# Treating primary progressive aphasia and elucidating neurodegeneration in the language network using transcranial direct current stimulation

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $754,211

## Abstract

PROJECT SUMMARY/ABSTRACT
This revised application responds to PAR-18-175: “Pilot Clinical Trials for the Spectrum of Alzheimer's Disease
and Age-related Cognitive Decline.” Primary progressive aphasia (PPA), a debilitating condition of language
loss affecting many patients with frontotemporal dementia (FTD) and Alzheimer's disease (AD), currently lacks
effective treatments. Recent studies suggest that transcranial direct current stimulation (tDCS), a form of
noninvasive neuromodulation, may show promise as an intervention for PPA. However, these research efforts
are hampered because they do not address important questions about plasticity in the language system, and
because they do not fully utilize knowledge regarding the properties of the language network in PPA to guide
treatment. This proposal aims to further advance investigation into tDCS as a potential intervention in PPA and
to establish which components of the language network in PPA are most capable of tDCS-induced behaviorally
relevant plasticity. Our proposal seeks to determine whether neuromodulation therapies in persons with PPA
should aim to strengthen connections in the most degenerated regions of the language network or bolster
compensatory changes in more intact areas. We will address this knowledge gap by pursuing a randomized,
sham-controlled crossover study of high-density tDCS (HD-tDCS) focused over the anterior regions of the left
hemisphere language network in participants with two PPA variants that are characterized by decreased word
production but which feature different sites of maximal degeneration. This will allow for comparison of
stimulation in a region that is degenerated in some subjects but relatively spared in others. Stimulation will be
paired with a behavioral language therapy aimed at augmenting tDCS effects in the language system. Our first
aim will be to determine how this intervention differentially impacts language performance in subjects with the
two PPA variants. We will then use network graph statistical analyses of neuroimaging data to characterize
language networks. We will focus on hubs as centers of critical connectivity in networks, and we propose that
measuring changes in the ability of regions in the language network to function as hubs (indexed by hub
scores) may be a way to describe how neurodegeneration impacts language network functions in PPA. Thus,
the second aim of the proposal will explore differences in hub scores across the language network at baseline
in our two PPA subtype groups. The third aim of the proposal will extend this approach by examining
behaviorally relevant changes in hub scores induced by tDCS. The final aim of the project will integrate and
extend prior findings by developing a model that employs clinical phenotypes, patterns of brain atrophy, and
hub score data to predict which individuals are most likely to benefit from our stimulation approach. Taken
together, this project will advance a potential intervention for a...

## Key facts

- **NIH application ID:** 9991713
- **Project number:** 5R01AG059763-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Roy H Hamilton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $754,211
- **Award type:** 5
- **Project period:** 2019-08-15 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991713

## Citation

> US National Institutes of Health, RePORTER application 9991713, Treating primary progressive aphasia and elucidating neurodegeneration in the language network using transcranial direct current stimulation (5R01AG059763-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991713. Licensed CC0.

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