The human amygdala in social processing: circuits, physiology, behavior, and neuromodulation

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SUMMARY: The purpose of the current proposal is to enable the PI to transition to independent research investigator, with expertise in electrophysiological analysis techniques to examine the real-time function of the emotional (affective) system in neurosurgery patients who undergo the placement of depth electrodes for clinical purposes. The proposed training plan includes structured mentoring, hands-on training in electrophysiology, didactic coursework, and a rigorous proposed research study. The proposed experiments leverage a highly specialized experimental setting: human epilepsy patients with depth electrodes implanted in the amygdala – central to social and emotion processing – for routine seizure focus monitoring in medically refractory epilepsy. In this setting, we can record local neuronal activity as well as apply small electrical currents to stimulate for research purposes. The proposed training in electrophysiology will enable the PI to examine the real-time function of the amygdala, which, when paired with her existing expertise in human neuroimaging and psychiatric behavioral measurement, will allow a thorough comparison of amygdala activity in social processing between depressed and non-depressed patients. This project examines the hypothesis that the amygdala plays a direct and causal role in social processing deficits observed in depression. Within the NIMH Research Domain Criterion Framework, the current proposal examines the role of the amygdala in social processing from the level of neural circuits, physiology, and behavior, and to examine the potential for amygdala neuromodulation to enhance social processing. Deeper understanding of the neural circuitry of social processing will facilitate the study and treatment of depression with implications for broader neuropsychiatric conditions as well. Results of this project will provide pilot data for an NIMH R01 application, and compliment the ongoing work of the applicant and the mentorship team. Coursework will include didactic, and hands-on training in electrophysiological analysis, didactic training in advanced statistical modeling to build upon the applicant’s current training through the Masters’ of Science in Clinical Research program, and continued training in research ethics. Therefore, this award would allow the PI to accomplish her goal of becoming an independent, academic research investigator, while advancing the research objective of evaluating the causal role of the amygdala in social processing deficits in depression and the neuromodulatory potential of amygdala stimulation to reduce these deficits.