Six intervals post-TMS are displayed (TMS was delivered during interval 1). Ipsilateral and contralateral data points are slightly offset on the x-axis for clarity. Errors are ±1 standard error of the mean.
Short TMS-tap interval
Medium TMS-tap interval
Long TMS-tap interval
ITI D
IFF
ER
EN
CE
(m
s)
81
Table 5.2. Trend analyses: Results of One-way Repeated-Measures ANOVAs for ITI Difference Scores with Interval (6 intervals post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10 for all).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Short TMS-tap interval Contralateral hand Linear 17.98 .002 .67 25.53 .001 .74 Quadratic 3.79 .083 .30 5.01 .052 .36 Cubic 15.55 .003 .63 18.20 .002 .67 Ipsilateral hand Linear 1.56 .244 .15 13.53 .005 .60 Quadratic 5.03 .052 .35 9.40 .013 .51 Cubic 6.78 .029 .43 3.53 .093 .28
Medium TMS-tap interval Contralateral hand Linear 39.19 <.001 .81 24.84 .001 .73 Quadratic 0.11 .747 .01 1.12 .317 .11 Cubic 9.12 .014 .50 2.58 .142 .22 Ipsilateral hand Linear 0.34 .575 .04 1.46 .258 .14 Quadratic 5.34 .046 .37 2.85 .126 .24 Cubic 5.04 .051 .36 43.25 <.001 .83
Long TMS-tap interval Contralateral hand Linear 37.43 <.001 .81 16.60 .003 .65 Quadratic 11.79 .007 .57 7.46 .023 .45 Cubic 0.20 .665 .02 0.49 .502 .05 Ipsilateral hand Linear 0.29 .602 .03 3.94 .079 .30 Quadratic 2.24 .169 .20 6.18 .035 .41 Cubic 0.18 .678 .02 0.10 .762 .01
82
Table 5.3. Two-way Repeated Measures ANOVA for ITI Difference Scores in Contralateral and Ipsilateral Hands, With Side of TMS (Left, Right) and Interval (6 intervals after TMS) as Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10 for all).
* df = degrees of freedom for effect and error.
The mean differences in ITI from pre-TMS values in the contralateral hand for the
interval of stimulation and the following interval are summarised in Table 5.4. As the
TMS-tap interval increased, the interval of stimulation began to be prolonged; at the
short TMS-tap interval, there was no change in ITI in the interval of stimulation, and a
large increase in the following interval, at the medium interval there was a small
increase in ITI in the interval of stimulation and a large increase in the following
interval, and at the long TMS-tap interval, there was a large increase in ITI in the
interval of TMS delivery with a small increase in ITI in the following interval.
Contralateral Hand Ipsilateral Hand Effect df* F-value p-value Partial η2 df F-value p-value Partial η2
Short TMS-tap interval Side of TMS 1, 9 0.37 .558 .04 1, 9 0.24 .637 .03 Interval 5, 45 25.71 <.001 .74 5, 45 6.28 <.001 .41 Side x Interval 5, 45 0.86 .513 .09 5, 45 1.20 .324 .12
Medium TMS-tap interval Side of TMS 1, 9 0.28 .609 .03 1, 9 1.41 .265 .14 Interval 5, 45 13.38 <.001 .60 5, 45 3.82 .006 .30 Side x Interval 5, 45 0.99 .433 .10 5, 45 1.05 .402 .10
Long TMS-tap interval Side of TMS 1, 9 3.50 .094 .28 1, 9 0.04 .840 .01 Interval 5, 45 9.28 <.001 .51 5, 45 1.75 .142 .16 Side x Interval 5, 45 0.10 .991 .01 5, 45 0.49 .784 .05
83
Table 5.4.
Mean Difference in ITI from Baseline (ms) for the Interval of TMS (Intl 1) and the Interval After TMS (Int 2) During Unimanual Tapping in the Contralateral Hand After TMS Over Left and Right M1 at Short, Medium, and Long TMS-Tap Intervals. Standard Deviations Are in Parentheses.
Short Medium Long Int 1 Int 2 Int 1 Int 2 Int 1 Int 2
Left TMS 6 (14) 105 (69) 18 (25) 84 (55) 51 (37) 24 (51)
Right TMS 9 (7) 94 (48) 34 (45) 69 (66) 59 (48) 28 (46)
In summary, TMS over left and right M1 increased ITI in the contralateral hand to a
similar extent. The timing of the effect changed systematically with TMS-tap interval
duration; at the shortest TMS-tap interval, the largest change in ITI occurred in the
interval after TMS, and as TMS-tap increased, the effect of TMS progressively shifted
toward the interval of stimulation, so that at the longest TMS-tap interval, the largest
change in ITI occurred in the interval of stimulation. There were small changes in ITI in
the hand ipsilateral to the side of TMS delivery after TMS over both left and right M1.
TMS-induced disruption of bimanual tapping
Figure 5.7 illustrates two distinct response types for an individual participant at the
short TMS-tap interval. Panels A and B of Figure 5.7 show the accelerometer output for
the ipsilateral and contralateral hands in a trial with fewer contralateral than ipsilateral
taps in the period after TMS. In this example, the second tap after TMS with the
contralateral hand coincided closely with the third tap of the ipsilateral hand.
Panels C and D of Figure 5.7 show the accelerometer output for ipsilateral and
contralateral hands in a trial with an equal number of ipsilateral and contralateral taps in
the period after TMS. These two distinct response types were identified at all TMS- tap
intervals; some trials had fewer contralateral taps than ipsilateral taps in the period
84
Figure 5.7. Accelerometer output for the ipsilateral and contralateral hands during bimanual tapping before and after TMS delivered at the short TMS-tap interval. Two types of trial are illustrated; A and B show ipsilateral and contralateral hands respectively from a trial with an unequal number of ipsilateral and contralateral taps, C and D show ipsilateral and contralateral hands respectively from a trial with an equal number of ipsilateral and contralateral taps. Inter-tap intervals are marked for the hand
1800 2000 2200 2400 2600 2800 3000
Time (ms)
A
B ITIc 2 ITIc 1
ITIi 2 ITIi 1
C
D
ITIi 2 ITIi 1
ITIc 2 ITIc 1
85
ipsilateral (ITIi) and contralateral (ITIc) to side of stimulation. The broken vertical line indicates the timing of TMS. after TMS (the contralateral hand appeared to “skip” a tap) and other trials had equal
numbers of ipsilateral and contralateral taps.
The number of trials observed for the “unequal taps” response type for each participant
is displayed in Table 5.5 as a function of side of stimulation and TMS-tap interval (four
trials were performed at each TMS-tap interval, so “equal taps” can be determined by
subtracting the number of “unequal taps” from 4). Overall there were more “equal taps”
responses after TMS over left M1 (70%) and more “unequal taps” responses after TMS
over right M1 (64%); this pattern of results held true for all TMS-tap intervals. The
frequencies of equal taps trials and unequal taps trials after TMS over left and right M1
were significantly different (χ2 = 28.11, p < .001).
Table 5.5
Number of trials which had more ipsilateral than contralateral taps after TMS for each participant, out of a total of four, as a function of side of stimulation and TMS-tap interval.
TMS over Left M1 TMS over Right M1
Participant Short Medium Long Short Medium Long
1 2 2 3 3 3 1 2 2 1 0 4 0 3 3 2 0 0 3 2 3 4 0 1 0 3 4 4 5 2 0 2 4 4 4 6 1 2 3 3 3 1 7 4 0 1 4 4 4 8 4 1 3 3 4 2 9 0 0 0 1 0 0
10 0 0 0 2 1 0
Sum 17 7 12 30 25 22
Figure 5.8 shows mean ITI difference scores for each type of response (left panels show
86
trials with unequal numbers of ipsilateral and contralateral taps, right panels show trials
with equal numbers of taps) for each TMS-tap interval after TMS over left and right
M1. Trends for these data are presented in Table 5.6 (trials with unequal numbers of
ipsilateral and contralateral taps) and Table 5.8 (trials with equal numbers of taps).
In the trials with more ipsilateral than contralateral taps (Figure 5.8, left panel), the
effects of TMS over left and right M1 were similar at all TMS-tap intervals. At the short
TMS-tap interval (top panel), trials with fewer contralateral than ipsilateral taps were
characterized by a long delay in the contralateral hand in the interval after TMS. This
delay was almost equivalent to the mean ITI pre-TMS; mean ITI difference score in the
contralateral hand in the interval after TMS over left M1 was 200 ms (SD 32 ms) and
after TMS over right M1 was 163 ms (SD 44 ms), compared to mean pre-TMS ITIs for
the respective hands 204 ms (SD 8 ms) and 211 ms (SD 13 ms). Although small, the
difference in changes in ITI with the contralateral hand between left and right TMS was
significant (a larger effect after left TMS than after right TMS; Table 5.7 shows the
repeated-measures ANOVA results comparing the effects of left and right TMS on
contralateral and ipsilateral responses). In these trials ITI difference scores in the
ipsilateral hand were close to zero for all intervals after TMS.
Similarly, at the medium TMS-tap interval, for trials with fewer contralateral than
ipsilateral taps (Figure 5.8, middle left panel), TMS over left and right M1 caused large
increases in ITI in the contralateral hand in the interval after TMS delivery and little
change in the ipsilateral hand. At the long TMS-tap interval, for trials with fewer
contralateral than ipsilateral taps (bottom left panel), there was a large increase in ITI in
the contralateral hand in the interval of TMS delivery over left and right M1 and in the
following interval, and little change in ITI with the ipsilateral hand. At the medium and
87
long TMS-tap intervals, there were no significant differences between left and right
TMS on either the contralateral hand or the ipsilateral hand.
A comparison of the ITI difference scores presented in the left panel of Figure 5.8 with
those presented in Figure 5.5 reveals a striking similarity; during bimanual tapping,
when the number of taps performed with the contralateral hand was fewer than the
number performed with the ipsilateral hand in the period after TMS (in other words,
when the contralateral hand appeared to “skip” a tap), the effects of TMS on the
contralateral and ipsilateral hand were very close to those observed during unimanual
tapping.
-20
30
80
130
180
230
-20
30
80
130
180
230
1 2 3 4 5 6-20
30
80
130
180
230
1 2 3 4 5 6
-20
30
80
130
180
230
-20
30
80
130
180
230
1 2 3 4 5 6-20
30
80
130
180
230
1 2 3 4 5 6
Unequal number of ipsilateral and contralateral taps Equal number of ipsilateral and contralateral taps
Left M1 TMS Right M1 TMS Left M1 TMS Right M1 TMS
Figure 5.8. Mean difference in inter-tap interval (ITI difference) from baseline during bimanual tapping with the ipsilateral ( ) and contralateral ( ) hands after TMS to the left and right M1 at short, medium, and long TMS-expected tap intervals. Left panel shows trials in which one extra tap was performed by the hand ipsilateral to the side of TMS compared to the contralateral hand, right panel shows trials with equal taps with ipsilateral and contralateral hands. Six intervals post-TMS are displayed. The inset figures show individual contralateral responses at the short TMS-tap interval after TMS to left and right M1. Ipsilateral and contralateral data points are slightly offset on the x-axis for clarity. Errors are ±1 standard error of the mean.
ITI D
IFF
ER
EN
CE
(m
s)
ITI D
IFF
ER
EN
CE
(m
s)
Short TMS-tap interval Short TMS-tap interval
Medium TMS-tap interval Medium TMS-tap interval
Long TMS-tap interval Long TMS-tap interval
Interval Interval
88
89
Table 5.6. Trend Analyses in Trials with Fewer Contralateral than Ipsilateral Taps After TMS: Results of One-way Repeated-Measures ANOVAs with Interval (6 intervals post-TMS) as the Within-subject Factor. Values in bold are significant at alpha < .05.
Left TMS Right TMS df F-value p-value Partial η2 df F-value p-value Partial η2
Short TMS-tap interval Contralateral hand Linear 6 43.52 .001 .88 9 35.70 <.001 .80 Quadratic 6 5.16 .064 .46 9 22.49 .001 .71 Cubic 6 249.30 <.001 .98 9 87.98 <.001 .91 4th Order 6 214.18 <.001 .97 9 198.55 <.001 .96 Ipsilateral hand Linear 6 1.24 .309 .17 9 1.58 .240 .15 Quadratic 6 0.12 .744 .02 9 0.09 .767 .01 Cubic 6 0.86 .389 .13 9 0.26 .621 .03 4th Order 6 0.86 .390 .12 9 4.64 .060 .34
Medium TMS-tap interval Contralateral hand Linear 4 17.92 .013 .82 7 35.57 .001 .84 Quadratic 4 10.97 .030 .73 7 0.10 .757 .02 Cubic 4 30.87 .005 .88 7 20.98 .003 .75 4th Order 4 47.98 .002 .92 7 64.65 <.001 .90 Ipsilateral hand Linear 4 8.86 .041 .69 7 0.83 .391 .11 Quadratic 4 0.61 .478 .13 7 2.14 .187 .23 Cubic 4 1.59 .276 .28 7 7.24 .031 .51 4th Order 4 0.92 .392 .19 7 0.03 .859 .01
Long TMS-tap interval Contralateral hand Linear 4 70.91 .001 .95 7 85.98 <.001 .92 Quadratic 4 7.22 .055 .64 7 7.71 .027 .52 Cubic 4 0.08 .786 .02 7 0.24 .636 .03 4th Order 4 2.32 .202 .37 7 1.75 .227 .20 Ipsilateral hand Linear 4 3.19 .148 .44 7 4.90 .062 .41 Quadratic 4 0.30 .612 .07 7 2.66 .147 .28 Cubic 4 0.11 .759 .03 7 0.47 .514 .06 4th Order 4 0.01 .925 .01 7 0.64 .451 .08
90
Table 5.7. Two-way Repeated Measures ANOVA for ITI Difference Scores in Contralateral and Ipsilateral Hands in Trials with Fewer Contralateral than Ipsilateral Taps; Side of TMS (Left, Right) is a Between-Subjects Factor and Interval (6 intervals after TMS) is a Within-Subjects Factor. Values in Bold are Significant at alpha < .05.
* df = degrees of freedom for effect and error.
The right panel of Figure 5.8 shows mean ITI difference scores in the contralateral and
ipsilateral hands for responses with equal numbers of ipsilateral and contralateral taps in
the period after TMS delivery, for each TMS-tap interval, after TMS over left and right
M1. The results of trend analyses for these data are presented in Table 5.8.
It can be seen from Figure 5.8 that in trials with an equal number of ipsilateral and
contralateral taps (right panel), the effect of TMS over left M1 on the contralateral hand
was attenuated as TMS-tap interval increased. The same was not true after TMS over
right M1; in these trials, after TMS over right M1, the effects were attenuated at all
TMS-tap intervals. The effects of TMS over left and right M1 at each TMS-tap interval
will be discussed in turn.
In the responses with an equal number of ipsilateral and contralateral taps at the short
TMS-tap interval (Figure 5.8, top right panel), TMS over left M1 increased the ITI in
Contralateral Hand Ipsilateral Hand Effect df* F-value p-value Partial η2 df F-value p-value Partial η2
Short TMS-tap interval Side of TMS 1, 15 2.51 .134 .14 1, 15 1.42 .252 .09 Interval 5, 75 172.21 <.001 .92 5, 75 1.11 .365 .07 Side x Interval 5, 75 2.38 .047 .14 5, 75 0.32 .898 .02
Medium TMS-tap interval
Side of TMS 1, 11 1.25 .287 .10 1, 11 1.46 .252 .12 Interval 5, 55 52.14 <.001 .83 5, 55 2.65 .032 .19 Side x Interval 5, 55 2.53 .039 .19 5, 55 1.06 .391 .09
Long TMS-tap interval Side of TMS 1, 11 0.02 .902 .01 1, 11 0.04 .840 .01 Interval 5, 55 22.47 <.001 .67 5, 55 1.15 .344 .10 Side x Interval 5, 55 0.54 .742 .05 5, 55 0.53 .751 .05
91
the contralateral hand in the interval after stimulation. After TMS over left M1, ITI in
the ipsilateral hand was greater than baseline from the second to the fifth interval. In
comparison, after TMS over right M1, the mean increase in ITI with the contralateral
hand in the interval after stimulation was smaller and there was a small decrease in ITI
in the following interval. After TMS over right M1, ITI difference scores with the
ipsilateral hand remained around zero. The changes in both contralateral and ipsilateral
ITI were greater after TMS over left M1 than after TMS over right M1 (Table 5.9 shows
the repeated-measures ANOVA results comparing the effects of left and right TMS on
contralateral and ipsilateral responses). On closer inspection of the data, contralateral
responses after TMS over right M1 varied greatly between individuals (shown in the
small right-hand insert in Figure 5.8); three individuals showed a sizeable increase in
ITI, one a small decrease in ITI, and the remainder showed no marked change in ITI
after TMS over right M1. In contrast, the individual responses after TMS over left M1
were consistent and large (shown in the small left-hand insert in Figure 5.8).
At the medium TMS-tap interval, in responses with equal numbers of ipsilateral and
contralateral taps, TMS over left M1 increased the ITI with the contralateral hand in the
interval after TMS delivery. ITI with the ipsilateral hand increased in the interval after
TMS and the following interval, and returned to baseline over the following two
intervals. The changes in ITI with the contralateral and ipsilateral hand after TMS over
right M1 were small. However, as for the short TMS-tap interval, contralateral
responses after TMS over right M1 varied across individuals (individual data not
shown).
At the long TMS-tap interval, in trials with equal numbers of ipsilateral and
contralateral taps, TMS over left M1 delayed the response in the contralateral hand in
the interval of TMS delivery. Contralateral ITI remained slightly above baseline in the
92
following interval before returning to baseline. ITI increased in the ipsilateral hand after
TMS over left M1 in the interval of TMS and remained elevated for the following
interval. After TMS over right M1 there was an increase in ITI in the contralateral hand
in the interval of TMS followed by a decrease in ITI in the following two intervals. The
changes in ITI in the ipsilateral hand after TMS over right M1 were small.
Table 5.8. Trend Analyses in Trials With Equal Numbers of Ipsilateral and Contralateral Taps After TMS: Results of One-way Repeated-measures ANOVAs with Interval (6 intervals post-TMS) as the Within-subject Factor for Each Hand and Each Side of Stimulation. Values in bold are significant at alpha < .05.
Left TMS Right TMS df F-value p-value Partial η2 df F-value p-value Partial η2
Short TMS-tap interval Contralateral hand Linear 8 9.13 .017 .53 6 0.09 .772 .02 Quadratic 8 0.33 .582 .04 6 0.99 .357 .14 Cubic 8 14.26 .005 .64 6 <0.01 .985 .01 4th Order 8 21.94 .002 .73 6 12.30 .013 .67 Ipsilateral hand Linear 8 0.04 .849 .01 6 3.36 .116 .36 Quadratic 8 11.78 .009 .60 6 1.68 .242 .22 Cubic 8 0.11 .746 .01 6 2.00 .207 .25 4th Order 8 3.29 .107 .29 6 0.41 .547 .06
Medium TMS-tap interval Contralateral hand Linear 9 26.34 .001 .74 5 0.59 .476 .11 Quadratic 9 0.13 .728 .01 5 0.68 .449 .12 Cubic 9 5.07 .051 .36 5 0.10 .767 .02 4th Order 9 11.59 .008 .56 5 0.70 .440 .12 Ipsilateral hand Linear 9 7.38 .024 .45 5 0.64 .460 .11 Quadratic 9 11.66 .008 .56 5 0.02 .895 .01 Cubic 9 11.28 .008 .56 5 0.37 .569 .07 4th Order 9 0.36 .561 .04 5 0.92 .382 .16
Long TMS-tap interval Contralateral hand Linear 9 11.87 .007 .57 6 16.74 .006 .74 Quadratic 9 4.46 .064 .33 6 61.02 <.001 .91 Cubic 9 0.40 .541 .04 6 27.17 .002 .82 4th Order 9 0.27 .616 .03 6 2.47 .167 .29 Ipsilateral hand Linear 9 6.05 .036 .40 6 0.45 .528 .07 Quadratic 9 3.72 .086 .29 6 1.94 .213 .24 Cubic 9 0.26 .620 .03 6 1.34 .292 .18 4th Order 9 0.37 .556 .04 6 1.60 .253 .21
93
Table 5.9. Two-way Repeated Measures ANOVA for ITI Difference Scores in Contralateral and Ipsilateral Hands in Trials with an Equal Number of Ipsilateral and Contralateral Taps, With Side of TMS (Left, Right) as a Between Subjects Factor and Interval (6 intervals after TMS) as a Within-Subjects Factor. Values in Bold are Significant at alpha < .05 (N=10 for all).
* df = degrees of freedom for effect and error.
In trials with an equal number of ipsilateral and contralateral taps, the larger and more
consistent contralateral effect after TMS over left M1 than right M1 was not related to a
difference in excitability of M1 at the time of stimulation as measured by the MEP.
Mean MEP amplitude after TMS over left M1 was 2.3 mV (SD = 1.3 mV) and 2.2 mV
after TMS over right M1 (SD = 0.8 mV), t(9) = 0.10, p = .92 (collapsed across TMS-tap
interval because there were no significant differences across the TMS-tap intervals).
Neither is a longer SP duration likely to explain the larger contralateral effect after TMS
over left M1; although SP was not measured during tapping, when measured prior to
testing, the SP after left TMS (M 123 ms, SD 17 ms) was shorter than the SP after right
TMS (M 138 ms, SD 28 ms), although this difference was not significant (t(9) = 1.74, p =
.12).
Contralateral Hand Ipsilateral Hand Effect df* F-value p-value Partial η2 df F-value p-value Partial η2
Short TMS-tap interval Side of TMS 1, 14 7.83 .014 .36 1, 14 9.23 .009 .40 Interval 5, 70 13.80 <.001 .50 5, 70 3.96 .003 .22 Side x Interval 5, 70 5.34 <.001 .28 5, 70 1.47 .211 .10
Medium TMS-tap interval Side of TMS 1, 14 6.26 .025 .31 1, 14 3.20 .095 .38 Interval 5, 70 4.98 .001 .26 5, 70 2.13 .072 .13 Side x Interval 5, 70 1.43 .222 .09 5, 70 1.85 .114 .12
Long TMS-tap interval Side of TMS 1, 15 2.89 .110 .37 1, 15 1.95 .183 .12 Interval 5, 75 7.54 <.001 .34 5, 75 1.47 .207 .09 Side x Interval 5, 75 1.38 .243 .08 5, 75 0.44 .817 .03
94
The mean difference in ITI from baseline in the contralateral hand for the interval of
stimulation (ITI1) and the following interval (ITI2) are summarised in Table 5.10 after
TMS over left and right M1 for the two trials types, and for all trials combined. For
trials with more ipsilateral than contralateral taps (unequal taps), as the TMS-tap
interval increased, the delay in the contralateral response in the interval of stimulation
became progressively larger; at the short TMS-tap interval, there was no change in ITI
in the interval of stimulation, and a large increase in the following interval, at the
medium interval there was a small increase in ITI in the interval of stimulation and a
large increase in the following interval (although there was a small decrease in the
interval of stimulation after left-sided stimulation), and at the long TMS-tap interval, the
greater increase in ITI occurred during the interval of TMS delivery with a smaller
increase in ITI in the following interval. This pattern of results is similar to those for
unimanual tapping (Table 5.4). The changes in ITI in the contralateral hand were
slightly larger during bimanual than unimanual tapping after TMS over both left and
right M1 for these trials. The pattern was similar although attenuated for the trials with
an equal number of ipsilateral and contralateral taps after TMS over left M1 and greatly
attenuated after TMS over right M1 (as discussed above, the attenuation of the response
after TMS over right M1 was due to a large variability in individual response patterns).
The changes in ITI in the contralateral hand for all trials combined were of a similar
magnitude to those for unimanual tapping (after TMS over both left and right M1).
95
Table 5.10.
Mean Difference in ITI from Baseline (ms) for the Interval of TMS (Intl 1) and the Interval After TMS (Int 2) During Bimanual Tapping in the Contralateral Hand After TMS Over Left and Right M1 at Short, Medium, and Long TMS-Tap Intervals. Standard Deviations Are in Parentheses.
Short Medium Long Int 1 Int 2 Int 1 Int 2 Int 1 Int 2
Unequal taps:
Left TMS 8 (16) 194 (42) -11 (14) 128 (45) 116 (56) 79 (53)
Right TMS 0 (15) 164 (46) 36 (39) 123 (34) 95 (55) 79 (39)
Equal taps:
Left TMS 0 (6) 89 (69) 7 (7) 69 (49) 40 (27) 17 (44)
Right TMS -9 (11) 17 (39) 5 (39) 18 (60) 53 (17) -22 (32)
All taps:
Left TMS 5 (14) 119 (89) 6 (23) 76 (65) 58 (56) 36 (53)
Right TMS 2 (12) 122 (52) 26 (34) 78 (66) 77 (49) 37 (44)
In summary, during bimanual tapping, two types of response were observed after TMS.
In some trials there was one less contralateral tap than ipsilateral tap in the post-TMS
period, whereas in other trials, the number of taps was equal for the contralateral and
ipsilateral hands. In the former, the effects of TMS over left and right M1 were similar,
and resembled the results observed during unimanual tapping. The increase in ITI for
the contralateral hand shifted from the interval after stimulation when TMS was
delivered close to an expected tap (short TMS-tap interval) to the interval of stimulation
when TMS was delivered earlier (long TMS-tap interval). In the ipsilateral hand, ITI
difference scores remained around zero after TMS over left and right M1 in these trials.
