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Neuropsychologia 48 (2010) 2595–2601

Contents lists available at ScienceDirect

Neuropsychologia

journa l homepage: www.e lsev ier .com/ locate /neuropsychologia

eural mechanisms underlying spatial realignment during adaptationo optical wedge prisms

eidi L. Chapmana, Ranmalee Eramudugollab, Maria Gavrilescuc, Mark W. Strudwickd,ndrea Loftuse, Ross Cunningtonb, Jason B. Mattingleyb,∗

School of Psychology, University of Birmingham, United KingdomQueensland Brain Institute & School of Psychology, The University of Queensland, Queensland 4072, AustraliaNational Neuroscience Facility, University of Melbourne, AustraliaCentre for Magnetic Resonance, The University of Queensland, AustraliaDepartment of Psychology, University of Western Australia, Australia

r t i c l e i n f o

rticle history:eceived 16 November 2009eceived in revised form 26 March 2010ccepted 3 May 2010vailable online 8 May 2010

eywords:rism adaptationpatial cognition

a b s t r a c t

Visuomotor adaptation to a shift in visual input produced by prismatic lenses is an example of dynamicsensory-motor plasticity within the brain. Prism adaptation is readily induced in healthy individuals, andis thought to reflect the brain’s ability to compensate for drifts in spatial calibration between differentsensory systems. The neural correlate of this form of functional plasticity is largely unknown, althoughcurrent models predict the involvement of parieto-cerebellar circuits. Recent studies that have employedevent-related functional magnetic resonance imaging (fMRI) to identify brain regions associated withprism adaptation have discovered patterns of parietal and cerebellar modulation as participants cor-rected their visuomotor errors during the early part of adaptation. However, the role of these regions in

arietal lobeerebellumpatial realignmentrror correctionMRI

the later stage of adaptation, when ‘spatial realignment’ or true adaptation is predicted to occur, remainsunclear. Here, we used fMRI to quantify the distinctive patterns of parieto-cerebellar activity as visuo-motor adaptation develops. We directly contrasted activation patterns during the initial error correctionphase of visuomotor adaptation with that during the later spatial realignment phase, and found sig-nificant recruitment of the parieto-cerebellar network – with activations in the right inferior parietallobe and the right posterior cerebellum. These findings provide the first evidence of both cerebellar and

ing th

parietal involvement dur

. Introduction

When participants point at targets under visual guidance whileearing prism lenses that displace the visual field laterally, theyemonstrate errors in pointing that are in the direction of theptical displacement. These errors rapidly decrease with repeatedointing, as the participant compensates for the misalignmentetween visual inputs and the felt position of the hand. When therism lenses are removed, pointing errors are again apparent, buthis time in the direction opposite to that of the prism-inducedisual displacement, indicating an adaptive shift in perceived handosition. This aftereffect reflects underlying neural adaptation to the

isuomotor disparity (Harris, 1965; Held, 1965; Redding, Rossetti,Wallace, 2005).In studies of prism adaptation, two distinct phases have been

dentified: error correction and spatial realignment (Redding &

∗ Corresponding author.E-mail address: j.mattingley@uq.edu.au (J.B. Mattingley).

028-3932/$ – see front matter © 2010 Elsevier Ltd. All rights reserved.oi:10.1016/j.neuropsychologia.2010.05.006

e spatial realignment phase of prism adaptation.© 2010 Elsevier Ltd. All rights reserved.

Wallace, 1993; Redding et al., 2005). Error correction, or strategiccontrol, describes a process of error reduction in movement planswhereby the participant anticipates an error and plans a movementthat minimises the perturbation (Redding & Wallace, 1993,1996).Although the initial pointing errors associated with prism adap-tation are reduced to zero within the first few reaches, a furtherperiod of repeated pointing is essential for the aftereffect (and spa-tial realignment) to develop fully (Redding & Wallace, 1993). In fact,strategic error correction (as indexed by the increasing accuracyof early pointing trials) and spatial realignment (as indexed by theaftereffect) are thought to be two interrelated but independent pro-cesses (Fernandez-Ruiz et al., 2007; Michel, Pisella, Prablanc, Rode,& Rossetti, 2007; Newport & Jackson, 2006; Redding & Wallace,1993, 1996).

