1165 Microsurgical Anatomy of the Human Superolateral Medial Forebrain Bundle: Current Evidence From Focused Fiber Microdissections and Population-Based Tractography

INTRODUCTION: A growing body of literature has endorsed the superolateral medial forebrain bundle (slMFB) as a key part of the reward circuit and promising deep brain stimulation (DBS) target for the treatment of OCD and depression. Human data regarding the slMFB originate from diffusion magnetic resonance imaging which is prone to false positive results and the absence of human histological evidence has led to questioning of the slMFB. Although detailed anatomical knowledge is crucial for precise targeting during DBS and understanding the anataomo-functional mechanism of the neuromodulatory therapeutic effects, the tract’s anatomy remains elusive. METHODS: We performed fiber micro-dissections in 10 human hemispheres and population-based tractography using an averaged diffusion MRI template generated from data of 1065 normal subjects. RESULTS: A distinct fiber tract is invariably identified in the subcortical territory of the anteromedial cortex, connecting the prefrontal cortex (PFC) and VTA. This tract enters the anterior limb of the internal capsule and follows the trajectory of the anterior thalamic radiations to reach BA10 and BA11 of the prefrontal cortex. Population based tractography allowed us to successfully reconstruct the MFB on a group average template using data from 1065 normal subjects. Our extracted results were consistent with the structure, trajectory, and connectivity of MFB fibers recorded during our microdissections. CONCLUSIONS: We provide structural in vivo and ex vivo data on the anatomy of what proved to be a distinct fiber tract previously described as the slMFB connecting the ventral tegmental area and PFC. The slMFB is a key part of the reward circuit and our previous DBS hotspot analysis using Lead-DBS demonstrated that this tract is being modulated during slMFB DBS. The results herein inform connectivity-derived neuromodulation models and can facilitate target selection for enhanced clinical efficacy and fewer autonomic side effects.