The change in contralateral ITI was greater after TMS over left M1 than right M1 at the
short TMS-tap interval only, and there were no differences in ipsilateral ITI between left
and right sided stimulation. In contrast, in trials in which the contralateral and ipsilateral
hands performed an equal number of taps, there was a larger effect on the contralateral
96
hand after TMS over left M1 than right M1. In these responses, after TMS over left M1,
the patterns of results for the contralateral hand were similar to those for the previous
type of response. There was an increase in ITI in the ipsilateral hand which lasted four
intervals. In contrast, after TMS over right M1 there was little change in ITI with either
hand, due to large inter-individual variability.
Comparing the ITI difference scores in the two response types reveals that in trials with
an equal number of ipsilateral and contralateral taps in the post-TMS period (Figure 5.8,
right panel), changes in ITI in the contralateral hand were smaller than in trials with an
unequal number of ipsilateral and contralateral taps (Figure 5.8, left panel) after both
left and right-sided stimulation and at all TMS-tap intervals.
5.3 Discussion
Few studies have examined the effects of single-pulse TMS on ongoing rhythmical hand
movements. This study disrupted unimanual and bimanual tapping by applying TMS
over left or right M1 at various times during the inter-tap-interval and examined
changes in the timing of taps with the ipsilateral and contralateral hands.
General effects of TMS on the contralateral hand
During unimanual and bimanual tapping, TMS over either hemisphere delayed the
response with the contralateral hand. The interval in which the delay occurred depended
on the timing of TMS relative to the next tap. For the short TMS-tap interval (when
TMS was delivered close to the expected time of a tap), the first tap after TMS was not
affected, but the next tap was delayed. As the TMS-tap interval increased, the first tap
after TMS became progressively more delayed. On face value, these results seem
contrary to previous research findings that show an increasing delay in voluntary
97
movement the closer in time TMS is delivered to the expected movement. However,
closer inspection of the timing of TMS relative to the EMG activity (rather than relative
to the next expected tap) indicates the current results are consistent with previous
findings (although the interval between TMS application and EMG activity was not
calculated, inspection of individual traces showed a consistent pattern of results). For
the short TMS-tap interval, at the time of TMS application, both the extensor muscle
activity, associated with raising the finger for the upcoming tap, and the flexor muscle
activity were complete. Therefore the first tap after TMS was completed without
interruption and the duration of the interval of stimulation was not affected. The first
burst of EMG activity expected after the delivery of TMS was the extensor muscle
activity associated with raising the finger for the second tap after TMS. TMS delayed
the onset of this activity, resulting in a delay of the second tap after TMS. Similarly for
the medium TMS-tap interval, TMS delayed the activity of the extensor muscle
associated with raising the finger for the second tap after stimulation, and this tap was
delayed. Previous studies timed TMS delivery relative to bursts of EMG activity in the
agonist muscles used in the task, and also measured movement onset from EMG
activity. For the short and medium intervals, the results are comparable to previous
findings; the closer the TMS occurred to an upcoming EMG burst, the longer the delay
between expected onset and actual onset of EMG burst, and hence the longer the delay
in the tap associated with that burst (J. T. Chen et al., 2005; Day et al., 1989). For the
long TMS-tap interval, TMS was sometimes delivered during a burst of extensor
muscle activity, which resulted in a silent period in that muscle and a delay of the next
two taps.
The effect of TMS on the contralateral hand during unimanual and bimanual tapping
was short-lived, consistent with a brief interruption of M1 output, with a preserved
98
pattern of agonist and antagonist EMG bursts on the return of EMG activity. These
results are consistent with those reported by Day et al. (1989) who found that TMS
delayed reaction time by delaying the onset of the agonist muscle activity, but without
changing the pattern of agonist and antagonist EMG bursts. The results of the current
study extend this finding to ongoing rhythmical movements. The delays after
stimulation at the long TMS-tap interval indicate that the effects of TMS can extend
beyond a single interval, which is consistent with recent evidence that the primary
motor cortex encodes not only the upcoming movement, but also future elements in a
sequence of movements (Lu & Ashe, 2005).
Contralateral and ipsilateral effects of TMS during unimanual tapping
The magnitude of the effect on the contralateral hand during unimanual tapping was
approximately equal after TMS over left and right M1, consistent with previous reports
of equivalent contralateral effects of left- and right-sided stimulation on unimanual RT
(Foltys et al., 2001). There were small ipsilateral effects after TMS over left M1 at the
short and medium TMS-tap intervals and after TMS over right M1 at the medium TMS-
tap interval; the effects were mostly shortened ITIs. Although a cortical explanation of
the ipsilateral effect cannot be excluded, the ipsilateral effect could be a result of
distraction, caused by the auditory click associated with TMS discharge. When a single
distractor tone is presented during metronome-paced tapping, the next tap in the
sequence is shifted in time in the direction of the “event onset shift”, that is, if the
distractor occurs before the metronome tone, the next tap occurs sooner than expected
(Repp, 2003`, 2006). These distractor effects are not limited to metronome-paced
tapping; the effect is similar if a distractor tone is delivered during self-paced tapping.
There was no systematic asymmetry in the effects of left- and right-sided stimulation on
the ipsilateral hand during unimanual tapping, consistent with a distractor effect.
99
Contralateral and ipsilateral effects of TMS during bimanual tapping
In contrast, during bimanual tapping, a number of asymmetrical effects of left- and
right-sided stimulation were found. First, it should be noted that the delays in taps with
the contralateral hand collapsed across all trials was of a similar magnitude during
unimanual and bimanual tapping for each TMS-tap interval (these data are presented in
Tables 5.5 and 5.10 for unimanual and bimanual tapping, respectively). This indicates
that the mean effect of TMS on the contralateral hand during bimanual tapping was of a
similar magnitude to the effect during unimanual tapping. Furthermore, no obvious
differences between the effects of left- and right-TMS on contralateral taps were
obvious in the bimanual data presented this way. However, closer inspection of the data
revealed two types of response after TMS; in some trials fewer taps were performed by
the contralateral hand than by the ipsilateral hand while in other trials an equal number
of taps were performed by the two hands. There was no systematic effect of the timing
of TMS on the proportion of each response type produced. However, there was an
asymmetry in the proportion of each response type after left- and right-sided
stimulation. After TMS over left M1, responses were more likely to fall into the “equal
taps” type, whereas after TMS over right M1, responses were more likely to fall into the
“unequal taps” type. This may be related to an asymmetry in SP duration after TMS
over left and right M1; the “unequal taps” responses (more common after right-sided
stimulation) were associated with longer contralateral delays than the “equal taps”
responses and the silent period was longer after TMS over right M1 than after TMS
over left M1 (a longer SP in the non-dominant hand has been reported previously`;
Priori et al., 1999).
In response series with fewer contralateral than ipsilateral taps, the effects of TMS were
almost identical to the effects of TMS on unimanual tapping; the timing of the effect in
100
the contralateral hand depended on the timing of TMS relative to the next tap, and there
was little effect on the response with the ipsilateral hand. However, for trials with equal
numbers of ipsilateral and contralateral taps, TMS over left M1 delayed the responses of
both the contralateral and ipsilateral hands, whereas TMS over right M1 caused a
variable delay in the response with the contralateral hand, and had little effect on the
ipsilateral hand. The ipsilateral effect after stimulation over left M1 was not a
shortening of ITIs, as observed during unimanual tapping, but a prolongation of ITIs
which lasted several cycles. The tendency to temporally couple the hands during
bimanual movements is strong (Kelso, Southard, & Goodman, 1979) and the increase in
ITIs with the ipsilateral hand after TMS over left M1 probably reflects an adjustment to
the rate of this hand in order to achieve resynchronisation of the hands after TMS. This
ipsilateral effect was not seen in trials with an unequal number of ipsilateral and
contralateral taps, and in these trials resynchronization of the two hands after TMS was
achieved rapidly; the delay in tapping with the contralateral hand approximated the
duration of one ITI, and the two hands became temporally re-coupled on the first
contralateral tap and the second ipsilateral tap after TMS. In contrast, in trials with an
equal number of ipsilateral and contralateral taps, the delay in the contralateral hand
after TMS over left M1 was smaller and the lag between the hands greater than in the
previous response type. In these trials, adjusting the rate of one or both hands was
required for the two hands to become resynchronized. The disruption to tapping with the
contralateral (dominant) hand in these trials was short-lived, whereas the disruption to
the ipsilateral (non-dominant) hand persisted over three or four ITIs. Thus, while the
pre-TMS tapping rate of the dominant hand was rapidly resumed after the initial
disruption caused by TMS, tapping of the non-dominant hand was altered to achieve
resynchronization. The ipsilateral effect seen after TMS over left M1, therefore, is likely
to be a secondary result of adjusting to the contralateral effect, rather than a direct
101
cortical result of TMS. These results can be conceptualized as the dominant hand
producing a master rhythm, which the non-dominant hand adapts to, resulting in
resynchronisation of the hands over several cycles of tapping.
That it was the dominant hand which appeared to produce the master rhythm and the
nondominant hand which followed suggests a greater influence of dominant hemisphere
processing on the nondominant hemisphere than vice versa during bimanual
coordination. Behavioural evidence for this can be seen in the greater degree of spatial
assimilation observed in the non-dominant hand than in the dominant hand when aiming
movements are made with the two hands concurrently over different distances
(Sherwood, 1994). Also, during cyclical bimanual movements, the phase of the non-
dominant hand is more strongly influenced by the phase of the dominant hand than vice
versa (Carson, 1993). Furthermore, transitions between asymmetric and symmetric
patterns of bimanual circle drawing are mediated by a change in the trajectory of the
non-dominant hand (Byblow, Carson, & Goodman, 1994; Wuyts, Summers, Carson,
Byblow, & Semjen, 1996) and intentional switches from in-phase to anti-phase
bimanual wrist movements are mediated by alterations to the rate of the non-dominant
hand while the dominant hand maintains its stable rhythm (de Poel, Peper, & Beek,
2006). In a recent study, resynchronization of bimanual coordination following an
external perturbation was shown to be mediated by a change in the rate of movement in
the non-dominant limb (de Poel, Peper, & Beek, 2007). The interpretation of these
results from the view that the dominant hemisphere exerts a stronger influence over the
non-dominant hemisphere is also supported by neurophysiological studies of bimanual
coordination. An EEG coherence study showed that during bimanual movements
cortical drive was greater from the dominant to the non-dominant primary sensorimotor
cortex than in the reverse direction (Serrien, Cassidy, & Brown, 2003). Furthermore,
102
TMS studies have shown greater inter-hemispheric inhibition of the nondominant
hemisphere by the dominant hemisphere than in the reverse direction (Netz, Ziemann, &
Homberg, 1995), suggesting that the dominant hemisphere is more efficient at inhibiting
unwanted influence from the non-dominant hemisphere than vice-versa.
During bimanual tapping, a further asymmetry was observed in the magnitude of the
contralateral effects after TMS over left and right M1. In responses with an unequal
number of taps with the ipsilateral and contralateral hands, the magnitude of the
contralateral effect was greater after TMS over left M1 than right M1 at the short TMS-
tap interval. For the responses with an equal number of taps with the ipsilateral and
contralateral hands, the magnitude of the contralateral effect was greater after TMS over
left M1 than after TMS over right M1 at short and medium TMS-tap intervals. This last
finding was due to large variability in individual contralateral responses after TMS over
right M1. A tentative explanation for these findings is that they result from a more
focussed drive from the dominant hemisphere and a more diffuse drive from the
nondominant hemisphere. It is conceivable that TMS applied during a period of focused
drive would result in consistently large responses, and TMS delivered during a period of
diffuse drive would result in more variable responses between trials or between
subjects. Although speculative, a recent study which showed more sharply defined
EMG bursts for dominant than nondominant hand movements, with temporally
segregation of bursts of reciprocal muscle activity in the dominant hand, and greater co-
contraction of antagonistic muscle pairs in the nondominant limb (Heuer, 2007) is
consistent with this hypothesis.
Two aspects of dominant motor control during bimanual coordination are suggested
from these results. Firstly, they suggest a privileged status of dominant hand movements
103
during bimanual coordination. The smaller period of disruption to the dominant hand
than nondominant hand in some bimanual trials suggests that programming of
movements by the dominant hemisphere takes priority (the dominant hand provides a
master rhythm to which the nondominant hand adapts). This is consistent with the
natural roles taken by the hands during bimanual tasks; with the dominant hand
performing the fine manipulations (the foreground task) while the nondominant hand
plays a stabilizing and orienting role (the background task). In the current study, the
privileged role of the dominant hand during a task requiring equivalent movements of
the two hands suggests that this is a basic feature of bimanual motor control. Secondly,
the results are consistent with a more focused drive from the dominant hemisphere and a
more diffuse drive from the nondominant hemisphere. This may be an important factor
in the superiority of the dominant hemisphere in fine motor control as it might permit
more precise specification of spatiotemporal and force characteristics of movement.
104
105
CHAPTER 6. DISRUPTION OF UNIMANUAL AND BIMANUAL CIRCLE
DRAWING WITH TMS
In the previous study, TMS over left and right M1 during a discrete response sequence,
unimanual tapping, caused large disruptions to tapping with the contralateral hand, but
had little effect on the ipsilateral hand. During bimanual tapping, two patterns of
responses were observed. In some trials the hand contralateral to the side of TMS
application was “stalled” by a period approximately equal to the duration of a tap. In
these trials, the two hands were quickly resynchronised (within a single tapping cycle)
and the results were essentially the same as those seen during unimanual tapping. In
other trials, tapping with the hand contralateral to TMS application was stalled for a
shorter duration, and in the post-TMS period, a period of adjustment was observed
during which the two hands became resynchronized. In these trials, two lateralized
effects of TMS were observed: the effect of TMS on the contralateral hand was greater
after TMS over left M1 than right M1, and prolonged changes in inter-tap interval were
observed in the nondominant hand regardless of the side of stimulation. The first of
these effects was speculated to be due to a sharper temporal tuning of dominant than
nondominant hemisphere processes, while the latter was likely due to a “master-slave”
effect (the dominant hand produced a master rhythm, which the nondominant hand
adopted, a process resulting in resynchronisation of the hands over several cycles of
tapping).
The following study extends these findings to a task which demanded a greater degree
of spatiotemporal coordination: unimanual and bimanual circle drawing. The use of the
circle-drawing task permitted the measurement of spatial as well as temporal aspects of
performance. The small-circle drawing task used in the study in Chapter 3 was chosen
for this study because it requires the use of distal effectors, and is therefore more
106
comparable to the finger tapping task used in the previous study than the large circle
drawing task.
Continuous circle drawing requires more complex spatiotemporal coordination than the
repetitive tapping task used in the previous study. As discussed in the introduction to
this section (Chapter 4), there is evidence to suggest that the greater contribution of left
M1 than right M1 to bimanual control may be related to task complexity rather than a
feature of bimanual control per se (Koeneke, Lutz, Wustenberg, & Jäncke, 2004). In the
current study, TMS over left M1 is predicted to disrupt ipsilateral spatial performance as
well as contralateral spatial performance, whereas TMS over right M1 is predicted to
disrupt only contralateral accuracy of circle drawing. These effects are likely to be seen
during both unimanual and bimanual drawing given the greater spatiotemporal
complexity of this task.
In addition to the difference in the degree of spatiotemporal complexity of the two tasks,
they are likely to differ in the neural control of timing. Repetitive discrete movements
and continuous movements have been shown to have distinct temporal control
mechanisms (Spencer & Zelaznik, 2003; Zelaznik, Spencer, & Ivry, 2002). Repetitive
discrete tasks like tapping are punctuated by distinct events (i.e., the finger contacting a
hard surface) whereas in continuous tasks like circle drawing, there are no obvious
events demarcating separate cycles. Timing of repetitive discrete movements involves
an explicit aspect of the task (contact of the finger with the table during tapping) and is
thought to be under cerebellar control (patients with cerebellar lesions show deficits in
the timing of discontinuous tasks`; Spencer, Zelaznik, Diedrichsen, & Ivry, 2003). In
contrast, during continuous movements, timing is thought to be an emergent property of
the movement itself. Patients with cerebellar lesions do not show deficits in the timing
107
of continuous movements, suggesting a different neural origin for the processes
governing the timing of this mode of coordination. After callosotomy temporal coupling
between the hands is disrupted for continuous bimanual movements indicating that the
coupling of the hands requires interhemispheric transfer of information, and suggesting
a cortical involvement in the timing mechanism for continuous tasks (Kennerley,
Diedrichsen, Hazeltine, Semjen, & Ivry, 2002). Kennerley and colleagues proposed that
the coupling between the hands might result from the neural specification within the
cortex of movement direction or muscle activity, with similar specifications in each
hemisphere reinforcing each other via callosal interconnections. The implication of
these observations for the current study is that one might expect more extensive
temporal disruptions to both hands after TMS during bimanual continuous circle
drawing than were seen during bimanual repetitive tapping since a disruption to
movement specification within one hemisphere will disrupt between-hand coupling
which relies on interhemispheric transfer of information.
Two effects of TMS have the potential to disrupt ongoing motor behaviour: the
immediate excitatory effects culminating in an MEP, which results in an immediate
perturbation to ongoing movement, and the activation of long-lasting inhibitory
processes, which can be observed as the silent period in active muscle. However, it is
possible to activate the inhibitory circuits using low-intensity TMS without producing
an MEP in the target muscle (Wassermann et al., 1993). Indeed, Chen and colleagues
(2005) successfully used sub-threshold TMS to disrupt unimanual and bimanual
tapping, with both contralateral and ipsilateral effects during bimanual tapping, and only
contralateral effects during unimanual tapping. Three intensities of TMS were used in
the current study: supra-threshold, threshold, and sub-threshold intensities. At the lower
intensities used in this study, the effect of activating inhibitory processes within M1 on
108
continuous motor behaviour was examined without the large initial disruption caused by
the production of an MEP. Cortical inhibitory circuits are thought to be critically
important in the precise modulation of force which is required during fine motor
coordination tasks, and have been shown to be asymmetrically activated in left and right
M1, implying a greater efficiency of inhibitory circuits in left than right M1 (Hammond
& Garvey, 2006). Given the more potent long-latency inhibitory circuits in the dominant
hemisphere, a lateralized effect of low intensity TMS on motor performance was
predicted, with larger effects expected after TMS over left M1 than after TMS over
right M1.
The effects of TMS on temporal and spatial aspects of performance during continuous
unimanual and bimanual circle drawing were examined. A differential effect of TMS
over left and right M1 on bimanual circle-drawing was predicted. Because of the
complex spatiotemporal requirements of the task, a greater contribution to the control of
bimanual drawing by left M1 is likely, therefore larger disruption to both hands is
expected after TMS over left M1 than after TMS over right M1 during bimanual
drawing. Additionally, because left M1 is implicated in ipsilateral control of the right
hand during sequential motor tasks, TMS over left but not right M1 is predicted to
disrupt ipsilateral performance during unimanual drawing. The effects of stimulation
over left M1 and right M1 on spatial accuracy, rate, spatial variability, and smoothness
of drawing were examined during unimanual and bimanual drawing.
6.1 Method
Participants
Ten right-handed subjects, 6 females and 4 males, with ages ranging from 22 to 42 years
(median age 28 years) participated. Handedness, measured as the Laterality Quotient
109
from the Edinburgh Handedness Inventory (Oldfield, 1971) ranged from 70 to 100
(median 80). A brief screening questionnaire was administered to exclude individuals
who had previous or current neurological conditions, aneurism clips, pace makers,
cochlear implants, or who were taking drugs with psychoactive effects (Appendix A). If
participants responded in the affirmative on any item they were excluded from the study.
TMS
Magnetic stimuli generated by a Magstim 2002 stimulator were delivered through a
figure-of-eight coil (70-mm diameter). The manually held coil was aligned in the para-
sagittal plane with the handle posterior to the coil, and with the coil tangential to the
scalp. Scalp sites were identified on a snugly fitting cap with pre-marked sites at 1-cm
spacings.
Procedure
Electromyographic activity was recorded from the first dorsal interosseus (FDI) via
surface electrodes taped over the belly and tendon of the FDI. The EMG signal was
amplified (1000x), filtered (high-pass 100 Hz; low-pass 2 kHz), and digitized at a
frequency of 2 kHz for 500 ms following stimulation. The optimal site for eliciting an
MEP from FDI was determined by systematically delivering four stimuli over adjacent
scalp sites at an intensity sufficient to produce an MEP discernible above background
EMG in active muscle. The active threshold was then determined by stimulating at the
optimal site and progressively increasing the stimulus intensity from below to above
threshold. Threshold was defined as the minimum intensity at which three of four
successive stimulations elicited an MEP discernible above background EMG. During
determination of the optimal site and threshold, subjects maintained a slight contraction
of the FDI by holding a pen to emulate the level of FDI activation during circle-
drawing.
110
Task. Participants traced the contours of two small circles (15-mm diameter, centres 120
mm apart) on a digitizing tablet (WACOM Intuos 2 Graphics Tablet, Model No. XD-
1212-U) continuously for 10 seconds, at a comfortable and individually determined
pace. Circles were drawn in the clockwise direction with the left hand and in the
counterclockwise direction with the right hand for biomechanical equivalence. Drawing
was performed with the forearm resting on the surface of the graphics tablet, which was
the position adopted naturally by participants using their right hand. Subjects were
instructed to adopt this position with the left hand to eliminate the tendency to use the
whole arm during left-hand drawing, thus limiting proximal movements and promoting
distal movements, and ensuring task equivalence across the hands. EMG activity in both
FDI muscles, X and Y coordinates of pen positions, and pen force on the digitizing
tablet were sampled at 100 Hz with a laptop computer. Each trial began when force was
detected from one or both pens on the graphics tablet, indicating that the subject had
begun drawing.
TMS was applied over the left or right hemisphere during each trial. TMS was triggered
when at least five seconds had elapsed since the start of drawing, and when the pen
passed through the horizontal midline (± 2 mm) of the shape being drawn, to the right of
the vertical midline for the left hand and to the left of the vertical midline for the right
hand (Figure 6.1). The data from the initial two seconds of each trial were used to
determine the horizontal and vertical midlines of the shape being drawn.
111
Figure 6.1. TMS was triggered when the pen position was within the grey boxed area (A or B for left and right, respectively). TMS was triggered relative to the position of the hand contralateral to the side of TMS delivery and the limits were determined from the initial 2 seconds of data acquired in each trial. Stimulation occurred when at least 5 seconds had elapsed in the trial, and when the pen was to the right or left of the vertical midline for the left and right hands respectively, and ± 2mm of the horizontal midline. Arrows indicate the direction of movement. Each participant completed three tasks: unimanual left, unimanual right, and bimanual
circle-drawing. TMS was delivered at three intensities (10% of stimulator output below
active motor threshold, active motor threshold, and 10% of stimulator output above
active motor threshold) and to both left and right M1 in a single testing session. Trials
were arranged in three blocks of 24 (one block at each of the three TMS intensities).
Each block consisted of two runs of 12 trials, one block for each side of TMS
stimulation. Each run consisted of four trials each of unimanual left, unimanual right,
and bimanual circle-drawing.
Data analysis
For each trial, EMG activity, time, and X and Y coordinates of the pen on the digitizing
tablet were stored for later analysis. The DC components of the X and Y waveforms
were removed and the data were dual band-pass filtered with the low cut-off frequency
determined as half the average peak frequency from the power spectra of X and Y
waveforms and the high cut-off determined using the method described by Winter
(2005). The purpose of the dual filtering process (filtering once in the forward and once
Left Right
15 mm A B
120 mm
112
in the reverse direction) was to correct the phase shift otherwise introduced by a single
filtering process. The linear excursion of the pen was calculated from consecutive X, Y
coordinate pairs. The data were separated into cycles, which were defined by every
second zero crossing in the Y dimension, with TMS occurring half-way through a cycle.
Period (time to complete one cycle) and circularity (defined below) were calculated for
each cycle in the pre- and post-TMS period. Circularity was calculated as described in
Chapter 3.
Differences between the hands and across tasks were expected in circularity and period
of circle drawing. To enable comparison of changes in circularity and period of circle
drawing after TMS across hands and tasks, each measure was normalized to baseline
(pre-TMS) values. The distribution of circularity scores is bounded by 0 and 1, therefore
it is appropriate to calculate the arcsine of these values to normalize the distribution.
However, statistical analyses of transformed scores produced similar results to ‘raw’
circularity scores, therefore non-transformed circularity results were used. Circularity
ratio was calculated for each cycle after TMS as the circularity during that cycle divided
by baseline circularity. Period difference scores were calculated for each cycle after
TMS as the period during that cycle minus the mean period in the 2.5 s prior to TMS.
Statistical analyses. Mean circularity and period scores prior to TMS were analysed
using two-way repeated measures ANOVAs with Hand (left and right) and Task
(unimanual and bimanual) as within-subject factors. The effects of TMS on circularity
and period were analysed for each hand after stimulation of left and right M1 in each
task (unimanual and bimanual). Separate one-way repeated-measures ANOVAs with
Cycle (5 cycles post-TMS) as the within-subject variable were conducted on circularity
ratio and period difference score for each hand and each side of TMS stimulation. Trend
113
analyses were performed to identify any systematic relationships between the
behavioural measures and the movement cycle after TMS. Two-way repeated-measures
ANOVAs were performed with Side of TMS and Cycle after TMS as within-subject
variables for ipsilateral and contralateral hands separately to examine the effects of side
of stimulation on circularity and period. An alpha-level of 0.05 was used for all
statistical tests, and partial eta squared (η2) values are presented as estimates of effect
size.
