Connectome Analysis of the Nucleus Accumbens: Refining Radiosurgical Targeting for Addictive Disorders

Addictions represent a major challenge not only for healthcare systems but also impose a significant socioeconomic burden affecting a large number of individuals worldwide. Various treatment modalities have been proposed, including pharmacological interventions, deep brain stimulation, and radiofrequency ablation, among others. Stereotactic radiosurgery has emerged as a non-invasive and precise alternative for addiction management. A thorough understanding of the nucleus accumbens (NAc) anatomy and its neural connections is essential to refine the radiosurgical target and optimize clinical outcomes.

Diffusion tensor imaging was acquired from 3-Tesla and 1.5-Tesla Magnetic Resonance Imaging scanners on five healthy subjects, using T1 and T2 sequences. Images were fused, with autosegmentation of NAc, ventral tegmental area, amygdala, hippocampus, hypothalamus, and periventricular gray; insula, medial/lateral orbitofrontal cortex, and dorsolateral frontal cortex were manually drawn. Connectivity to NAc was assessed visually with fractional anisotropy thresholds (20-10). Five densest fiber connections were combined for target selection, aligned to the anterior and posterior commissure, and coordinates and structures were transferred to Gamma Plan for treatment planning.  Results: The strongest connections were found between the medial orbitofrontal cortex (mOFC), hypothalamus, ventral tegmental area (VTA), periventricular gray (PVG), and amygdala to the NAc. The mOFC-NAc and the hippocampus-NAc connections are the most and least robust, respectively. Stereotactic coordinates were derived for connectome-based targeting, proposing a 90 Gy dose to the NAc shell, predominantly, and aligning to it the 20 Gy isodose line for neuromodulation. The right and left NAc received > 20 Gy in 75.2% and 55.6% of their volumes, respectively. The optic apparatus received ≤ 5.4 Gy as Dmax.

Radiosurgery has proved to be a safe modality in the treatment of functional disorders and may offer a new treatment option for refractory addiction. Connectivity-based radiosurgery visualizes most of the NAc connections and may enhance patient-specific targeting.