1.1. Lesion studies of prism adaptation

The neural circuitry underlying each phase of adaptationremains unclear. Human lesion data indicate a role for the cerebel-lum in both spatial realignment and error correction; either process

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an be independently impaired, depending on the regions damagedithin this structure (Fernandez-Ruiz et al., 2007; Martin, Keating,oodkin, Bastian, & Thach, 1996; Pisella et al., 2005). The parietal

obe also appears to be involved in the strategic error correctionhase of adaptation, but its role in spatial realignment is somewhatontentious. Bilateral lesions of the parietal lobe can impair thebility to strategically correct for errors induced by prismatic dis-lacement (Newport & Jackson, 2006; Pisella et al., 2004) while stillnabling the development of an aftereffect (although see NewportJackson, 2006). However, both bilateral and unilateral parietal

esions often produce abnormally large aftereffects of prism adap-ation and generalization to other, untrained, spatial behavioursPisella et al., 2004; Sarri et al., 2008), implying parietal involve-

ent in at least modulating the degree of spatial realignmentMichel, 2006). Based on such lesion data, current models of prismdaptation propose a network of parietal and cerebellar regionsnvolved in detecting the visual-motor misalignment produced byrisms and invoking changes to internal models of movement toccommodate for this (e.g., Michel, 2006; Newport & Jackson, 2006;isella, Gilles, Farne, Tilikete, & Rossetti, 2006; Ramnani, 2006;edding & Wallace, 2006; Serino, Angeli, Frassinetti, & Ladavas,006). What does this mean for the intact brain? Findings fromhe few available brain imaging studies of prism adaptation sup-ort a role for parietal and cerebellar regions in the initial errororrection phase (Clower et al., 1996; Danckert, Ferber, & Goodale,008; Luauté et al., 2009). There have been no imaging studies,owever, that have clearly identified neural mechanisms distinc-ive to realignment. Identifying the neural correlates of this laterhase is critical for understanding the therapeutic effects of prismdaptation in parietal patients (e.g., Pisella et al., 2006) as well ashe mechanisms behind short-term plasticity of spatial maps inhe normal brain. Thus the primary goal of the present study waso examine the neural basis of prism-induced spatial realignmentn the healthy brain.

.2. Neuroimaging of prism adaptation

Several studies have examined neural activation patterns asso-iated with the initial error correction phase of prism adaptationClower et al., 1996; Danckert et al., 2008; Luauté et al., 2009).ogether, their findings strongly implicate the inferior parietal cor-ex, contralateral to the pointing arm, in the process of detectingnd consciously correcting for the prism-induced misalignmentetween vision and perceived hand position. In their pioneeringtudy, Clower et al. (1996) measured changes in regional cerebrallood flow (rCBF) associated with pointing movements under the

nfluence of laterally displacing prisms. In their study, the direc-ion of displacement of the prism lenses was reversed every fiverials, thus forcing the participant to continually correct for therism-induced errors in pointing. Under these conditions, activa-ion within the left intraparietal sulcus (IPS) was associated withrror correction during prism adaptation. More recently, Danckertt al. (2008) used fMRI to investigate the neural basis of error cor-ection over the course of the first ten pointing trials of prismdaptation. Their findings confirmed a role for the left anteriorntraparietal sulcus during the first three trials of prism exposure

hen participants were experiencing large pointing errors, rela-ive to later trials on which errors had been reduced. In addition,ncreased activity in regions within the anterior cingulate and pri-

ary motor cortex were also found to be associated with thesearly error correction trials. Further evidence for the role of the

arietal lobe in correcting for prism-induced errors comes from aecent event-related fMRI study in which trial-by-trial decreasesn the magnitude of the BOLD response within the left anteriorPS closely matched participants’ behavioural reduction in point-ng errors (Luauté et al., 2009). Luauté et al. (2009) also reported

logia 48 (2010) 2595–2601

a trial-by-trial increase in activation within the posterior occipitalsulcus (POS) over the same period of error reduction. The authorssuggested that these two sites, IPS and POS, might be involved inerror detection and correction, respectively.

Unlike previous studies, Luauté et al. (2009) allowed partici-pants to continue pointing well beyond the initial error correctionphase, thus imaging the entire adaptation process (including spa-tial realignment) for the first time. Crucially, the only sub-thresholdactivation that the authors could attribute to the later, spatialrealignment period (and thus to development of the aftereffect) wasa gradual, but subtle increase in cerebellar activity that outlastedthe initial period of error correction. The trial-by-trial analysisis an elegant approach for exploring brain activation associatedwith a temporally unfolding process such as adaptation. However,unlike error correction, spatial realignment is not associated withan observable behaviour during the course of adaptation, and nei-ther its point of initiation nor its rate of development are known. Inthis context, the slight increase in cerebellar activation observed byLuauté et al. (2009) could have multiple possible causes, includingslow, random variations in the hemodynamic signal, as the authorsthemselves acknowledge.

