Anthony N. Carlsen

Proac�ve inhibi�on does not differen�ally affect preparatory ac�va�on between limbsNeil M. Drummond

Erin K. Cressman School of Human Kine�cs, University of O�awa, O�awa, Canada

BackgroundÜ A conditional stop-signal task requires participants to plan and initiate a bimanual limb movement as fast as possible in response to a go-signal, but to inhibit a specified movement/limb in response to an infrequent stop-signal, while the response for all other movements/limbs should nevertheless be

1,2,3made .

Ü A startling acoustic stimulus (SAS > 120 dB) has been shown to provide added activation, resulting in 8,9the involuntary triggering of the prepared response . A SAS has been shown to simultaneously

trigger two independently prepared movements, which enables a SAS to be used to study the 10activation related to each hand independently .

Ü Essential to this conditional stop paradigm is that advance information is given about which movement/limb may need to be stopped, allowing participants to prepare in advance which limb

1,2,3might have to be stopped .

Ü Performance in this task has been linked to a selective stopping mechanism, decribed as proactive inhibition. Hallmarks of proactive inhibition are decreased corticospinal excitability (CE) only in the limb

4,5,6 5,7that was cued to maybe stop , and less interference (slowing of RT) in the (other) responding limb .

60

30

050 100 200 300 400 500 600 700

Triceps

Biceps

Triceps

Biceps

ControlStartle

Dis

pla

cem

ent (d

eg)

Time (ms)

Modified from Claffey et al., 2010

Contact Informa�on

NeuroMotor.caNeil.Drummond@uo�awa.ca Erin.Cressman@uo�awa.ca Tony.Carlsen@uo�awa.ca

Methods

MSR: prepare to stop right hand

Maybe Stop Right M

MSL: prepare to stop left hand

Maybe Stop Left W

Maybe Stop XXX M

Null: TMS rest baseline

Null

X

X

X

MSX: prepare to stop left or right hand

0 Go SSD StopTMS

2-3.5 s preparatory period

MSR: prepare to stop right handMaybe

Stop Right

M

X

MSR: prepare to stop right handMaybe

Stop Right

M

X

GET READY

Simple reac�on �me task

Simple condi�onal stop-signal task

Exp 1. SAS + simple condi�onal stop-signal task (n=9)

Choice condi�onal stop-signal task

Exp 2. Control choice condi�onal stop-signal task (n=6)

MVF - 3 trialsSimple reac�on �me task - 20 trialsCondi�onal stop-signal task - 164 trials- 20 prac�ce trials and 144 tes�ng trials- 6 tes�ng blocks consis�ng of 24 trials each- Each block contained 6 trials per cue type (i.e., MSR, MSL, MSX, NULL)- 3/6 go trial (50%), 2/6= stop trial (33%), 1/6 = go trial + SAS (17%)

Condi�onal stop-signal task - 330 trials- 90 prac�ce trials and 240 tes�ng trials- 8 tes�ng blocks consis�ng of 30 trials - MSR & MSL: 4/6 go trial (67%), 2/6= stop trial (33%)- MSX: 8/12 go trial (67%), 4/12= stop trial (33%)- NULL: 6/6 (100%)

2 s response period 1 feedback s

Go Only: prepare to go with both hands

1. TMS extensor carpi radialis hotspot and res�ng motor threshold procedure2. Maximum voluntary isometric force (MVF) test3. Simple reac�on �me task - simple bimanual response (40% MVF extension)4. Condi�onal stop-signal task - simple bimanual response (40% MVF extension)

Single pulse TMS 112% of res�ng motor threshold (mean s�mulator output = 49 %)- TMS delivered 1 s a�er cue offset on every tes�ng trial- Counterbalanced le� or right hemisphereStartling acous�c s�mulus (120 dB white noise)- SAS delivered concurrent with go- Simple reac�on �me task (5 SAS/ 20 trials)- Condi�onal stop-signal task (18 SAS / 144 trials)

