Project Summary/Abstract This is the second renewal on a line of inquiry characterizing the neural basis of the maturation of reward and motivation through the adolescent period, a time of critical vulnerability to the emergence of major psychopathol- ogy (e.g., substance use disorder, schizophrenia, mood disorders), which are typically impacted by deficiencies in these systems. Building on the findings from the first two grants using functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography, and reward learning assessments, indicating heightened influence of reward/motivation (i.e., dopaminergic) systems in adolescence, we now propose to study their wider effects on establishing adult trajectories by characterizing developmental changes in habit formation and relatedly, stabili- zation of neural activity. The neural mechanisms that underlie maturation to established neurocognitive behav- iors have not been studied in human development and can provide unique insights into how adult trajectories are formed. The central hypothesis is that neurobehavioral processes underlying stabilization of behavior from adolescence to adulthood are supported by frontolimbic specialization and stabilization of neural activity. We will study 192 typically developing 10-26 year-olds with habit tasks in fMRI and EEG, and 45 pediatric epilepsy patients with intracerebral EEG. In Aim 1, we will characterize the neurodevelopment of habit formation as a probe for how modes of stable behavior are acquired defining adulthood, which rodent models have found is limited in adolescence and has not been studied in humans. We will use a well-established habit task and determine developmental changes in behavior and BOLD fMRI activity. In Aim2, we will characterize how changes in frontostriatal systems including using non-invasive indirect measures of dopamine through brain tissue iron, which in the previous grant we found is closely associated with dopamine, and functional connectivity, which our previous grant found specializes through adolescence, underlie neurocognitive stabilization into adult- hood. Finally, in order to understand how neural systems are stabilizing through adolescence into adult- hood, in Aim 3, we will characterize developmental changes in oscillations and in the variability of neural activity in key regions involved in habit formation using electroencephalography (EEG) and intracerebral stereo-eletroenceph- alography (sEEG). sEEG will be performed in collaboration with our co-investigator, a pediatric neurosurgeon who implants electrodes in preparation for resection due to epilepsy, providing critical data for characterizing de- velopmental changes in neural activity directly. These studies have never been performed in human development and can provide novel evidence regarding the neural mechanisms underlying normative establishment of adult trajectories informing how these may lead to maladaptive trajectories such as in psychopathology, which emerges during the transition from adolescence to adulthood.

Project Narrative How cognition and brain function stabilize in the transition from adolescence to adulthood is not understood limiting our understanding of the formation of normative and importantly non-normative adult trajectories, such as in mental illness, which predominantly emerges during this transition. Here, informed by the important results of the earlier grants in this line of inquiry regarding brain development in the reward system, we propose innovative new studies to understand how changes in brain and reward behavior from adolescence to adulthood lead to retaining established behaviors. Together, these studies will provide new integrated evidence of how brain development leads to establishing adult trajectories informing impaired trajectories in mental illness.