Charting Neurodevelopment Along a Sensorimotor-Association Cortical Axis: Patterns of Plasticity, Environmental Susceptibility, and Psychiatric Vulnerability

Human cortical development is protracted, heterochronous, sculpted by the environment, and associated with the emergence of diverse psychiatric conditions. Elucidating how developmental plasticity asynchronously progresses across the cortex is vital for understanding which cortical regions will be impacted by positive and negative environments and psychiatric insults and interventions at distinct developmental stages. Prior research has provided consistent evidence that cortical maturation occurs earlier in sensory and motor cortices and later in association cortices. However, beyond this coarse division in developmental timing between these two domains of cortex, there is marked variability in cortical development that remains undercharacterized—and therefore unaccounted for by contemporary accounts of human brain development. This thesis seeks to put forth a model of child and adolescent cortical maturation that accounts for our species’ rich spatiotemporal developmental variability and psychiatric vulnerability. It first reviews existing knowledge concerning human brain development and brain organization and hypothesizes that maturation unfolds along an evolutionarily-rooted, hierarchical, and graded sensorimotor-to-associative axis of cortical organization. It discusses how the unfolding of development along this axis endows transmodal association cortices with both unique neurobiological properties and heightened inter-individual developmental variability and vulnerability. The thesis next leverages a proposed functional signature of plasticity illuminated by animal models to empirically evaluate the hypothesized developmental model. It provides evidence that human cortical development indeed progresses along a sensorimotor-association axis from ages 8 to 18 years and demonstrates how environmental influences on the maturating brain are shaped by this developmental program. Finally, the thesis explores neural correlates of diminished reward responsiveness, a psychiatric risk factor, in a transdiagnostic sample of adolescents and young adults. It shows that this risk factor is dimensionally and selectively associated with lower levels of glutamate within transmodal association cortices and subcortical areas that comprise the brain’s reward network. Together, the work presented here may help to inform environmental and psychiatric interventions for youth that incorporate basic principles of developmental plasticity and are delivered while the brain is undergoing demarcated periods of malleability.