6.2 Results
Baseline (pre-TMS) performance
Circularity. Table 6.1 shows mean circularity for the left and right hands in unimanual
and bimanual tasks prior to TMS. There was a significant effect of Hand (F(1,9) = 50.47,
p<.001, partial η2 = 0.85); shapes drawn with the left hand were less circular than
shapes drawn with the right hand during both unimanual and bimanual tasks.
Circularity during unimanual drawing did not differ significantly from circularity during
bimanual drawing. However, the left hand was less accurate during bimanual than
unimanual drawing, and the effect size for Task was moderate (partial η2 = 0.27),
although there was no significant effect of Task (F(1,9) = 3.31, p=.10) and no significant
interaction between Task and Hand (F(1,9) = 2.49, p=.15, partial η2 = 0.22).
114
Table 6.1.
Mean circularity for each hand in unimanual and bimanual circle drawing. Standard deviations are in parentheses. (N=10).
Left Right Mean
Unimanual 0.91 (0.01) 0.97 (0.01) 0.94 (0.01)
Bimanual 0.88 (0.06) 0.97 (0.01) 0.92 (0.03)
Mean 0.89 (0.03) 0.97 (0.01) 0.93 (0.01)
Period. Table 6.2 shows mean period for the left and right hands in unimanual and
bimanual tasks prior to TMS. There was a significant effect of Hand (F(1,9) = 112.60,
p<.001, partial η2 =.93) and Task (F(1,9) = 6.06, p = .036, partial η2 = .40) and a
significant interaction between Hand and Task (F(1,9) = 93.80, p < .001, partial η2 = .91).
During the unimanual task, period was longer with the left hand than the right hand
whereas during the bimanual task the period of the two hands was equal. The period of
the left hand was shorter and the period of the right hand was longer in bimanual than
unimanual drawing.
Table 6.2.
Mean period of circle drawing (ms) for each hand during unimanual and bimanual tasks. Standard deviations are in parentheses. N=10.
Left Right Mean
Unimanual 557 (98) 472 (103) 519 (99)
Bimanual 539 (112) 539 (111) 539 (111)
Mean 553 (104) 505 (106) 529 (105)
TMS was delivered over left and right M1, during unimanual and bimanual drawing and
this procedure was repeated at three TMS intensities: suprathreshold, threshold, and
subthreshold intensities. The effects of stimulation on circularity and period were
115
examined for the ipsilateral and contralateral hands. Each section begins with an
overview of the findings, followed by a detailed analysis.
TMS at 10% above threshold
During unimanual circle drawing, TMS over left M1 decreased circularity with the
ipsilateral and contralateral hands to a similar extent whereas TMS over right M1
decreased circularity only in the contralateral hand. TMS over both left and right M1
caused a large increase in period in the contralateral hand in the cycle after TMS. The
effect of TMS on ipsilateral period was small compared to the effect on contralateral
period after TMS over both left and right M1.
During bimanual circle drawing, TMS over left M1 caused a decrease in circularity with
both the contralateral and ipsilateral hand. TMS over right M1 caused a large decrease
in circularity with the contralateral hand and a small but consistent decrease in
circularity with the ipsilateral hand. The effects of TMS on period of circle drawing
were similar after stimulation over left and right M1. In each case, both ipsilateral and
contralateral hands were affected. There was a delay in the effect on the ipsilateral hand,
and the effect on contralateral hand was greatest during the cycle following the cycle of
stimulation.
Unimanual performance: Circularity. Figure 6.2 shows the tracings from a
representative subject for each hand during unimanual circle drawing. Two cycles
before and four cycles after TMS over left M1 and right M1 are shown. Two features of
these tracings are worth noting. First, a large disruption to circle drawing with the
contralateral hand occurred after TMS over both left M1 and right M1; this disruption
was not evident in the cycle during which TMS was delivered, but during the following
116
cycle. Second, ipsilateral circle drawing was disrupted after TMS over left M1 but not
after TMS over right M1. This can also be seen in the group data presented in Figure
6.3, which shows mean circularity ratios after TMS over left M1 and right M1. After
TMS over left M1 there was no decrease in circularity during the cycle in which TMS
was applied for either hand and the greatest decrease occurred during the following
cycle for both hands. Circularity returned to pre-stimulus levels over the following three
cycles. Trends (linear, quadratic and cubic) for these data are presented in Table 6.3.
In contrast, TMS over right M1 caused a large decrease in circularity in the contralateral
hand but had no effect on circularity in the ipsilateral hand (Figure 6.3, right panel).
Although circularity decreased in the contralateral hand during the cycle in which TMS
was applied, the greatest decrease did not occur until the following cycle. Circularity in
the contralateral hand returned to baseline levels over the following two cycles.
117
HAND
LEFT M1 TMS
Ipsilateral Contralateral
RIGHT M1 TMS
HAND
Ipsilateral Contralateral CYCLE
TMS - 2
TMS - 1
1
2
3
4
Figure 6.2. Sample tracings during the unimanual task with the ipsilateral and contralateral hands after TMS over left and right M1 showing disruption to both ipsilateral and contralateral drawing after TMS over left M1 but only to contralateral drawing after TMS over right M1.
118
Table 6.3. Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratios with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10).
1 2 3 4 50
0.7
0.8
0.9
1.0
1.1
1 2 3 4 5
C
Figure 6.3. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
Results of two-way repeated-measures ANOVAs comparing the effects of TMS over
left and right M1 are presented in Table 6.4. Note that the structure of these analyses is
different to the structure of the data in Figure 6.3; Figure 6.3 presented contralateral and
ipsilateral data together for each side of stimulation to allow a comparison of interlimb
changes in circularity, whereas the analyses in Table 6.4 were performed to determine if
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 2.39 .157 .21 10.26 .011 .53 Quadratic 5.24 .048 .37 0.02 .878 .00 Cubic 2.92 .122 .24 8.76 .016 .49
Ipsilateral Hand Linear 0.77 .402 .08 2.20 .172 .20 Quadratic 16.97 .003 .65 0.64 .444 .07 Cubic 4.85 .055 .35 3.24 .105 .26
Cycle
CIR
CU
LAR
ITY
RA
TIO
Left M1 TMS Right M1 TMS
119
there was a lateralized effect of TMS on the contralateral hand and on the ipsilateral
hand. The decrement in circle drawing with the contralateral hand was more
pronounced after TMS over right M1 than after TMS over left M1, reflected in a
significant interaction between Side of TMS and Cycle in the contralateral data.
Ipsilateral circularity was disrupted after TMS over left but not right M1, reflected in a
significant interaction between Side of TMS and Cycle in the ipsilateral data.
Table 6.4 Two-way Repeated Measures ANOVA for Circularity Ratios in Contralateral and Ipsilateral Hands During Unimanual Drawing. Side of TMS (Left, Right) and Cycle (6 cycles after TMS) are Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10).
* df = degrees of freedom for effect and error.
The delayed maximal effect of TMS on circle drawing can be seen in Figure 6.4 which
shows X- and Y-pen excursion in the contralateral hand after TMS over left and right
M1. The shapes drawn during each cycle are shown at the top of the figure. TMS was
timed to occur midway through cycle 1, as indicated by the solid vertical line. The
effect of TMS on X- and Y-excursion began during cycle 1 and tended to be simple
over- or under-excursions in the X- and Y-planes. Later effects were more complex as
seen in both the X-Y- excursion plots and shapes drawn during cycle 2. The early
excitatory effect of TMS can be observed in the EMG activity; during cycle 1 a large
MEP is present. Peaks in the EMG trace can also be seen during cycle 2 which coincide
with the large disruptions in X- and Y-excursion. This participant was chosen because
her responses were particularly pronounced, making excursions in the X- and Y-planes
Contralateral Hand Ipsilateral Hand Effect df* F-value p-value Partial η2 df F-value p-value Partial η2
Side of TMS 1, 9 3.60 .090 .29 1, 9 3.74 .085 .29 Cycle 4, 36 6.87 <.001 .43 4, 36 4.52 .005 .33 Side TMS x Cycle 4, 36 3.86 .010 .30 4, 36 4.29 .006 .32
120
more obvious, however, in all cases, the largest responses were observed in the second
cycle.
Figure 6.5 shows X- and Y-pen excursion in a typical trial in the ipsilateral hand after
TMS over left and right M1. The effect of TMS over left M1 was evident as simple
under-excursions in both X- and Y-planes during cycle 2. There was no apparent effect
on X- and Y- pen excursion in the ipsilateral hand after TMS over right M1.
-10
X-e
xcur
sion
(m
m)
Y-e
xcur
sion
(m
m)
10
10
-10
Time (s) 10 4 Time (s) 10 4
1 2 3 1 2 3 Cycle: Cycle:
-1
1
EM
G a
mpl
itude
(m
V)
Figure 6.4. An example of X- and Y-pen excursions with the contralateral hand and EMG activity in the FDI during unimanual circle drawing after TMS over left and right M1. Dashed horizontal lines indicate mean excursion prior to TMS, solid vertical lines indicate time of TMS delivery, and dashed vertical lines indicate the endpoints of each cycle. The three small figures above each set of plots show shapes drawn in cycles 1 to 3 (arrow indicates drawing direction, dot indicates TMS timing).
Left M1 TMS Right M1 TMS
121
X-e
xcur
sion
(m
m)
Y-e
xcur
sion
(m
m)
Time (s) 10 4
-10
10
-10
10
Time (s) 104
1 2 3 Cycle: 1 2 3 Cycle:
Figure 6.5. An example of X- and Y-pen excursions with the ipsilateral hand during unimanual circle drawing after TMS over left and right M1. Dashed horizontal lines indicate mean excursion prior to TMS, solid vertical lines indicate time of TMS delivery, and dashed vertical lines indicate the segregation of data into discrete cycles for analysis (note TMS was delivered midway through cycle 1). The three small figures above each set of plots show the shapes drawn during cycles 1 to 3.
Unimanual Performance: Period. Mean period difference scores (change from mean
period in the 2.5 s before TMS) after TMS over left and right M1 are shown in Figure
6.6. TMS over left M1 caused a large increase in contralateral period and a small
delayed increase in ipsilateral period. There was a small increase in period in the
contralateral hand in the cycle in which TMS was applied and a much greater increase
during the following cycle after which period returned to baseline levels. In contrast,
ipsilateral period did not change from baseline until two cycles after TMS delivery and
remained elevated for the following two cycles. Trends (linear, quadratic and cubic) for
these data are presented in Table 6.5.
Similarly, TMS over right M1 caused a large increase in contralateral period and a small
increase in ipsilateral period (Figure 6.6, right panel). The increase in contralateral
Left M1 TMS Right M1 TMS
122
period was greatest during the cycle following the one in which TMS was delivered and
it gradually returned to baseline over the following three cycles. There was a small
increase in period in the ipsilateral hand during the cycle of TMS delivery, followed by
a decrease in circularity and a secondary small increase in period in later cycles.
Table 6.5. Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores with Cycle (6 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 5.29 .047 .37 3.43 .097 .28 Quadratic 2.84 .126 .24 16.27 .003 .64 Cubic 6.08 .036 .40 10.11 .011 .53
Ipsilateral Hand Linear 7.57 .022 .46 0.90 .366 .09 Quadratic 1.71 .223 .16 6.88 .028 .43 Cubic 0.40 .541 .04 3.32 .102 .27
Figure 6.6. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
Cycle
PE
RIO
D D
IFF
ER
EN
CE
(m
s)
Left M1 TMS Right M1 TMS
1 2 3 4 5-20
20
60
100
140
1 2 3 4 5
123
The results of two-way repeated-measures ANOVAs are presented in Table 6.6 (note
the structure of the ANOVA is different to the structure of data in Figure 6.6). There
was no significant difference between the effects of left and right TMS on the changes
in period in the contralateral hand. The changes in period in the ipsilateral hand after
TMS over left and right M1 followed a different evolution over time, and this was
reflected in a significant Side of TMS x Cycle interaction.
Table 6.6 Two-way Repeated Measures ANOVA for Period Difference Scores in Contralateral and Ipsilateral Hands During Unimanual Drawing. Side of TMS (Left, Right) and Cycle (5 cycles after TMS) are Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10) .
* df = degrees of freedom for effect and error.
Bimanual performance: Circularity. Figure 6.7 shows the tracings from a representative
subject for each hand during bimanual circle drawing. Two cycles before and four
cycles after TMS over left and right M1 are shown. TMS over both left and right
M1disrupted performance with the contralateral hand. Drawing with the ipsilateral hand
was disrupted more after TMS over left M1 than after TMS over right M1.
Contralateral Hand Ipsilateral Hand Effect df* F-value p-value Partial η2 df F-value p-value Partial η2
Side of TMS 1, 9 0.30 .597 .03 1, 9 0.26 .622 .03 Cycle 4, 36 12.19 <.001 .58 4, 36 2.44 .065 .21 Side TMS x Cycle 4, 36 0.64 .636 .07 4, 36 2.82 .039 .24
124
HAND
LEFT M1 TMS
Ipsilateral
RIGHT M1 TMS
HAND Ipsilateral Contralateral Contralateral
HAND CYCLE
TMS - 2
TMS - 1
1
2
3
4
Figure 6.7. Sample tracings during the bimanual task with the ipsilateral and contralateral hands after TMS over left and right M1 showing disruption to contralateral circle-drawing in the cycle of TMS delivery and the following cycle and the greatest disruption to ipsilateral circle drawing in the cycle after TMS delivery over left M1.
Bimanual circularity is summarised in Figure 6.8. TMS over left M1 caused a decrease
in circularity with both the contralateral and the ipsilateral hand (left panel). After TMS
over left M1, the greatest decrease in circularity in the contralateral hand was during the
cycle of stimulation and circularity remained below baseline in the following cycle
before returning to pre-TMS values. Circularity with the ipsilateral hand decreased in
the cycle after TMS and remained low for the next three cycles. The data describing the
125
changes in circularity with the contralateral and ipsilateral hands after TMS over left
M1 had no significant linear, quadratic, or cubic trends (Table 6.7). Individual
participants’ responses with the contralateral and ipsilateral hands after TMS over left
M1 were variable, and are shown in the inset figures in Figure 6.8 (A and B,
respectively). Circularity decreased in the contralateral hand after TMS for most
participants; however one participant had a very large response. When this participant
was excluded from the analysis there was a significant linear trend (F(1,9) = 8.13, p =
.02, partial η2= .51). The responses in the ipsilateral hand were very variable, with no
consistent pattern, although circularity decreased for all participants.
TMS over right M1 caused a large decrease in circularity with the contralateral hand
and a small decrease in circularity with the ipsilateral hand (Figure 6.8, right panel). In
the contralateral hand, there was a large decrease in circularity during the cycle of TMS
delivery and an even larger decrease in the cycle after TMS, followed by a return to
baseline over the next three cycles. Ipsilateral circularity decreased slightly in the cycle
after TMS.
The results of two-way repeated-measures ANOVAs comparing the effects of TMS
over left and right M1 on circularity are presented in Table 6.8.The effect of TMS on
circularity in the contralateral hand during the bimanual task was greater after TMS
over right than left M1. The effects of TMS over left and right M1 on ipsilateral
circularity were not significantly different.
126
Table 6.7. Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratios During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 3.25 .105 .26 37.08 <.001 .80 Quadratic 0.94 .358 .10 0.08 .784 .01 Cubic 3.62 .089 .29 3.26 .104 .27
Ipsilateral Hand Linear 0.65 .440 .07 2.28 .165 .20 Quadratic 3.72 .089 .29 5.41 .045 .38 Cubic 0.16 .694 .02 1.39 .268 .13
Figure 6.8. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity. The inset graphs show individual data for the contralateral (A) and ipsilateral (B) hand after TMS over left M1 (the scale is the same as that in the large plots which resulted in truncation of two responses).
Cycle
CIR
CU
LAR
ITY
RA
TIO
Left M1 TMS Right M1 TMS
A B
1 2 3 4 50
0.7
0.8
0.9
1.0
1.1
1 2 3 4 5
C
127
Table 6.8. Two-way Repeated Measures ANOVA for Circularity Ratios in Contralateral and Ipsilateral Hands. Side of TMS (Left, Right) and Cycle (5 cycles after TMS) are Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10) .
* df = degrees of freedom for effect and error.
Bimanual performance: Period. After TMS over left M1, both contralateral and
ipsilateral period increased from baseline (Figure 6.9, left panel). Contralateral period
increased during the cycle in which TMS was delivered then gradually returned to
baseline over the following four cycles. No significant trends described these data
(Table 6.9). The inset figure in the left panel of Figure 6.9 shows individual data for the
contralateral hand, showing two different patterns of response to TMS over left M1; for
six of 10 participants period increased and for the remainder period decreased. There
was no change in ipsilateral period during the cycle in which TMS was delivered, the
greatest increase occurring in the following cycle, after which period decreased to
baseline levels gradually over the following three cycles.
Contralateral Hand Ipsilateral Hand Effect df* F-value p-value Partial η2 df F-value p-value Partial η2
Side of TMS 1, 9 23.59 .001 .72 1, 9 3.10 .112 .26 Cycle 4, 36 11.69 <.001 .56 4, 36 0.89 .480 .09 Side TMS x Cycle 4, 36 8.61 <.001 .49 4, 36 0.81 .528 .08
128
Table 6.9. Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 3.05 .114 .25 4.21 .070 .32 Quadratic 0.24 .638 .03 1.89 .202 .17 Cubic 0.03 .868 .01 2.68 .136 .23
Ipsilateral hand Linear 0.23 .644 .02 0.79 .397 .08 Quadratic 6.41 .032 .42 0.76 .405 .08 Cubic 0.84 .384 .08 3.59 .091 .28
Figure 6.9. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity. The inset figure represents individual responses in the contralateral hand after TMS over left M1 (period increased for 6 participants and decreased for 4).
TMS over right M1 caused an increase in both ipsilateral and contralateral period
(Figure 6.9, right panel). Contralateral period increased slightly in the cycle of TMS
delivery and was greatest during the following cycle, returning to baseline over the next
three cycles. There were no significant trends in the contralateral period data after TMS
Cycle
PE
RIO
D D
IFF
ER
EN
CE
(m
s)
Left M1 TMS Right M1 TMS
1 2 3 4 5-20
20
60
100
140
1 2 3 4 5
129
over right M1, although the linear trend approached significance (Table 6.9). Ipsilateral
period increased in the cycle after TMS delivery and returned to baseline over the
following three cycles. The function describing the changes in ipsilateral period had a
cubic component which approached significance.
The effects of stimulation over left and right M1 on period were similar, and there were
no significant effects of Side of TMS or significant interactions between Side of TMS
and Cycle in either the contralateral or the ipsilateral hand (Table 6.10).
Table 6.10. Two-way Repeated Measures ANOVA for Period Difference Scores in Contralateral and Ipsilateral Hands During Bimanual Drawing. Side of TMS (Left, Right) and Cycle (5 cycles after TMS) are Within-Subjects Variables. Values in Bold are Significant at alpha < .05 (N=10) .
* df = degrees of freedom for effect and error.
In summary, during unimanual circle-drawing, suprathreshold TMS over left M1
disrupted circularity with both the contralateral and ipsilateral hand, whereas TMS over
right M1 disrupted only the contralateral hand. The effect on contralateral circularity
was larger after TMS over right than left M1. The circularity results were similar during
bimanual and unimanual circle-drawing, except that during bimanual drawing the
ipsilateral hand was also affected by TMS over right M1. However, the changes in
ipsilateral circularity were larger after TMS over left than right M1. During unimanual
drawing, TMS over left and right M1 caused an increase in period in the contralateral
hand, and a small increase in the ipsilateral hand. During the unimanual task, the
changes in period after TMS over left and right M1 were equivalent. During bimanual
Contralateral Hand Ipsilateral Hand Effect df* F-value p-value Partial η2 df F-value p-value Partial η2
Side of TMS 1, 9 1.41 .265 .14 1, 9 0.84 .384 .08 Cycle 4, 36 3.74 .012 .29 4, 36 2.36 .072 .21 Side TMS x Cycle 4, 36 0.88 .485 .09 4, 36 0.57 .689 .06
130
drawing, period increased in the contralateral and ipsilateral hand to an equivalent
extent. There were no lateralized effects of TMS on changes in period.
TMS at threshold
The effects of TMS at threshold intensity on contralateral and ipsilateral performance
were attenuated compared to the effects at suprathreshold intensity. However, similar to
the effects at higher intensity, the effects on circularity with the contralateral hand was
greater after TMS over right than left M1 during unimanual drawing. During bimanual
drawing TMS caused a decrease in circularity with the ipsilateral but not the
contralateral hand, and TMS over right M1 caused a decrease in circularity with the
contralateral but not the ipsilateral hand. Period changes were seen in both hands after
TMS over left and right M1.
Unimanual performance: Circularity. There was little change in circularity after TMS
over left M1 in either the ipsilateral or the contralateral hand (Figure 6.10), although a
linear trend in the ipsilateral data approached significance (Table 6.11) and there was a
significant linear trend in the contralateral data. There was a significant decrease in
circularity in the contralateral hand after TMS over right M1.
Contralateral circularity was affected more after TMS over right M1 than left M1 (a
significant Side of TMS x Cycle interaction, F(4,36) = 3.29, p = .02, partial η2 = .27).
There was no significant difference in the effects of TMS over left and right M1 on
ipsilateral circularity.
131
Table 6.11 Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratios During Unimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Threshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 6.76 .029 .43 12.49 .006 .58 Quadratic 3.83 .082 .30 0.01 .914 <.01 Cubic 2.60 .141 .22 0.16 .696 .02
Ipsilateral Hand Linear 4.89 .055 .35 0.09 .768 .01 Quadratic <0.01 .950 <.01 3.28 .104 .27 Cubic 0.20 .664 .02 1.45 .259 .14
Figure 6.10. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1 at threshold intensity. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
Unimanual performance: Period. After TMS over left M1, period increased slightly in
the contralateral hand in the cycle after TMS, after which it returned to pre-TMS levels
(Figure 6.11, left panel). Linear and cubic trends approached significance (Table 6.12).
Period increased in the ipsilateral hand three cycles after TMS delivery and this increase
was maintained during the following cycle. After TMS over right M1, there was a small
Cycle
CIR
CU
LAR
ITY
RA
TIO
Left M1 TMS Right M1 TMS
1 2 3 4 50
0.7
0.8
0.9
1.0
1.1
1 2 3 4 5
132
increase in period in the contralateral hand (Figure 6.11, right panel), although no
significant trends described this data. There was a small increase in period in the
ipsilateral hand.
Table 6.12
Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores During Unimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Threshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 4.03 .076 .31 0.94 .359 .09 Quadratic 0.87 .376 .09 0.05 .822 <.01 Cubic 4.57 .061 .34 1.56 .243 .15
Ipsilateral Hand Linear 7.27 .025 .45 0.78 .401 .08 Quadratic 0.03 .875 <.01 0.06 .805 <.01 Cubic 3.46 .096 .28 12.51 .006 .58
Figure 6.11. Mean period difference scores with contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1 at threshold intensity. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
Cycle
PE
RIO
D D
IFF
ER
EN
CE
(m
s)
Left M1 TMS Right M1 TMS
1 2 3 4 5-20
20
60
100
140
1 2 3 4 5
133
There was no significant differences between changes in period in the contralateral hand
after TMS over left M1 and right M1, but there was a significant interaction between
Side of TMS and Cycle for the ipsilateral data (F(4,36) = 2.80, p = .04, partial η2 = .24).
Bimanual performance: Circularity. TMS over left M1 had no effect on circularity in
the contralateral hand (Figure 6.12, left panel). There was a decrease in circularity in the
ipsilateral hand which began during the third cycle and continued for the following two
cycles. TMS over right M1 caused a decrease in circularity in the contralateral hand
during the cycle of TMS and the following cycle (Figure 6.12, right panel). There was
no effect of TMS over right M1 on circularity with the ipsilateral hand. Trends for these
data are presented in Table 6.13.
Contralateral circularity was affected more by TMS over right M1 than TMS over left
M1 (significant effect of Side of TMS, F(1,9) = 6.70, p = .03, partial η2 = .43). In
contrast, ipsilateral circularity was affected more by TMS over left M1 than TMS over
right M1 (significant Side of TMS x Cycle interaction, F(4,36) = 2.99, p = .03, partial η2
= .25).
134
Table 6.13
Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratio During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Threshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 5.70 .041 .39 7.38 .024 .45 Quadratic 0.69 .427 .07 0.07 .803 .01 Cubic 0.38 .553 .04 2.40 .155 .21
Ipsilateral Hand Linear 4.31 .068 .32 3.83 .082 .30 Quadratic 0.56 .475 .06 1.54 .246 .15 Cubic 4.49 .063 .33 0.54 .481 .06
Figure 6.12. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1 at threshold intensity. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
Bimanual performance: Period. TMS over left M1 caused a slight increase in ipsilateral
period (Figure 6.13), although this was not significant, and there was no change in
contralateral period. TMS over right M1 caused a slight increase in both ipsilateral and
contralateral period, although neither change was significant. Table 6.14 shows trends
Cycle
CIR
CU
LAR
ITY
RA
TIO
Left M1 TMS Right M1 TMS
1 2 3 4 50
0.7
0.8
0.9
1.0
1.1
1 2 3 4 5140
135
for these data. There was no difference between the effects of TMS over left and right
M1 on changes in period in either the contralateral or ipsilateral hand.
