Structural and functional topography of the anterior limb of the internal capsule in treatment-resistant psychiatric disorders

The anterior limb of the internal capsule (ALIC) is a major target for deep brain stimulation (DBS) in obsessive-compulsive disorder and other treatment-resistant psychiatric disorders. Although anatomical studies have demonstrated a highly organized topography of prefrontal pathways within the ALIC, it remains unclear whether these organizational principles are preserved in treatment-resistant psychiatric patients and whether they predict stimulation-induced network engagement. We applied anatomically informed diffusion tractography to patients with treatment-resistant obsessive-compulsive disorder (n=18) and treatment-resistant depression (n=5) undergoing ALIC DBS. To assess functional network engagement, we analyzed cerebro-cerebral evoked potentials (CCEPs) elicited by single-pulse stimulation of ALIC DBS contacts while recording from ventral prefrontal cortex (vPFC) electrodes in depression patients. Diffusion tractography demonstrated preservation of established ALIC topography in treatment-resistant psychiatric patients, including the dorsoventral organization of prefrontal projections and the mediolateral organization of subcortical pathways. CCEP analyses revealed a corresponding functional organization: ventral ALIC stimulation preferentially engaged medial vPFC sites, whereas dorsal stimulation preferentially engaged lateral vPFC sites in the left hemisphere. These findings demonstrate that stimulation-induced network responses follow known anatomical principles of ALIC organization, and outcome that will support more precise and individualized neuromodulatory strategies for neuropsychiatric disorders.