Cerebellar subregions support social cognition in early behavioural variant frontotemporal dementia

Abstract

Social cognitive deficits manifest early in behavioral variant frontotemporal dementia (bvFTD), compromising individuals’ ability to interpret social cues, empathize, and maintain interpersonal relationships. Current neurobiological models emphasize cortical network disruption, particularly within the salience, semantic appraisal, and default mode networks, as primary contributors to social dysfunction. However, despite the increasingly recognized role of the cerebellum in higher-order cognitive and socioemotional processes, its contributions to social deficits remains underexplored in bvFTD.

Here, we investigated the unique and network-level influences of cerebellar subregions on social cognition across experimental and real-world assessments in early-stage bvFTD. A total of 107 individuals with bvFTD and 100 healthy controls were evaluated across three social domains: theory of mind (ToM) (The Awareness of Social Inference Test-Social Inference-Enriched, TASIT-SIE; Cognitive Emotional Perspective Taking Test), emotion reading (Dynamic Affect Recognition Test; TASIT-Emotion Evaluation Test; Comprehensive Affect Testing System), and real-life empathy (Revised Self-Monitoring Scale; Interpersonal Reactivity Index). Using a functional cerebellar parcellation, we extracted volumes of posterior cerebellar subregions implicated in social-linguistic and multiple-demand networks from participants’ structural MRIs. To address the high collinearity between cerebellar and cortical atrophy patterns, we applied sequential regression, partial least squares correlation, and dominance analysis to characterize brain-behavior relationships. Additionally, supplementary structural equation modelling (SEM) examined whether the associations between cerebellar integrity and social cognition was mediated by executive functioning.

Our results showed that cerebellar subregional integrity contributed to social cognitive deficits in individuals with early-stage bvFTD. Cerebellar subregions, particularly right Crus I and II, showed the strongest and most selective contribution to high-level inferential Theory of Mind performance. Tasks involving dynamic emotion stimuli exhibited a more distributed pattern of cerebello-cerebral involvement. By contrast, questionnaire-based measures of real-world social functioning were less prominently represented in the latent covariance structure. SEM further showed that cerebellar integrity remained directly associated with social cognition after accounting for executive functioning, whereas the indirect association through executive functioning was not significant.

These findings highlight the task-dependent nature of cerebellar involvement in social cognition, and demonstrate that time-limited experimental tasks, particularly those involving inferential reasoning about beliefs and affect, are likely to be especially valuable in detecting subtle cerebello-cerebral network dysfunction that questionnaire-based measures may overlook. Our results extend cortex-centric models of social dysfunction in bvFTD by demonstrating that cerebellar subregions contribute to distributed cerebello-cerebral systems associated with social cognitive performance. These findings provide a foundation for future longitudinal and mechanistic studies of cerebello-cerebral dysfunction in neurodegenerative disease.