Table 6.14
Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Threshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 0.05 .831 .01 0.13 .724 .02 Quadratic 1.64 .233 .15 0.66 .437 .07 Cubic 0.14 .719 .02 1.02 .339 .102
Ipsilateral Hand Linear 1.06 .330 .11 0.11 .752 .01 Quadratic 0.04 .852 <.01 2.44 .153 .213 Cubic 1.27 .290 .12 0.55 .478 .06
Figure 6.13. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1 at motor threshold intensity. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
Cycle
Left M1 TMS Right M1 TMS
PE
RIO
D D
IFF
ER
EN
CE
(m
s)
1 2 3 4 5-20
20
60
100
140
1 2 3 4 5
136
TMS at 10% below threshold
The effects of TMS at 10% below threshold on circularity and period were small and
followed a similar pattern to the effects of TMS at threshold. TMS over left M1 caused
a decrease in ipsilateral but not contralateral circularity during unimanual and bimanual
drawing, whereas TMS over right M1 caused a decrease in contralateral circularity. The
effects of TMS over left M1 were also greater in the ipsilateral hand and after TMS over
right M1 were greater in the contralateral hand.
Unimanual performance: Circularity. TMS over left M1 (Figure 6.14, left panel) caused
a small decrease in ipsilateral circularity ratio, but no change in contralateral circularity.
There was no significant change in circularity ratio after TMS over right M1 in either
the contralateral or ipsilateral hand (Figure 6.14, right panel). Table 6.15 shows the
trends for these data.
137
Table 6.15
Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratio During Unimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Subthreshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 1.65 .231 .16 5.62 .042 .38 Quadratic 1.74 .220 .16 0.04 .842 <.01 Cubic 2.16 .176 .19 3.68 .087 .29
Ipsilateral Hand Linear 10.74 .010 .54 14.36 .004 .62 Quadratic 2.24 .169 .20 1.23 .296 .12 Cubic 0.84 .384 .09 1.61 .236 .15
Figure 6.14. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during unimanual circle-drawing after TMS over left and right M1 at sub-threshold intensity. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
Unimanual performance: Period. After TMS over left M1 (Figure 6.15, left panel),
there was a small increase in period in the ipsilateral hand, but no significant change in
contralateral period. After TMS over right M1, ipsilateral period was not affected, but
Cycle
CIR
CU
LAR
ITY
RA
TIO
Left M1 TMS Right M1 TMS
1 2 3 4 50
0.7
0.8
0.9
1.0
1.1
1 2 3 4 5
138
contralateral period increased for 5 cycles after TMS (Figure 6.15, right panel). Trends
for these data are shown in Table 6.16.
Table 6.16 Trend analyses: Results of One-way Repeated-Measures ANOVAs for period Difference Scores During Unimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Subthreshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 1.16 .310 .11 1.32 .280 .13 Quadratic 0.94 .357 .10 1.60 .238 .15 Cubic 0.68 .431 .07 1.38 .270 .14
Ipsilateral Hand Linear 5.82 .044 .38 1.98 .193 .18 Quadratic 0.55 .477 .06 >0.01 .990 <.01 Cubic 0.10 .753 .01 2.35 .159 .21
Figure 6.15. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during unimanual drawing after TMS over left and right M1 at sub-threshold intensity. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
Cycle
PE
RIO
D D
IFF
ER
EN
CE
(m
s) Left M1 TMS Right M1 TMS
1 2 3 4 5-20
20
60
100
140
1 2 3 4 5
139
The changes in contralateral period were larger after TMS over left than right M1
(significant effect of Side of TMS, F(1,9) = 11.16, p = .009, partial η2 = .55). In contrast,
the changes in ipsilateral period were larger after TMS over right M1, although this
difference was not significant.
Bimanual performance: Circularity. Circularity decreased in the ipsilateral hand after
TMS over left M1 in the cycle of TMS delivery and remained lower than baseline for
the next four cycles (Figure 6.16, left panel). There was no change in the contralateral
hand. There were no significant changes in circularity after TMS over right M1 for
either hand (Figure 6.16, right panel). Trends for these data are presented in Table 6.17.
There was no significant difference between the effects of TMS over left and right M1
on contralateral circularity, however, TMS over left M1 caused a greater reduction in
ipsilateral circularity than TMS over right M1 (significant effect of Side of TMS, F(1,9) =
11.18, p = .009, partial η2 = .55).
140
Table 6.17 Trend analyses: Results of One-way Repeated-Measures ANOVAs for Circularity Ratio During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Subthreshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 0.40 .542 .04 0.82 .390 .08 Quadratic >0.01 .952 >.01 0.30 .600 .03 Cubic 0.69 .427 .07 3.84 .082 .30
Ipsilateral Hand Linear 0.13 .728 .01 0.07 .800 .01 Quadratic 0.83 .385 .08 0.28 .607 .03 Cubic 2.51 .148 .22 1.99 .192 .18
Figure 6.16. Mean circularity ratio with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1 at sub-threshold intensity. Circularity ratio was calculated at the circularity during each cycle divided by mean circularity prior to TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
Bimanual performance: Period. There were small increases in period in both the
ipsilateral and contralateral hand after TMS over left M1, beginning in the cycle after
TMS delivery (Figure 6.7, left panel), although there were no significant trends for
either hand. No significant change occurred in ipsilateral or contralateral period after
CIR
CU
LAR
ITY
RA
TIO
Left M1 TMS Right M1 TMS
Cycle 1 2 3 4 5
0
0.7
0.8
0.9
1.0
1.1
1 2 3 4 5
141
TMS over right M1 (Figure 6.17, right panel). Trends for these data are presented in
Table 6.18.
Table 6.18 Trend analyses: Results of One-way Repeated-Measures ANOVAs for Period Difference Scores During Bimanual Drawing with Cycle (5 cycles post-TMS) as the Within-subjects Factor for Each Hand and Each Side of Stimulation, at Subthreshold TMS Intensity. Values in Bold are Significant at alpha < .05 (N=10).
Left TMS Right TMS F-value p-value Partial η2 F-value p-value Partial η2
Contralateral hand Linear 0.29 .603 .03 0.38 .554 .04 Quadratic 3.00 .117 .25 0.06 .808 .06 Cubic 0.10 .763 .01 0.05 .829 .05
Ipsilateral Hand Linear 0.17 .693 .02 0.02 .904 <.01 Quadratic 4.39 .066 .33 0.13 .724 .01 Cubic 0.05 .833 .01 0.21 .660 .02
Figure 6.17. Mean period difference scores with the contralateral ( ) and ipsilateral ( ) hand during bimanual circle-drawing after TMS over left and right M1 at sub-threshold intensity. Period difference scores were calculated as the period of each cycle minus the mean period before TMS. Error bars are ± 1 standard error of the mean. Points of ipsilateral and contralateral data sets are slightly offset on the x-axis for clarity.
There was no significant difference between the effects of TMS over left and right M1
on changes in period in either the contralateral or ipsilateral hand.
PE
RIO
D D
IFF
ER
EN
CE
(m
s)
Left M1 TMS Right M1 TMS
Cycle 1 2 3 4 5-20
20
60
100
140
1 2 3 4 5
142
6.3 Discussion
The main findings of this study were: suprathreshold TMS over primary motor cortex
during continuous circle drawing caused enduring decreases in circularity and increases
in period. The greatest effects on both circularity and period were delayed relative to the
time of TMS application. Left hemispheric stimulation decreased circularity with both
the contralateral hand and the ipsilateral hand whereas right hemispheric stimulation
decreased circularity only with the contralateral hand. This lateralized effect of TMS on
circularity was not limited to the bimanual case, but was also apparent during unimanual
drawing. In contrast, period of circle drawing was affected equally by stimulation over
left and right M1. During unimanual drawing, stimulation over both left and right M1
increased period with both hands and the increase was larger in the contralateral hand
than in the ipsilateral hand. During bimanual drawing, period of drawing with the
contralateral hand and the ipsilateral hand were affected to a similar extent by TMS over
both left and right M1. Stimulation using lower TMS intensities caused smaller
decreases in circularity and increases in period than suprathreshold TMS. The changes
in circularity and period after TMS at the lower intensities were most evident in the
ipsilateral hand after TMS over left M1, and the contralateral hand after TMS over right
M1.
At lower TMS intensities, left sided stimulation was predicted to have a greater effect
than right sided stimulation, due to the greater potency of inhibitory circuits in the
dominant M1 than nondominant M1 (Hammond, Faulkner, Byrnes, Mastaglia, &
Thickbroom, 2004). However, these predictions were not born out by the results of
threshold and sub-threshold stimulation in this study. Firstly, as expected, changes in
circularity and period after TMS at threshold and sub-threshold intensities were of a
smaller magnitude than after suprathreshold TMS. There were small changes in
143
circularity at both threshold and sub-threshold intensities, which were more obvious
during bimanual than unimanual drawing. However, contrary to the predicted lateralized
effect, the largest decreases in circularity occurred in the ipsilateral hand after TMS over
left M1, and in the contralateral hand after TMS over right M1. The period data showed
a similar trend; the changes in period during unimanual drawing after threshold or sub-
threshold TMS were greater in the ipsilateral hand after TMS over left M1, and the
contralateral hand after TMS over right M1. During bimanual drawing, the changes in
period with the ipsilateral and contralateral hand were of a similar magnitude, and there
was little difference between the effects of left and right sided stimulation (similar to the
effect of supra-threshold stimulation on changes in period). Although many of the
changes in circularity and period after TMS at threshold and sub-threshold intensities
failed to reach significance, the general impression was that when performance
decrements were observed, it was the performance with the nondominant hand that was
most affected, regardless of the hemisphere being stimulated.
It seems unlikely that physiological processes in M1, such as the activation of
intracortical inhibitory circuits, could account for the contralateral effects after TMS
over right M1 and the ipsilateral effects after TMS over left M1, as the activation of
these circuits would be expected to have a greater effect on the contralateral hand than
the ipsilateral hand regardless of side of stimulation. A more plausible explanation is
that the nondominant hand was less resistant to interference by the startling effect of the
TMS acoustic stimulus than the dominant hand. Startle effects have been noted for low
intensity acoustic stimuli (Blumenthal, 1988). At first blush, it is difficult to see how an
autonomic response to the click associated with discharge of the TMS pulse could
account for the lateralized motor effects observed in the present study (the nondominant
hand was affected more than the dominant hand by both left and right-sided
144
stimulation). Yet the changes in circularity and period after TMS at the lower intensities
do imply that control of the nondominant hand was the more sensitive to disruption than
control of the dominant hand. What might be the basis of this observation?
Asymmetries in the direction of attention could account for the effects during bimanual
coordination. There is evidence that the dominant hand is the main focus of attention
during bimanual coordination (Peters, 1981), which is consistent with the role taken by
each hand during naturally occurring bimanual tasks (the dominant hand usually
performs the task requiring directed attention, while the nondominant hand performs a
stabilizing role, and receives only indirect attention). However, this is unlikely to
account for the effects during unimanual drawing. There is evidence that participants
are able to prepare themselves for and resist the disruptive effects of TMS (Bonnard,
Camus, de Graaf, & Pailhous, 2003). In the current study no trials were delivered
without TMS, and knowing that a TMS pulse would occur around the middle of a trial
might have changed the behaviour of the participants; the current results might reflect a
greater ability to prepare for a disruption to the dominant hand. However, a more
parsimonious explanation which could account for the effects of low intensity stimuli
during both unimanual and bimanual coordination relates to a mechanical asymmetry
between drawing with the dominant and nondominant hand. In Chapter 3 it was noted
that more pressure was applied during circle drawing with the dominant than the
nondominant hand, which might result from a difference in confidence between drawing
with the dominant and nondominant hand (LaRoque & Obrzut, 2006). Greater force
applied with the dominant than nondominant hand, would have provided greater
friction, and may have afforded more stability to the dominant hand, rendering it less
susceptible than the nondominant hand to perturbation.
145
The effects of suprathreshold TMS are likely to represent those effects seen after lower
intensity stimulation (due to mechanical stability differences between the hands), plus
any physiological effects of stimulation at a higher intensity. The effects after
suprathreshold stimulation were much larger than the effects seen after lower intensity
TMS pulses. In addition, qualitative differences between the effects after suprathreshold
stimulation and lower-intensity stimulation suggest that the magnitude of the difference
between these effects must represent physiological effects. Several features of these
qualitative differences deserve elaboration.
Firstly, the effect of suprathreshold TMS over left M1 on circularity was not immediate,
but emerged during the cycle after TMS. The effect of TMS over right M1 on circularity
emerged during the cycle of TMS but was greatest in the cycle after TMS. In both cases
the effects endured for several cycles after TMS. There was evidence in the X- and Y-
excursion data of small changes during the cycle of TMS, followed by greater changes
in the cycle after TMS. The small disruption to drawing during the cycle of TMS was
probably caused by a combination of immediate excitatory effects of TMS on M1
(resulting in a muscle twitch) and more sustained inhibitory effects of TMS on M1.
However, the greatest disruption to circle drawing occurred in the cycle after TMS, by
which time both the immediate excitatory and the more sustained inhibitory effects of
TMS would have resolved. This delayed effect on performance may have resulted, at
least in part, from the return of EMG activity after the silent period, which is consistent
with the timing of large secondary disruption to circle drawing evident in the tracings,
circularity index, and X- and Y-excursion data during the cycle after TMS.
Secondly, the effects of TMS on circularity were lasting; a return to stable, pre-TMS
levels of accuracy did not occur immediately, but developed over several cycles. By
146
comparison, the time to return to stable simple rhythmic movements after mechanical
perturbation is relatively short; during a cyclical finger flexion-extension task
disruptions caused by a mechanical perturbation were overcome and a stable pattern of
movement re-established within a single cycle of movement (around 500 ms`; Kay,
Saltzman, & Kelso, 1991). This represents a much shorter adjustment period than that
observed in the present study. The enduring effect of TMS on circularity may reflect a
long period of post-TMS trajectory adjustments in order to return to a stable pattern of
drawing. Alternatively, the lasting effect on circularity may reflect an enduring effect of
TMS itself on M1 and motor output. Evidence from recent neurophysiological studies
implicates M1 in high-level aspects of motor control. Although traditionally labelled the
primary output stage of the motor cortex, a recent study in monkeys showed that for
complex sequences, neurons in M1 represent not only the movement being performed,
but also upcoming sequences of movements (Lu & Ashe, 2005). Furthermore, electrical
stimulation of M1 can produce complex, multijoint movements in the monkey that
resemble natural movements, suggesting that M1 encodes relatively high-level motor
plans (Graziano, Aflalo, & Cooke, 2005). The prolonged effect of TMS on circularity
may therefore reflect a disruption to the representation of upcoming movements,
although it is not possible to distinguish between the two alternative explanations in the
present study.
Suprathreshold TMS over left M1 caused approximately equal disruption to ipsilateral
and contralateral circularity whereas TMS over right M1 caused a large disruption to
contralateral circularity and very little disruption to ipsilateral circularity. Neuroimaging
data suggests that coupled bimanual movements are controlled predominantly by the
dominant hemisphere (Jäncke et al., 1998; Serrien, Cassidy, & Brown, 2003; Viviani,
Perani, Grassi, Bettinardi, & Fazio, 1998). However, in the present study, the effects of
147
TMS on circularity were similar during unimanual and bimanual drawing; in both cases,
changes in ipsilateral circularity were greatest after TMS over left M1. This contrasts
with previous TMS studies which have shown no lateralized effect of TMS during
bimanual reaction time (Foltys et al., 2001) or during bimanual tapping (J. T. Chen et
al., 2005). It also contrasts with the previous study (Chapter 5) where lateralised effects
of TMS were only seen during bimanual finger-tapping. However, the task in the
current experiment required a more complex modulation of the activity of many hand
muscles for accurate circle drawing than the simple finger flexion-extension required in
the previous tasks. In this respect, the circle-drawing task can be thought of as a
sequencing task in that it requires the sequencing of many sub-movements to produce a
smooth circular movement. Neuroimaging and lesion studies have shown that left M1 is
dominant for complex sequences of hand movements (Rao et al., 1993; Salmelin, Forss,
Knuutila, & Hari, 1995; Verstynen, Diedrichsen, Albert, Aparicio, & Ivry, 2005; Wyke,
1971). Furthermore, as discussed in the introduction to this chapter, it has been
suggested that the greater activation of the dominant hemisphere during bimanual
compared to unimanual motor performance is not due to a difference in task (unimanual
versus bimanual) per se, but due to a difference in the complexity of the tasks (Koeneke,
Lutz, Wustenberg, & Jäncke, 2004). The greater effect after TMS over left M1 on
ipsilateral circularity in the current study, regardless of mode of drawing, provides
support for the dominance of the left hemisphere in the preparation of complex
sequential movements rather than a specific role in bimanual coordination.
In contrast to the effects of TMS on circularity, there was no difference between the
effects of left- and right-sided stimulation on period of circle drawing. During
unimanual drawing, TMS over both left and right M1 caused large increases in period
of circle drawing in the contralateral hand and small changes (mostly increases) in
148
period of circle drawing in the ipsilateral hand. During bimanual drawing, TMS over
both left and right M1 caused increases in period of circle drawing with the ipsilateral
and contralateral hand. The increase in period in the contralateral hand preceded the
increase in period in the ipsilateral hand; there was a slight increase in period in the
cycle of TMS with the contralateral hand but not with the ipsilateral hand and a larger
increase in period in the cycle after TMS with both hands. The changes in period with
the two hands were of a similar magnitude and followed a similar time course during
bimanual drawing, suggesting that the hands became tightly temporally coupled soon
after the disruptive effects of TMS. Furthermore, after TMS over right M1, disruption to
the temporal control of both the ipsilateral and contralateral hands occurred without
major changes in ipsilateral circularity. In other words, the dominant hand maintained
spatial accuracy after TMS over right M1, but slowed to match the nondominant hand.
This observation contrasts with the finding in the previous study, which found that
during bimanual finger tapping, TMS increased the inter-response interval mainly with
the contralateral hand. These contrasting effects provide further support for the
hypothesis that different timing mechanisms are invoked during repetitive discrete
response tasks and continuous tasks (Spencer & Zelaznik, 2003; Zelaznik, Spencer, &
Ivry, 2002).
In summary, the effects of subthreshold and threshold TMS were likely due to the
nondominant hand being less resistant to interference by the startling effect of the TMS
acoustic stimulus than the dominant hand due to mechanical differences in drawing with
the two hands. The effects of suprathreshold TMS were qualitatively and quantitatively
different from those evoked by lower intensity stimulation. Left hemispheric stimulation
decreased circularity with both the contralateral and the ipsilateral hand whereas right
hemispheric stimulation decreased circularity only with the contralateral hand. The
149
lateralized effect of TMS on circularity was not limited to the bimanual case, but was
also apparent during unimanual drawing. These results contrast with the findings of the
previous study in which lateralized effects of TMS were seen only during bimanual
finger tapping. This suggests a role for the left hemisphere in control of complex
sequential organization of movement by both hands, and is consistent with lesions
studies which show left hemisphere lesions result in sequencing deficits with both
hands, whereas right hemisphere lesions result in sequencing deficits with the
contralateral hand only (Haaland & Harrington, 1994).
150
151
CHAPTER 7. UNIMANUAL AND BIMANUAL PERFORMANCE AFTER
UNILATERAL STROKE
Deficits in motor control following a stroke are common; between 70 and 85 percent of
stroke survivors are estimated to suffer from acute hemiparesis (Dobkin, 2004). While
some functional recovery occurs following a stroke, between 55 and 70 percent of
patients experience lasting impairments in upper limb functioning three to six months
post-stroke (Kwakkel, Kollen, van der Grond, & Prevo, 2003; Lai, Studenski, Duncan,
& Perera, 2002). Furthermore, even patients who have good recovery of strength on the
affected side often have enduring deficits in fine motor control (Heald, Bates, Cartlidge,
French, & Miller, 1993; Kunesch, Binkofski, Steinmetz, & Freund, 1995). In a group of
patients with lesions of the primary motor cortex, strength in the arm contralateral to the
lesion recovered considerably six weeks after the infarct, and four of seven patients had
no residual weakness at this stage (Kunesch, Binkofski, Steinmetz, & Freund, 1995).
Hand function also improved in these patients, but no patient gained a score indicating
‘no disturbance’ on a test of hand function (assessing, among other things, hand-writing,
buttoning, and tying shoelaces). Heald and colleagues (1993) found that manual motor
control (measured by performance on a peg moving task) remained outside the normal
range in a group of stroke patients, despite recovery of hand strength one year after a
stroke. Considering the importance of the use of our hands in our everyday lives,
recovery of upper limb function is a primary concern for stroke patients.
One approach to improving upper limb function that has been gaining support is
bilateral training. A recent review argued that bilateral arm training is a necessary
adjunct to unilateral training in regaining meaningful arm function (McCombe Waller &
Whitall, 2008); given that many of our daily activities require bimanual coordination,
152
for good functional recovery it makes sense to re-train bimanual movements. There has
been a recent surge in the use of “constraint induced movement therapy” which has the
potential to produce large improvements in functional outcomes by restraining the use
of the unaffected limb of stroke patients in order to encourage use of the affected limb
(Taub, Uswatte, & Pidikiti, 1999). This protocol has been shown to have substantial and
lasting effects 2 years after the intervention (Taub et al., 2006). A recent study
compared constraint induced movement therapy and bilateral training in a group of
patients with mild to moderate deficits after hemiparetic stroke and found that the
greatest improvements for functional outcomes were seen in the constraint group;
however, some benefits to upper function were only observed in the group who received
bilateral training (Lin, Chang, Wu, & Chen, 2009). This finding suggests that
incorporating cooperative bimanual behaviour within the rehabilitation regime may be
as important as constraining the unaffected limb. Additionally, training only on
unimanual tasks may not maximize recovery of bimanual functioning because such
training does not include an important aspect of bimanual behavior: the between-hand
coordinative aspect of bimanual coordination.
In normal bimanual movement, there is a strong tendency toward temporal synchrony
between the hands (e.g.`, Franz, Zelaznik, & McCabe, 1991; Semjen, Summers, &
Cattaert, 1995). Furthermore, when two different movements are produced
concurrently, an integration of features of the motor response of one limb into the motor
response of the other limb is seen, a phenomenon termed ‘assimilation’ (e.g.`, Franz,
1997; Marteniuk, MacKenzie, & Baba, 1984). These effects have traditionally been
viewed as constraints on bimanual movement (i.e., each hand is constrained by what the
other hand is doing); however, in the context of motor control after a stroke, the
153
coupling of movements of the two hands may result in the facilitation of the
performance of the affected limb.
Several studies have investigated the effects of bilateral training on functional
improvements after stroke. Passive movement of the affected limb using a bilateral
training protocol has been shown to improve functional outcome for the affected limb in
some but not all patients (J. W. Stinear & Byblow, 2004). Whitall and colleagues (2000)
found that bilateral arm training led to improvement on functional tests of everyday
functioning, strength, and range of motion with the paretic arm in chronic hemiparetic
stroke patients however there was no comparison group included in the study against
which the relative effectiveness of bilateral training could be assessed. Using a similar
protocol, Luft and colleagues (2004) compared bilateral arm training with rhythmic
auditory cueing standard training exercises (matched for dose) on impaired limb
function. After training three times a week for six weeks there was no difference in
functional outcome between the groups as a whole. However, some participants
receiving bilateral training had significant increases in brain activation (measured with
functional magnetic resonance imaging), and these participants had greater
improvements in functioning than the control group. Mudie and Matyas (2000) also
reported greater improvements in the paretic limb in tests of functional unimanual
performance (e.g., simulated drinking) after bilateral than after unilateral whole-arm
training. Similarly, Summers et al. (2007) found that six sessions of bilateral training
led to a decrease in movement time with the impaired limb on the trained task (placing a
wooden dowel on a shelf) and an increase in functional ability with the impaired limb,
whereas six sessions of unilateral training was not associated with movement time or
functional improvements.
154
The beneficial effects of bilateral training in all of these studies were examined for
unimanual movements of the affected limb. Given the importance of bimanual
coordination in everyday functioning, another important outcome of rehabilitation
strategies after stroke is an improvement in the functioning of the two limbs together.
Few studies have assessed the effects of bilateral training on bilateral performance. Two
studies found that bilateral training and unilateral training (of the affected limb)
improved bilateral performance to a similar extent (Desrosiers, Bourbonnais, Corriveau,
Gosselin, & Bravo, 2005; Platz, Bock, & Prass, 2001). Each of these studies included
only mild or moderately affected patients and the study by Desrosiers and colleagues
used unilateral or bilateral training in addition to usual care (some components of which
were bilateral activities), which limits the interpretations of the findings. A study
comparing unilateral and bilateral whole-arm training for patients with severe
impairments and another in patients with moderate deficits found no beneficial effect of
bilateral training, suggesting that this approach may not be beneficial in more severely
affected patients (Mudie & Matyas, 2001; Tijs & Matyas, 2006).
