Cerebellar-Cortical Connectivity Is Linked to Social Cognition Trans-Diagnostically

Abstract

Background: Psychotic disorders are characterized by impairment in social cognitive processing, which is associated with poorer community functioning. However, the neural mechanisms of social impairment in psychosis remain unclear. Social impairment is a hallmark of other psychiatric illnesses as well, including autism spectrum disorders (ASD), and the nature and degree of social cognitive impairments across psychotic disorders and ASD are similar, suggesting that mechanisms that are known to underpin social impairments in ASD may also play a role in the impairments seen in psychosis. Specifically, in both humans and animal models of ASD, a cerebellar–parietal network has been identified that is directly related to social cognition and social functioning. In this study we examined social cognition and resting-state brain connectivity in people with psychosis and in neurotypical adults. We hypothesized that social cognition would be most strongly associated with cerebellar–parietal connectivity, even when using a whole-brain data driven approach. Methods: We examined associations between brain connectivity and social cognition in a trans-diagnostic sample of people with psychosis ( n = 81) and neurotypical controls ( n = 45). Social cognition was assessed using the social cognition domain score of the MATRICS Consensus Cognitive Battery. We used a multivariate pattern analysis to correlate social cognition with resting-state functional connectivity at the individual voxel level. Results: This approach identified a circuit between right cerebellar Crus I, II and left parietal cortex as the strongest correlate of social cognitive performance. This connectivity-cognition result was observed in both people with psychotic disorders and in neurotypical adults. Conclusions: Using a data-driven whole brain approach we identified a cerebellar–parietal circuit that was robustly associated with social cognitive ability, consistent with findings from people with ASD and animal models. These findings suggest that this circuit may be marker of social cognitive impairment trans-diagnostically and support cerebellar–parietal connectivity as a potential therapeutic target for enhancing social cognition.

The posterior cerebellum supports implicit learning of social belief sequences

“…Moreover, although research on cerebellar patients has demonstrated that cerebellar injury leads to impairments in social functioning (Wang, Kloth, & Badura, 2014), implicit social learning might still be relatively preserved, suggesting possibilities for improved social treatment of patients. In this perspective, our findings implicate potential neural targets (cerebellar Crus I/II) for improving social cognitive functioning by brain stimulations (Brady et al, 2020). Also, although the present Belief SRT task focused on implicit learning in a restricted way which may still be far away from real social interaction, it might constitute an important diagnostic test on implicit social sequence learning.…”

The GM2 gangliosidoses: Unlocking the mysteries of pathogenesis and treatment

“…The turnover and remodeling of dendritic spines of Purkinje cells is an important aspect of neuronal plasticity required for development, learning and adaptation [ 116 , 117 ]. These processes have been widely implicated in disorders such as autism [ 118 , 119 ] and psychiatric illness [ 120 , 121 ]. Dendritic sprouting, pruning and membrane maintenance are metabolically expensive as demonstrated by the effects caused by dysfunctional mitochondrial fission and migration onto dendritic arborizations of Purkinje cells and the role of accumulating reactive oxygen species contributes to cerebellar degeneration [ 122 ].…”

The Role of the Posterior Cerebellum in Dysfunctional Social Sequencing

“…For example, addicted patients have long-lasting impairments in emotional recognition [43][44][45][46] and display reduced social mentalizing skills [25,[47][48][49][50][51]. Similar mentalizing dysfunctions have been observed in depression [15], obsessive-compulsive disorder [18], and schizophrenia [26,27].…”

“…More importantly, we further suggest that the posterior cerebellum may play a central role in social dysfunctions observed in many clinical pathologies. Indeed, deficits in mentalizing at large, and in the posterior cerebellum in particular, may play a crucial role in the onset and maintenance of psychiatric disorders related to limited mentalizing and emotion recognition, such as autism spectrum disorder [12][13][14], depression [15,16], bipolar disorder [17], obsessive compulsive disorder [18][19][20][21], addiction [22][23][24][25], and schizophrenia [26][27][28][29][30].…”