Inhibitory neural activity produces a significant BOLD response in human cortical areas Archana Purushotham, Seong-Gi Kim Center for Magnetic Resonance Research, Depts of Radiology and Biomedical Engineering, University of Minnesota, USA Acknowledgements: Robert Jech, Tommy Vaughan, Gregor Adriany, Peter Andersen

Introduction Understanding the neural correlates of BOLD activity: Does it result from excitation alone, or from both excitation and inhibition? Arthurs and Boniface, Trends in Neurosciences 2002

Waldvogel et. al., Nature 2000 Task: simple push-button; go/no-go trials Confirmed inhibition in primary motor cortex (M1) by TMS fMRI: no significant change from baseline for M1 during no- go task; present in pre-supplementary motor area. Inhibition is metabolically much less demanding than excitation: does not give rise to an observable BOLD response in M1. Our hypothesis: Being a very simple task, the inhibitory component accompanying no-go trials is very small, insufficient to give rise to a detectable BOLD response in M1

Objective To determine the BOLD correlates of inhibitory neural activity in the human motor cortex, using a delayed, pre-cued directed go/no-go task.

Paradigm A delayed, cued joystick go/no-go task: Variable, pseudo-randomized delay periods : 0, 2, 4 and 7 sec No-go trials occurred 20% of the time: after 7.3 seconds, centre circle turned black instead of green Trial epochs : 30 or 35 seconds long; trials

Data Acquisition fMRI Single-shot 64 x 64 EPI images using a 4 Tesla MRI system 9 normal adult, right-handed human subjects 5 axial sections of thickness 5 mm each, including the primary, supplementary (SMA) and pre-motor areas TR = 1sec for most subjects; 0.5 sec for 2 subjects Structural images 128 x 128 T1-weighted (FLASH or segmented EPI) Electromyography Surface EMG of flexors and extensors of forearm, simultaneously for 3 subjects, pre-fMRI training for 1.

Data Analysis fMRI epochs grouped by delay period and averaged to get mean timecourse for each delay condition EMG epochs checked for untimely activity, and behavioural data for errors; corresponding epochs excluded Cross-correlation based on the no-delay epoch time-course used to generate maps (3 maps based on different thresholds) Timecourses detrended linearly if drifts were apparent

Data Analysis (contd.) Primary and supplementary motor areas demarcated manually using structural images Epoch time-courses created by averaging over activated voxels in each area Compared time-courses for 7-second delay condition (go) versus no-go condition, for each area Used data from subjects with sufficient SNR (judging from comparability of preparation activity for go and no-go tasks)

Does a state of preparedness to move exist? Reaction time (msec) Delay period (sec) 0247

Surface electromyogram of forearm muscles Time (sec) Go trial No-go trial

Activation map based on no-delay movement Central sulcus SMAM1 Regions of interest Contra.

SMA (n = 7; CC = 0.7) Time (sec) BOLD % change Prep. Go/ No-go

M1 (n = 7; CC = 0.7) Time (sec) BOLD % change Prep. Go/ No-go

Consistency of observed result Three statistical thresholds (CC = 0.6, 0.7, 0.8) used for analysis : result independent of threshold Across subjects: 6 out of 7 subjects clear inhibition-related BOLD response in M1 1 subject amplitude change very low; not individually convincing

Higher order motor areas (including SMA) Primary motor area Muscular activity Go cueNo-go cue Schematic of neural activity Prep. cue

Evoked potential recording: preliminary data P A Contra.Ipsi.

Cz (midline) Time w.r.t appearance of go/no-go cue (100 msec) Evoked potential ( V) go no-go

C3 (contralateral) Time (100 msec) Evoked potential ( V) go no-go

Inhibitory synaptic activity in the primary motor area during non-performance of a prepared task is associated with a significant BOLD signal. The amplitude of the BOLD signal peak due to inhibition is comparable to that due to preparation. Conclusion

C4 (ipsilateral) Time (100 msec) Evoked potential ( V)