Several studies have investigated inter-limb coordination dynamics after unilateral
stroke. Movements with the impaired limb tend to be slower than movements with the
unimpaired limb, and there is a tendency for the arms to become temporally coupled
during bimanual movements (as observed in unimpaired individuals). This is often
achieved by a slowing of the unimpaired arm rather than facilitation of performance
with the impaired arm (Garry, van Steenis, & Summers, 2005; Kilbreath, Crosbie,
Canning, & Lee, 2006; Rice & Newell, 2001; Steenbergen, Hulstijn, de Vries, &
Berger, 1996). However, other studies have shown facilitation of performance with the
impaired limb when coupled with the unimpaired limb compared to unilateral
movements of the impaired limb alone. Faster movements with the impaired limb have
155
been shown during rapid bimanual aiming than unimanual aiming (Harris-Love,
McCombe Waller, & Whitall, 2005; Rose & Winstein, 2005) and Cunningham and
colleagues showed a trend towards smoother trajectories of elbow extensions during
bilateral movements than during unilateral movements (Cunningham, Phillips Stoykov,
& Walter, 2002). Furthermore, in-phase bimanual circle drawing facilitated
performance with the paretic arm in children with spastic hemiparesis compared to
unimanual performance (Volman, Wijnroks, & Vermeer, 2002) although a similar study
in stroke patients showed no facilitation of the paretic arm (Lewis & Byblow, 2004).
The inconsistencies in the studies of bilateral coordination dynamics may be in part due
to the differences in the complexities of tasks used. Stroke patients have obvious
difficulties with complex bimanual coordination; when participants attempted to
oscillate one limb at twice the frequency of the other limb’s movements, right-
hemispheric stroke patients were largely unsuccessful, reverting to a 1:1 in-phase
coordination pattern between the limbs (Rice & Newell, 2004). Taken together these
findings suggest that the tendency of the motor system to couple the actions of the two
hands may facilitate performance on the impaired side after stroke. Indeed, a recent
meta-analysis indicated that bilateral training, either alone, or combined with sensory
feedback, is an effective training protocol for functional arm recovery after stroke
(Stewart, Cauraugh, & Summers, 2006). However, it remains to be determined what
types of bimanual actions facilitate performance with the impaired limb and which tasks
have therapeutic potential for which patients.
The current study provided a preliminary examination of bimanual coordination in
participants who had suffered a unilateral stroke using the two tasks for which normal
results were presented in Chapters 2 and 3. Bimanual tapping and circle-drawing
performance was compared to unimanual performance in the impaired and unimpaired
156
limb in patients with mild, moderate, and severe upper-limb deficits. The findings from
the previous two chapters that support left hemispheric control of bimanual movement,
suggest that patients with left hemisphere lesions will demonstrate greater impairment
in bimanual coordination than patients with right hemisphere lesions. Furthermore, a
recent study showed greater interlimb coupling in patients with right hemisphere lesions
than in patients with left hemisphere lesions (Lewis & Perreault, 2007). It is predicted
that patients with right hemisphere lesions will show a greater facilitation of
performance with the affected limb during bimanual coordination than patients with left
hemisphere lesions.
7.1 Method
Participants
Participants were 12 individuals who had suffered a unilateral cerebral vascular accident
(age range 49 to 60). Four patients had mild, 4 had moderate, and 4 had severe upper
limb motor deficits. Individuals in the mild group had subjective motor deficits on
dexterous tasks such as writing, but all were able to use the affected limb in everyday
tasks, individuals in the moderate group were more obviously affected, but still had
some independent ability with the affected limb, and individuals in the severe group had
very limited ability to control the affected limb (although a prerequisite for participation
was having enough motor ability to grasp a pen with the affected limb). Individual
characteristics (age, sex, time since stroke, and side of stroke) are presented in table 7.1.
All participants were right handed (self reported writing hand) pre-stroke, except P7.
Patients were recruited from the occupational therapy department of a major teaching
hospital and from an inpatient rehabilitation unit, the occupational therapist responsible
for the rehabilitation of each patient judged each patient to be either mildly, moderately,
157
or severely motor impaired. All participants were capable of comprehending task
instructions, although no formal assessment of cognitive ability was performed, and all
gave informed written consent to participate.
Table 7.1
Characteristics of the patient groups.
Participant Sex Age Lesion side (hemisphere)
Months since stroke
Mild P1 M 59 Right 84 P2 M 60 Left 2 P3 F 49 Left 5 P4 F 58 Left 120
Moderate P5 M 53 Right 3 P6 F 54 Right 24 P7 M 57 Right 1.5 P8 M 61 Left 2
Severe P9 F 63 Right 2 P10 F 54 Right 1 P11 M 69 Left 1.5 P12 M 50 Left 1.5
Procedure
Each participant was tested in a single session. All participants completed the tapping
task. Participants with a mild or moderate deficit completed both small and large circle
drawing tasks; participants with a severe deficit completed only the large circle drawing
task. One participant (P6) refused circle-drawing with her affected arm, and one
participant (P9) was unable to attempt bimanual circle-drawing.
Tapping. Participants sat comfortably with their elbows flexed at approximately 90
degrees and both hands resting on a desk surface (palm down). Participants were
instructed to tap at a fast steady pace for ten seconds with their left hand alone, with
158
their right hand alone, or with both hands together, by extending and flexing their index
finger(s) around the metacarpal-phalangeal joint, keeping their hand and other fingers
flat on the table. Finger movement was measured with a miniature accelerometer
mounted in a resin block, attached to the index finger of each hand. Output from the
accelerometers was sampled from the audio input of a computer.
Inter-tap intervals (ITIs) were determined as the time between successive contacts in
ms. Coefficients of variation (CV) of the ITIs were calculated as a measure of tapping
variability as the standard deviation of ITIs on each trial divided by mean trial ITI
(expressed as a percentage).
Circle drawing. Participants traced the contours of circles (either 15-mm or 70-mm
diameter), centres 120 mm apart, on a digitizing tablet (WACOM Intuos 2 Graphics
Tablet, Model No. XD-1212-U) continuously for 10 seconds, at a comfortable and
individually determined pace. Some participants could not complete a sufficient number
of cycles for analysis with the affected limb in the 10 seconds; for these participants, the
duration of tracing was extended to 20 seconds. Circles were drawn in the clockwise
direction with the left hand and in the counter-clockwise direction with the right hand to
maintain biomechanical equivalence. For the small circle targets, drawing was
performed with the forearm resting on the surface of the graphics tablet, which was the
position adopted naturally by participants using their right hand. Subjects were
instructed to adopt this position with the left hand to eliminate the tendency to use the
whole arm during left-hand drawing, thus limiting proximal movements and promoting
distal movements, and ensuring task equivalence across the hands. For the large circle
targets, participants were free to adopt a comfortable drawing position. Each trial began
when force was detected from one pen (for unimanual drawing) or both pens (for
159
bimanual drawing) on the graphics tablet, indicating that the subject had begun drawing.
Circularity was used to assess accuracy of drawing. Circularity was calculated as
described in Chapter 3
RMS jerk was calculated as a measure of drawing smoothness. Jerk was calculated as
the third derivative of linear distance with respect to time.
Task order. Each participant completed the tapping task followed by the circle-drawing
task. Two trials of each task were completed. Task order was selected to progress from
easiest to most difficult: within each task, participants completed unimanual trials with
their unaffected limb first, followed by unimanual trials with their affected limb,
followed by bimanual trials. For participants who completed both small- and large-
circle drawing tasks, large circles were drawn first then small circles.
Control data. A preliminary analysis of the control data revealed no significant
differences between the results for participants aged over 50 and the whole group,
therefore the means from Chapter 2 (tapping data) and Chapter 3 (circle-drawing data)
are presented for comparison with the stroke patients’ data.
7.2 Results
Participants were classified into mild, moderate, and severe groups. However, forming
averages of each measure within groups was uninformative due to the large between-
subject variability in performance. Therefore individual results are presented.
160
Unimanual and bimanual tapping
Mean inter-tap interval (ITI) is shown in Figure 7.1 for each participant (affected limb is
indicated at top of each panel) and controls. The mild group of participants tapped at
around the same rate as control participants (tapping by P1 was slightly slower than
controls with both hands). Unimanual tapping was slower with the affected hand for all
participants except P4 who tapped faster with her right (affected) hand than her left
(unaffected) hand. There was little difference between tapping rates in the unimanual
and bimanual modes for any participant in this group.
In the moderate group (Figure 7.1, middle panel), tapping was slower with the affected
than the unaffected hand during unimanual tapping for all participants. This difference
was maintained during bimanual tapping for the three participants with left-hand
impairment (P5, P6, and P7), but not for the participant with right-hand impairment
(P8). Nevertheless, tapping with the affected hand was faster during bimanual than
unimanual tapping for three participants (P5, P6, P8), whereas for P7, tapping with the
affected hand was slower during bimanual than unimanual tapping.
There was little difference between unimanual and bimanual tapping rates on the
unaffected side for two participants (P6 and P8), and two tapped sightly slower with the
unaffected hand during bimanual than unimanual tapping (P5 and P7). None of the
participants in the moderate group showed the usual coupling of the hands during
bimanual tapping.
In the severe group (Figure 7.1, bottom panel), tapping was slower with the affected
than the unaffected hand during unimanual and bimanual tapping for all participants.
Furthermore, the affected hand was slower during bimanual than unimanual tapping for
161
all participants. The unaffected hand was also slower during bimanual than unimanual
tapping for all participants except P10. A comparison of the moderate and severe group
data suggests that although both were slower than the mild group, there was little
difference in tapping rates between the moderate and severe groups. However,
observations of the performance of patients in the severe group revealed a general
inability to perform the individuated movements of the index finger required to perform
the task as instructed; instead these participants adopted a strategy of tapping with the
whole hand or arm. Comparisons between the hands for this group should also be
interpreted cautiously; despite the fact that all participants tapped slower with the
affected than the unaffected side, it is likely that the differences between the hands are
underrated since they tapped in the instructed manner with the unaffected hand during
both unimanual and bimanual tapping. Nevertheless, tapping rates of the two hands
became more alike during bimanual tapping for two of the participants (P9 and P11),
and these two participants came close to achieving coupled tapping of the two hands.
There was no obvious pattern in the rates of tapping to support the hypothesis that
bimanual performance would be more impaired in patients with left hemisphere lesions
than in patients with right hemisphere lesions, and no indication in this group of patients
that bimanual facilitation of performance was greater for those with right hemisphere
lesions than those with left hemisphere lesions.
162
Figure 7.1. Mean inter-tap interval (ITI) during unimanual (Uni) and bimanual (Bi) tapping with the left ( ) and right ( ) hands for patients with mild, moderate, and severe deficits and mean control values. The affected limb is indicated at the top of each panel. Errors of control values are ±1 standard error of the mean.
ITI (
ms)
LEFT RIGHT
P1 P2 P3 P4
ITI (
ms)
0
200
400
600
800
1000
1200
0
200
400
600
800
1000
1200
0
200
400
600
800
1000
1200
ITI (
ms)
P5 P6 P7 P8
P9 P10 P11 P12
Uni Bi Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi Uni Bi
Controls
Uni Bi
RIGHT LEFT
RIGHT LEFT
Mildly affected
Moderately affected
Severely affected
Controls
Uni Bi
Controls
Uni Bi
163
Figure 7.2 shows variability of tapping (CV of ITI) for all participants and controls. For
the mild group (top panel), tapping was more variable with the affected hand than with
the unaffected hand for all participants except P4 in the unimanual mode. Bimanual
tapping was more variable than unimanual tapping with the affected hand for all
participants in this group.
In the moderate group (Figure 7.2, middle panel), tapping was more variable with the
affected hand than with the unaffected hand for all participants except P5 (for P5 the
variability of the hands was equivalent during unimanual tapping). Of the three
participants in this group who tapped faster with the affected hand during bimanual than
unimanual tapping (P5, P6, and P8), one tapped with markedly less variability on the
affected side during bimanual than unimanual tapping (P8), one tapped with slightly
less variability (P6), and one with more variability (P5) on the affected side during
bimanual than unimanual tapping. The participant who tapped slower with the affected
hand during bimanual than unimanual tapping (P7) was also more variable on the
affected side during bimanual than unimanual tapping.
In the severe group, tapping was more variable with the affected hand than the
unaffected hand during unimanual tapping for all participants except P10 (for whom
variability of the two hands was equivalent during unimanual tapping). All participants
were more variable during bimanual than unimanual tapping with the affected hand
except P11. Despite the greater variability with the affected hand for three of the
participants during bimanual than unimanual tapping, the unaffected hand was less
variable during bimanual than unimanual tapping for three of the participants.
There was no obvious pattern in the results to differentiate the performance of patients
with left and right sided lesions.
164
Figure 7.2. Coefficient of variation of inter-tap interval during unimanual (Uni) and bimanual (Bi) tapping with the left ( ) and right ( ) hands for Patients with mild, moderate, and severe deficits and mean control values. The affected limb is indicated at the top of each panel. Errors of control values are ±1 standard error of the mean.
CV
of I
TI
LEFT RIGHT
P1 P2 P3 P4
CV
of I
TI
CV
of I
TI
P5 P6 P7 P8
P9 P10 P11 P12
Uni Bi Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi Uni Bi
RIGHT LEFT
RIGHT LEFT
0
20
40
60
80
100
120
140
160
0
20
40
60
80
100
120
140
160
0
20
40
60
80
100
120
140
160
Controls
Uni Bi
Mildly affected
Moderately affected
Severely affected
Controls
Uni Bi
Controls
Uni Bi
165
In summary, unimanual and bimanual tapping was slower and more variable with the
affected than with the unaffected hand for most participants. There was no indication of
a difference between the performance of the patients with left hemisphere lesions and
the performance of the patients with right hemisphere lesions. In the mild group,
performance on the tapping task did not appear to differ to performance by controls, and
no benefit of bimanual tapping was observed on the affected side for these participants.
In the moderately affected group, the hands did not become perfectly coupled during
bimanual tapping (tapping with the affected hand was slower than with the unaffected
hand, bimanually, for all participants), however, the difference in tapping rates between
the hands was reduced for three participants; for these participants there was evidence
of facilitation of tapping with the affected hand (tapping rate increased) during bimanual
tapping, with little or no change on the unaffected side. For all participants in the
severely affected group, tapping was slower on the affected side during the bimanual
than unimanual task, indicating little evidence of a benefit of pairing the affected with
the unaffected limb on tapping rate, although for two participants the tapping rates of
the hands became more alike during bimanual compared to unimanual tapping, and
there was less variability of tapping on the affected side during bimanual than
unimanual tapping for one of these participants.
Unimanual and bimanual circle-drawing
Figures 7.3, 7.4, and 7.5 show unimanual and bimanual tracings of small and large
circles with the left and right hands from participants in the mild, moderate, and severe
groups, respectively. Small circles drawn with the right (affected) hand by the mildly
affected participant (Figure 7.3) were less circular than circles drawn with the left
(unaffected hand). Small circles drawn with both hands appeared to be segmented (i.e.,
composed of multiple submovements) during unimanual drawing. This was less obvious
166
on the affected side during bimanual drawing, reflected in a larger value for circularity
on the affected side during bimanual drawing compared to unimanual drawing.
Differences between the hands were less obvious for large circles during unimanual
drawing, and performance with both hands deteriorated during bimanual drawing.
Submovements were particularly obvious in circles drawn with the affected hand by the
participant in the moderate group (Figure 7.4). Drawing was disordered with the
affected (left) hand in the unimanual mode when tracing both small and large circles,
and improved in the bimanual mode (shapes were more circular, were composed of
fewer submovements, and drawn with fewer cycles of acceleration-deceleration during
bimanual than unimanual drawing). There was little difference between unimanual and
bimanual performance with the unaffected hand.
The severely affected participant (Figure 7.5) also showed segmented drawing with the
affected (right) hand in the unimanual mode. Drawing with the affected limb was very
difficult and laboured; each cycle took 5.9 seconds to complete. During bimanual
drawing, the participant could not produce circles with the affected limb, but accuracy
with the unaffected limb was maintained.
167
Figure 7.3. Example of responses by a participant in the mild group (P2) with left hemispheric lesion during unimanual and bimanual drawing of small (template diameter = 15 mm) and large (template diameter = 70 mm) circles. Mean circularity (Circ), period (Per; s), X-diameter (X; mm), Y-diameter (Y; mm) and number of cycles of acceleration/ deceleration (Ac/Dec) are shown for each trial.
Left hand
(unaffected)
Right hand
(affected)
Small Circles
Unimanual
Bimanual
Circ: 0.87 Per: 1.00
X: 12.4 Y: 18.7
Ac/Dec: 3.7
Circ: 0.79 Per: 1.38
X: 9.6 Y: 11.9
Ac/Dec: 4.6
Circ: 0.78 Per: 1.49
X: 14.5 Y: 20.4
Ac/Dec: 5.7
Circ: 0.87 Per: 1.52
X: 8.2 Y: 10.4
Ac/Dec: 5.6
Left hand
(affected)
Right hand
(affected)
Large Circles
Unimanual
Bimanual
Circ: 0.92 Per: 1.77
X: 58.9 Y: 73.2
Ac/Dec: 6.2
Circ: 0.94 Per: 2.29
X: 47.8 Y: 62.6
Ac/Dec: 8.0
Circ: 0.80 Per: 2.73
X: 44.7 Y: 78.4
Ac/Dec: 9.2
Circ: 0.80 Per: 2.61
X: 31.4 Y: 54.1
Ac/Dec: 7.5
20 mm
10 mm
168
Figure 7.4. Example of responses by a participant in the moderate group (P5) with right hemispheric lesion during unimanual and bimanual drawing of small (template diameter = 15 mm) and large (template diameter = 70 mm) circles. Mean circularity (Circ), period (Per; s), X-diameter (X; mm), Y-diameter (Y; mm) and number of cycles of acceleration/ deceleration (Ac/Dec) are shown for each trial.
Small Circles Left hand
(affected)
Right hand
(unaffected)
Circ: 0.77 Per: 1.06
X: 11.5 Y: 17.6
Ac/Dec: 3.1
Circ: 0.46 Per: 1.87
X: 13.3 Y: 17.0
Ac/Dec: 6.7
Unimanual Circ: 0.97 Per: 0.90 X: 13.8 Y: 14.3
Ac/Dec: 4.2
Circ: 0.95 Per: 1.09 X: 11.9 Y: 11.7
Ac/Dec: 4.2
Bimanual
10 mm
Circ: 0.98 Per: 1.12
X: 66.1 Y: 68.9
Ac/Dec: 3.7
Circ: 0.75 Per: 1.89
X: 65.0 Y: 63.6
Ac/Dec: 6.3
Bimanual
Unimanual
Large Circles
Left hand
(affected)
Right hand
(unaffected)
Circ: 0.93 Per: 2.03
X: 59.3 Y: 59.2
Ac/Dec: 10.8
Circ: 0.81 Per: 1.95
X: 56.0 Y: 63.1
Ac/Dec: 5.8 20 mm
169
Figure 7.5. Example of responses by a participant in the severe group (P12) with left hemispheric lesion during unimanual and bimanual drawing of large circles (template diameter = 70 mm). Mean circularity (Circ), period (Per; s), X-diameter (X; mm), Y-diameter (Y; mm) and number of cycles of acceleration/ deceleration (Ac/Dec) are shown for each trial.
Figure 7.6 shows mean circularity for each participant and controls during unimanual
and bimanual circle drawing of small and large circles (the severe group did not draw
small circles). For the mild group, circularity during small circle drawing was not
markedly different from control data. The participant with a right sided lesion (P1) was
more accurate with the unaffected (right) than the affected (left) hand, but circularity
with the affected hand was not different from control data, and there was little change
with either hand during bimanual drawing. One participant with a left sided lesion (P2)
was more accurate with the unaffected (left) hand than the affected (right) hand during
unimanual drawing, and performance on the affected side improved in the bimanual
mode, although accuracy with the unaffected hand was worse when coupled with the
Left hand
(unaffected)
Right hand
(affected)
Large Circles
Unimanual
Bimanual
Circ: 0.96 Per: 2.4
X: 64.5 Y: 62.7
Ac/Dec: 6.9
Circ: 0.50 Per: 5.97
X: 72.0 Y: 53.8
Ac/Dec: 6.9
Circ: 0.94 Per: 3.3
X: 67.9 Y: 69.3
Ac/Dec: 5.4
Circ: 0.47 Per: 19.3
X: 15.4 Y: 19.7
Ac/Dec: N/A 20 mm
170
affected hand. The other two participants with right-sided lesions (P3 and P4)
performed better with the affected (right) hand during both unimanual and bimanual
drawing. Circles with the affected hand were more accurate during bimanual than
unimanual drawing for P3 and less accurate during bimanual than unimanual drawing
for P4. During large circle drawing for the mild group, there was very little difference in
circularity between the hands. Furthermore, the results were similar to the control data
for all participants except P2; for this participant circularity was less with both hands in
the bimanual than unimanual mode.
For the two participants in the moderate group with right-sided lesions (P5 and P7)
small circles were less circular when drawn with the affected (left) hand than with the
unaffected (right) hand during both unimanual and bimanual drawing. Circles with the
affected hand were more accurate during bimanual than unimanual drawing for P5, and
less accurate during bimanual than unimanual drawing for P7. The participant with a
right sided lesion performed better with the affected (right) hand than the unaffected
(left) hand, but performance with both hands was worse during bimanual than
unimanual drawing. Accuracy of large-circle drawing by the moderate group was
similar to small-circle drawing.
In the severe group, circularity of large circle drawing was greater on the unaffected
side than the affected side for all participants during unimanual and bimanual drawing.
Furthermore, circularity was less during bimanual drawing than unimanual drawing
with the affected hand for all participants (P9 could not complete bimanual drawing).
There was no evidence that patients with left hemisphere lesions performed worse than
patients with right hemisphere lesions during bimanual circle drawing.
Figure 7.6. Mean circularity during unimanual (Uni) and bimanual (Bi) small-circle (top row) and large-circle (bottom row) drawing with the left ( ) and right ( ) hands for each participant and mean control values. Affected limb is indicated at the top of each figure. Errors of control values are ±1 standard error of the mean.
CIR
CU
LAR
ITY
C
IRC
ULA
RIT
Y
RIGHT LEFT
Uni Bi Uni Bi Uni Bi Uni Bi
0.0
0.2
0.4
0.6
0.8
1.0
0.0
0.2
0.4
0.6
0.8
1.0
Uni Bi Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi Uni Uni Bi Uni Bi Uni Bi
Uni Bi
Uni Bi
RIGHT LEFT
LEFT RIGHT
Mild Moderate Controls
RIGHT LEFT RIGHT LEFT
P1 P2 P3 P4 P5 P7 P8 Controls
P1 P2 P3 P4 P5 P7 P8 Controls P9 P10 P11 P12
Severe Controls Mild Moderate
17
1
172
Figure 7.7 shows mean period of the left and right hands during unimanual and
bimanual drawing of small and large circles for each participant and mean control
values. In the mild group, during small-circle drawing, the pattern of results for all but
one participant (P2) was similar to the control results; period of drawing was longer
with the left hand than the right hand in unimanual drawing, and period of drawing with
the left and right hands were the same during bimanual drawing. P2 was slower with the
affected hand during unimanual drawing, but like the other participants, during
bimanual drawing the period of circle drawing with the two hands was equivalent.
Period of large-circle drawing followed a similar pattern.
In the moderate group, both of the participants with right-sided lesions were slower on
the affected (left) side than on the unaffected side during unimanual small circle
drawing. The participant with a left sided lesion (P8) was slower on the unaffected (left)
side than on the affected (right) side during unimanual drawing. Only one participant
(P5) showed the usual coupling of the hands during bimanual drawing and this
represented a decrease in period of drawing on the affected side, and an increase on the
unaffected side; for the other two, the difference between the hands was maintained (P8)
or increased (P7) during bimanual drawing. Period of large-circle drawing followed a
similar pattern, and two participants showed near-coupling of the hands during
bimanual drawing (P5 and P8).
In the severe group, drawing was slower on the affected side than the unaffected side for
all participants during unimanual drawing. Bimanual drawing was too disordered on the
affected side to calculate period for P11. Rate of drawing with the affected limb was
faster during bimanual than unimanual drawing for P10, and for this participant, the
period of each hand was almost equivalent during bimanual drawing. The affected hand
173
was slower during bimanual than unimanual drawing for P12. Period of drawing with
the unaffected limb was similar during unimanual and bimanual drawing for all
participants who attempted the bimanual task.
Rate of circle drawing did not vary with side of lesion and there was no evidence that
the patients with left hemisphere lesions were more impaired on the bimanual circle
drawing task than patients with right hemisphere lesions.
Figure 7.7. Mean period of circle drawing during unimanual (Uni) and bimanual (Bi) small-circle (top panel) and large-circle (bottom panel) drawing with the left ( ) and right ( ) hands for each participant and mean control values. Affected limb is indicated at the top of each figure. Errors of control values are ±1 standard error of the mean. * Bimanual drawing by P11 was too disordered with the affected limb to calculate period.
PE
RIO
D (
s)
PE
RIO
D (
s)
RIGHT LEFT
Uni Bi Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi Uni Uni Bi Uni Bi Uni Bi
Uni Bi
Uni Bi
RIGHT LEFT
LEFT RIGHT
0
1
2
3
4
5
6
0
1
2
3
4
5
6
Mild Moderate
Severe Controls
Controls
Mild Moderate
RIGHT LEFT RIGHT LEFT
* 0
1
2
3
4
5
6
7
P1 P2 P3 P4 P5 P7 P8 Controls
P1 P2 P3 P4 P5 P7 P8 Controls
P9 P10 P11 P12
17
4
175
Figure 7.8 shows RMS jerk (the third derivative of distance with respect to time) for
the left and right hands during unimanual and bimanual drawing of small and large
circles for each participant and mean control values. The RMS jerk provides a
measure of the smoothness of the trajectories produced during circle-drawing. RMS
jerk values for the mild group were small, and of a similar magnitude to control
values. RMS jerk was generally smaller with the right than the left hand for all
participants, regardless of side of lesion, and there were only marginal differences
between the values during unimanual and bimanual drawing, indicating equally
smooth trajectories during unimanual and bimanual drawing in this group.
