Evaluation of the role of cortical and striatal GABAergic functionality in compulsion development through impairment in feed-forward motor control by functional magnetic resonance imaging (1H-MRI) and magnetic resonance spectroscopy (1H-MRS)

Introduction The literature emphasized that disturbed feed-forward motor control (FFMC) can have a role in etiopathogenesis of OCD, efference copy (EC) is central component of FFMC and saccadic eye movements are associated with EC. It has been hypothesized that saccades that are not associated with alteration of an action can be a sign of dysfunctional EC which can be cause of incompletion of motor behavior (compulsion) and it may be associated with altered GABAergic functionality in the brain's cortical and striatal regions. Method An ecologically valid paradigm has been developed and conducted during functional imaging: Briefly, subjects first watched videos of anxiety-provoking scenarios and immediately after that, they watched handwashing videos. They were asked to press a button to close the tap on the screen when satisfied with the adequacy of handwashing. Subjects saccadic eye movements (SEM) were monitored during fMRI recording. There were two conditions: The last saccade towards the tap before pressing the button to close it was considered as a positive decision condition (PD), while SEM to the tap without closing it was considered as a negative decision condition (ND). ND was accepted as the behavioral trace of dysfunctional EC. The functional dynamics of ND and PD states were compared between 14 OCD patients and 12 non-OCD controls. In addition, GABA levels in bilateral supplementary motor areas (SMA) and bilateral putamen were evaluated by MR spectroscopy after the fMRI recording. Then the subjects were given self-report questionnaires, including the degree of disgust evoked by the scenarios. The data obtained from the study was analyzed using MATLAB, SPSS 17 (IBM, USA) and Statistical Parameter Mapping 12 (SPM12) programs. Results The behavioral data of the paradigm confirmed that the paradigm works: Student t-test revealed that compared to the controls, OCD group closed the tap significantly later than the controls (p<0.001), was more disgusted with the scenarios (p<0.001), and looked at the tap more frequently without closing the tap (p=0.034). In fMRI data analysis using ANOVA, at the p(FWE)<0.05 level, significant group X task interaction was revealed in many brain regions, including both supplementary motor areas (SMA). GABA level (GABA/creatinine ratio) was positively correlated with % signal change(%SC) of the right SMA (rSMA) in ND condition, while it was negatively correlated with %SC in the rSMA in PD condition. In addition, in ND condition %SC of rSMA showed negative correlation with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores (r=-0.468, p= 0.016). Conclusion Our findings suggest that decreased activation of SMA, which is negatively correlated with GABA level is associated with increased hand washing. When interpreted together with the higher number of NDs and lower activation of SMAs in ND condition in the OCD group, these findings indicate that dysfunctional EC can be associated with formation of compulsive behavior.