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Intracranial Neural Mechanisms of Fear Response in Humans with and without Anxiety-Related Disorders

Award Number: F31MH127922
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2026

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Intracranial Neural Mechanisms of Fear Response in Humans with and without Anxiety-Related Disorders - PROJECT SUMMARY/ABSTRACT Accumulating evidence from rodent studies suggests that the expression of fear emerges from electrophysiological changes within a neural network that includes the ventromedial prefrontal cortex (vmPFC), basolateral amygdala (BLA), and anterior hippocampus (aHPC)5. It is unclear whether this network exhibits similar dynamics during fear-related states in humans and how this activity is altered during inappropriate expression of fear that is often observed in individuals with anxiety-related disorders such as post-traumatic stress disorder (PTSD) or generalized anxiety disorder (GAD). The proposed study will investigate the relationship between deep brain activity (intracranial electroencephalographic and single unit) and physiological response (skin conductance response, pupil size, and heart rate/variability) in humans who are implanted with microwire electrodes for clinical evaluation and treatment of epilepsy who will complete a virtual reality fear conditioning task. Over the project period, the study will have access to 25 rare participants with and without anxiety disorders (i.e. post-traumatic stress disorder [PTSD] and/or generalized anxiety disorder [GAD]) implanted with depth electrodes in the vmPFC, BLA, and/or aHPC through an ongoing collaboration between clinical and basic science leaders at UCLA and the Veteran’s Administration Greater Los Angeles Healthcare System. Since our studies address basic questions surrounding the role of vmPFC-BLA-aHPC dynamics in regulating fear response, a process often compromised in psychiatric disease, it is anticipated that findings will bridge decades of human and animal fear-related research and lay the scientific foundation for improved understanding and treatment of anxiety-related disorders. In addition to completing the described research, I will undergo extensive professional and academic training to prepare me for my ultimate-goal of becoming a neurosurgeon-scientist. This will include mentorship from basic scientist experts in invasive human recording compatible experiments (Dr. Nanthia Suthana) and high level statistical analysis (Dr. Jonathan Kao) in addition to clinical and investigative guidance from a neurosurgeon- scientist (Dr. Jean Phillipe Langevin). Through working with these individuals along with my senior collaborators (Drs. Michelle Craske and Michael Fanselow), I will learn to design clinically relevant behavioral experiments, record invasive human neurophysiology, obtain expert knowledge in neuroscience and neuroanatomy, achieve a highly developed skillset for signals processing and statistical analysis and hone my clinical, writing, and presentation skills.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $53,974 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	3	3/14/2024	NON-COMPETING CONTINUATION	$52,694
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	001	3	8/15/2024	NON-COMPETING CONTINUATION	$1,280
														Subtotal = $53,974

Issue Date FY: 2023 ( Subtotal = $39,552 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	2	3/21/2023	NON-COMPETING CONTINUATION	$39,552
														Subtotal = $39,552

Issue Date FY: 2022 ( Subtotal = $38,610 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	002	1	7/5/2022	NEW	$716
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	001	1	3/10/2022	NEW	$0
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Mental Health Research Grants	000	1	3/10/2022	NEW	$37,894
														Subtotal = $38,610

Grand Total All Awards = $132,136

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Intracranial Neural Mechanisms of Fear Response in Humans with and without Anxiety-Related Disorders

Award Number: F31MH127922

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2026

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