Single pulse TMS 112% of res�ng motor threshold (mean s�mulator output = 46 %)- TMS delivered 1 s a�er cue offset on every tes�ng trial- Counterbalanced le� or right hemisphere

1. TMS extensor carpi radialis hotspot and threshold procedure2. Condi�onal stop-signal task - choice bimanual response (40 deg flexion or extension)

Procedure

Trial Breakdown

S�mula�on

Procedure

Trial Breakdown: Majid et al., 2013 replica�on

S�mula�on

0 Go SSD StopTMS

2-3.5 s preparatory period 2 s response period 1 feedback s

SCM EMG

Force transducer (Nano25, ATI inc.)

Straps

Brace

Agonist EMG

SAS

TMS coil

Cued Ambiguous

Condition

Inte

rfe

ren

ce (

secs

)

0.15

0.10

0.05

0.00MSL MSX

Cue

FD

I M

EP

AM

P (

mV

)

0.12

0.8

0.4

0.0MSR

-20

-10

0

10

20

30

40

50

Stop-cued Non-cued Ambiguous

Exp.2 Choice CSST

Exp.1 Simple CSST

% W

rist

Ext

en

sor

Mo

du

la�

on

0

50

100

150

200

250

300

MSR MSL MSX

Sto

pp

ing

Inte

rfe

ren

ce e

ffe

ct (

ms)

Subj. 3Subj. 5

Subj. 3Subj. 5

Subj. 5Subj. 9

0

0.2

0.4

0.6

0.8

1

Go Only MSR MSL MSXPro

po

r�o

n o

f st

artl

ed

(SC

M+

) SA

S tr

ials

-100

-80

-60

-40

-20

0

% S

CM

+ M

od

ula

�o

n

-100

-80

-60

-40

-20

0

Q100

Stop-c

ued

Non-cued

Ambig

uous

Stop-c

ued

Non-cued

Ambig

uousQ30

Results

Fig 2. Propor�on of bilateral startled (SCM+) SAS trials as a func�on of trial type.The data presented are group means, subjects who had a SCM+ during that trial type are indicated above. Error bars represent within-subject 95% CI.

Fig 3. Within subject % SCM+ modula�on of Q30 & Q100 as a func�on of cue type during the condi�onal stop-signal task rela�ve to the simple RT task [(stop signal-simple)/simple *100]. The data presented are means (SE) of subjects who had a SCM+ during the condi�onal stop-signal task. Stop-cued is SCM on the same side which was cued to stop (e.g., right SCM - maybe stop right), Non-cued is the SCM opposite to the cued stop side (e.g., right SCM- maybe stop le�), and Ambiguous is SCM during the MSX cue.

Fig 6. Group mean stopping interference effect as a func�on of trial type during the condi�onal stop-signal task (Exp 1). The stopping interference effect indicates the delay in RT rela�ve to go of the con�nuing hand during stop-trials. The reduced interference during Maybe Stop Right (MSR) & Maybe Stop Le� (MSL) trials compared to Maybe Stop Unknown (MSX) indicates the use of selec�veproac�ve inhibi�on. Error bars represent within-subject 95% CI.

Fig 7. Group mean modula�on of MEP amplitude rela�ve to null trials for each condi�onal stop-signal task cue type [(cue-null)/null *100]. The red bars are data from Exp 1. which only had a single known bimanual response and the grey bars are data from Exp 2. which had a 2 choice bimanual response. Note the elevated and similar level of excitability for stop-cued and non-cued hands in Exp 1., whereas Exp 2. demonstrates a significant reduc�on in excitability in the stop-cuedhand compared to the non-cued hand. Error bars represent within-subject 95% CI.