The lack of clear behavioural markers for spatial realignmentposes methodological complexities for isolating activation patternsrelated to realignment. In fact, error correction and realignmentare not necessarily sequential processes, and likely overlap in time(Redding & Wallace, 1993; Redding et al., 2005). Processes relat-ing to realignment are nevertheless predicted to dominate duringthe later trials of adaptation (Redding & Wallace, 1993; Reddinget al., 2005). In the present study, we employed a blocked fMRIdesign to directly compare brain activation elicited during the ini-tial half of adaptation trials (including the error correction phase)with that during the later half of trials (corresponding principally tospatial realignment). Blocking the adaptation session in this man-ner allowed us to contrast trials predominantly associated withrealignment against the earlier trials in which minimal realignmentwas expected to have occurred. By subtracting neural responsesfor error correction from those associated with spatial realign-ment, and assuming an overlapping transition from one phase tothe next, this approach provides a conservative estimate of theactivation unique to spatial realignment. Crucially, our approachyielded robust neural responses during the spatial realignmentphase, which included subregions of the cerebellum and the infe-rior parietal cortex.

2. Methods

2.1. Participants

Fourteen right-handed male participants (20–42 years) with no history ofneurological disease participated. All participants gave informed consent. One par-ticipant’s data set was removed due to large head movements during scanning(>5 mm), and another data set was removed due to a technical error during datacollection.

2.2. Materials and procedure

To enable participants to easily alternate between prismatic and normal visionwithin the scanner, they wore plastic goggles modified to include a 10◦ wedge-based optical prism lens over the left eye and a neutral (non-shifting) lens over theright eye (Fig. 1C). The prism lens shifted the visual field to the left. Participantsalways performed the task with one eye covered so that vision was either normal ordisplaced to the left. Adaptation with monocular vision produces the same effectsas adaptation with binocular vision (Redding et al., 2005) and this approach hasbeen successfully used in the scanner environment (Danckert et al., 2008; Luauté et

al., 2009). To cover the unused eye, a rod was used to remotely shift an occludingpatch (5 cm radius) without the need for participants to move their head. Duringthe prism adaptation conditions, the neutral lens was occluded and vision was viathe prism lens. Following adaptation, the prism lens was occluded, allowing visionvia the neutral lens. Pointing without prismatic displacement – called de-adaptation– revealed aftereffects and a gradual return to normal pointing accuracy.

H.L. Chapman et al. / Neuropsychologia 48 (2010) 2595–2601 2597

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of the participant’s subjective straight-ahead (SSA) was obtained. This is a standardmeasure of the effectiveness of adaptation used in neurologically normal partici-pants as well as in patients with spatial neglect (Colent, Pisella, Bernieri, Rode, &Rossetti, 2000; Redding et al., 2005; Sarri et al., 2008). Here, participants vieweda central fixation cross-through the clear lens and were required to aim the laserpointer at the cross. They then closed their eyes and depressed the trigger. Thus,

Fig. 2. Pointing errors during the adaptation phase. The left portion of the graph dis-plays mean pointing errors during the error correction phase of prism adaptation. Amarked leftward bias in errors is apparent, which reduces over successive trials. The

ig. 1. (A) Participant pointing with manipulandum to back-projected stimuli. (B) Lhe barrel of the manipulandum (top left). The manipulandum was mounted on a hoC) A leftward-shifting, wedge-based prism lens was placed over the participant’s liewing condition (adaptation or de-adaptation) an occluding patch was manoeuvr

Participants used a manipulandum containing an MR-compatible laser pointerFig. 1A and B) to point at visual targets during scanning. Participants held this

anipulandum with their right hand while supine in the scanner. Stimuli wereack-projected onto a screen at the end of the scanner bed. Participants receivedisual feedback for pointing accuracy by squeezing a trigger on the manipulandumith the right index finger, thereby projecting a laser spot onto the screen (Fig. 1B).

arget stimuli were vertical yellow bars presented against a calibrated grid of whiteines. The targets appeared at one of two horizontal positions (4◦ and 6◦) to the leftr right of the centre of the display screen. Pointing accuracy was video recordeduring the experiment for off-line scoring using the grid.

.3. Localiser task

We adopted a region-of-interest (ROI) approach to our analyses. To identifyegions of activation specific to prism adaptation and to control for irrelevant acti-ation associated with motor planning and execution of the pointing responses, wemployed a separate localiser task designed to identify brain regions relevant toisual aiming. The localiser task was composed of three conditions in which par-icipants viewed all stimuli through the neutral lens. In one condition, the targettimulus was presented at varying locations and participants had to point to thearget as accurately as possible and squeeze the trigger of the manipulandum toeceive visual feedback on their pointing accuracy. In the second condition, partic-pants kept the laser pointer aimed at the centre of the screen and as each targetppeared, fixated the target and squeezed the trigger (projecting the laser point athe central location). The third condition involved simply maintaining visual fixa-ion on a central cross on the screen. The conditions were presented in blocks andach was repeated twice during the localiser task. Practice trials and instructionsere provided at the beginning of each block.

