Mechanistic basis of salience network oscillations that control anxiety trajectories

The proposed program of research proposes to advance the effort to predict anxiety trajectories by linking observable clinical anxiety phenotypes to the underpinning interplay of molecular and circuit events. Oscillations within the salience network (anterior cingulate, insula, and amygdala) during negative emotional states offer both scalability (via EEG, MEG) and mechanistic insight into the anxiety itself. In this groundbreaking study, we use unprecedented high-resolution neurosurgical mapping of this network to define regional and frequency-band interactions in the salience network. To test the causal impact of these salience network oscillations, we will systematically induce salience network oscillations in mice using optogenetics and large-scale electrophysiology while measuring anxiety using computational behavioral sequencing. Finally, we will unravel the genomic underpinnings that sculpt these oscillations, bridging the gap between molecular signatures and psychiatric phenotypes using single cell sequencing across mouse and human amygdala. Collectively, these efforts converge to illuminate the pathophysiological tapestry woven by anxiety and trauma, guiding us toward targeted interventions with the potential to recalibrate the anxious brain's circuitry.