Mechanisms underlying capsulotomy for refractory obsessive-compulsive disorder: neural correlates of negative affect processing overlap with deep brain stimulation targets

Abstract

Ablative procedures such as anterior capsulotomy are potentially effective in refractory obsessive-compulsive disorder (OCD). Converging evidence suggests the ventral internal capsule white matter tracts traversing the rostral cingulate and ventrolateral prefrontal cortex and thalamus is the optimal target for clinical efficacy across multiple deep brain stimulation targets for OCD. Here we ask which prefrontal regions and underlying cognitive processes might be implicated in the effects of capsulotomy by using both task fMRI and neuropsychological tests assessing OCD-relevant cognitive mechanisms known to map across prefrontal regions connected to the tracts targeted in capsulotomy. We tested OCD patients at least 6 months post-capsulotomy (n = 27), OCD controls (n = 33) and healthy controls (n = 34). We used a modified aversive monetary incentive delay paradigm with negative imagery and a within session extinction trial. Post-capsulotomy OCD subjects showed improved OCD symptoms, disability and quality of life with no differences in mood or anxiety or cognitive task performance on executive, inhibition, memory and learning tasks. Task fMRI revealed post-capsulotomy decreases in the nucleus accumbens during negative anticipation, and in the left rostral cingulate and left inferior frontal cortex during negative feedback. Post-capsulotomy patients showed attenuated accumbens-rostral cingulate functional connectivity. Rostral cingulate activity mediated capsulotomy improvement on obsessions. These regions overlap with optimal white matter tracts observed across multiple stimulation targets for OCD and might provide insights into further optimizing neuromodulation approaches. Our findings also suggest that aversive processing theoretical mechanisms may link ablative, stimulation and psychological interventions.

Evidence Accumulation and Neural Correlates of Uncertainty in Obsessive-Compulsive Disorder

“…It is conceivable that capsulotomy may allow neural reprogramming of the lateral and ventromedial pathways but perhaps less so the dorsomedial prefrontal pathways implicated in the current study. This echoes a recent study from our group using the same population showing that capsulotomy-induced clinical improvement may be related to more rostral anterior cingulate activity in aversive processing ( 47 ). In addition, the lack of an effect of capsulotomy despite improvements in symptoms suggests that our findings may link to trait-related effects or the risk for the development of OCD rather than state-related symptom improvement, which is consistent with a previous study indicating decision making under ambiguity as a neurocognitive endophenotype for OCD ( 48 ).…”

Imaging-Based Biomarkers in Neurological Diseases-A Critical Review

“…These biomarkers aid in the knowledge of the brain circuits involved in the pathophysiology of OCD [140][141][142]. MRI-based measurements of cortical thickness can identify regional abnormalities in individuals with OCD, particularly in regions associated with cortico-striato-thalamo-cortical circuits [143][144][145].…”