Objectives/Aims Surgical procedures targeting the anterior limb of the internal capsule (aLIC) can be effective in medically refractory obsessive-compulsive disorder (OCD). The aLIC consists of white-matter tracts connecting cortical and subcortical structures. Here we assess how specific aLIC tracts are affected in OCD and which tracts predicts improvement post-capsulotomy.

Methods Large-scale diffusion imaging was used to compare detailed white- matter connectivity via aLIC between OCD patients (n=100) and healthy controls (n=88). For each individual, the fractional anisotropy and tract counts were calculated for each white-matterfiber bundle connecting a functionally defined prefrontal and subcortical region. Correlations between tractography measures and pre- and post- capsulotomy clinical outcomes (in obsessive-compulsive, anxiety and depression scores 6 months after surgery) were assessed in 41 OCD patients. We focused on the dorsolateral prefrontal cortex and dorsal cingulate, regions implicated in prediction of capsulotomy and stimulation outcomes.

Results Hierarchical clustering dendograms show an aLIC organization clustering lateral and dissociating ventral and dorsal prefrontal-thalamic tracts highly relevant to targeting. OCD patients had lower aLIC fractional anisotropy across prefrontal cortical-subcortical regions compared to healthy controls (p=0.023, FDR-adjusted). Greater fractional anisotropy and tract counts of the dorsolateral prefrontal-thalamic and -subthalamic tracts in OCD patients predicted greater post-capsulotomy obsessive-compulsive improvements. In contrast, greater counts of the dorsal cingulate-thalamic tracts predicted surgical outcome mediated by depressive and anxiety improvements.

Conclusions These findings shed light on the critical role of the aLIC in OCD and potentially leads towards precision targeting to optimize outcomes as a function of symptom dimension in OCD.