The Cerebellum Gets Social: Evidence from an Exploratory Study of Cerebellar, Neurodevelopmental, and Psychiatric Disorders

Abstract

Social prediction is a key feature of social cognition (SC), a function in which the modulating role of the cerebellum is recognized. Accordingly, cerebellar alterations are reported in cerebellar pathologies, neurodevelopmental disorders, and psychiatric conditions that show SC deficits. Nevertheless, to date, no study has directly compared populations representative of these three conditions with respect to SC and cerebellar alterations. Therefore, the present exploratory study aimed to compare the SC profiles of individuals with cerebellar neurodegenerative disorders (CB), autism (ASD), bipolar disorder type 2 (BD2), or healthy subjects (HS) using a battery of social tests requiring different degrees of prediction processing. The patterns of cerebellar gray matter (GM) alterations were compared among the groups using voxel-based morphometry. Compared to HS, the clinical groups showed common SC deficits in tasks involving a moderate to high level of prediction. The behavioral results of the clinical groups are consistent with the presence of overlapping GM reduction in cerebellar right Crus II, an area notably involved in complex social processing and prediction. Although exploratory and preliminary, these results deepen the cerebellar role in social prediction and highlight the transdiagnostic value of the cerebellum in social functioning and prediction in pathologies of different aetiologies, forecasting novel possibilities for shared interventions.

Functional recruitment and connectivity of the cerebellum supports the emergence of Theory of Mind in early childhood

“…In accordance with this theory, our findings suggest a significant contribution of early-life changes in the cerebellum to ToM development, insofar as the cerebellum stores information that support the subsequent prediction of mental states. Our results also align with evidence suggesting that the socio-cognitive deficits of ASD are associated with functional and structural abnormalities of the cerebellum 40,41,31,12 . Our observation of the role of the Crus I-II in ToM development may function as a framework of cerebellar regions and cerebro-cerebellar connections crucial for ToM in typically developing children, generating hypotheses for targeted studies in these regions in pediatric populations (e.g., children with ASD).…”

“…However, the contribution of the cerebellum to the emergence of ToM in terms of local functional changes and connectivity with the cerebral cortex remains elusive. This is especially relevant in light of clinical research showing that cerebellar injury during development often results in severe and persistent changes in social behavior later in development, often in the context of neurodevelopmental and psychiatric disorders such as autism spectrum disorder (ASD) and schizophrenia 29,30,31,32,11 . Strikingly, there seems to be a discrepancy between the effect of cerebellar abnormalities present from in early childhood compared to lesions occurred in adulthood: early-life cerebellar disruptions lead to dramatic changes in social behavior, whereas damage in adulthood leads to social deficits that tend to be milder and dissipate more quickly 10 .…”

Fecal microbiota transplantation in a child with severe ASD comorbidities of gastrointestinal dysfunctions—a case report

“…These substances may pass through the leaky gut and blood–brain barrier, and eventually the effects on the functional brain areas associated with ASD. For example, social cognition of ASD has been shown to be altered in cerebellar gray matter ( 31 ). To sum up, factors caused by changes in the flora, such as immunity, metabolites, and neurotransmitters, may collectively influence the etiology of ASD by exacerbating the severity of symptoms.…”

Effective connectivity analysis of resting-state mentalizing brain networks in spinocerebellar ataxia type 2: A dynamic causal modeling study

“…Over the last decades, an extensive literature has provided evidence that SCA2 is also associated with a wide range of impairments in higher-order functions also including complex social cognitive functions ( Clausi et al, 2021a , Lupo et al, 2018 , Moriarty et al, 2016 , Sokolovsky et al, 2010 ). Generally speaking, studies conducted on patients affected by cerebellar neurodegenerative disorders have provided general agreement on cerebellar participation to higher order social functions, showing the presence of deficits in different subcomponents of social cognitive domains, such as emotion and belief recognition, prediction of intentions, social judgements, and mentalizing or theory of mind ( Clausi et al, 2021a , Clausi et al, 2019 , D’Agata et al, 2011 , Olivito et al, 2023 , Sokolovsky et al, 2010 , Tamaš et al, 2021 ). Altogether, these studies suggest that alterations in these specific domains are due to structural damage confined to the Crus I-II and to changes in the functional flow of information between these cerebellar lobules and regions of the social brain, such as the precuneus, the medial prefrontal cortex (mPFC), and the temporo-parietal junction (TPJ) ( Clausi et al, 2019 , Olivito et al, 2023 ).…”

“…Generally speaking, studies conducted on patients affected by cerebellar neurodegenerative disorders have provided general agreement on cerebellar participation to higher order social functions, showing the presence of deficits in different subcomponents of social cognitive domains, such as emotion and belief recognition, prediction of intentions, social judgements, and mentalizing or theory of mind ( Clausi et al, 2021a , Clausi et al, 2019 , D’Agata et al, 2011 , Olivito et al, 2023 , Sokolovsky et al, 2010 , Tamaš et al, 2021 ). Altogether, these studies suggest that alterations in these specific domains are due to structural damage confined to the Crus I-II and to changes in the functional flow of information between these cerebellar lobules and regions of the social brain, such as the precuneus, the medial prefrontal cortex (mPFC), and the temporo-parietal junction (TPJ) ( Clausi et al, 2019 , Olivito et al, 2023 ). With respect to studies in SCA2, in-depth analyses of neurobiological underpinnings of mentalizing deficits in this population of patients have provided additional insight into understanding cerebellar-cerebral mentalizing networks ( Clausi et al, 2021a , Olivito et al, 2020 ).…”