# Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $735,123

## Abstract

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.

## Key facts

- **NIH application ID:** 9972029
- **Project number:** 1R01AG062543-01A1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Ying-Hui Chou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $735,123
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972029

## Citation

> US National Institutes of Health, RePORTER application 9972029, Enhancement of Hippocampal Plasticity Using Repetitive Transcranial Magnetic Stimulation (1R01AG062543-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972029. Licensed CC0.

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