Trajectories of Cortico-Cerebellar Connectivity, Social Competence, and Internalizing Symptoms in Adolescents Born Very Preterm

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PROJECT SUMMARY: Children born very preterm (VPT, <32 weeks’ gestation) are at increased risk for social competency impairments compared to their term-born peers, including social communication deficits and poorer quality peer relationships leading to peer victimization and social rejection. Further, internalizing disorders are 2- 3 times higher in VPT children, with symptoms evident in early childhood and lasting into adulthood. Critically, how social competence impairments evolve and persist into adolescence, and the extent that known risk factors associated with VPT birth, including psychosocial adversity and executive dysfunction, shape their trajectory to increase risk for internalizing disorders remains unknown. Additionally, the cerebellum is a key structure adversely impacted by VPT birth, and aberrant cerebellar development is now recognized as a major risk factor for social communication deficits. Altered cerebellar development, along with its functional interactions with the Frontoparietal and Default Mode Networks involved in socio-emotional function, may be a key mechanism linking VPT birth, social impairment, and internalizing disorders. We posit that individual-specific patterns of cortico- cerebellar connectivity and related white matter tract (i.e., cerebellar peduncle) development underlie the evolution of social competence deficits, and in turn, internalizing disorders that persist or worsen at age 14-15, a critical period when peer interactions become more sophisticated and central. This process begins during infancy and extends to adolescence, with psychosocial risk playing a pivotal modifying role. Advances in MRI methodology now enable characterization of structural and functional brain networks with unparalleled spatial and temporal resolution. We couple innovative MRI techniques with detailed social-interaction and psychiatric assessments in a unique, longitudinal cohort of VPT and term-born adolescents (N=302; 137 VPT and 165 term- born) with high rates of psychosocial adversity now aged 14-15 years. The cohort has been followed since birth, undergoing prospective high-quality neonatal and school-age structural and functional connectivity MRI scans and longitudinal assessments of social competence, socio-emotional functioning, and psychosocial and familial risk at ages 2, 5, and 9-10 years (>80% retention at all waves). Continued evaluation of this valuable cohort provides an unprecedented opportunity to determine: 1) trajectories of social competence and internalizing symptoms for better identification of adolescents at greatest risk for psychopathology and 2) how trajectories of cortico-cerebellar structural and functional connectivity underlie these deficits. State-of-the-art MRI acquisition and analyses will characterize the deleterious effects of VPT birth on cortico-cerebellar connectivity into adolescence. We will delineate links between cortico-cerebellar connectivity, social competence, and internalizing disorders to elucidate modifiable psychosocial exposures and improve individual-level neuroimaging, behavior, and psychosocial predictive models that inform the timing of preventative interventions during sensitive periods of brain and socio-emotional development to mitigate risk for internalizing disorders.