RMS jerk values for all participants in the moderate group were substantially larger
than control values. Furthermore, the values were large for both hands indicating that
the trajectories of both hands were less smooth than those produced by control
participants. For small circles drawn unimanually, RMS jerk was greater on the
affected side than the unaffected side for two participants (P5 and P8). For P7, RMS
jerk was greater on the unaffected (right) side than the affected (left) side; this
participant was left handed, so this represents smoother drawing with the dominant
hand than the non-dominant hand. For all participants, on the affected side, RMS jerk
was approximately the same during unimanual and bimanual drawing. For unimanual
large circle drawing RMS jerk was greater on the affected side than on the unaffected
side for all participants. RMS jerk on the affected side was smaller during bimanual
than unimanual drawing for P5 and larger during bimanual than unimanual drawing
for P8 (RMS jerk could not be calculated for P7).
In the severe group, RMS jerk was larger with the affected hand than with the
unaffected hand. Only one participant (P10) produced sufficient cycles with the
Figure 7.8. RMS jerk during unimanual (Uni) and bimanual (Bi) small-circle (top panel) and large-circle (bottom panel) drawing with the left ( ) and right ( ) hands for each participant and mean control values. Affected limb is indicated at the top of each figure. Errors of control values are ±1 standard error of the mean. * Too few cycles produced by P7 with affected limb during bimanual drawing and drawing by P11, and P12 with the affected limb was too disordered to calculate RMS jerk.
RM
S J
ER
K (
mm
.s-3
) R
MS
JE
RK
(m
m.s
-3)
RIGHT LEFT
Uni Bi Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi
Uni Bi Uni Bi Uni Bi Uni Uni Bi Uni Bi Uni Bi
Uni Bi
Mild Moderate
Severe
Uni Bi
RIGHT LEFT
LEFT RIGHT
Controls
Controls
RIGHT LEFT
Mild Moderate
LEFT RIGHT
0
5
10
15
20
25
30
35
0
5
10
15
20
25
30
35
*
x1000
x1000
* *
P1 P2 P3 P4 P5 P7 P8 Controls
P1 P2 P3 P4 P5 P7 P8 Controls P9 P10 P11 P12
17
6
177
affected limb during bimanual drawing for RMS jerk to be calculated; for P10, RMS
jerk was larger during bimanual than unimanual drawing on the affected side.
In summary, for most participants circle drawing was less accurate, slower, and less
smooth with the affected than the unaffected hand. There was no suggestion in the data
of a greater bimanual deficit in patients with left hemisphere lesions than in patients
with right hemisphere lesions. There was evidence that all participants in the mild group
temporally coupled the hands during bimanual drawing, and for two participants the
affected side benefited from being paired with the unaffected hand during bimanual task
(accuracy of small circle drawing improved). In the moderately affected group, there
was no evidence of temporal coupling of the hands during bimanual drawing, but
accuracy of circle drawing was greater for one participant in the bimanual than
unimanual mode. Circle-drawing in the severely affected group was severely impaired
during the unimanual task and pairing the affected limb with the unaffected limb
worsened their performance with the affected limb.
7.3 Discussion
No overall differences between the performance of patients with left hemisphere lesions
and the performance of patients with right hemisphere lesions were observed. The study
was limited by small sample size and a heterogeneous mixture of patients (subacute and
acute, left and right sided stroke, and degree of deficit), which limited the comparison
between patients with left hemisphere lesions to observational evaluation. Previous
research has shown interlimb coupling to be more similar to control patterns in patients
with right than left hemisphere lesions (Lewis & Perreault, 2007), however, this
178
observation was based on a comparison between in-phase and anti-phase bimanual
coordination tasks within the two groups of stroke patients. A closer examination of the
in-phase coordination tasks reveals that the performance of stroke patients with left-
hemisphere lesions was similar to performance by patients with right-hemisphere
lesions. Furthermore, the effects of long term bimanual intervention (as used in
rehabilitation programs) on functional outcomes may differ from the effects of short
term bimanual coordination; a recent study found that patients with left hemispheric
lesions showed greater functional improvements than patients with right hemisphere
lesions after a six-week bilateral arm training intervention (McCombe Waller &
Whitall, 2005), which is in direct contrast to the predictions based on dominant
hemispheric control of bilateral movement. Whether bilateral training is beneficial
might therefore depend on a number of factors, including whether the task is symmetric
or asymmetric, as well as the side of the lesion. These issues warrant empirical
evaluation in larger studies.
The results of the current study provide evidence that, irrespective of lesion side, in
some stroke patients with mild-to-moderate motor deficits, the affected hand benefits
when acting with the unaffected hand. In the severely affected group of patients the
affected hand did not benefit when acting with the unaffected hand. The finding of a
benefit for mild to moderate but not severe patients is consistent with other studies
which have shown a benefit of bilateral training in mild-to-moderately affected stroke
patients (Mudie & Matyas, 2000; Summers et al., 2007), but not severely affected stroke
patients (Mudie & Matyas, 2001).
179
The tasks used in the current study differed in the degree of spatiotemporal complexity:
tapping required the repetitive reciprocal activation of flexors and extensors, whereas
circle-drawing required a more complex multi-joint coordination and the sequential
activation of different muscles in a precise sequence. With increasing severity of deficit
there appeared to be a decrease in the ability to precisely control the sequential
activation of muscles in time. The mild group had no deficit on the simpler task of
tapping, but some evidence of impaired control on the more spatiotemporally
demanding task of circle-drawing. The moderate and severe groups showed evidence of
impairment on both tapping and circle drawing. The obvious spatial submovements
present in the circles drawn with the affected limb by some participants in all severity
groups (Figures 7.3 to 7.5) suggests an inability to fractionate the activation of
sequential movements in time. This is similar to the observation that after a stroke to the
primary motor cortex or corticospinal tract, patients have a reduced ability to produce
fractionated movements of the fingers (C. E. Lang & Schieber, 2004), and the degree of
independence of finger movement was shown to correlate with hand function.
Submovements in the current study were more obvious during small circle drawing, but
were also present during large circle drawing for moderately and severely affected
patients, possibly reflecting a gradient in submovement presence related to severity of
impairment. An increase in the number of submovements has been demonstrated
previously in the velocity profile of aiming movements made by stroke patients (Rohrer
et al., 2002). Furthermore, a study on infants showed that submovements become fewer
and more blended during development (von Hofsten, 1991), a similar pattern to that
seen during recovery from stroke (Rohrer et al., 2002; Rohrer et al., 2004). In the
current study, at least for the mildly and moderately affected patients, the appearance of
submovements in the trajectories of circles was reduced during bimanual drawing
180
compared to unimanual drawing. This is similar to the smoother drawing (fewer cycles
of acceleration-deceleration and smaller jerk, and appearance of fewer submovements)
seen during bimanual than unimanual drawing of small circles in normal participants in
Chapter 3. The explanation for the findings in Chapter 3 could equally apply to the
observation in the stroke patients: features of the movement trajectories of the
unaffected limb may have become integrated into the motor response of the affected
limb, resulting in smoother trajectories with the affected limb.
Interlimb coupling
In the current study, there was evidence in some participants in the mild group of
temporal coupling of the hands and a benefit of bimanual coupling on the performance
of the affected limb during the more spatiotemporally demanding task of circle-drawing.
Some patients in the moderately affected group showed evidence of temporal coupling
and a benefit of bimanual coupling during both tapping and circle-drawing. In contrast,
the severe group showed little evidence of coupling of the hands and evidence of a
worsening of performance on the affected side when the affected hand was paired with
the unaffected hand during both tapping and the more demanding circle-drawing task.
The results suggest that temporal coupling of the limbs is crucial for facilitation of the
affected limb during the bimanual tasks used in the current study. An implication of
these findings is that if brain damage that is extensive enough to disable temporal
coupling between the limbs, bimanual facilitation is also eliminated.
An inability to temporally couple the limbs after stroke might result from a number of
causes. The degree of impairment during unimanual movements after stroke is at least
partly related to the degree of motor unit recruitment possible (Gowland, deBruin,
181
Basmajian, Plews, & Burcea, 1992), and integrity of the corticospinal system (Ward et
al., 2006). In contrast, normative data which shows that bilateral movements are
associated with increased interactions between the two sensorimotor cortices (Serrien,
Cassidy, & Brown, 2003), and data in “split brain” individuals who have impairments in
bimanual coupling during continuous bimanual movements (Kennerley, Diedrichsen,
Hazeltine, Semjen, & Ivry, 2002), suggests that bimanual coupling is probably mediated
via transcallosal connections. It is not possible to rule out damage to the corpus
callosum in the participants who could not couple the limbs in the current study.
However, it is likely that both spared transcallosal connections, and at least a partially
intact corticospinal system are necessary for functional coupling of the limbs.
Mechanisms of facilitation of performance with the impaired limb
The performance deficits with the affected limb reflect impaired neural control by the
damaged hemisphere contralateral to the affected hand, and the improvements in the
performance of the affected limb when it is paired with the unaffected limb are unlikely
to result from an improvement in the capacity of the affected hemisphere to control the
affected limb. Rather, the improvements in the performance of the hand contralateral to
the lesion are likely to result from the undamaged hemisphere playing a role in the
control of that limb during bimanual coordination.
Neuroimaging studies have shown that bimanual movements are associated with
increases in the activity of M1 in the affected hemisphere of stroke patients compared to
unimanual movements of the affected limb (Staines, McIlroy, Graham, & Black, 2001).
This increase in activity in M1 of the damaged hemisphere during bimanual movements
is likely to be the result of interhemispheric facilitation from the undamaged
182
hemisphere. Consistent with this hypothesis is the finding that short-term bilateral
training in normal individuals increased intracortical facilitation (ICF) and reduced
short-latency intracortical inhibition (SICI) bilaterally (McCombe Waller, Forrester,
Villagra, & Whitall, 2008).
Longer-term changes in brain functioning associated with functional improvement after
bimanual training might involve a “rebalancing” of excitatory and inhibitory processes.
Several studies have shown asymmetries in intracortical inhibition and excitation
between the lesioned and non-lesioned hemispheres after stroke; reduced intracortical
inhibition has been demonstrated in the non-lesioned hemisphere compared to normal
levels of inhibition seen in controls (Butefisch, Netz, Wessling, Seitz, & Homberg,
2003; Liepert, Storch, Fritsch, & Weiller, 2000), and increased transcallosal inhibition
from the non-lesioned to the lesioned hemisphere has also been demonstrated (Murase,
Duque, Mazzocchio, & Cohen, 2004). The enhancement of intracortical facilitation and
reduction in intracortical inhibition bilaterally with bimanual movements could
contribute to a rebalancing of these processes, which might lead to functional
improvements in the impaired limb. An active-passive bilateral therapy (active
movement of the unaffected limb coupled with passive movement of the affected limb)
was shown to increase M1 excitability in the lesioned hemisphere and increase M1
inhibition in the non-lesioned hemisphere (C. M. Stinear, Barber, Coxon, Fleming, &
Byblow, 2008). Furthermore, there is evidence that recovery of motor function after a
stroke is correlated with a normalization of the excitatory-inhibitory asymmetries
between the hemispheres (Rossini, Calautti, Pauri, & Baron, 2003), and a reduced
representation of the affected limb in the non-lesioned hemisphere (Summers et al.,
2007).
183
Rebalancing the levels of excitation and inhibition within and between the hemispheres
is unlikely to represent the complete story of recovery of motor function after stroke. As
noted above, reduced motor unit recruitment is associated with poor performance on
arm function tasks, implying that the increasing the drive to effectors must be achieved
for functional recovery. Increased excitability within the lesioned hemisphere is one
mechanism by which increased drive may be achieved. Recruitment of additional motor
areas is likely to represent another. In rats, after pharmacological inactivation of areas of
M1, a rapid unmasking of connections from adjacent cortical areas has been shown to
occur (Jacobs & Donoghue, 1991). Indeed, large extensions of cortical maps of the M1
hand area have been shown in patients with subcortical lesions and good recovery of
hemiplegia (Weiller, Ramsay, Wise, Friston, & Frackowiak, 1993). Furthermore, the
extent of cortical map shift has been shown to correlate with grip strength with larger
map area tending to be associated with better function of the affected limb
(Thickbroom, Byrnes, Archer, & Mastaglia, 2004), and an enlargement of cortical hand
area has been shown to correlate with functional improvement in a study assessing
longitudinal changes in brain organization after cortical stroke (Traversa, Cicinelli,
Bassi, Rossini, & Bernardi, 1997).
Conclusions
In a subset of stroke patients with mild-to-moderate deficits, performance of the
affected limb was enhanced during bimanual coordination. Temporal coupling between
the limbs might be crucial for this facilitation of performance. The findings of the
current study have implications for identifying which stroke patients are likely to
benefit from bilateral training. Although it would be premature to decide which
184
participants would benefit from bilateral training from their performance on a few trials,
it is reasonable to assume that if temporal coupling of the limbs is essential for
facilitation of the affected limb, individuals who are unable to achieve such coupling
will not benefit from bilateral training. The inability of some participants in the current
study to couple the limbs may have been associated with residual weakness or spasticity
in the affected limb. A recent study using an active-passive bilateral training approach
showed that unilateral training preceded by active-passive bilateral training was more
effective than unilateral training alone in a group of stroke patients with upper limb
weakness (C. M. Stinear, Barber, Coxon, Fleming, & Byblow, 2008). Bilateral coupling
of the arms using this passive approach may prove beneficial for those participants with
deficits which are severe enough to limit active coupling. Identifying which patients
will benefit from bilateral training and under which conditions will be important for
maximising results from rehabilitation.
185
GENERAL DISCUSSION
The first section of this thesis examined between-hand differences in the dynamics of
performance during unimanual and bimanual coordination. During tapping, the
dominant hand was faster (for rapid tapping but not slow tapping) and less temporally
variable (at both tapping rates) than the nondominant hand (Chapter 2). The ability to
tap faster with the dominant than nondominant hand has been largely attributed to a
faster transition between movement directions by the dominant hand than by the
nondominant hand (Peters, 1980). Furthermore, during fast rhythmical finger
oscillations, muscle activation patterns in the dominant hand are characterized by
sharply defined, non-overlapping contractions of flexor and extensor muscles, whereas
in the nondominant hand they are characterized by greater co-contractions of these
muscles, indicating a more precise control of their reciprocal activation with the
dominant hand than with the non-dominant hand (Heuer, 2007).
During circle drawing, the dominant hand was faster, more accurate, less temporally
and spatially variable, and produced smoother trajectories than the nondominant hand
(Chapter 3). These asymmetries were most obvious during small circle drawing which
required precise control of the fine hand muscles. In contrast to the tapping task, in
which better performance seems be related to the ability to specify non-overlapping
antagonist muscle activity and to sharply define the onset and offset of this activity, in
the circle drawing task, superior performance seems to require a greater ability to
“blend” the activity of sequential muscles (contrast the circular shapes drawn by the
dominant hand with the “triangular” shapes drawn by the nondominant hand).
186
The substrate for these asymmetries in motor control is still largely speculative.
However, several lines of evidence suggest that greater interconnectivity in the
dominant than nondominant M1 might mediate the superiority of the dominant hand for
fine motor control. Within M1, γ-aminobutyric acid (GABA) mediated inhibitory
circuits appear to play a particularly important role in shaping dexterous movements. In
monkeys, if the relative activity of these circuits is disrupted (by applying either a
GABA agonist or antagonist), independent finger movement is abolished (Matsumura,
Sawaguchi, Oishi, Ueki, & Kubota, 1991). Matsumura et al. suggested that precise
levels of inhibitory activity in M1 are necessary for correct spatiotemporal control of
hand movements. In humans, greater neuropil volume in dominant than nondominant
M1 suggests more profuse intracortical connections in the dominant than nondominant
hemisphere (Amunts et al., 1996). Furthermore, evidence from our laboratory and
others’ indicates that both short latency inhibitory circuits (Civardi, Cavalli, Naldi,
Varrasi, & Cantello, 2000; Hammond, Faulkner, Byrnes, Mastaglia, & Thickbroom,
2004) and long latency inhibitory circuits (Hammond & Garvey, 2006) are more potent
in dominant M1 than in non-dominant M1 of right-handers. It has been argued that the
short-latency inhibitory circuits are important for producing independent muscle
contractions (Reynolds & Ashby, 1999; C. M. Stinear & Byblow, 2003), while the long-
latency inhibitory circuits, which produce a longer-lasting inhibition than the short-
latency circuits, might modulate features of sustained activity (Rosenkranz & Rothwell,
2003). Although the exact functional role of these circuits remains unclear, the greater
efficacy of the inhibitory circuits in the dominant than nondominant hemisphere points
to a role in the spatiotemporal shaping of motor output involved in dexterous
movements.
187
During bimanual coordination the actions of the hands became synchronized. Rate
asymmetries that had been present during unimanual movements were abolished during
bimanual coordination. Two other asymmetries between the hands were also attenuated
during bimanual coordination. Firstly, temporal variability of the two hands became
more alike during bimanual coordination. This was only observed during the rapid
tapping task and the attenuation represented a benefit to the nondominant hand with no
apparent change in performance of the dominant hand. There was also an attenuation of
the asymmetry in smoothness of circle drawing (cycles of acceleration/deceleration)
during bimanual coordination. This was only seen during small-circle drawing, and as
for temporal variability, it represented an improvement in the performance of the
nondominant hand, with no apparent change in the performance of the dominant hand,
which suggests an integration of features of the movement trajectory of the dominant
limb into the trajectory of the nondominant limb. A second measure of trajectory
smoothness (RMS jerk) was smaller for both hands during bimanual than unimanual
small circle drawing (although the absolute asymmetry between the hands was the same
during unimanual and bimanual coordination). The apparent discrepancy between the
two measures of movement smoothness might be due to a faster rate of circling with the
dominant hand during unimanual than bimanual modes which could have contributed to
its smaller jerk when coupled with the nondominant hand (i.e. the smaller jerk is
secondary to a decreased rate of movement). The rate of drawing with the nondominant
hand did not change markedly from unimanual to bimanual drawing (if anything its rate
was slightly faster in the bimanual mode) so this cannot explain the smoother
trajectories with the nondominant hand during bimanual movements. Apart from the
RMS jerk measure, what is common to the attenuation of the asymmetries in temporal
variability and trajectory smoothness is that they were both the result of unidirectional
188
effects; the performance of the nondominant hand improved during bimanual coupling,
with little change in performance with the dominant hand. If performance asymmetries
between the hands during unimanual movement represent differences between the
neural control of the dominant and nondominant hemispheres, then the improvements in
the performance of the nondominant hand when it is paired with the “superior”
dominant hand are unlikely to result from an improvement in the capacity of the
nondominant hemisphere to control the nondominant hand. A more plausible
explanation is that the dominant hemisphere plays a role in controlling the nondominant
hand during bimanual coordination. This explanation is consistent with the findings of
brain imaging and EEG studies, which show greater activation in left than right M1
during bimanual than unimanual coordination (Jäncke et al., 1998; Viviani, Perani,
Grassi, Bettinardi, & Fazio, 1998) and greater coherence from the dominant to the
nondominant sensorimotor cortex during bimanual movements, suggesting greater
cortical drive from the dominant than from the nondominant hemisphere during
bimanual movements (Serrien, Cassidy, & Brown, 2003).
Despite the attenuation of performance asymmetries during bimanual movement
discussed above, several asymmetries persisted: temporal variability of self-paced
tapping, temporal variability of circle drawing, spatial accuracy (circularity, X- and Y-
amplitudes) of circle drawing, spatial variability of circle drawing, and smoothness of
large circle drawing. There was no obvious distinction between those features of
movements for which the asymmetries between the hands were attenuated during
bimanual movement, and those which were not. For the discrete repetitive movements,
temporal variability improved for the nondominant hand during fast, but not self-paced
tapping. Furthermore, the asymmetry during fast tapping was diminished but not
189
abolished during bimanual coupling. During self-paced tapping, the difference in
variability between the hands was small, so it is possible that the performance of the
nondominant hand could not benefit further from bimanual coupling. This might also
account for the finding that there was no attenuation of asymmetries in temporal
variability during circle drawing. The unimanual asymmetries between the hands across
most features of movements in the continuous task were greater during small than large
circle drawing. However, the magnitude of the asymmetry during unimanual
coordination does not predict the features of movement which become more alike
during bimanual coordination and the features which do not; for example, the
asymmetry in accuracy of unimanual small-circle drawing (circularity) was relatively
large and the magnitude of this asymmetry was maintained during bimanual drawing.
Neither a simple temporal-spatial, magnitude of unimanual asymmetry, nor discrete-
continuous distinction could therefore classify those features for which the asymmetry
was attenuated during bimanual movement and those which remained. Nevertheless,
exploring which conditions lead to an attenuation of between-hand asymmetries, and for
which features of movement, may lead to important insights into on the control
mechanisms underlying interlimb coordination.
The second section of the thesis examined the effects of disrupting motor control with
TMS over the left or right primary motor cortex (M1) on the ongoing coordination
patterns between the hands. TMS over left and right M1 during unimanual tapping
(Chapter 5) caused large disruptions to tapping with the contralateral hand, but had little
effect on the ipsilateral hand. During bimanual tapping, two patterns of responses were
observed. In some trials the hand contralateral to the side of TMS application was
“stalled” by a period approximately equal to the duration of a tap. In these trials, the two
190
hands were quickly resynchronised (within a single tapping cycle) and the results were
essentially the same as those seen during unimanual tapping. In other trials, tapping
with the hand contralateral to TMS application was stalled for a shorter duration, and in
the post-TMS period, a period of adjustment was observed during which the two hands
became resynchronized. In these trials, two lateralized effects of TMS were observed:
prolonged changes in inter-tap interval were observed in the left hand regardless of the
side of stimulation, and the effect of TMS on the contralateral hand was greater after
TMS over left M1 than right M1. The first of these lateralized effects (prolonged
changes in inter-tap interval were observed in the left hand regardless of the side of
stimulation) was attributed to a “master-slave” effect (the dominant hand produced a
master rhythm, which the non-dominant hand adopted, a process resulting in
resynchronisation of the hands over several cycles of tapping). The second of these
lateralized effects (a larger effect after TMS over left M1 than right M1) was because
TMS over left M1 caused consistently large disruptions to the contralateral hand,
whereas TMS over right M1 caused more variable individual responses. A tentative
explanation for these findings is that they result from a more (temporally) focused drive
from the dominant hemisphere and a more diffuse drive from the nondominant
hemisphere. It is possible that TMS applied during a period of focused drive would
result in consistently large responses, and TMS delivered during a period of diffuse
drive would result in more variable responses. A recent study which showed more
sharply defined EMG bursts for dominant than nondominant hand movements, with
temporal segregation of bursts of reciprocal muscle activity in the dominant hand and
greater co-contraction of antagonistic muscle pairs in the nondominant limb (Heuer,
2007) is consistent with this hypothesis. Similarly, the dominant hemisphere has a
greater acuity for processing temporal information than the nondominant hemisphere
191
(Hammond, 1981`, 1982; Nicholls & Whelan, 1998). This suggests that a greater acuity
of processing within the dominant than nondominant hemisphere might be more a
widespread feature of this hemisphere. Furthermore, the neural substrate for such an
asymmetry could be the more profuse horizontal connections and more effective short
latency intracortical inhibitory control in the dominant than nondominant hemisphere,
discussed above. More profuse interconnections between motor representations within
the dominant than nondominant hemisphere would support a finer spatiotemporal acuity
of motor output from this hemisphere.
In Chapter 6, subthreshold, threshold, and suprathreshold TMS were delivered over
primary motor cortex during continuous circle drawing. The effects of subthreshold and
threshold TMS were qualitatively different from those evoked by suprathreshold TMS.
At the lower intensities, the effects were almost exclusively observed on the left hand,
regardless of side of stimulation. It seems unlikely that physiological processes in M1
could account for the contralateral effects after TMS over right M1 and ipsilateral
effects after TMS over left M1. Rather, the effect of TMS on the left hand at the lower
intensities was likely due to the left hand being less resistant to interference by the
startling effect of the TMS acoustic stimulus than the right hand; less pressure was
applied during circle drawing with the left hand than with the right hand, which may
have afforded less stability to the left hand, rendering it more susceptible than the right
hand to perturbation.
Suprathreshold TMS caused large enduring decreases in circularity and increases in
period. The greatest effects on both circularity and period were delayed relative to the
time of TMS application. Left hemispheric stimulation decreased circularity with both
192
the left hand and the right hand whereas right hemispheric stimulation decreased
circularity only with the left hand. These effects were much larger than the effects seen
after lower intensity TMS pulses, suggesting physiological processes rather than
mechanical stability differences between the hands. The lateralized effect of TMS on
circularity was not limited to the bimanual case, but was also apparent during
unimanual drawing. This suggests a role for the left hemisphere in control of complex
sequential organization of movement by both hands, and is consistent with lesions
studies which show left hemisphere lesions result in sequencing deficits with both
hands, whereas right hemisphere lesions result in sequencing deficits with the
contralateral hand only (Haaland & Harrington, 1994).
