Anterior limb of the internal capsule tractography: relationship with capsulotomy outcomes in obsessive-compulsive disorder

Abstract

Objectives Surgical procedures targeting the anterior limb of the internal capsule (aLIC) can be effective in patients with selected treatment-refractory obsessive-compulsive disorder (OCD). The aLIC consists of white-matter tracts connecting cortical and subcortical structures and show a topographical organisation. Here we assess how aLIC streamlines are affected in OCD compared with healthy controls (HCs) and which streamlines are related with post-capsulotomy improvement. Methods Diffusion-weighted MRI was used to compare white-matter microstructure via the aLIC between patients with OCD (n=100, 40 women, mean of age 31.8 years) and HCs (n=88, 39 women, mean of age 29.6 years). For each individual, the fractional anisotropy (FA) and streamline counts were calculated for each white-matter fibre bundle connecting a functionally defined prefrontal and subcortical region. Correlations between tractography measures and pre-capsulotomy and post-capsulotomy clinical outcomes (in obsessive-compulsive, anxiety and depression scores 6 months after surgery) were assessed in 41 patients with OCD. Results Hierarchical clustering dendrograms show an aLIC organisation clustering lateral and dissociating ventral and dorsal prefrontal–thalamic streamlines, findings highly relevant to surgical targeting. Compared with HCs, patients with OCD had lower aLIC FA across multiple prefrontal cortical–subcortical regions (p<0.0073, false discovery rate-adjusted). Greater streamline counts of the dorsolateral prefrontal–thalamic tracts in patients with OCD predicted greater post-capsulotomy obsessive-compulsive improvement (p=0.016). In contrast, greater counts of the dorsal cingulate–thalamic streamlines predicted surgical outcomes mediated by depressive and anxiety improvements. Conclusions These findings shed light on the critical role of the aLIC in OCD and may potentially contribute towards precision targeting to optimise outcomes in OCD.