.4. Experimental tasks

In the main experiment, participants alternated between vision through therism lens (adaptation) and vision through the neutral lens (de-adaptation). Each ofhese conditions was composed of two runs. Vision was through the prism lens forhe first two runs with participants commencing prism adaptation in Run 1 (errororrection) and continuing prism adaptation in Run 2 (spatial realignment). Par-icipants de-adaptated by pointing at targets using vision through the clear lens inuns 3 and 4. In the initial adaptation condition, participants looked through the

rism lens and pointed at the visual target. Upon pointing the manipulandum attarget, depending on the instructions for the condition, participants could eitherepress the trigger and receive visual feedback with the projection of the laser spotnto the screen (experimental task), or not squeeze the trigger (no-visual feed-ack) and receive no information about the accuracy of their responses (baselineask). Importantly, this feedback was provided only at the end of each movement, to

pot projection was controlled by pulling a trigger to release a barrier at the end oftal pivot that allowed it to swivel with side-to-side wrist movements (below right).

and a neutral (non-shifting) lens was placed over the right eye. Depending on theer one of the lenses, and shifted to the other lens when the condition changed.

prevent online guidance. The first run of the adaptation condition was the error cor-rection phase, during which pointing errors were initially in the direction of prismdisplacement and gradually reduced to zero over successive pointing trials (Fig. 2).

This was followed by a second run (spatial realignment phase) with a continua-tion of pointing trials. Following adaptation (i.e., after Run 2), a single trial measure

right portion of the graph displays two measures of the aftereffect of prism adap-tation. The first was obtained as participants made subjective straight-ahead (SSA)estimates with their eyes closed. The second shows the pointing error displayed onthe first trial of the de-adaptation phase, where participants viewed targets throughthe neutral lens. Both measures of the aftereffect show a strong rightward bias inpointing, indicating true adaptation to the leftward-shifting prisms.

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articipants did not have visual feedback of pointing accuracy. This measurementf SSA revealed rightward aftereffects of adaptation, as predicted (Fig. 2).

The de-adaptation condition followed the measure of SSA. Participants nowiewed the visual display through the neutral lens and repeated the target-pointingask for two runs as in the adaptation condition. During these runs, the adaptiveftereffects that were developed while viewing through the prism lens graduallyeduced to zero. Activation during each of the four experimental runs was con-rasted with a baseline condition in which participants performed the same pointingask, with either the prism or neutral lens, but without visual feedback (i.e., whilehe laser spot was not visible). The baseline conditions involved the same visualisplay and motor demands as in the experimental conditions, but did not elicitdaptation because of the lack of visual feedback after each pointing response. Par-icipants performed three repetitions of the experimental and baseline conditionsegularly interleaved during the scanning session. All pointing responses were mon-tored from the scanner control room: pointing actions with visual feedback wereecorded to video for analysis; and pointing movements executed without feedbacki.e., no trigger squeeze) were carefully monitored via an infrared camera positionedn the scanner bed.

.5. Imaging procedure

The BOLD effects of each test condition were recorded using echo planar imag-ng (EPI) performed in a 1.5T Siemens Sonata MR scanner equipped with a circularolarised headcoil (TR: 3000 ms; TE: 40 ms; FA: 90◦; slice thickness: 3.5 mm; no. oflices: 32; gap: 0.4 mm; FOV: 230 × 230; matrix: 64 × 64; bandwidth: 2004 Hx/pix;n-plane voxel size: 3.6 mm × 3.5 mm). For individual data registration, a high-esolution 3D T1-weighted coronal image was acquired (MP RAGE: TR: 1930 ms;E: 3.93 ms; TI: 1000 ms; FA: 15◦; FOV: 240 × 240; matrix: 256 × 256; bandwidth:30 Hz/pix; voxel size: 0.9 mm × 0.9 mm × 0.9 mm).

.6. Imaging analysis

Statistical analysis was performed on the blocked design paradigm, and dataere analysed with the general linear model method in SPM5 (Wellcome Depart-ent of Imaging Neuroscience). The first six scans of each run were discarded to

llow equilibration of saturation effects. For pre-processing, images were realignedo the first image of the functional series to reduce the effects of head motion, spa-ially normalised onto a template with a voxel size of 2 mm3, and smoothed withGaussian kernel with a full width at half maximum (FWHM) of 8 mm. No data

et showed greater than 2 mm in translation or 2 mm in rotation. Data were con-olved with a canonical hemodynamic response function and contrast images werealculated for each condition within individual data sets.

