Cerebellum-Midbrain Reward Circuitry in Humans: an in vivo dissection

Emerging research in non-human animals implicates cerebellar projections to the ventral tegmental area (VTA) in reward driven behaviors, but the circuits have not been characterized in humans. In this study we mapped the cerebello-VTA structural connectivity in humans. We visualized and measured the structural connections by performing probabilistic tractography on diffusion weighted imaging data from the Human Connectome Project (HCP). We uncovered the topographical organization of the connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. The results revealed that afferents from the cerebellum to the VTA predominantly originate in the right hemisphere interposed nucleus and paravermis, and terminate mostly in ipsilateral VTA. The paravermis of the crus I cerebellar lobule sends the most connections to the VTA compared to the other lobules. Finally, we discovered a medial-to-lateral gradient of connectivity, such that medial cerebellum has the highest connectivity with the VTA, and connectivity decreases laterally. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans. These maps provide critical foundation for future studies to investigate cerebellar involvement in social, affective, and reward-driven behaviors, as well as clinical manifestations at the extremes of those behaviors. Key Points 1. In humans, all cerebellar deep nuclei send projections to the VTA, which is similar to the connectivity profile found in non-human animals. The paravermis of Crus I contributes the most connections of the neocerebellum, and the interposed nucleus contributes the most connections among the deep nuclei. 2. There is a medial-to-lateral gradient of connectivity, such that more lateral segments of the cerebellum send fewer connections to the VTA. 3. These findings have implications for understanding normal and dysfunctional motivated behavior. ### Competing Interest Statement The authors have declared no competing interest.