Altered Neurocognitive Functional Connectivity and Activation Patterns Underlie Psychopathology in Preadolescence

Abstract Background Neurocognitive deficits are common among youth with mental disorders, and patterns of aberrant brain function generally cross diagnostic boundaries. This study investigated associations between functional neurocircuitry and broad transdiagnostic psychopathology dimensions in the critical preadolescent period when psychopathology is emerging. Methods Participants were 9- to 10-year-olds from the Adolescent Brain Cognitive Development Study. Factor scores of general psychopathology, externalizing, internalizing, and thought disorder dimensions were calculated from a higher-order model of psychopathology using confirmatory factor analysis (N = 11,721) and entered as explanatory variables into linear mixed models to examine associations with resting-state functional connectivity (n = 9074) and neural activation during the emotional n-back task (n = 6146) when covarying for sex, race/ethnicity, parental education, and cognitive function. Results All dimensions of psychopathology were commonly characterized by hypoconnectivity within the dorsal attention and retrosplenial-temporal networks, hyperconnectivity between the frontoparietal and ventral attention networks and between the dorsal attention network and amygdala, and hypoactivation of the caudal middle frontal gyrus. Externalizing pathology was uniquely associated with hyperconnectivity between the salience and ventral attention networks and hyperactivation of the cingulate and striatum. Internalizing pathology was uniquely characterized by hypoconnectivity between the default mode and cingulo-opercular networks. Connectivity between the cingulo-opercular network and putamen was uniquely higher for internalizing pathology and lower for thought disorder pathology. Conclusions These findings provide novel evidence that broad psychopathology dimensions are characterized by common and dissociable patterns, particularly for externalizing pathology, of functional connectivity and task-evoked activation throughout neurocognitive networks in preadolescence.