El Jammal, R.; Suzuki, H.; Mattar, L. S.; Hamre, T.; Soubra, S.; Ryan, M. A.; Mathura, R. K.; Mathew, S. J.; Allawala, A.; Storch, E. A.; Vanegas Arroyave, N.; Banks, G. P.; Pouratian, N.; Patriat, R.; Goodman, W. K.; Provenza, N. R.; Sheth, S. A.; Bartoli, E.; Heilbronner, S. R.

Introduction The anterior limb of the internal capsule (ALIC) is a major white matter highway connecting prefrontal cortical (PFC) regions to the thalamus, brainstem, and subthalamic nucleus. Structural and functional abnormalities within the ALIC circuit have been associated with many neuropsychiatric disorders, including obsessive-compulsive disorder (OCD) and depression, and deep brain stimulation (DBS) may provide effective treatment to some of these patients. However, it remains unclear whether the well-characterized topographic organization of the ALIC observed in healthy individuals and preclinical models is preserved in treatment-resistant psychiatric populations. Methods We first used diffusion tractography to evaluate the topography of PFC and subcortical fibers through the ALIC in patients with treatment-resistant OCD (n=18) and depression (n=5). In depression patients, we also evaluated ALIC topography using cerebro-cerebral evoked potentials (CCEPs) elicited by single-pulse electrical stimulation (SPES) of DBS leads in the ALIC and recordings in the ventral PFC (vPFC). Results The topographic organization of PFC and subcortical projections is preserved in the ALIC among treatment-resistant psychiatric patients, consistent with patterns observed in healthy individuals and preclinical models. CCEP recordings in the ventral PFC showed a ventral ALIC to medial vPFC/dorsal ALIC to lateral vPFC response pattern in the left hemisphere, but not in the right. Conclusion Our findings confirm that topographic patterns within the ALIC previously identified using preclinical models and healthy controls are preserved in treatment-resistant psychiatric patients. Furthermore, by linking white matter topography to stimulation effects, this work supports more precise and individualized neuromodulatory strategies for neuropsychiatric disorders.