Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning
About This Grant
Project Summary/Abstract The ability to reduce fear responses through extinction when threats are no longer present is essential for mental health. Deficits in extinction underlie fear-related disorders such as post-traumatic stress disorder (PTSD). A critical gap remains in understanding the neural mechanisms underlying fear extinction, which poses a major barrier to developing more effective therapeutic interventions. The amygdala (AMY)-prefrontal circuits are critical in fear extinction. In animal models, the lateral nucleus of AMY (LA) receives sensory inputs and initiates fear learning, while the basal nucleus of AMY (BA) integrates regulatory inputs from the ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (dACC) for appropriate fear response. However, due to species-specific differences between animal and human neurobiology, the nucleus-specific contributions of the AMY and their interactions with vmPFC/dACC in human fear extinction and regulation remain poorly understood. Clinically indicated stereoelectroencephalography (SEEG) electrodes, which allow direct recording and stimulation of AMY-prefrontal circuits, provide a unique opportunity to address this critical gap. The long-term goal of the candidate is to uncover the neural mechanisms underlying fear processing through intracranial electrophysiology and neuromodulation in humans, and to bridge systems and affective neuroscience with the development of targeted therapeutic interventions. The objective here is to determine the causal dynamics of the AMY-prefrontal circuits involved in fear extinction learning in epilepsy patients undergoing SEEG monitoring. Specifically, this proposal will address three Aims: (1) Determine the intrinsic and stimulation-induced dynamics of human AMY-prefrontal circuits (K99). The study will create an unambiguous delineation of cause-effect relationships in AMY-vmPFC-dACC circuits by delivering single-pulse and high-frequency electrical stimulation to the circuits. (2) Characterize nucleus-specific and lateralized dynamics of AMY-prefrontal circuits during fear extinction (K99/R00). The study will reveal the neural dynamics of LA, BA, and left/right AMY-prefrontal circuits in fear extinction and regulation. (3) Determine the modulatory effects of theta-burst stimulation of AMY nuclei on fear extinction (R00). Theta-burst stimulation will be applied to the LA and BA during extinction learning. Dr. Xie will conduct this research and training through the Epilepsy and Human Brain Mapping Program (one of the highest-rated epilepsy programs in the United States) at WashU Medicine, the Grady Trauma Project (the largest civilian research project on the effects of trauma and PTSD in the world) at Emory University, and the National Center for Adaptive Neurotechnologies (the only neurotechnology center in the United States that is funded by NIH). In the K99 phase, Dr. Xie will receive training in five key areas to lead successful intracranial electrophysiology and brain stimulation studies: psychophysiology, neuromodulation, neural analytics & modeling, clinical research, and career development. The training gained from pursuing the proposed aims will be essential for Dr. Xie to attain his independence as a researcher in systems/affective neuroscience and neuromodulation.
Grant Summary
Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning is a NIMH - National Institute of Mental Health grant providing up to $103K for university, nonprofit, healthcare org. Applications are due 2028-07-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $103K
2028-07-31
- 1Confirm your organization is eligible for Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning from NIMH - National Institute of Mental Health, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIMH - National Institute of Mental Health before the deadline.
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Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning: Frequently Asked Questions
Who is eligible for the Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning?
Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning is offered by NIMH - National Institute of Mental Health and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning provide?
Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning provides up to $103K per award from NIMH - National Institute of Mental Health. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning deadline?
Applications for Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning are due 2028-07-31 (open). Because deadlines can change, verify the date with the funder, NIMH - National Institute of Mental Health, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning?
To apply for Causal Dynamics of Human Amygdala-Prefrontal Circuits during Fear Extinction Learning, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIMH - National Institute of Mental Health.