Developmental changes in the reconfiguration of brain networks and their association with psychiatric traits during adolescence

Project Summary/Abstract: Research Project (2) Developmental changes in the reconfiguration of brain networks and their association with psychiatric traits during adolescence Adolescence is typically defined as the transition from childhood to adulthood. It is a critical period for neural changes, including maturation of the brain’s major cognitive networks, but also a period of increased vulnerability to psychopathology. The incidence of psychiatric disorders increases exponentially from adolescence to adulthood, with 75% of cases being first diagnosed before the age of 24 years. It is therefore critical to understand the impact of adolescent development on brain network architecture and the alterations that may lead to the onset of mental illness. It is well accepted that the brain is functionally organized into multiple interacting networks. Extensive literature has also demonstrated that the brain connectome shows age-related alterations, with the largest changes happening during adolescence. While these findings have significantly advanced the field, the vast majority of the underlying studies have focused on a single cognitive state such as a specific cognitive task or a resting-state, with the assumption that the brain network definition remain unchanged across cognitive states. However, it is now clear that it is not the case, and that this dynamic brain reconfiguration plays a major role in both cognition and psychopathology. Thus, our currently incomplete view may limit our overall capacity to identify the impact of adolescent brain development on such dynamic network reconfiguration, as well as its association with cognitive ability and risk for developing mental disorders. Based on our prior studies and pilot analyses, we show that collecting functional magnetic resonance imaging (fMRI) data from both resting- state and several cognitive tasks will improve the characterization of the brain functional connectome and its links to psychopathology in adolescence. In this context, the aim of this application is to combine these imaging data with cognitive and behavioral information to provide an integrative framework that quantifies the dynamic reconfiguration of the brain connectome across cognitive states from adolescence to adulthood. To achieve this, we will use both resting-state and task-based fMRI from 160 typically-developing participants aged 12 to 25 years. We will identify developmental changes in both the spatial (Aim 1) and functional (Aim 2) reconfigurations of the major brain networks by cognitive states. Our third aim (Aim 3) will provide an integrative view of developmental changes in the brain’s dynamic networks and behavior by conducting robust multivariate analyses, which will test the degree to which brain network organization measures are associated with psychiatric traits during adolescence. We aim to demonstrate a progressive increase in network reconfiguration across states as a function of age and propose that such changes reflect better functioning and lower-risk for psychopathology. By mapping the brain connectome in this critical age window, this work has the potential to elucidate how developmental brain network alterations contribute to psychiatric traits and ultimately the risk of developing mental illness during the transition to adulthood.