17 Neuromodification of refractory obsessive-compulsive disorder (OCD): evidence from cognitive, structural and functional remodelling of anterior capsulotomy

Objectives Converging evidence supports the effectiveness of anterior capsulotomy in the management of selected patients with refractory obsessive-compulsive disorder (OCD). Less is understood about the post-operative neural changes that contribute to clinical improvements or impairments that might occur which potentially could be avoided. The objective of this study is to identify the neuropsychological changes underlying the symptomatic relief in capsulotomy using an affective task-based fMRI study, and to discern potential post-operative cognitive changes associated with the surgery itself. Methods A task-based fMRI study using a modified aversive monetary incentive delay paradigm with negative imagery (separated into two phases: anticipation and feedback) and subsequent expectancy violation was applied to study emotional regulation, with specific focus on the functional changes along the fronto-striatal pathway. Selected tests from the Cambridge Neuropsychological Automated Test Battery (CANTAB) covering attention, memory and executive function known to be impaired in OCD were administered to assess the cognitive function in three groups of age, gender matched participants: OCD patients (OCD), OCD capsulotomy patients (at least six months after surgery, CAP), and healthy controls (HC). Voxel-based morphometry (VBM) was applied to detect whole-brain grey matter volume differences between HC, OCD and CAP, and its association with cognitive deficits. Results CAP showed lower OCD severity (Yale Brown Obsessive Compulsive Score), and better activities of daily living and quality of life scores compared to OCD controls with no differences in depression or anxiety scores. Task-based fMRI revealed decreased nucleus accumbens (NAc) activity during aversive anticipation in CAP, which correlated with the symptomatic ratings after surgery. Whole-brain analyses during the feedback phase found interaction effects in the left pregenual anterior cingulate cortex (pgACC) and the left inferior frontal cortex (IFG), where CAP showed lower activity towards the aversive outcome and towards the expected but missing aversive image during the expectancy violation phase, with both positively correlated with symptomatic ratings. Attenuated functional connectivity between seed NAc and pgACC was found in CAP as expected during aversive versus neutral anticipation (aversive>neutral), suggesting a surgical impact of capsulotomy through downregulating the functional communication along the fronto-striatal pathway. Cognitive testing focusing on the differences between OCD and CAP or the potential effect of capsulotomy showed greater impairments in CAP in paired associative learning (PAL). All other cognitive measures were no different from OCD controls. CAP exhibited overall reduction of grey matter volume (GMV) in the ventral striatum, thalamus and left inferior frontal gyrus (IFG) relative to OCD controls. The total PAL error in CAP was associated with lower GMV in the left inferior frontal gyrus. Conclusions We show improvements in OCD severity, quality of life and disability post-capsulotomy. Potential impairments in cognitive status were limited to associative learning correlating with lower left inferior frontal cortex volumes which may reflect underlying severity or be related to capsulotomy effects. Our findings suggest targeting connectivity between NAc and pgACC, similar to the optimal target for deep brain stimulation in OCD, with post-operative effects modifying aversive processing. In contrast, potentially preserving tracts to the left inferior frontal cortex might be indicated. Our study contributes to the literature of anterior capsulotomy as an effective and well-tolerated treatment option for selected patients with refractory OCD and highlights overlaps between deep brain stimulation and capsulotomy in optimal targeting.