Cross-species brain-wide mapping reveals convergent mesocorticolimbic engagement by nucleus accumbens deep brain stimulation.

Nucleus accumbens (NAc) deep brain stimulation (DBS) has been increasingly explored as a treatment modality for refractory neuropsychiatric disorders. Uncovering the accumbens network that is engaged by DBS is a critical step forward in understanding how modulating this important node impacts the broader mesocorticolimbic circuit. Using whole-brain clearing and unbiased, brain-wide neural activity mapping, we found that NAc DBS increases neural activity in a coordinated mesocorticolimbic network in mice. Simultaneous intracranial electrophysiology recordings from the human NAc and brief stimulation epochs of analogous mesocorticolimbic nodes revealed patterns of connectivity between these regions and the NAc. Altogether, these results link brain-wide network mapping in mice with a hypothesis-driven test of human NAc connectivity, consistent with a coordinated mesocorticolimbic network that may be relevant to the mechanisms of NAc DBS.