Although distinct effects were observed when TMS was delivered during the repetitive
discrete tapping task and during the continuous circle drawing task, these different
effects do not necessarily reflect the event-timing and emergent timing distinction
between the tasks (Ivry & Richardson, 2002). Studies which have provided evidence for
such a distinction have either exploited individual differences in timing variability (e.g.,
correlations between timing variability on two tasks; Zelaznik, Spencer, & Ivry, 2002),
compared timing variability as a function of interval across two tasks (Ivry & Hazeltine,
1995), or examined timing in different tasks after brain injury or surgery (Kennerley,
Diedrichsen, Hazeltine, Semjen, & Ivry, 2002; Spencer, Zelaznik, Diedrichsen, & Ivry,
2003; Tuller & Kelso, 1989). The studies in this thesis were not designed to provide
evidence for or against the distinction between event and emergent timing; different
individuals participated in the two different tasks, so correlations between temporal
variabilities across tasks could not be calculated; neither were the studies designed to
calculate variability as a function of temporal interval.
193
The final study assessed bimanual motor control after unilateral stroke. In these
participants, unimanual and bimanual tapping was slower and more variable with the
affected than with the unaffected hand for most participants. Likewise, circle drawing
was less accurate, slower, and less smooth with the affected than the unaffected limb.
Furthermore, circle drawing with the affected side was characterized by obvious non-
blended sub-movements in the trajectories, much like the sub-movements seen in small
circles drawn by control participants with the non-dominant limb. The presence of sub-
movements suggests a degrading of the ability to successfully blend movement
components within the damaged hemisphere. Others have shown that submovements
become more blended in infants during development (von Hofsten, 1991) and in stroke
patients during recovery (Rohrer et al., 2002; Rohrer et al., 2004). For several
participants with mild to moderate deficits in the current study the sub-movements were
more blended during bimanual drawing than during unimanual drawing. This may
reflect an integration of features of the movement trajectory of the unaffected limb into
the trajectory of the affected limb, resulting in spatially smoother trajectories with the
affected limb. Furthermore, there was evidence of coupling of the limbs during
bimanual coordination for some participants in the mild and moderate group, and some
of these participants also showed evidence of facilitation of performance with the
affected limb when combined with the unaffected limb. This is similar to the previous
point that in control participants, performance with the nondominant hand improved
during bimanual movement. The performance deficits with the affected limb reflect
impaired neural control by the damaged hemisphere contralateral to the affected hand,
and the improvements in the performance of the affected limb when it is paired with the
unaffected limb are unlikely to result from an improvement in the capacity of the
affected hemisphere to control the affected limb. Rather, the improvements in the
194
performance of the hand contralateral to the lesion are likely to result from the
undamaged hemisphere playing a role in the control of that limb during bimanual
coordination. This is analogous to the mechanism proposed for the improvements in
nondominant limb performance, with the dominant limb playing a roe in the control of
the nondominant limb during bimanual movement.
That the participants whose affected-limb performance improved during bimanual
movement were limited to those who showed evidence of temporal coupling between
the limbs suggests that temporal coupling is crucial for the facilitation of the affected
limb during bimanual coordination. One implication of these findings is that if brain
damage is extensive enough to disable temporal coupling between the limbs, bimanual
facilitation is also eliminated. The findings also have therapeutic implications in
identifying which stroke patients are likely to benefit from bilateral training. The
inability of some participants in the current study to couple the limbs may have been
associated with residual weakness in the affected limb and an alternative approach to
rehabilitation would need to be considered for this group. One approach which makes
the benefits of bilateral training available for such individuals is an active-passive
training approach, which has been shown to be more effective than unilateral training in
a group of stroke patients with upper limb weakness (C. M. Stinear, Barber, Coxon,
Fleming, & Byblow, 2008). The observation that temporal coupling is essential for
facilitation of the affected limb needs to be verified empirically in order to identify
which patients will benefit from different bilateral rehabilitation regimes.
195
REFERENCES
Amassian, V. E., Cracco, R. Q., Maccabee, P. J., Bigland-Ritchie, B., & Cracco, J. B. (1991).
Matching focal and non-focal magnetic coil stimulation to properties of human
nervous system: mapping motor unit fields in motor cortex contrasted with altering
sequential digit movements by premotor-SMA stimulation. Electroencephalography &
Clinical Neurophysiology Supplement, 43, 3-28.
Amunts, K., Schlaug, G., Schleicher, A., Steinmetz, H., Dabringhaus, A., Roland, P. E., et al.
(1996). Asymmetry in the human motor cortex and handedness. Neuroimage, 4(3),
216-222.
Aranyi, Z., & Rosler, K. M. (2002). Effort-induced mirror movements. A study of transcallosal
inhibition in humans. Experimental Brain Research., 145(1), 76-82.
Barker, A. T., Jalinous, R., & Freeston, I. L. (1985). Non-invasive magnetic stimulation of human
motor cortex. Lancet., 1(8437), 1106-1107.
Ben-Shaul, Y., Drori, R., Asher, I., Stark, E., Nadasdy, Z., & Abeles, M. (2004). Neuronal activity
in motor cortical areas reflects the sequential context of movement. Journal of
Neurophysiology, 91(4), 1748-1762.
Bennett, K. M., & Lemon, R. N. (1996). Corticomotoneuronal contribution to the fractionation
of muscle activity during precision grip in the monkey. Journal of Neurophysiology,
75(5), 1826-1842.
Blumenthal, T. D. (1988). The startle response to acoustic stimuli near startle threshold: effects
of stimulus rise and fall time, duration, and intensity. Psychophysiology, 25(5), 607-
611.
Bohning, D. E., Shastri, A., Wassermann, E. M., Ziemann, U., Lorberbaum, J. P., Nahas, Z., et al.
(2000). BOLD-f MRI response to single-pulse transcranial magnetic stimulation (TMS).
Journal of Magnetic Resonance Imaging, 11(6), 569-574.
Bonnard, M., Camus, M., de Graaf, J., & Pailhous, J. (2003). Direct Evidence for a Binding
between Cognitive and Motor Functions in Humans: A TMS Study. Journal of Cognitive
Neuroscience, 15(8), 1207-1216.
Boyce, R. R., & Clark, W. A. V. (1964). The Concept of Shape in Geography. Geographical
Review, 54(4), 561-572.
Brinkman, C. (1984). Supplementary motor area of the monkey's cerebral cortex: short- and
long-term deficits after unilateral ablation and the effects of subsequent callosal
section. J. Neurosci., 4(4), 918-929.
Brinkman, J., & Kuypers, H. G. (1972). Splitbrain monkeys: cerebral control of ipsilateral and
contralateral arm, hand, and finger movements. Science, 176(34), 536-539.
Buchanan, J. J., & Ryu, Y. U. (2005). The interaction of tactile information and movement
amplitude in a multijoint bimanual circle-tracing task: Phase transitions and loss of
stability. The Quarterly Journal of Experimental Psychology Section A: Human
Experimental Psychology, 58(5), 769 - 787.
196
Burle, B., Bonnet, M., Vidal, F., Possamai, C. A., & Hasbroucq, T. (2002). A transcranial magnetic
stimulation study of information processing in the motor cortex: relationship between
the silent period and the reaction time delay. Psychophysiology, 39(2), 207-217.
Butefisch, C. M., Netz, J., Wessling, M., Seitz, R. J., & Homberg, V. (2003). Remote changes in
cortical excitability after stroke. Brain., 126(Pt 2), 470-481.
Byblow, W. D., Carson, R. G., & Goodman, D. (1994). Expressions of asymmetries and
anchoring in bimanual coordination. Human Movement Science, 13(1), 3-28.
Byblow, W. D., Lewis, G. N., Stinear, J. W., Austin, N. J., & Lynch, M. (2000). The subdominant
hand increases in the efficacy of voluntary alterations in bimanual coordination.
Experimental Brain Research, 131(3), 366-374.
Carson, R. G. (1993). Manual asymmetries: Old problems and new directions. Human
Movement Science, 12(5), 479-506.
Carson, R. G., Riek, S., Mackey, D. C., Meichenbaum, D. P., Willms, K., Forner, M., et al. (2004).
Excitability changes in human forearm corticospinal projections and spinal reflex
pathways during rhythmic voluntary movement of the opposite limb. Journal of
Physiology, 560(Pt 3), 929-940.
Carson, R. G., Smethurst, C. J., Oytam, Y., & de Rugy, A. (2007). Postural Context Alters the
Stability of Bimanual Coordination by Modulating the Crossed Excitability of
Corticospinal Pathways. J Neurophysiol, 97(3), 2016-2023.
Carson, R. G., Thomas, J., Summers, J. J., Walters, M. R., & Semjen, A. (1997). The dynamics of
bimanual circle drawing. Quarterly Journal of Experimental Psychology A, 50(3), 664-
683.
Chen, J. T., Lin, Y. Y., Shan, D. E., Wu, Z. A., Hallett, M., & Liao, K. K. (2005). Effect of
transcranial magnetic stimulation on bimanual movements. Journal of
Neurophysiology, 93(1), 53-63.
Chen, R., Gerloff, C., Hallett, M., & Cohen, L. G. (1997). Involvement of the ipsilateral motor
cortex in finger movements of different complexities. Annals of Neurology, 41(2), 247-
254.
Chen, R., Yaseen, Z., Cohen, L. G., & Hallett, M. (1998). Time course of corticospinal excitability
in reaction time and self-paced movements. Annals of Neurology., 44(3), 317-325.
Chiappa, K. H., Cros, D., Kiers, L., Triggs, W., Clouston, P., & Fang, J. (1995). Crossed inhibition
in the human motor system. Journal of Clinical Neurophysiology, 12(1), 82-96.
Civardi, C., Cavalli, A., Naldi, P., Varrasi, C., & Cantello, R. (2000). Hemispheric asymmetries of
cortico-cortical connections in human hand motor areas. Clinical Neurophysiology,
111(4), 624-629.
Collyer, C. E., Broadbent, H. A., & Church, R. M. (1994). Preferred rates of repetitive tapping
and categorical time production. Perception & Psychophysics, 55(4), 443-453.
Cunningham, C. L., Phillips Stoykov, M. E., & Walter, C. B. (2002). Bilateral facilitation of motor
control in chronic hemiplegia. Acta Psychologica, 110(2-3), 321-337.
197
Day, B. L., Rothwell, J. C., Thompson, P. D., Maertens de Noordhout, A., Nakashima, K.,
Shannon, K., et al. (1989). Delay in the execution of voluntary movement by electrical
or magnetic brain stimulation in intact man. Evidence for the storage of motor
programs in the brain. Brain, 112(Pt 3), 649-663.
de Poel, H. J., Peper, C. L., & Beek, P. J. (2006). Intentional switches between bimanual
coordination patterns are primarily effectuated by the nondominant hand. Motor
Control, 10(1), 7-23.
de Poel, H. J., Peper, C. L. E., & Beek, P. J. (2007). Handedness-related asymmetry in coupling
strength in bimanual coordination: furthering theory and evidence. Acta Psychologica,
124(2), 209-237.
Debaere, F., Swinnen, S. P., Beatse, E., Sunaert, S., Van Hecke, P., & Duysens, J. (2001). Brain
areas involved in interlimb coordination: a distributed network. Neuroimage, 14(5),
947-958.
Desrosiers, J., Bourbonnais, D., Corriveau, H., Gosselin, S., & Bravo, G. (2005). Effectiveness of
unilateral and symmetrical bilateral task training for arm during the subacute phase
after stroke: a randomized controlled trial. Clinical Rehabilitation, 19(6), 581-593.
Diedrichsen, J., Hazeltine, E., Nurss, W. K., & Ivry, R. B. (2003). The Role of the Corpus Callosum
in the Coupling of Bimanual Isometric Force Pulses. J Neurophysiol, 90(4), 2409-2418.
Dobkin, B. H. (2004). Strategies for stroke rehabilitation. The Lancet Neurology, 3(9), 528-536.
Donchin, O., Gribova, A., Steinberg, O., Bergman, H., & Vaadia, E. (1998). Primary motor cortex
is involved in bimanual coordination. Nature, 395(6699), 274-278.
Donoghue, J. P., Leibovic, S., & Sanes, J. N. (1992). Organization of the forelimb area in squirrel
monkey motor cortex: representation of digit, wrist, and elbow muscles. Experimental
Brain Research, 89(1), 1-19.
Drewing, K., & Aschersleben, G. (2003). Reduced timing variability during bimanual coupling: A
role for sensory information. The Quarterly Journal of Experimental Psychology A:
Human Experimental Psychology, 56A(2), 329-350.
Evarts, E. V. (1966). Pyramidal tract activity associated with a conditioned hand movement in
the monkey. Journal of Neurophysiology, 29(6), 1011-1027.
Flash, T., & Hogan, N. (1985). The coordination of arm movements: an experimentally
confirmed mathematical model. J. Neurosci., 5(7), 1688-1703.
Foltys, H., Sparing, R., Boroojerdi, B., Krings, T., Meister, I. G., Mottaghy, F. M., et al. (2001).
Motor control in simple bimanual movements: a transcranial magnetic stimulation and
reaction time study. Clinical Neurophysiology, 112(2), 265-274.
Franz, E. A. (1997). Spatial coupling in the coordination of complex actions. Quarterly Journal of
Experimental Psychology. A, Human Experimental Psychology, 50(3), 684-704.
Franz, E. A., Eliassen, J. C., Ivry, R. B., & Gazzaniga, M. S. (1996). Dissociation of spatial and
temporal coupling in the bimanual movements of callosotomy patients. Psychological
Science, 7(5), 306-310.
198
Franz, E. A., Rowse, A., & Ballantine, B. (2002). Does Handedness Determine Which Hand Leads
in a Bimanual Task? Journal of Motor Behavior, 34(4), 402.
Franz, E. A., Zelaznik, H. N., & McCabe, G. (1991). Spatial topological constraints in a bimanual
task. Acta Psychologica, 77(2), 137-151.
Fuhr, P., Agostino, R., & Hallett, M. (1991). Spinal motor neuron excitability during the silent
period after cortical stimulation. Electroencephalography & Clinical Neurophysiology,
81(4), 257-262.
Garry, M. I., van Steenis, R. E., & Summers, J. J. (2005). Interlimb coordination following stroke.
Human Movement Science, 24(5-6), 849-864.
Georgopoulos, A. P., Kalaska, J. F., & Massey, J. T. (1981). Spatial trajectories and reaction
times of aimed movements: effects of practice, uncertainty, and change in target
location. J Neurophysiol, 46(4), 725-743.
Glencross, D. J., Piek, J. P., & Barrett, N. C. (1995). The coordination of bimanual synchronous
and alternating tapping sequences. Journal of Motor Behavior, 27(1), 3-15.
Goble, D. J., & Brown, S. H. (2008). The biological and behavioral basis of upper limb
asymmetries in sensorimotor performance. Neuroscience & Biobehavioral Reviews,
32(3), 598-610.
Gowland, C., deBruin, H., Basmajian, J. V., Plews, N., & Burcea, I. (1992). Agonist and
antagonist activity during voluntary upper-limb movement in patients with stroke.
PHYS THER, 72(9), 624-633.
Graziano, M. S., Aflalo, T. N., & Cooke, D. F. (2005). Arm movements evoked by electrical
stimulation in the motor cortex of monkeys. Journal of Neurophysiology, 94(6), 4209-
4223.
Guiard, Y. (1987). Asymmetric division of labor in human skilled bimanual action: The
kinematic chain as a model. Journal of Motor Behavior, 19(4), 486-517.
Guilford, J. P. (1965). Fundamental statistics in psychology and education (4th ed.). New York:
McGraw-Hill Book Company.
Haaland, K. Y., Elsinger, C. L., Mayer, A. R., Durgerian, S., & Rao, S. M. (2004). Motor sequence
complexity and performing hand produce differential patterns of hemispheric
lateralization. Journal of Cognitive Neuroscience, 16(4), 621-636.
Haaland, K. Y., & Harrington, D. L. (1989). Hemispheric control of the initial and corrective
components of aiming movements. Neuropsychologia, 27(7), 961-969.
Haaland, K. Y., & Harrington, D. L. (1994). Limb-sequencing deficits after left but not right
hemisphere damage. Brain & Cognition, 24(1), 104-122.
Haaland, K. Y., Harrington, D. L., & Knight, R. T. (2000). Neural representations of skilled
movement. Brain, 123(Pt 11), 2306-2313.
Hammond, G. R. (1981). Finer temporal acuity for stimuli applied to the preferred hand.
Neuropsychologica, 19, 325-329.
199
Hammond, G. R. (1982). Hemispheric differences in temporal resolution. Brain and Cognition,
1, 95-118.
Hammond, G. R., Bolton, Y., Plant, Y., & Manning, J. (1988). Hand asymmetries in interresponse
intervals during rapid repetitive finger tapping. Journal of Motor Behavior, 20(1), 67-
71.
Hammond, G. R., Faulkner, D., Byrnes, M., Mastaglia, F., & Thickbroom, G. (2004). Transcranial
magnetic stimulation reveals asymmetrical efficacy of intracortical circuits in primary
motor cortex. Experimental Brain Research, 155(1), 19-23.
Hammond, G. R., & Garvey, C.-A. (2006). Asymmetries of long-latency intracortical inhibition in
motor cortex and handedness. Experimental Brain Research, 172(4), 449-453.
Harris-Love, M. L., McCombe Waller, S., & Whitall, J. (2005). Exploiting Interlimb Coupling to
Improve Paretic Arm Reaching Performance in People With Chronic Stroke. Archives of
Physical Medicine and Rehabilitation, 86(11), 2131-2137.
Hashimoto, T., Inaba, D., Matsumura, M., & Naito, E. (2004). Two different effects of
transcranial magnetic stimulation to the human motor cortex during the pre-
movement period. Neuroscience Research, 50(4), 427-436.
Heald, A., Bates, D., Cartlidge, N. E., French, J. M., & Miller, S. (1993). Longitudinal study of
central motor conduction time following stroke. 2. Central motor conduction
measured within 72 h after stroke as a predictor of functional outcome at 12 months.
Brain, 116(Pt 6), 1371-1385.
Heffner, R. S., & Masterton, R. B. (1983). The role of the corticospinal tract in the evolution of
human digital dexterity. Brain, Behavior & Evolution, 23(3-4), 165-183.
Helmuth, L. L., & Ivry, R. B. (1996). When two hands are better than one: Reduced timing
variability during bimanual movements. Journal of Experimental Psychology: Human
Perception & Performance, 22(2), 278-293.
Heuer, H. (2007). Control of the dominant and nondominant hand: exploitation and taming of
nonmuscular forces. Experimental Brain Research, 178(3), 363-373.
Hogan, N., & Flash, T. (1987). Moving gracefully: quantitative theories of motor coordination.
Trends in Neurosciences, 10(4), 170-174.
Hore, J., Watts, S., Tweed, D., & Miller, B. (1996). Overarm throws with the nondominant arm:
kinematics of accuracy. Journal of Neurophysiology, 76(6), 3693-3704.
Ilmoniemi, R. J., Virtanen, J., Ruohonen, J., Karhu, J., Aronen, H. J., Naatanen, R., et al. (1997).
Neuronal responses to magnetic stimulation reveal cortical reactivity and connectivity.
NeuroReport., 8(16), 3537-3540.
Inghilleri, M., Berardelli, A., Cruccu, G., & Manfredi, M. (1993). Silent period evoked by
transcranial stimulation of the human cortex and cervicomedullary junction. Journal of
Physiology, 466, 521-534.
200
Ivry, R. B., & Hazeltine, R. E. (1995). Perception and production of temporal intervals across a
range of durations: evidence for a common timing mechanism. Journal of Experimental
Psychology, Human Perception and Performance, 21(1), 3-18.
Ivry, R. B., & Richardson, T. C. (2002). Temporal Control and Coordination: The Multiple Timer
Model. Brain and Cognition, 48(1), 117-132.
Iwano, S., Nakamura, T., Kamioka, Y., & Ishigaki, T. (2005). Computer-aided diagnosis: A shape
classification of pulmonary nodules imaged by high-resolution CT. Computerized
Medical Imaging and Graphics, 29(7), 565-570.
Jacobs, K. M., & Donoghue, J. P. (1991). Reshaping the cortical motor map by unmasking latent
intracortical connections. Science, 251(4996), 944-947.
Jäncke, L., Peters, M., Himmelbach, M., Nösselt, T., Shah, J., & Steinmetz, H. (2000). fMRI study
of bimanual coordination. Neuropsychologia, 38(2), 164-174.
Jäncke, L., Peters, M., Schlaug, G., Posse, S., Steinmetz, H., & Muller-Gartner, H. (1998).
Differential magnetic resonance signal change in human sensorimotor cortex to finger
movements of different rate of the dominant and subdominant hand. Cognitive Brain
Research, 6(4), 279-284.
Kagerer, F. A., Summers, J. J., & Semjen, A. (2003). Instabilities during antiphase bimanual
movements: are ipsilateral pathways involved? Experimental Brain Research, 151(4),
489-500.
Kansaku, K., Muraki, S., Umeyama, S., Nishimori, Y., Kochiyama, T., Yamane, S., et al. (2005).
Cortical activity in multiple motor areas during sequential finger movements: an
application of independent component analysis. Neuroimage, 28(3), 669-681.
Kawashima, R., Yamada, K., Kinomura, S., Yamaguchi, T., Matsui, H., Yoshioka, S., et al. (1993).
Regional cerebral blood flow changes of cortical motor areas and prefrontal areas in
humans related to ipsilateral and contralateral hand movement. Brain Research,
623(1), 33-40.
Kay, B. A., Saltzman, E. L., & Kelso, J. A. (1991). Steady-state and perturbed rhythmical
movements: a dynamical analysis. Journal of Experimental Psychology: Human
Perception & Performance, 17(1), 183-197.
Kazennikov, O., Hyland, B., Wicki, U., Perrig, S., Rouiller, E. M., & Wiesendanger, M. (1998).
Effects of lesions in the mesial frontal cortex on bimanual co-ordination in monkeys.
Neuroscience, 85(3), 703-716.
Kazennikov, O., Wicki, U., Corboz, M., Hyland, B., Palmeri, A., Rouiller, E. M., et al. (1994).
Temporal Structure of a Bimanual Goal-directed Movement Sequence in Monkeys.
European Journal of Neuroscience, 6(2), 203-210.
Kelso, J. A. (1984). Phase transitions and critical behavior in human bimanual coordination. Am
J Physiol Regul Integr Comp Physiol, 246(6), R1000-1004.
Kelso, J. A., Southard, D. L., & Goodman, D. (1979). On the coordination of two-handed
movements. Journal of Experimental Psychology: Human Perception & Performance,
5(2), 229-238.
201
Kennerley, S. W., Diedrichsen, J., Hazeltine, E., Semjen, A., & Ivry, R. B. (2002). Callosotomy
patients exhibit temporal uncoupling during continuous bimanual movements. Nature
Neuroscience., 5(4), 376-381.
Kermadi, I., Liu, Y., Tempini, A., Calciati, E., & Rouiller, E. M. (1998). Neuronal activity in the
primate supplementary motor area and the primary motor cortex in relation to spatio-
temporal bimanual coordination. Somatosensory & Motor Research, 15(4), 287-308.
Kilbreath, S. L., Crosbie, J., Canning, C. G., & Lee, M. J. (2006). Inter-limb coordination in
bimanual reach-to-grasp following stroke. Disability & Rehabilitation, 28(23), 1435-
1443.
Kim, S. G., Ashe, J., Hendrich, K., Ellermann, J. M., Merkle, H., Ugurbil, K., et al. (1993).
Functional magnetic resonance imaging of motor cortex: hemispheric asymmetry and
handedness. Science, 261(5121), 615-617.
Koeneke, S., Lutz, K., Wustenberg, T., & Jäncke, L. (2004). Bimanual versus unimanual
coordination: what makes the difference? Neuroimage, 22(3), 1336-1350.
Kornatz, K. W., Christou, E. A., & Enoka, R. M. (2005). Practice reduces motor unit discharge
variability in a hand muscle and improves manual dexterity in old adults. J Appl Physiol,
98(6), 2072-2080.
Kunesch, E., Binkofski, F., Steinmetz, H., & Freund, H.-J. (1995). The pattern of motor deficits in
relation to the site of stroke lesions. European Neurology, 35(1), 20-26.
Kuypers, H. G. J. M. (1981). Anatomy of the descending pathways. In V. B. Brooks (Ed.),
Handbook of Physiology Section 1: The Nervous System (Vol. II Motor control, Part 1,
pp. 597-666). Bethesda, Maryland: American Physiological Society.
Kwakkel, G., Kollen, B. J., van der Grond, J., & Prevo, A. J. H. (2003). Probability of Regaining
Dexterity in the Flaccid Upper Limb: Impact of Severity of Paresis and Time Since Onset
in Acute Stroke. Stroke, 34(9), 2181-2186.
Lai, S.-M., Studenski, S., Duncan, P. W., & Perera, S. (2002). Persisting Consequences of Stroke
Measured by the Stroke Impact Scale. Stroke, 33(7), 1840-1844.
Lang, C. E., & Schieber, M. H. (2004). Reduced muscle selectivity during individuated finger
movements in humans after damage to the motor cortex or corticospinal tract. Journal
of Neurophysiology, 91(4), 1722-1733.
Lang, W., Obrig, H., Lindinger, G., Cheyne, D., & Deecke, L. (1990). Supplementary motor area
activation while tapping bimanually different rhythms in musicians. Experimental Brain
Research, 79(3), 504-514.
