Direct Intracranial Electrophysiological Mapping of Insular Circuits for Anxiety in the Human Brain

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PROJECT SUMMARY/ABSTRACT Anxiety is a common symptom across psychiatric disorders and is associated with worse quality of life and impairment. However, the existing treatments for anxiety remain limited despite its widespread prevalence. My career goal is to become an academic psychiatrist and neuroscientist focused on the neural circuits underlying various dimensions of anxiety in the human brain with the aim of developing targeted novel therapeutics. Previous studies suggest that the anterior insular cortex is a critical node within a larger corticolimbic `anxiety network,' which mediates various dimensions of anxiety. It is one of the most heavily implicated regions across all anxiety disorders and frequently observed in anxiety-related task studies. Despite the large body of evidence implicating the insular cortex across serious mental illness, the underlying role of insular circuits in anxiety remains unclear. Intracranial electrophysiological mapping with high density recordings offers a unique and promising method to study insular networks with high spatiotemporal resolution. To date, there are no studies that have investigated insular neurophysiology in the context of anxiety-related symptoms using iEEG. In our pilot studies, we found preliminary evidence that insular activity in distinct spectral bands correlates with dimensions of anxiety. We also found evidence that stimulation of the anterior insula can elicit an increase in self-reported anxiety associated with propagation of activity to downstream corticolimbic structures. This proposal builds upon these preliminary findings to validate our model that distinct spatiotemporally overlapping insular circuits mediate specific anxiety-related processes through coordinate oscillatory activity. Aim 1 utilizes a task-based approach to identify insular representations of anxiety-related symptoms and behaviors using intracranial recordings. Aim 2 tests the role of insular activity on anxiety-related symptoms and downstream corticolimbic networks using direct electrical stimulation. To address these research goals, I will need additional training in advance signal processing, affective neuroscience, and biostatistics. My rigorous training plan and expert mentoring team will provide me with the experience necessary to become a fully independent investigator able to bring advanced systems neuroscience approaches to basic mental health research.