Involvement of the human cerebellum in reinforcement learning via its connection with the ventral tegmental area (VTA)

• Applicants: Professorin Dr. Ulrike Bingel; Professor Dr. Matthias Brand; Professorin Dr. Dagmar Timmann-Braun
• Subject Area: Human Cognitive and Systems Neuroscience
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 531188394

Current studies provide strong evidence that the cerebellum contributes to cognitive, behavioral, emotional and social functions. Furthermore, there is increasing evidence that cerebellar dysfunction contributes to a wide range of mental disorders including addiction and chronic pain. How the cerebellum might contribute to this wide range of functions and diseases, however, is only little understood. Recent animal studies suggest that the cerebellum may process not only sensorimotor signals, but also reward signals and therewith contributes to reinforcement learning, a form of learning which is typically associated with the mesostriatal and mesocorticolimbic dopaminergic system. These observations may be key to understand the contribution of the cerebellum to non-motor control. A central structure involved in non-motor reward related behavior is the ventral tegmental area (VTA). A recent study in rodents found a direct, monosynaptic efferent connection between the fastigial nuclei (and likely all other cerebellar nuclei) and the VTA. The VTA plays a central role in addiction, but has also been shown to be involved in avoidance behavior. The overarching aim of the proposed project is to test the hypothesis that the cerebellum contributes to reinforcement learning in humans via its connection with the VTA. We will use an appetitive and aversive Pavlovian to instrumental transfer (PIT) task. The appetitive and aversive PIT task will allow us to investigate the contribution of the cerebellum to reinforcement learning in a highly comprehensive manner, including (i) appetitive and aversive classical conditioning, (ii) appetitive and aversive instrumental conditioning, as well as (iii) the transfer of appetitive and aversive Pavlovian-CS associations to instrumental approach and avoidance behaviors (PIT effects). PIT effects have high ecological validity, and govern many behaviors in health and many diseases. While enhanced appetitive PIT effects have been reported in non-substance-related addictive disorders, patients with chronic back pain show reduced appetitive PIT effects. High-resolution functional magnetic resonance imaging (fMRI) acquired at 7T will permit us to perform studies at the level of the cerebellar cortex, cerebellar nuclei and the VTA including their functional interactions. If successful in healthy human participants, a pilot behavioral study will be performed in patients with non-substance-related addictive behaviors and chronic primary pain, which will be continued and extended to a 7T fMRI study in a possible second funding period. Our study will help to elucidate how the cerebellum may contribute to non-motor function in the healthy human brain, and will give first answers to how the cerebellum may contribute to common mental disorders.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Sen Cheng; Dr. Tamas Spisak, Ph.D.