LaRoque, S. D., & Obrzut, J. E. (2006). Pencil Pressure and Anxiety in Drawings: A Techno-
Projective Approach. Journal of Psychoeducational Assessment, 24(4), 381-393.
Latash, M. L., Danion, F., & Bonnard, M. (2003). Effects of transcranial magnetic stimulation on
muscle activation patterns and joint kinematics within a two-joint motor synergy.
Brain Research, 961(2), 229-242.
202
Lewis, G. N., & Byblow, W. D. (2004). Bimanual coordination dynamics in poststroke
hemiparesis. Journal of Motor Behavior, 36(2), 174-188.
Lewis, G. N., & Perreault, E. J. (2007). Side of lesion influences bilateral activation in chronic,
post-stroke hemiparesis. Clinical Neurophysiology, 118(9), 2050-2062.
Liepert, J., Classen, J., Cohen, L. G., & Hallett, M. (1998). Task-dependent changes of
intracortical inhibition. Experimental Brain Research, 118(3), 421-426.
Liepert, J., Storch, P., Fritsch, A., & Weiller, C. (2000). Motor cortex disinhibition in acute
stroke. Clinical Neurophysiology, 111(4), 671-676.
Lin, K.-c., Chang, Y.-f., Wu, C.-y., & Chen, Y.-a. (2009). Effects of Constraint-Induced Therapy
Versus Bilateral Arm Training on Motor Performance, Daily Functions, and Quality of
Life in Stroke Survivors. Neurorehabil Neural Repair, 23(5), 441-448.
Lu, X., & Ashe, J. (2005). Anticipatory activity in primary motor cortex codes memorized
movement sequences.[see comment]. Neuron, 45(6), 967-973.
Luft, A., McCombe Waller, S., Whitall, J., Forrester, L. W., Macko, R., Sorkin, J., et al. (2004).
Repetitive Bilateral Arm Training and Motor Cortex Activation in Chronic Stroke: A
Randomized Controlled Trial. JAMA October, 292(15), 1853-1861.
Mack, L., Gonzalez Rothi, L. J., & Heilman, K. M. (1993). Hemispheric specialization for
handwriting in right handers. Brain & Cognition, 21(1), 80-86.
Marteniuk, R. G., MacKenzie, C. L., & Baba, D. M. (1984). Bimanual movement control:
Information processing and interaction effects. Quarterly Journal of Experimental
Psychology. A, Human Experimental Psychology, 36A(2), 335-365.
Matsumura, M., Sawaguchi, T., Oishi, T., Ueki, K., & Kubota, K. (1991). Behavioral deficits
induced by local injection of bicuculline and muscimol into the primate motor and
premotor cortex. Journal of Neurophysiology, 65(6), 1542-1553.
Matsunaga, K., Uozumi, T., Tsuji, S., & Murai, Y. (1998). Age-dependent changes in
physiological threshold asymmetries for the motor evoked potential and silent period
following transcranial magnetic stimulation. Electroencephalography & Clinical
Neurophysiology, 109(6), 502-507.
McCombe Waller, S., Forrester, L., Villagra, F., & Whitall, J. (2008). Intracortical inhibition and
facilitation with unilateral dominant, unilateral nondominant and bilateral movement
tasks in left- and right-handed adults. Journal of the Neurological Sciences, 269(1-2),
96-104.
McCombe Waller, S., Harris-Love, M., Liu, W., & Whitall, J. (2006). Temporal coordination of
the arms during bilateral simultaneous and sequential movements in patients with
chronic hemiparesis. Experimental Brain Research, 168(3), 450-454.
McCombe Waller, S., & Whitall, J. (2005). Hand dominance and side of stroke affect
rehabilitation in chronic stroke. Clinical Rehabilitation, 19(5), 544-551.
McCombe Waller, S., & Whitall, J. (2008). Bilateral arm training: Why and who benefits?
NeuroRehabilitation, 23(1), 29-41.
203
Meyer, B. U., & Voss, M. (2000). Delay of the execution of rapid finger movement by magnetic
stimulation of the ipsilateral hand-associated motor cortex. Experimental Brain
Research, 134(4), 477-482.
Mudie, M. H., & Matyas, T. A. (2000). Can simultaneous bilateral movement involve the
undamaged hemisphere in reconstruction of neural networks damaged by stroke?
Disability & Rehabilitation, 22, 23-37.
Mudie, M. H., & Matyas, T. A. (2001). Responses of the Densely Hemiplegic Upper Extremity to
Bilateral Training. Neurorehabil Neural Repair, 15(2), 129-140.
Murase, N., Duque, J., Mazzocchio, R., & Cohen, L. G. (2004). Influence of interhemispheric
interactions on motor function in chronic stroke. Annals of Neurology, 55(3), 400-409.
Netz, J., Ziemann, U., & Homberg, V. (1995). Hemispheric asymmetry of transcallosal inhibition
in man. Experimental Brain Research, 104(3), 527-533.
Newell, K. M., & Van Emmerik, R. E. (1989). The acquisition of coordination: Preliminary
analysis of learning to write. Human Movement Science. Vol, 8(1), 17-32.
Nicholls, M. E. R., & Whelan, R. E. (1998). Hemispheric asymmetries for the temporal
resolution of brief tactile stimuli. Journal of Clinical & Experimental Neuropsychology,
20(4), 445-456.
Nickerson, R. S. (1970). The effect of preceding and following auditory stimuli on response
times to visual stimuli. Acta Psychologica, Amsterdam, 33, 5-20.
Oldfield, R. (1971). The assessment and analysis of handedness: The Edinburgh inventory.
Neuropsychologia, 9(1), 97-113.
Palmer, E., & Ashby, P. (1992). Corticospinal projections to upper limb motoneurones in
humans. Journal of Physiology, 448, 397-412.
Palmer, E., Cafarelli, E., & Ashby, P. (1994). The processing of human ballistic movements
explored by stimulation over the cortex. Journal of Physiology, 481(Pt 2), 509-520.
Pascual-Leone, A., Brasil-Neto, J. P., Valls-Solé, J., Cohen, L. G., & Hallett, M. (1992). Simple
reaction time to focal transcranial magnetic stimulation. Comparison with reaction
time to acoustic, visual and somatosensory stimuli. Brain, 115 Pt 1, 109-122.
Perrig, S., Kazennikov, O., & Wiesendanger, M. (1999). Time structure of a goal-directed
bimanual skill and its dependence on task constraints. Behavioural Brain Research,
103(1), 95-104.
Peters, M. (1976). Prolonged practice of a simple motor task by preferred and nonpreferred
hands. Perceptual & Motor Skills, 43(2), 447-450.
Peters, M. (1980). Why the preferred hand taps more quickly than the non-preferred hand:
Three experiments on handedness. Canadian Journal of Psychology, 34(1), 62-71.
Peters, M. (1981). Attentional asymmetries during concurrent bimanual performance.
Quarterly Journal of Experimental Psychology. A, Human Experimental Psychology, 1,
95-103.
204
Peters, M. (1985). Constraints in the performance of bimanual tasks and their expression in
unskilled and skilled subjects. The Quarterly Journal of Experimental Psychology
Section A, 37(2), 171-196.
Peters, M. (1989). The relationship between variability of intertap intervals and interval
duration. Psychological Research, 51(1), 38-42.
Peters, M., & Durding, B. (1979). Left-handers and right-handers compared on a motor task.
Journal of Motor Behavior, 11(2), 103-111.
Phillips, J. G., Gallucci, R. M., & Bradshaw, J. L. (1999). Functional asymmetries in the quality of
handwriting movements: a kinematic analysis. Neuropsychology, 13(2), 291-297.
Platz, T., Bock, S., & Prass, K. (2001). Reduced skilfulness of arm motor behaviour among motor
stroke patients with good clinical recovery: does it indicate reduced automaticity? Can
it be improved by unilateral or bilateral training? A kinematic motion analysis study.
Neuropsychologia, 39(7), 687-698.
Pollok, B. C. A., Muller, K., Aschersleben, G., Schnitzler, A., & Prinz, W. (2004). Bimanual
coordination: neuromagnetic and behavioral data. Neuroreport, 15(3), 449-452.
Priori, A., Oliviero, A., Donati, E., Callea, L., Bertolasi, L., & Rothwell, J. C. (1999). Human
handedness and asymmetry of the motor cortical silent period. Experimental Brain
Research, 128(3), 390-396.
Rao, S. M., Binder, J. R., Bandettini, P. A., Hammeke, T. A., Yetkin, F. Z., Jesmanowicz, A., et al.
(1993). Functional magnetic resonance imaging of complex human movements.
Neurology, 43(11), 2311-2318.
Repp, B. H. (2003). Phase attraction in sensorimotor synchronization with auditory sequences:
Effects of single and periodic distractors on synchronization accuracy. Journal of
Experimental Psychology: Human Perception and Performance, 29(2), 290-309.
Repp, B. H. (2006). Does an auditory distractor sequence affect self-paced tapping? Acta
Psychologica, 121(1), 81-107.
Reynolds, C., & Ashby, P. (1999). Inhibition in the human motor cortex is reduced just before a
voluntary contraction [see comments]. Neurology, 53(4), 730-735.
Rice, M. S., & Newell, K. M. (2001). Interlimb coupling and left hemiplegia because of right
cerebral vascular accident. Occupational Therapy Journal of Research, 21, 12-28.
Rice, M. S., & Newell, K. M. (2004). Upper-extremity interlimb coupling in persons with left
hemiplegia due to stroke. Archives of Physical Medicine and Rehabilitation, 85(4), 629-
634.
Rohrer, B., Fasoli, S., Krebs, H. I., Hughes, R., Volpe, B., Frontera, W. R., et al. (2002).
Movement Smoothness Changes during Stroke Recovery. J. Neurosci., 22(18), 8297-
8304.
Rohrer, B., Fasoli, S., Krebs, H. I., Volpe, B., Frontera, W. R., Stein, J., et al. (2004).
Submovements grow larger, fewer, and more blended during stroke recovery. Motor
Control, 8(4), 472-483.
205
Romaiguère, P., Possamai, C. A., & Hasbroucq, T. (1997). Motor cortex involvement during
choice reaction time: a transcranial magnetic stimulation study in man. Brain Research,
755(2), 181-192.
Rose, D. K., & Winstein, C. J. (2005). The co-ordination of bimanual rapid aiming movements
following stroke. Clinical Rehabilitation, 19(4), 452.
Rosenkranz, K., & Rothwell, J. C. (2003). Differential effect of muscle vibration on intracortical
inhibitory circuits in humans. The Journal of Physiology, 551(2), 649-660.
Rossini, P. M., Calautti, C., Pauri, F., & Baron, J. C. (2003). Post-stroke plastic reorganisation in
the adult brain. Lancet Neurology, 2, 493-502.
Rouiller, E. M., Babalian, A., Kazennikov, O., Moret, V., Yu, X. H., & Wiesendanger, M. (1994).
Transcallosal connections of the distal forelimb representations of the primary and
supplementary motor cortical areas in macaque monkeys. Experimental Brain
Research, 102(2), 227-243.
Ryu, Y. U., & Buchanan, J. J. (2004). Amplitude Scaling in a Bimanual Circle-Drawing Task:
Pattern Switching and End-Effector Variability. Journal of Motor Behavior, 36(3), 265-
279.
Sadato, N., Yonekura, Y., Waki, A., Yamada, H., & Ishii, Y. (1997). Role of the supplementary
motor area and the right premotor cortex in the coordination of bimanual finger
movements. Journal of Neuroscience, 17(24), 9667-9674.
Salmelin, R., Forss, N., Knuutila, J., & Hari, R. (1995). Bilateral activation of the human
somatomotor cortex by distal hand movements. Electroencephalography & Clinical
Neurophysiology, 95(6), 444-452.
Sato, K. C., & Tanji, J. (1989). Digit-muscle responses evoked from multiple intracortical foci in
monkey precentral motor cortex. J Neurophysiol, 62(4), 959-970.
Sawaki, L., Okita, T., Fujiwara, M., & Mizuno, K. (1999). Specific and non-specific effects of
transcranial magnetic stimulation on simple and go/no-go reaction time. Experimental
Brain Research, 127(4), 402-408.
Schluter, N. D., Rushworth, M. F., Passingham, R. E., & Mills, K. R. (1998). Temporary
interference in human lateral premotor cortex suggests dominance for the selection of
movements. A study using transcranial magnetic stimulation. Brain, 121(Pt 5), 785-
799.
Schmidt, S. L., Oliveira, R. M., Krahe, T. E., & Filgueiras, C. C. (2000). The effects of hand
preference and gender on finger tapping performance asymmetry by the use of an
infra-red light measurement device. Neuropsychologia, 38(5), 529-534.
Semjen, A., Summers, J. J., & Cattaert, D. (1995). Hand Coordination in Bimanual Circle
Drawing. Journal of Experimental Psychology: Human Perception and Performance,
21(5), 1139-1157.
Serrien, D. J., Cassidy, M. J., & Brown, P. (2003). The importance of the dominant hemisphere
in the organization of bimanual movements. Human Brain Mapping, 18(4), 296-305.
206
Sherwood, D. E. (1990). Practice and assimilation effects in a multilimb aiming task. Journal of
Motor Behavior, 22(2), 267-291.
Sherwood, D. E. (1994). Hand preference, practice order, and spatial assimilations in rapid
bimanual movement. Journal of Motor Behavior, 26(2), 123-134.
Singh, L. N., Higano, S., Takahashi, S., Kurihara, N., Furuta, S., Tamura, H., et al. (1998).
Comparison of ipsilateral activation between right and left handers: a functional MR
imaging study. Neuroreport, 9(8), 1861-1866.
Spencer, R. M. C., & Zelaznik, H. N. (2003). Weber (Slope) Analyses of Timing Variability in
Tapping and Drawing Tasks. Journal of Motor Behavior, 35(4), 371-381.
Spencer, R. M. C., Zelaznik, H. N., Diedrichsen, J., & Ivry, R. B. (2003). Disrupted Timing of
Discontinuous But Not Continuous Movements by Cerebellar Lesions. Science,
300(5624), 1437-1439.
Staines, W. R., McIlroy, W. E., Graham, S. J., & Black, S. E. (2001). Bilateral movement enhances
ipsilesional cortical activity in acute stroke: a pilot functional MRI study. Neurology,
56(3), 401-404.
Steenbergen, B., Hulstijn, W., de Vries, A., & Berger, M. (1996). Bimanual movement
coordination in spastic hemiparesis. Experimental Brain Research, 110(1), 91-98.
Stephan, K. M., Binkofski, F., Halsband, U., Dohle, C., Wunderlich, G., Schnitzler, A., et al.
(1999). The role of ventral medial wall motor areas in bimanual co-ordination. A
combined lesion and activation study. Brain, 122(Pt 2), 351-368.
Stephan, K. M., Binkofski, F., Posse, S., Seitz, R. J., & Freund, H. J. (1999). Cerebral midline
structures in bimanual coordination. Experimental Brain Research, 128(1-2), 243-249.
Stewart, K. C., Cauraugh, J. H., & Summers, J. J. (2006). Bilateral movement training and stroke
rehabilitation: A systematic review and meta-analysis. Journal of the Neurological
Sciences, 244(1-2), 89-95.
Steyvers, M., Etoh, S., Sauner, D., Levin, O., Siebner, H., Swinnen, S., et al. (2003). High-
frequency transcranial magnetic stimulation of the supplementary motor area reduces
bimanual coupling during anti-phase but not in-phase movements. Experimental Brain
Research, 151(3), 309-317.
Stinear, C. M., Barber, P. A., Coxon, J. P., Fleming, M. K., & Byblow, W. D. (2008). Priming the
motor system enhances the effects of upper limb therapy in chronic stroke. Brain,
131(5), 1381-1390.
Stinear, C. M., & Byblow, W. D. (2003). Role of intracortical inhibition in selective hand muscle
activation. Journal of Neurophysiology., 89(4), 2014-2020.
Stinear, J. W., & Byblow, W. D. (2004). Rhythmic bilateral movement training modulates
corticomotor excitability and enhances upper limb motoricity poststroke: a pilot study.
Journal of Clinical Neurophysiology, 21, 124-131.
207
Stucchi, N., & Viviani, P. (1993). Cerebral dominance and asynchrony between bimanual two-
dimensional movements. Journal of Experimental Psychology, Human Perception and
Performance, 19, 1200-1220.
Summers, J. J., Kagerer, F. A., Garry, M. I., Hiraga, C. Y., Loftus, A., & Cauraugh, J. H. (2007).
Bilateral and unilateral movement training on upper limb function in chronic stroke
patients: A TMS study. Journal of the Neurological Sciences, 252(1), 76-82.
Swinnen, S. P. (2002). Intermanual coordination: from behavioural principles to neural-
network interactions. Nature Reviews Neuroscience, 3(5), 350-361.
Swinnen, S. P., Jardin, K., & Meulenbroek, R. (1996). Between-limb asynchronies during
bimanual coordination: effects of manual dominance and attentional cueing.
Neuropsychologia, 34(12), 1203-1213.
Swinnen, S. P., & Wenderoth, N. (2004). Two hands, one brain: cognitive neuroscience of
bimanual skill. Trends in Cognitive Sciences, 8(1), 18-25.
Tanji, J., & Kurata, K. (1982). Comparison of movement-related activity in two cortical motor
areas of primates. Journal of Neurophysiology, 48(3), 633-653.
Taub, E., Uswatte, G., King, D. K., Morris, D., Crago, J. E., & Chatterjee, A. (2006). A Placebo-
Controlled Trial of Constraint-Induced Movement Therapy for Upper Extremity After
Stroke. Stroke, 37(4), 1045-1049.
Taub, E., Uswatte, G., & Pidikiti, R. (1999). Constraint-Induced Movement Therapy: a new
family of techniques with broad application to physical rehabilitation--a clinical review.
Journal of Rehabilitation Research & Development, 36(3), 237-251.
Taylor, J. L., Wagener, D. S., & Colebatch, J. G. (1995). Mapping of cortical sites where
transcranial magnetic stimulation results in delay of voluntary movement.
Electroencephalography & Clinical Neurophysiology: Electromyography & Motor
Control, 97(6), 341-348.
Teulings, H. L., Contreras-Vidal, J. L., Stelmach, G. E., & Adler, C. H. (1997). Parkinsonism
reduces coordination of fingers, wrist, and arm in fine motor control. Experimental
Neurology., 146(1), 159-170.
Thickbroom, G., Byrnes, M., Archer, S., & Mastaglia, F. (2004). Motor outcome after subcortical
stroke correlates with the degree of cortical reorganization. Clinical neurophysiology :
official journal of the International Federation of Clinical Neurophysiology, 115(9),
2144-2150.
Tijs, E., & Matyas, T. A. (2006). Bilateral Training Does Not Facilitate Performance of Copying
Tasks in Poststroke Hemiplegia. Neurorehabil Neural Repair, 20(4), 473-483.
Todor, J. I., & Kyprie, P. M. (1980). Hand differences in the rate and variability of rapid tapping.
Journal of Motor Behavior, 12(1), 57-62.
Toyokura, M., Muro, I., Komiya, T., & Obara, M. (1999). Relation of bimanual coordination to
activation in the sensorimotor cortex and supplementary motor area: Analysis using
functional magnetic resonance imaging. Brain Research Bulletin, 48(2), 211-217.
208
Traversa, R., Cicinelli, P., Bassi, A., Rossini, P. M., & Bernardi, G. (1997). Mapping of motor
cortical reorganization after stroke. A brain stimulation study with focal magnetic
pulses. Stroke, 28(1), 110-117.
Truman, G., & Hammond, G. R. (1990). Temporal regularity of tapping by the left and right
hands in timed and untimed finger tapping. Journal of Motor Behavior, 22(4), 521-535.
Tuller, B., & Kelso, J. A. (1989). Environmentally-specified patterns of movement coordination
in normal and split-brain subjects. Experimental Brain Research, 75(2), 306-316.
Ullen, F., Forssberg, H., & Ehrsson, H. H. (2003). Neural Networks for the Coordination of the
Hands in Time. J Neurophysiol, 89(2), 1126-1135.
Verstynen, T., Diedrichsen, J., Albert, N., Aparicio, P., & Ivry, R. B. (2005). Ipsilateral Motor
Cortex Activity During Unimanual Hand Movements Relates to Task Complexity.
Journal of Neurophysiology, 93(3), 1209-1222.
Verstynen, T., Konkle, T., & Ivry, R. B. (2006). Two Types of TMS-Induced Movement Variability
After Stimulation of the Primary Motor Cortex. J Neurophysiol, 96(3), 1018-1029.
Viviani, P., Perani, D., Grassi, F., Bettinardi, V., & Fazio, F. (1998). Hemispheric asymmetries and
bimanual asynchrony in left- and right-handers. Experimental Brain Research, 120(4),
531-536.
Volkmann, J., Schnitzler, A., Witte, O. W., & Freund, H. (1998). Handedness and asymmetry of
hand representation in human motor cortex. Journal of Neurophysiology, 79(4), 2149-
2154.
Volman, M. J. M., Wijnroks, A., & Vermeer, A. (2002). Bimanual circle drawing in children with
spastic hemiparesis: effect of coupling modes on the performance of the impaired and
unimpaired arms. Acta Psychologica, 110(2-3), 339-356.
von Hofsten, C. (1991). Structuring of early reaching movements: A longitudinal study. Journal
of Motor Behavior. Vol, 23(4), 280-292.
Walsh, V., & Rushworth, M. (1999). A primer of magnetic stimulation as a tool for
neuropsychology. Neuropsychologia, 37(2), 125-135.
Ward, N. S., Newton, J. M., Swayne, O. B. C., Lee, L., Thompson, A. J., Greenwood, R. J., et al.
(2006). Motor system activation after subcortical stroke depends on corticospinal
system integrity. Brain, 129(3), 809-819.
Wassermann, E. M., Pascual-Leone, A., Valls-Solé, J., Toro, C., Cohen, L. G., & Hallett, M.
(1993). Topography of the inhibitory and excitatory responses to transcranial magnetic
stimulation in a hand muscle. Electroencephalography & Clinical Neurophysiology:
Electromyography & Motor Control, 89(6), 424-433.
Weiller, C., Ramsay, S. C., Wise, R. J., Friston, K. J., & Frackowiak, R. S. (1993). Individual
patterns of functional reorganization in the human cerebral cortex after capsular
infarction. Annals of Neurology, 33(2), 181-189.
Weiss, P., & Jeannerod, M. (1998). Getting a Grasp on Coordination. News Physiol Sci, 13(2),
70-75.
209
Whitall, J., McCombe Waller, S., Silver, K., & Macko, R. F. M. D. (2000). Repetitive Bilateral Arm
Training With Rhythmic Auditory Cueing Improves Motor Function in Chronic
Hemiparetic Stroke. Stroke October, 31(10), 2390-2395.
Wilson, S. A., Lockwood, R. J., Thickbroom, G. W., & Mastaglia, F. L. (1993). The muscle silent
period following transcranial magnetic cortical stimulation. Journal of the Neurological
Sciences, 114(2), 216-222.
Wilson, S. A., Thickbroom, G. W., & Mastaglia, F. L. r. n. (1993). Topography of excitatory and
inhibitory muscle responses evoked by transcranial magnetic stimulation in the human
motor cortex. Neuroscience Letters, 154(1-2), 52-56.
Wing, A. M., & Kristofferson, A. B. (1973). Response delays and the timing of discrete motor
responses. Perception & Psychophysics, 14(1), 5-12.
Winter, D. A. (2005). Biomechanics and motor control of human movement (3rd ed.). Hoboken,
New Jersey: John Wiley & Sons.
Wuyts, I. J., Summers, J. J., Carson, R. G., Byblow, W. D., & Semjen, A. (1996). Attention as a
mediating variable in the dynamics of bimanual coordination. Human Movement
Science, 15(6), 877-897.
Wyke, M. (1971). The effects of brain lesions on the performance of bilateral arm movements.
Neuropsychologia, 9(1), 33-42.
Yamanishi, J.-i., Kawato, M., & Suzuki, R. (1980). Two coupled oscillators as a model for the
coordinated finger tapping by both hands. Biological Cybernetics, 37(4), 219-225.
Zelaznik, H. N., Spencer, R. M. C., & Ivry, R. B. (2002). Dissociation of Explicit and Implicit
Timing in Repetitive Tapping and Drawing Movements. Journal of Experimental
Psychology: Human Perception and Performance, 28(3), 575-588.
Zelaznik, H. N., Spencer, R. M. C., Ivry, R. B., Baria, A., Bloom, M., Dolansky, L., et al. (2005).
Timing variability in circle drawing and tapping: probing the relationship between
event and emergent timing. Journal of Motor Behavior, 37(5), 395-403.
Ziemann, U., Tergau, F., Netz, J., & Homberg, V. (1997). Delay in simple reaction time after
focal transcranial magnetic stimulation of the human brain occurs at the final motor
output stage. Brain Research, 744(1), 32-40.
Zoghi, M., Pearce, S. L., & Nordstrom, M. A. (2003). Differential modulation of intracortical
inhibition in human motor cortex during selective activation of an intrinsic hand
muscle. Journal of Physiology, 550(Pt 3), 933-946.
210
211
APPENDIX A
Name:______________________ Date: ___________ Medical History
Yes No Comments
Brain Surgery Shunt Craniotomy Aneurysm clip Craniotomy Cardiac surgery Pacemaker CABG Valve replacement Ear surgery Tubes Cochlear implants
Hearing aid Epilepsy Migraine Medication Braces Other