Elucidating Cerebellar Contributions to Social Cognition: A Transdiagnostic Investigation

PROJECT SUMMARY Many individuals living with serious psychiatric disorders – including those that span the psychosis, autism, and anxiety spectrums – experience significant social dysfunction and disability secondary to mental illness. Unfortunately, social impairments are generally not addressed by psychiatric medications and psychosocial

interventions for social dysfunction are often difficult to access or otherwise limited in their scope (i.e., intended for a discrete diagnostic group) or clinical benefit. Thus, novel therapeutics capable of addressing social dysfunction across diagnostic groups are needed but will rely on improved understanding of the neurobiological

mechanisms that underlie these impairments. Notably, social cognition – and in particular, mentalizing (i.e., the ability to make inferences about the mental states of others) – plays an important role in functional outcomes among individuals with mental illness. Though mentalizing has known neural underpinning in the cerebral brain

regions that comprise the mentalizing network (MN; i.e., medial prefrontal cortex, precuneus, temporoparietal junction), emerging data suggests that the posterior cerebellum (Crus II) plays a critical role in social cognitive processing that has not been examined among individuals with serious mental illness. More specifically, the

posterior cerebellum may act as a forward controller with cerebral MN regions – which, given the accessibility of the cerebellum for neurostimulation relative to cerebral regions of the MN, may have critical implications for translational interventions. In this proposed project, we will develop a brain network model of dynamic

interactions between key brain regions involved in mentalizing among a transdiagnostic sample of youth and young adults (14-30) selected specifically for prominent social dysfunction secondary to a psychiatric illness. By investigating network models in a sample of individuals during the phase of life in which the majority of mental

illnesses emerge or escalate, we can minimize the influence of confounding factors related to more chronic illness or long-term use of psychiatric medications. Crucially, we will also examine the extent to which cerebellar activity and connectivity is associated with lab-based, validated measures of functional and social-cognitive

performance to better understand neural factors that may be most impactful on critical functional outcomes. Findings from this study have notable potential to define a novel treatment target for a future translational clinical trial studying neuromodulation of cerebellar regions most strongly associated with devastating and difficult-to-

treat social dysfunction.