.7. Functional ROIs

Analysis of the localiser task revealed eight functional regions of interest thatere specifically involved in pointing under visual guidance, independent of visualisplay characteristics and basic motor demands (Fig. 3A). These regions werebtained by contrasting the condition in which participants aimed and pointed atach target, with the condition in which participants looked at the target but aimednd pointed at a central location – holding constant the visual detection of targetsnd operation of the laser pointer. Eight ROIs were defined within parietal and cere-ellar regions (thresholded at pFDR-corrected < 0.05, cluster size > 20 voxels) (Fig. 3A).sing the MarsBaR toolbox for SPM (Brett et al., 2002), we determined the peak-oxel within each of these regions, which was then used to compare percent BOLDignal changes in the experimental task. The MNI coordinates for each of the ROIsere: bilateral superior parietal lobes (−34, −36, 62 (left BA3); 14, −62, 60 (rightA7)), inferior parietal lobes (−52, −30, 28 (left BA40 – supramarginal gyrus); 42,50, 46 (right BA40 – supramarginal gyrus); 36, −78, 30 (right BA39 – angular gyrus)nd cerebellum (−20, −64, −24 (left posterior lobe); 16, −50, −20 (right anteriorobe); 16, −58, −50 (right posterior lobe)).

These regions of interest were used in subsequent analyses of the experimentalask to test for changes associated with the two phases of prism adaptation (errororrection and spatial realignment). In SPM5, second level t-tests were performed byubtracting the prism lens condition without visual feedback from the prism adap-ation condition with visual feedback. This was performed separately for each of theun types (error correction and spatial realignment) – yielding activation specifico each phase of adaptation. The outcome of this contrast was then used in singleample t-tests for the error correction and spatial realignment phases. Paired sample-tests were then performed by comparing error correction with spatial realignmentn order to define regions with greater activation during one phase relative to thether. For each of the three t-tests, parameter estimates were extracted for the eightOIs defined above using MarsBaR. Activity patterns during error correction and spa-ial realignment are presented as mean percent signal change for the group (Fig. 3B).

.8. Behavioural analysis

The accuracy of participants’ pointing responses during the experimental tasksas determined by measuring the distance of the laser point from the target, relative

o the calibrated grid. Errors to the right of the target were scored as positive and

logia 48 (2010) 2595–2601

errors to the left were scored as negative. Individual results were collated to providegroup mean responses for each condition over the 18 trials of each run. Aftereffects,measured as subjective straight-ahead estimates, were recorded for each of the threeadaptation cycles for each participant.

3. Results

3.1. Behavioural data

As apparent from Fig. 2, participants initially displayed largeleftward errors in pointing during the error correction phase ofprism adaptation. These errors rapidly reduced to zero by the end ofthe error correction phase and pointing accuracy was maintainedthroughout the ensuing spatial realignment phase. This was con-firmed statistically. We conducted a two-way repeated measuresanalysis of variance on pointing errors (distance between point-ing response and target) obtained during the first nine trials ofeach adaptation phase. Thus the factors of the ANOVA were adap-tation phase (error correction and spatial realignment) and trial(trials 1–9 for each phase). This revealed a significant interactionbetween phase and trial (F(8,96) = 2.10, p < 0.05, �p

2 = 0.15). Simpleeffects analyses indicated that pointing errors reduced significantlyacross trials in the error correction phase (F(8,96) = 4.45, p < 0.01,�p

2 = 0.27 (Bonferroni corrected ˛ = 0.025); see Fig. 2), but did notchange across trials in the spatial realignment phase (F(8,96) = 1.55,p > 0.10). Furthermore, a direct comparison of the first trial of eachphase showed a significantly larger pointing error during error cor-rection than spatial realignment (t(12) = 2.79, p < 0.017). Followingadaptation, participants’ estimate of subjective straight-ahead was5.03◦ (SEM = 0.57) to the right of the mid-sagittal axis, confirm-ing the development of spatial realignment (t(12) = 3.54, p < 0.005).This rightward aftereffect was also apparent on initial trials ofthe de-adaptation condition (mean = 2.26◦, SEM = 0.41) (t(12) = 5.2,p < 0.001).

