Thursday, December 26, 2024 12/26/2024

Neural correlates of active avoidance learning and their interactions with fear extinction mechanisms in PTSD patients

Award Number: R01MH123736
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Primary characteristics of posttraumatic stress disorder (PTSD) include persistent fears and excessive maladaptive avoidance behaviors. Preclinical models of PTSD have heavily investigated the brain mechanisms of fear inhibition and active avoidance learning. Significant progress has been made in translating fear conditioning and extinction data into the human brain and their implications have helped further our understanding of PTSD psychopathology. The mechanisms of active avoidance, however, have scarcely been examined in the human brain, especially within the context of maladaptive responses as in the case of PTSD. The studies proposed in this application are designed to begin to fill this scientific gap. We will use a novel conditioning and active avoidance paradigm (CAAP) to examine the neural correlates of active avoidance and fear extinction learning and explore how extinction modulates active avoidance responses in participants with and without a PTSD diagnosis using functional magnetic resonance imaging (fMRI). PTSD psychopathology involves dysfunctional limbic-frontal activity including the ventromedial prefrontal cortex (vmPFC), hippocampus (HPC), and amygdala. Studies of avoidance in rodents and a few fMRI studies in healthy humans suggest that the vmPFC and striatum mediate threat response by toggling the expression of fear vs. avoidance responses. Participants (healthy controls with trauma exposure, and patients diagnosed with PTSD) will undergo the novel (validated) two- day CAAP. On day 1, participants will undergo Pavlovian fear conditioning, immediately followed by an active avoidance conditioning phase. Avoidance is achieved by pressing a button to prevent a shock from occurring but will not terminate the conditioned stimulus (CS). Pavlovian fear extinction learning (button removed; no avoidance possible) will follow. On day 2, recall of extinction learning will be tested. Before the start of the recall test, participants will receive a small monetary endowment and will be told that this money could be used to pay for shock avoidance during the recall test. The first aim is to Identify neural correlates of active avoidance. The second aim is to study activations after the CS+ terminates that index the relief from the avoided shock. The third aim is to examine neural correlates of extinction-to-avoidance transfer. The proposed studies are expected to provide a more integrated mechanistic understanding of the psychopathology of PTSD and reduce the gap between the rodent literature and human neuroimaging in avoidance research.


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: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	002	4	12/4/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$767,156
2025	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Mental Health Research Grants	001	3	12/4/2024	NON-COMPETING CONTINUATION	-$663,226
2025	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Mental Health Research Grants	000	2	12/4/2024	NON-COMPETING CONTINUATION	-$103,930
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $678,226 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Mental Health Research Grants	001	4	8/29/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$678,226
2024	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Mental Health Research Grants	000	3	8/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $678,226

Issue Date FY: 2023 ( Subtotal = $663,226 )
2023	2023	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Mental Health Research Grants	000	3	4/7/2023	NON-COMPETING CONTINUATION	$663,226
														Subtotal = $663,226

Issue Date FY: 2022 ( Subtotal = $696,852 )
2022	2022	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Mental Health Research Grants	000	2	6/7/2022	NON-COMPETING CONTINUATION	$696,852
														Subtotal = $696,852

Issue Date FY: 2021 ( Subtotal = $756,037 )
2021	2021	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Mental Health Research Grants	000	1	5/11/2021	NEW	$756,037
														Subtotal = $756,037

Grand Total All Awards = $2,794,341

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Neural correlates of active avoidance learning and their interactions with fear extinction mechanisms in PTSD patients

Award Number: R01MH123736

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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