1. Cardiff University Brain Research Imaging Centre
Distinct neural pathways underlying response inhibition revealed by fMRI
Leah Maizey
Cardiff University Brain Research Imaging Centre

2. Source of inhibitory control
Aim to find locus of inhibitory control
Assumed to be situated in prefrontal cortex
Exert top-down control
Right inferior frontal gyrus
Pre-SMA
Inhibitory Control vs.
General updating
Confounded by non-inhibitory processes
Are these regions also crucial to updating in the absence of inhibition?

3. fMRI study
AIM: to explore common and distinct regions of activation associated with inhibitory and non-inhibitory action updating.
Right inferior frontal gyrus
Pre-SMA
1. Focus on rIFG and preSMA
2. Subcortical pathways underlying response execution and response inhibition

4. Non-inhibitory action
Behavioural task
Inhibitory action
updating
STOP
Non-inhibitory action
updating
DOUBLE
No action
updating
IGNORE

5. Procedure
Training Session
Scan Session
>>

6. Expectations
1. Response inhibition = Uniquely activated under stop conditions
2. Non-inhibitory action updating = Uniquely activated under double conditions
3. General action updating processes = Regions common to both tasks

7. Results
Stop
Double
Overlap

8. Pre-SMA & rIFG
Response inhibition
Inconclusive

9. rIFG crucial for response inhibition?
 Not found in other studies.....
 Difference in task demands?
> Error rates associated with stopping
Chatham et al. (2012). PLoS ONE.
> Response conflict associated with stopping?

10. fMRI study Part II 3 aims:
 Response execution recruits direct pathway
Net product of increasing thalamico-cortico output
 Response inhibition recruits indirect & hyperdirect
Net product of reducing thalamico-cortico output
3 aims:
1. To establish whether pattern of activity conforms
2. To establish spatial distribution of activity
3. To establish interrelations amongst regions
Albin et al. (1989); Alexander & Crutcher (1990). Trends in Neuroscience; Nambu et al. (2002), Current Opinion in Neurobiology

11. fMRI study Part II  Difficult to uncover basal ganglia activity
Novel analytic approach.
 Conventional contrasts
signal > no-signal
 203 separate contrasts
e.g. double signal > stop signal
stop fixations > double no-signal
ignore signal > double fixations....
 Categorised- response execution vs. inhibition
 Averaged %BOLD across categories

12. Pathways confirmed?
Multiplied %BOLD for each category within each ROI by +1 or -1.
 Upregulation: +1
Downregulation: -1
 Sum
e.g. Response execution contrasts applied to direct pathway
STR=1.2 Gpi/SN=0.2 THAL=1.3
(1.2 x 1) + (0.2 x -1) + (1.3 x 1) = 2.3
 > 0 = conform
 < 0 = does not conform
 one-sample t-tests
Inhibitory
Excitatory +1 -1 -1 +1 +1 +1 -1 -1

13. Pathways confirmed? Data conforms to pattern predicted by each pathwaydf p BF
Direct
2.13 29
.021
2.06
Indirect
3.36
<.001
16.46
Hyperdirect
3.29
14.31
Response execution 
Response inhibition 
Response inhibition 

14. Spatial distribution
2. To establish spatial distribution of activity
2-way ANOVA: condition (execution vs. inhibition) and site (16 ROIs)
Interaction effect: F(15,928)=16.48, p<0.001
Main effect of site: F(15,928)=13.43, p<0.001
Main effect of condition: F(1,928)=7.55, p=0.01
Together these findings indicate that individual ROIs are recruited differentially under conditions of response execution and response inhibition.

15. Spatial distribution
Left hemisphere activity under conditions of response execution
ROI t p BF
IFG
-4.34
<.001
171.52
STR
4.18
114.38
GPe
3.21
.003
11.97
THAL
2.7
.01
4.62
-4.2
121.55
2.37
.024
2.13
Left
Right

16. Spatial distribution
Right hemisphere activity under conditions of response inhibition
ROI t p BF
Pre-SMA
7.19
<.001
225367
IFG
8.57
606215
STR
4.49
7.94
GPe
3.58
248.98 SN
4.52
27.54
STN
4.43
269.46
THAL
4.96
805.65
Right

17. Interrelations between ROIs
 Moderator/mediator analyses (Baron & Kenny, 1986).
 Effect of adding covariate (additional ROI) on p-value.
 Reduced p-value, but still significant = moderation.
Explains some but not all activity.
e.g. Pre-SMA: p<.001. Addition of rIFG: p=.01
 Reduced p-value, but no-longer significant = mediation.
Explains all activity.
e.g. Pre-SMA: p<.001. Addition of rIFG: p=.06
 Can infer direction of influence.

18. Interrelations between ROIs

19. Interrelations between ROIs
rIFG
r pre-SMA
subcortical

20. Conclusions & Next Steps
 rIFG crucial to response inhibition
 Lateralisation of activity under conditions of response execution and response inhibition
 rIFG directional influence over right pre-SMA and right subcortical structures
 BUT....difference in response control demands....
 More stringent control over non-inhibitory processes needed
 Exploration- requires replication
 Concurrent TMS-fMRI- functional coupling

21. Thank you for listening.
Acknowledgements
Chris Chambers (Cardiff University)
John Evans (Cardiff University)
Chris Allen (Cardiff University)
Frederick Verbruggen (University of Exeter)
Thank you for listening.