CEREBELLUM-VENTRAL TEGMENTAL AREA INTERACTIONS DURING FEAR EXTINCTION IN CEREBELLAR DEGENERATION AT 7 T FMRI

Fear extinction relies on learning that a previously threatening cue no longer predicts an aversive outcome. A key driver is the unexpected omission of an expected aversive stimulus, a better-than-expected event thought to generate a reward-like prediction error (Kalisch et al., 2019, Trends Cogn. Sci.). In rodents, ventral tegmental area (VTA) neurons signal such omission-related prediction errors during extinction (Salinas-Hernandez et al., 2018, eLife). In a recent 7 T fMRI study in young and healthy humans, we observed activity in both the cerebellum and VTA during unexpected omissions of an aversive electric stimulation, together with increased cerebellum-VTA functional connectivity across multiple phases of a three-day fear conditioning paradigm (Nio et al., 2025, eLife). Using the same paradigm and 7 T scanner, we now study patients with pure cerebellar degeneration (SCA6 and SCA27B) and age- and sex-matched healthy controls. Fear and extinction learning are assessed using skin conductance and pupil size responses. Task-based 7 T fMRI is used to measure activation and connectivity in the cerebellar cortex and VTA during unexpected omission events, complemented by parametric modulation with trial-wise prediction error estimates derived from computational modeling based on reinforcement learning. We hypothesize that cerebellar cortical omission-related responses will be relatively preserved in patients, consistent with largely intact granule cell layer and afferent input, whereas VTA responses and cerebellum-VTA coupling will be reduced, reflecting impaired cerebellar output related to extinction-related prediction error processing. Preliminary behavioral and fMRI results from patients and controls will be presented.