# Interleaved TMS-fMRI for Hippocampal Stimulation: Modeling Dose-Response Relationship in Amnestic Mild Cognitive Impairment

> **NIH NIH R21** · UNIVERSITY OF ARIZONA · 2023 · $185,398

## Abstract

Project Summery/Abstract
Theta burst stimulation (TBS) is a non-invasive brain stimulation technique that has emerged as
a promising therapy for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However,
little effort has been undertaken to optimize the application of TBS for these populations. Previous
animal in vitro studies have found that TBS could induce long-term potentiation (LTP) in adult rat
hippocampal slices in a dose-dependent manner. The maximum LTP effect was observed after
TBS sessions were repeated three times, with a 60-minute break between each session. The
dose-response curve was flattened when TBS applications did not have adequate interludes. This
points to an array of parameters that must be properly tuned to achieve the desired TBS effects.
The purpose of the study is to investigate the effects of spaced TBS at a superficial brain region
connected to the hippocampus in individuals with amnestic MCI (aMCI). TBS will be applied inside
an MRI scanner interleaved with fMRI to visualize the immediate response to the hippocampal
stimulation. Aim 1 of the study will determine the effects of spaced TBS on memory performance
and hippocampal function in individuals with aMCI. Aim 2 will establish dose-response
relationship of the spaced TBS effect. Thirty-eight individuals with aMCI will be randomly assigned
to one of the two TBS groups: active TBS or sham TBS. We hypothesize that 1) the spaced TBS
protocol will enhance memory function, strengthen hippocampal functional connectivity, and
increase hippocampal activation compared to the sham TBS, and 2) a positive dose-response
relationship of the TBS effect will be observed. By leveraging cutting edge MRI-compatible TBS,
findings of our innovative study may suggest mechanisms of spaced hippocampal TBS in aMCI.
Ultimately, understanding how brain responds to the spaced TBS will enable development of an
optimized TBS therapeutic protocol for individuals with MCI and AD.

## Key facts

- **NIH application ID:** 10599331
- **Project number:** 5R21AG077153-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Ying-Hui Chou
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $185,398
- **Award type:** 5
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10599331

## Citation

> US National Institutes of Health, RePORTER application 10599331, Interleaved TMS-fMRI for Hippocampal Stimulation: Modeling Dose-Response Relationship in Amnestic Mild Cognitive Impairment (5R21AG077153-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10599331. Licensed CC0.

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