3.2. fMRI data

3.2.1. Error correction (early prism adaptation)In order to identify brain regions recruited during the early

phase of prism adaptation, we subtracted the first run of the prismlens condition without visual feedback from the early (error correc-tion) run of the prism adaptation condition with visual feedback.Of the ROIs defined above, several sites of activation were signif-icantly associated with the early phase of adaptation. A posteriorregion within the left cerebellum (t = 3.59, p < 0.02) and an anteriorsite within the right cerebellum were active during error correction(t = 4.26, p < 0.01). Within the right parietal cortex, regions withinboth the right superior parietal lobule (SPL) (t = 3.13, p < 0.04) andright inferior parietal lobule (IPL) – supramarginal gyrus (t = 3.03,p < 0.04) were activated during error correction. The latter infe-rior parietal site was located along the anterior intraparietal sulcus(aIPS). Because the early phase of adaptation as defined in ourstudy is likely to have included some degree of spatial realign-ment, caution is necessary in attributing the observed pattern ofactivation specifically to error correction. Some sites were, how-ever, consistent with those obtained in previous imaging studies.For example, a region within the right cerebellum was also asso-ciated with error correction in the study by Luauté et al. (2009).The aIPS has previously been implicated in the detection of errorsin motor planning during action initiation (Desmurget et al., 1999;Tunik, Frey, & Grafton, 2005), in the representation and updating

of action goals (Rice, Tunik, & Grafton, 2006), and in motor skilllearning (Della-Maggiore, Malfait, Ostry, & Paus, 2004; Tunik, Rice,Hamilton, & Grafton, 2007). Interestingly, our right IPL site (42, −50,46) is slightly inferior to a region associated with the early stage ofadaptation reported in the Luauté et al.’s study (40, −54, 66). It is

H.L. Chapman et al. / Neuropsychologia 48 (2010) 2595–2601 2599

Fig. 3. (A) Eight regions of interest (ROIs) were identified based on a separate localiser task. These included the right and left cerebellum, bilateral inferior parietal lobe (IPL)a trated( hite bs l realigg

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lso close to an area in the contralateral hemisphere identified inlower et al.’s (1996) PET study (−50, −50, 40), and to a subregionf aIPS that positively co-varied with pointing error (−46, −54, 56)n Luauté et al.’s study. We did not observe left hemisphere activ-ty associated with error correction, and neither of our left parietalOIs was located near aIPL.

.2.2. Spatial realignment (late prism adaptation)For the spatial realignment phase of adaptation, subtraction of

he no-visual feedback condition from the visual feedback condi-ion revealed bilateral activation of the cerebellum and the rightarietal cortex. Significant activation was also observed within the

eft posterior lobe of the cerebellum (t = 4.40, p < 0.004), the rightnterior cerebellum (t = 4.26, p < 0.01) and the right posterior cere-ellum (t = 4.81, p < 0.002). These results are consistent with thending that cerebellar activity is associated with the later, spatialealignment phase of adaptation (Luauté et al., 2009). In addition,e observed significant activation within the right SPL (t = 2.98,< 0.05) and the right anterior IPL (t = 4.38, p < 0.004), both of whichere also associated with error correction in our study. We also

ound significant activity within the angular gyrus of the right infe-ior parietal cortex (t = 3.63, p < 0.02).

.2.3. Spatial realignment versus error correction (late versusarly prism adaptation)

To identify neural activation patterns specific to the critical

eriod of spatial realignment, we contrasted activation duringpatial realignment with that during error correction (spatialealignment > error correction). This crucial contrast represents theifference of the subtraction between each experimental condi-ion and its baseline – holding constant motor, proprioceptive and

significantly higher activation during spatial realignment versus error correction.ars) and spatial realignment phase (black bars) of adaptation. Asterisks denote anment phases. These regions include the right posterior cerebellum, right angular

visual functions unrelated to the progression of prism adaptation.This analysis yielded three regions within which neural activityincreased significantly during spatial realignment relative to errorcorrection, all within the right hemisphere: the posterior cerebel-lum (t = 1.99, p < 0.04); the angular gyrus (t = 1.95, p < 0.04); and theanterior IPL (t = 1.93, p < 0.04). Fig. 3B shows the increase in activ-ity in the right cerebellum and inferior parietal lobe for each ofthe ROIs. The parietal and cerebellar regions identified here werealso associated with error correction, but crucially they were sig-nificantly more active during realignment than error correction.The opposite contrast was also conducted (error correction > spatialrealignment) to identify regions specifically associated with errorcorrection. But this comparison revealed no significant activationswithin the functionally defined ROIs. Taken together, these resultssuggest that the right anterior IPL and the cerebellum increase theiractivity over the course of adaptation until realignment is achieved,and that the right angular gyrus is further activated during spatialrealignment.

4. Discussion

Consistent with current models of adaptation (Newport &Jackson, 2006; Pisella et al., 2006; Ramnani, 2006), and with thefMRI findings to date (Clower et al., 1996; Danckert et al., 2008;Luauté et al., 2009), our results provide evidence for the involve-ment of parietal and cerebellar structures during prism adaptation.

