Project Summary Postmortem studies indicate that synaptic pruning continues through adolescence into adulthood in prefrontal cortex (PFC) at time when cognitive abilities optimize and major psychopathologies (e.g., schizophrenia, mood disorders, substance use disorders) emerge. However, understanding this process in vivo and its effects on maturation of neurocognitive function is not well understood. The recently funded parent R01 proposes a suite of MR-based acquisitions to assess synaptic pruning in vivo using ultra high field (7 Tesla) 31P MRI, diffusion weighted imaging (DWI) and MR spectroscopic imaging (MRSI). This competing supplement aims to extend this work in two aims. First, we will add critical direct characterizations of synaptic pruning from a subset of adult participants from the parent grant using the tracer [11C]UCB-J which has been well validated as the gold standard in vivo measure of synapse density. Regional and whole-brain analyses will characterize the relationship between MR and PET-based measures of synaptic density to demonstrate how MRI can be used to assess developmental synapse reduction. Second, we will use EEG data collected from all the participants of the parent grant to understand how PFC synaptic pruning supports neurocognitive maturation via development of electrophysiological properties of functional brain activity. Adolescent pruning of excitatory synapses has been proposed as a mechanism for optimizing cortical signal processing, driving the rebalancing of excitatory- inhibitory (E/I) signaling associated with adolescent brain plasticity. Interactions among these neural signaling systems support the development of oscillatory activity, suppression of spontaneous neural firing, and enhancement of cortical signal-to-noise ratios, which together support the emergence of adult levels of reliable cognitive processing. EEG data will be used to assess both periodic (oscillatory) and aperiodic (non-cyclical) activity, to characterize how synaptic pruning reshapes these aspects of neural signal processing through adolescence. This study will not only increase the impact of our ongoing studies, but importantly will provide a first-ever comprehensive assessment of how reliable, accessible measurements of synaptic pruning can be used to assess cortical signal processing. This will have a wide ranging impact in stimulating research related to synaptic pruning across disciplines: pruning has been linked to a number of mental health and neurodevelopmental disorders, including schizophrenia, autism, ADHD, bipolar disorder, and more. Providing the field with validated tools to better assess these processes in vivo using accessible methodologies such as MRI and EEG, in conjunction with the results emerging from the proposed studies characterizing adolescent neurodevelopment, will advance our understanding of the neurophysiological mechanisms driving plasticity through this critical period, and how disruptions to these process...