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Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

Award Number: R01AG062543
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation - Emerging evidence indicates that dysfunction of hippocampal synaptic plasticity, which precedes neuronal degeneration during the progression of Alzheimer's disease (AD), underlies the hallmark cognitive impairment. Although there are currently no effective disease modifying treatments for AD, recent preclinical studies in animal models of AD have suggested that repetitive transcranial magnetic stimulation (rTMS) promotes hippocampal synaptic plasticity and, ultimately, improves learning and memory abilities. In this application, we will utilize MRI-based neuronal connectivity maps as a guide to precisely propagate the neuronal excitation elicited by the superficial rTMS pulse to the hippocampus. The premise of this image-guided approach is supported by both previously published research in healthy adults and our pilot data in individuals with amnestic mild cognitive impairment (aMCI). Our preliminary findings demonstrate that applying a single dose of rTMS over a superficial brain region that is structurally connected to the hippocampus can transiently modulate hippocampal activity and enhance associative memory function. The specific aims of this project are to 1) determine the behavioral effect of hippocampal rTMS on memory function, 2) verify MRI-guided rTMS effects on hippocampal functional connectivity; and 3) develop a personalized, image-guided hippocampal rTMS protocol. Sixty individuals with aMCI will be enrolled in the double-blind, randomized, sham-controlled, crossover study with three rTMS conditions: excitatory stimulation, inhibitory stimulation, and sham stimulation. Each participant will complete 10 stimulation sessions for each condition with a 4-week interval between conditions to avoid potential carry-over effects. Building on preliminary data, here we will rigorously test our hypothesis that active rTMS protocols have a stronger modulation effect on both memory function and hippocampal functional connectivity, compared with sham rTMS in individuals with aMCI. Furthermore, data acquired from aims 1 and 2 will be used to develop statistical models to predict responses to rTMS intervention. The proposed research uses interventions grounded in precision medicine to provide an innovative platform that integrates MRI (including functional MRI and diffusion-tensor imaging) and rTMS to improve memory function in individuals with aMCI. This project represents a critical step in developing a non-invasive hippocampal stimulation protocol that should greatly benefit patients with Alzheimer's disease.


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: 2026 ( Subtotal = $0 )
2026	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	000	5	1/22/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $678,098 )
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	000	5	2/14/2024	NON-COMPETING CONTINUATION	$610,288
2024	2024	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Aging Research	001	5	7/1/2024	NON-COMPETING CONTINUATION	$67,810
														Subtotal = $678,098

Issue Date FY: 2023 ( Subtotal = $678,098 )
2023	2023	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	000	4	3/7/2023	NON-COMPETING CONTINUATION	$678,098
														Subtotal = $678,098

Issue Date FY: 2022 ( Subtotal = $699,098 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	001	3	6/1/2022	NON-COMPETING CONTINUATION	$69,910
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	000	3	1/31/2022	NON-COMPETING CONTINUATION	$629,188
														Subtotal = $699,098

Issue Date FY: 2021 ( Subtotal = $678,098 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	001	2	1/29/2021	NON-COMPETING CONTINUATION	$678,098
2021	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	000	1	10/22/2020	NEW	$0
														Subtotal = $678,098

Issue Date FY: 2020 ( Subtotal = $735,123 )
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Aging Research	000	1	4/28/2020	NEW	$735,123
														Subtotal = $735,123

Grand Total All Awards = $3,468,515

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Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

Award Number: R01AG062543

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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