Importantly, our findings show that neural responses in the rightcerebellum and inferior parietal lobe are recruited during the later,spatial realignment phase of prism adaptation. These findings sup-port and extend the existing theoretical framework regarding thetwo processes thought to underlie adaptation.

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.1. Parietal and cerebellar roles in error correction

For the early (error correction) phase of prism adaptation, weound significant activation within the left posterior and right ante-ior cerebellum, along with activation in the right SPL and alsohe right anterior IPL. Although some of these activations mayepresent the early stages of realignment, together with previ-us findings, our results suggest a role for parietal and cerebellartructures in error correction. The cerebellum has a well docu-ented role in comparing motor output (efference) and the visual

rror resulting from this output (visual reafference) (Ramnani,006), as well as the correction of prism-induced visuomotor errorsBaizer, Kralj-Hans, & Glickstein, 1999; Martin et al., 1996; Pisellat al., 2005). Cerebellar lesions slow the error correction processnd can also prevent the development of adaptation after effectsFernandez-Ruiz et al., 2007; Martin et al., 1996).

We found parietal (right anterior IPL and SPL) activation duringhe early phase of adaptation. A role for anterior IPL during the errororrection phase of adaptation agrees with the literature on visuallyuided, online error correction in humans (Della-Maggiore et al.,004; Desmurget et al., 1999; Tunik et al., 2005; Tunik et al., 2007).hese studies report that the anterior portion of the intraparietalulcus is a critical site for the detection of errors during visuallyuided reaching and grasping. All three studies that have examinedrror correction in the context of prism adaptation have reportedctivation of the anterior IPL (Clower et al., 1996; Danckert et al.,008; Luauté et al., 2009). The region identified by Clower et al. was

ocated along the bank of the intraparietal sulcus (−50, −50, 40), anrea close to the regions identified by studies of online error cor-ection (Della-Maggiore et al., 2004; Desmurget et al., 1999; Tunikt al., 2005; Tunik et al., 2007). Luauté et al. (2009) demonstratedilateral aIPS activation (left: −30, −68, 40; right: 40, −54, 66) asso-iated with the early phase of adaptation, although only activity ineft aIPS (contralateral to the pointing arm; −48, −58, 52) was mod-lated as participants reduced their pointing errors. Danckert et al.2008) also reported increased activity in left aIPL (−38, −42, 46)uring early trials where pointing errors were greatest. Together,hese studies implicate the aIPL contralateral to the pointing arm inetecting or correcting errors associated with prismatic displace-ent. Our aIPL activation, however, was ipsilateral to the acting

imb. It is possible that there was bilateral aIPL activity in our study,ut we used a ROI approach based on an independent localiser scanhat yielded ipsilateral aIPL activity only. There is also some uncer-ainty as to whether parietal error detection or correction in aIPL istrictly lateralised (Tunik et al., 2007), and it is possible that botheft and right aIPL contribute to strategic error processing duringointing tasks. Explicit manipulation of pointing arm (i.e., left oright) during the error correction phase of adaptation is necessaryo address this issue. Finally, it is conceivable that the activity webserved within right aIPL during the early phase of prism adap-ation reflects neural responses associated in part with the initialealignment phase.

The SPL has also been implicated in correction of pointing move-ents during other types of visual perturbation, such as visual field

otation (Inoue et al., 1997) and inversion (Richter et al., 2002).ilateral lesions of the SPL are known to impair the coordination ofisual information with hand movements (optic ataxia). A study ofne such patient revealed a complete inability to reduce rightwardointing errors caused by right displacing prisms, as well as a fail-re to demonstrate aftereffects, despite accurate target-pointingerformance before and after prism exposure (Newport & Jackson,

006). However, another study reported normal error correctionnd adaptation following bilateral SPL lesions (Pisella et al., 2004).hese findings suggest that the SPL may contribute to strategic errororrection during prism adaptation, but that it is not critical forpatial realignment.