100

200

300

400

500

600

700

800

900

Go Only MSR MSL MSX MSR MSL MSX MSR MSL MSX MSR MSL MSX0

Group Mean Subject 3 Subject 5 Subject 9

Go Only Go Only Go Only

Pre

mo

tor

reac

�o

n �

me

(m

s)

SCM+SCM-CTL

Fig 1. Premotor reac�on �me (ms) as a func�on of trial type during control (CTL) and startle trials (SCM+/-). Group Mean as well as individual trial data from subjects 3, 5, and 9 are presented. The condi�onal stop-signal task data from these three subjects are shown as these were the only subjects which a SAS elicited a bilateral startle response (SCM+). Control trials are represented by the dark shades, startle trials which did not result in a bilateral SCM response (SCM-) are represented by the light shade, and startle trials which did result in a bilateral SCM response (SCM+) are represented by the vibrant shade. Go only = simple RT, Maybe stop right = MSR, Maybe stop le� = MSL, Maybe stop unknown = MSX. Error bars on group mean data represent within-subject 95% CI.

Fig 4. Mean difference in premotor reac�on �me (ms) between the right and le� response (right - le�) during control and SCM+ trials as a func�on of trial type. Grey bars are group means during control trials,black bars are the subset mean of subjects who startled during control trials, red bars are the subset meanof SCM+ SAS trials. Error bars = SEM.

-40

-30

-20

-10

0

10

20

30

40

50

60

Rig

ht

- le

� r

eac�

on

�m

e (m

s)

Right first

Le� first

MSR

MSXMSL

Group CTLSubset CTLSubset SCM+

0

10

20

30

40

50

60

70

Non-cuedStop-cued Ambiguous

Group CTLSubset CTLSubset SCM+

Peak

fo

rce

(% M

VF)

Fig 5. Peak force (%MVF) achieved for control responses and SCM+ responses as a func�on of cue type duringthe condi�onal stop-signal task. Grey bars are group means during control trials, black bars are the subset meanof subjects who startled during control trials, red bars are the subset mean of SCM+ SAS trials. Error bars = SEM.

Hypotheses

L

R

L

R

L

R

L

R

L

R

L

R

Maybe Stop UnknownMaybe Stop Right Maybe Stop Left

Control go trial

SAS trial

How does proactive inhibition affect preparation and activation related to the initiation of both responses, particularly that of the non-cued limb which does not have to be stopped?

Q:

DiscussionÜPresentation of the SAS during the conditional stop-signal task rarely resulted in a startle response (SCM+).

ÜThe difference in CE results between Exp 1. & 2. and the large decrease in the startle response suggests that proactive inhibition is suppressing subcortical regions, with large increases in cortical activation related to the initiation of the response in Exp 1. masking the small inhibitory effect typically seen in CE.

ÜDespite behavioural evidence of proactive inhibition of a single response, the results suggest that preparatory activation related to the initiation of the two responses was not different between limbs.

ÜExp 1. TMS results revealed that corticospinal excitability (CE ) was not different between non-cued and stop-cued limbs, and was significantly higher than at rest.

ÜBehavioural results revealed that proactive inhibition was used for task performance, as indicated by the small stopping interference effect in MSR & MSL conditions.

ÜExp 2. TMS results revealed that CE was significantly reduced in the stop-cued hand compared to the non-cued hand.

ÜIt appears that if a startle response was elicited, both left and right responses were initiated simultaneously regardless of inhibitory cue.

References1. Aron & Verbruggen (2008). Psych Sci, 9(11), 1146-1153. 2. Jahfari et al. (2010). J Cog Neurosci, 22(7), 1479-1492. 3. Claffey et al. (2014). Neuropsychologia, 48, 541-548. 4. Cai et al. (2011). J Neurosci, 31(16), 5965-5969. 5. Greenhouse et al. (2012). J Neurophysiol, 107(1), 384-392.6. Majid et al. (2013). J Neurosci, 33(33), 13259-13269. 7. Jahfari et al. (2011). J Neurosci, 31(18), 6891-6899. 8. Carlsen et al. (2012). Clin Neurophysiology, 123, 21-33. 9. Maslovat et al. (2015). Neurosci Let, 606, 151-155. 10. Carlsen et al. (2009). Psychophysiol, 46(2), 241-251.