Project Summary/Abstract Adults with autism spectrum disorder (ASD) suffer from depression at up to four times the rate of the general population. Mindfulness-Based Stress Reduction (MBSR), a standardized 8-week intervention, is effective in treating mood comorbidities in ASD. In our data, MBSR participation elicited increased middle cingulate cortex activity during self-reflection, which correlated with depression reduction. Further, MBSR appears to modulate a neurophysiological marker of emotion regulation implicated in depression. The long-term goal of this research is to elucidate the neurobiological mechanisms driving MBSR’s therapeutic effects in adults with ASD. The specific aims of this proposal are to characterize MBSR-induced changes to 1) self-reflection neurocircuitry via effective connectivity and 2) emotional regulation neurophysiology. Significance: This study will identify multimodal brain dynamics underlying MBSR’s therapeutic effects in adults with ASD. Findings will inform biologically-based interventions for integrative health. Methods: Aim 1 leverages state-of-the-art effective connectivity brain mapping of self-reflection functional MRI; Aim 2 utilizes emotional regulation EEG data to capture neurophysiological event-related potentials. Exploratory Aim 3 will identify the combination of brain measures that best predicts depression reduction. Mr. Pagni aspires to become a leader in using multimodal neural imaging techniques to identify neural network properties that support long-term therapeutic and cognitive outcomes. His long-term goal is to lead an interdisciplinary clinical laboratory dedicated to understanding the brain basis of integrative health practices. As a behavioral technician, he provided applied behavioral therapy for children with ASD. Early in his Ph.D. program, he performed behavioral pharmacology research, equipping him with a foundation in cellular and molecular mechanisms driving depressive phenotypes. In his current lab, he has gained expertise in mindfulness-based therapies; fMRI analyses in ASD; and EEG data collection. The training plan will fulfill the following goals to complement his current expertise: 1) advanced fMRI analysis (effective connectivity); 2) EEG analysis (event- related potential); 3) brain-behavior relationships (partial least squares) and 4) ASD therapies and clinical trials. Training in neuroimaging methods and clinical trials will occur primarily at Arizona State University (ASU). ASU is a well-regarded, R1 institution with collaborations at Barrow Neurological Institute’s top-notch neuroimaging facilities. Mr. Pagni will receive additional state-of-the-art neuroimaging analysis training at Banner Alzheimer’s Institute. ASU’s Psychology Department also affords Mr. Pagni an optimal environment for implementing EEG techniques and learning best practices in clinical trial research. Together these institutes provide a supportive environment for Mr. Pagni to excel in multimodal brain ...