Cerebellar–Cerebral Connectivity Changes and Social Prediction Processes in Cerebellar Neurodegenerative Disease

The cerebellum is a key node for detecting and adjusting social-prediction internal models. Yet social-prediction has not been studied in neurodegenerative cerebellar patients (CNDp). Thus, we examined CNDp social-prediction abilities and related cerebellar-cerebral networks, using tailored tasks and resting-state fMRI. Thirteen adult CNDp and twenty-six matched controls (CN) completed three computerized prediction tasks, where contextual priors activate specific internal models setting expectations which might influence ambiguous targets’ classification (emotion expression recognition, personality-traits recognition, non-social objects recognition). Accuracy and response times were analysed trough a 2x2x3 mixed-effects ANOVA [(within-subject factors: target ambiguity (more vs. less ambiguous), priors-target congruency (congruent vs. incongruent); between-subject factor: groups (CNDp vs. CN)]. A specific congruency index, reflecting whether response modulation was driven by contextual influence or by prediction-errors updates, was calculated on performance efficiency expressed as Rate-Correct Score, and analysed trough a 2x2 mixed-effects ANOVA (within-subject factor: target ambiguity; between-subject factor: groups). Participants underwent 3T brain MRI, including T1-weighted and resting-state fMRI sequences. Voxel-based morphometry was used to assess cerebellar volume differences and identify cerebellar regions of interest to be used in a Seed-Based fMRI analysis to examine cerebellar-cerebral functional connectivity (FC) changes. We extracted cerebellar-cerebral FC values from patients’ altered connectivity clusters and examined correlations with congruency indices. Overall, CNDp performed worse in the personality-traits task, where they showed higher reliance on contextual cues. CNDp cerebellar atrophy extended to social posterior lobules, which in turn exhibited decreased FC with cerebral regions involved in mentalizing and/or prediction. CNDp higher congruency indices in personality-traits task, reflecting greater contextual influence and failure to revise responses based on prediction-error updating, significantly correlated with decreased right cerebellar lobule VIII-right putamen FC. These findings revealed a specific cerebellar-cerebral underconnectivity pattern affecting error-based prediction updating in mentalizing, opening new avenues for further investigating cerebellar-basal ganglia networks as potential interface in social-predictive brain.