# Circuit-specific neuromodulation for the treatment of apathy in Alzheimer's Disease

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $210,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Apathy is among the most debilitating and the least treatable neuropsychiatric symptoms in Alzheimer’s
Disease (AD). Previous studies have highlighted prefrontal-striatal circuits involved in the neuropathogenesis
of apathy. Specifically, a dorsal circuit, encompassing dorsolateral prefrontal cortex and dorsal striatum, and
instantiating goal-directed planning; and a ventral circuit, encompassing ventromedial prefrontal cortex and
ventral striatum, and instantiating motivation/reward valuation. In addition, both circuits are heavily reliant upon
dopamine (DA) availability. This proposal will demonstrate that these circuits can be differentially modulated
with repetitive Transcranial Magnetic Stimulation (rTMS) in a group of 20 AD patients with apathy. First,
advanced estimates of structural and functional connectivity from striatal regions will be used to derive
individualized cortical rTMS targets. Next, patients will undergo three experimental sessions on separate days
in which they are stimulated at the dorsal circuit target, the ventral circuit target, and a control target. The
impact of rTMS will be measured with simultaneous MR-PET scanning which will assess both changes in
resting-state functional connectivity (FC) and striatal 11C-raclopride BPND (a proxy of dopamine
availability/release). Behavioral changes resulting from stimulation will be assessed with validated apathy and
mood measures and with activation on fMRI tasks of planning and reward. We hypothesize that rTMS will
preferentially modulate FC and DA availability only in the circuit stimulated and that this will be accompanied
by specific changes in executive and motivational aspects of apathy. This work will pollinate larger clinical trials
which systematically assess the ability of this intervention to improve apathy in neurodegenerative patients.

## Key facts

- **NIH application ID:** 10507686
- **Project number:** 1R21AG078985-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Mark Christian Eldaief
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $210,000
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507686

## Citation

> US National Institutes of Health, RePORTER application 10507686, Circuit-specific neuromodulation for the treatment of apathy in Alzheimer's Disease (1R21AG078985-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10507686. Licensed CC0.

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