A Multilevel Characterization of Sensory Cortical Disinhibition in Post-Traumatic Intrusions - Project Summary/Abstract Intrusive memories of a traumatic experience are prevalent among individuals exposed to trauma and are leading predictors of the onset, maintenance, and severity of transdiagnostic post-traumatic mental health difficulties. Clinical accounts of these intrusive memories highlight their vivid, mostly visual, sensory details that emerge involuntarily to intrude on conscious thought and elicit a spontaneous reliving of the trauma in the “here and now”. Despite these sensory-rich features, extant biological models of trauma-related intrusive memories (TR- IMs) have largely overlooked the sensory cortex in favor of a prefrontal cortex-hippocampus circuit. The present proposal aims to fill this gap through a multilevel characterization of intrinsic sensory cortical disinhibition and its impacts on large-scale neural networks and the day-to-day phenomenological experience of TR-IMs. Combining magnetic resonance spectroscopy (MRS), electroencephalography (EEG), and functional magnetic resonance imaging (fMRI) in trauma-exposed adults (N = 75), this project will link lower levels of inhibitory neural activity (alpha oscillations) and an imbalance in excitatory/inhibitory neurotransmitter systems (glutamate/GABA) to perturbations in the intrinsic functional organization of resting-state neural network dynamics. Ecological momentary assessments (EMAs) of TR-IMs in this sample will further link such sensory cortical disinhibition to the vivid, sensory-perceptual properties of TR-IMs, offering a novel candidate mechanism for therapeutic interventions in sensory cortical disinhibition. An additional sample of non-trauma exposed adults (N = 25) with intrusive memories of non-traumatic negative life events will undergo the same neuroimaging and EMA protocol to further delineate the specificity of this mechanism to trauma exposure. Taken together, this project will offer the first multilevel characterization of the sensory system in survivors of trauma, spanning molecules, circuits, and ecological self-reports, and pave the way for future investigations utilizing neuromodulation to mechanistically test the proposed sensory cortical disinhibition model of trauma intrusions. Drawing on the expertise from a complementary team of mentors (Drs. Isabelle Rosso, Fei Du, and Diego Pizzagalli) and collaborators (Drs. Christian Webb, Joshua Brown, Lauren Bylsma, and Fabio Ferrarelli), the applicant will receive in-depth, hands-on training in 1) neurochemistry methods and analysis, 2) ecological momentary assessments, 3) multimodal data integration and conceptual model development, and 4) neuromodulation techniques for mechanistic and therapeutic research. The acquired data and proposed training plan will launch the applicant into an independent research career at McLean Hospital, integrating multimodal neuroimaging, ambulatory clinical assessments, and advanced neuromodulation techniques to develop novel, mechanism- based interventions for transdiagnostic post-traumatic sequelae.