logia 48 (2010) 2595–2601

4.2. Parietal and cerebellar involvement in spatial realignment

We identified several regions that significantly increased in acti-vation during the late spatial realignment phase relative to theearly phase of adaptation. This included the right posterior cere-bellum, the right angular gyrus and the right anterior IPL. Ourfindings represent the first report of both parietal and cerebellarcontributions to spatial realignment in prism adaptation. Currentunderstanding of cerebellar function implicates these regions ascritical for updating internal models of motor behaviour (Ramnani,2006). Cerebellar lesion studies have also shown that the devel-opment of spatial realignment and adaptation aftereffects relieson intact subregions within the cerebellum (Martin et al., 1996).By contrast, the role of parietal structures during the late phaseof adaptation remains poorly understood. Our findings show thatthe angular gyrus and aIPL are associated with updating of cere-bellar internal models. These parietal regions could (i) play a directrole in updating cerebellar models; (ii) modulate the developmentof realignment; or (iii) express the consequences of realignmenton sensory maps of space. There is evidence to suggest a pari-etal role in regulating the aftereffects of adaptation (Rode, Pisella,Rossetti, Farne, & Boisson, 2003; Rossetti & Rode, 2002; Sarri etal., 2008). Patients with unilateral (Sarri et al., 2008) or bilateralparietal damage (Pisella et al., 2004) undergo error reduction ina normal fashion during adaptation, but demonstrate significantlyenhanced aftereffects (often up to 100% of the prism-induced dis-placement). Importantly, the effects of adaptation also generalize toa range of spatial and attentional tasks to an extent that is not seenin neurologically healthy individuals (Pisella et al., 2006; Reddinget al., 2005). We found that anterior IPL is not only active dur-ing the early phase of adaptation, but also continues to increase inactivity during the late spatial realignment phase, along with thecerebellum. Indeed, Michel (2006) has recently proposed that errorsignals generated within the inferior parietal lobe may modulatethe degree of spatial realignment that occurs within the cerebellumduring prism adaptation. This is supported by behavioural evidencethat reducing healthy observers’ awareness of the prism-inducedvisuomotor error by incrementally introducing the lateral shift cansignificantly enhance adaptation aftereffects (Michel et al., 2007) –and presumably the degree of spatial realignment. Thus, a plausi-ble interpretation of our finding that aIPL and cerebellum are bothactive during spatial realignment is that errors detected by aIPL helpto regulate the plasticity of internal models within the cerebellum.

We suggest that realignment-associated activation of the rightangular gyrus reflects the transfer of adaptive aftereffects to spatialprocessing and attention. Pisella et al. (2006) hypothesised that thegeneralization of the effects of left-shifting prisms on spatial cog-nition might be mediated through parieto-cerebellar connectionsbetween the right parietal lobe and left cerebellum. The angu-lar gyrus is a key node within the spatial attention network, andhas been identified as a critical lesion site for producing unilat-eral spatial neglect (Mort et al., 2003). The angular gyrus is alsolinked with monitoring action intention and determining ones ownauthorship of an action (Farrer et al., 2008), suggesting a gener-alized role for this region in matching internal spatial maps withaction goals. A recent study showed that damage to white mat-ter underlying the posterior portion of the inferior parietal lobe(MNI coordinates: 24, −59, 36) is significantly associated with afailure to show prism-induced recovery from spatial neglect symp-toms (Sarri et al., 2008). Our findings differ from those of Luauté etal. (2009), who proposed that activation of the superior temporal

gyrus (STG) reflects generalization of spatial realignment to spatialcognition. Temporal regions have not been implicated in any of thecurrent models of prism adaptation, although the STG is known tobe involved in spatial attentional functions and is associated withspatial neglect (Karnath, Ferber, & Himmelbach, 2001; Karnath,

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ruhmann Berger, Kuker, & Rorden, 2004). Also, neuroanatomicalClower, West, Lynch, & Strick, 2001; Ramnani et al., 2006) andunctional connectivity (Krienen & Buckner, 2009) studies reportegligible connectivity between the temporal lobe and the cerebel-

um. In contrast, there are prominent cerebellar projections into thenferior parietal lobe in humans (Krienen & Buckner, 2009; Ramnanit al., 2006), and into area 7b as well as LIP and 7a in the macaqueClower et al., 2001). Thus, we suggest that the angular gyrus islikely candidate for the expression of spatial realignment in theormal brain.

There are as yet no data to support the possibility that thearietal cortex is a critical site for the development of spatialealignment. Available lesion data suggest this is unlikely, butxperiments that directly examine this hypothesis are lacking. Forxample, reversible disruption of parietal areas via transcranialagnetic stimulation (TMS) during the late phase of prism adap-

ation could determine whether aftereffects can be abolished, orhether the magnitude of aftereffects can be modulated.

. Conclusion

In summary, we have provided evidence for both cerebellarnd inferior parietal lobe activity during the spatial realignmenthase of prism adaptation in normal, healthy adults. These findingsave implications for our understanding of the neural mechanismsnderlying visuomotor adaptation in the normal brain, the mod-lation of adaptive aftereffects, and their translation to spatialognition.

cknowledgements

This research was supported by grants from ANZ Trustees (H.C.nd J.B.M) and the National Health and Medical Research CouncilAustralia) (J.B.M. and R.E.).

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