# Targeting language-specific and executive-control networks with transcranial direct current stimulation in aphasic AD

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $828,275

## Abstract

This project aims in developing treatments for an atypical Alzheimer's disease (AD) variant, usually affecting
the left hemisphere and comprising the logopenic variant primary progressive aphasia (lvPPA), thus, PPA-AD.
There are no pharmacological treatments available for PPA, and the only treatment shown to alleviate language
deficits is speech-language therapy. Treatment research in AD has emphasized targeting neuronal synaptic
transmission. We were amongst the first groups in the world to show the efficacy of a neuromodulation technique
that targets synaptic transmission (transcranial direct current stimulation, tDCS) in providing significant
symptomatic relief of language impairments in PPA. In the largest-to-date, double-blind, sham-controlled clinical
trial we demonstrated the efficacy of tDCS as an adjuvant for speech-language therapy for the treatment of
naming and spelling deficits in PPA. However, the efforts to slow language degeneration are hindered by the
fact that these individuals also suffer from additional cognitive deficits. This is especially true for individuals with
AD etiology (pathology and atrophy distribution). Early in the disease, individuals with PPA-AD present with
additional cognitive deficits such as verbal short-term memory impairment, even believed to be a primary
underlying cause of language deficits. However, treatment of these deficits has not been investigated in PPA-
AD using neuromodulation approaches. To address this gap, the proposed research aims to answer the following
question: How can we implement neurostimulation-based treatments to maximally generalize their
benefits to vital language/cognitive functions? We will do that by employing: (a) a behavioral therapy that
directly targets verbal short-term and working memory (vSTM/WM) deficits and that has been shown to
effectively generalize even to untrained language functions in post-stroke aphasia, and, (b) targeted neuro-
stimulation (high-definition tDCS) based on recent network-neuroscience and neuro-rehabilitation models. In
Aim 1, we will compare the efficacy of tDCS delivered over the left supramarginal gyrus (LSMG) vs. the left
dorsolateral prefrontal cortex (LDLPFC), both coupled with vSTM/WM behavioral treatment, specifically
examining the generalization of treatment effects to untrained vital language-specific and executive cognitive
functions in PPA-AD. In Aim 2, we will implement neuroimaging techniques to understand the mechanisms of
tDCS-induced changes in terms of: (a) network functional connectivity, (b) previous and novel metabolites such
as GABA and glutathione (related to oxidative stress in neurodegeneration), and (c) blood oxygenation, using
perfusion imaging. Finally, in Aim 3, we will evaluate novel predictors of responsiveness to tDCS such as
perfusion, sex and sleep, thus complementing our previously identified clinical, neural and behavioral predictors
(variant, brain volume and initial language/cognitive performance). A better ...

## Key facts

- **NIH application ID:** 10522359
- **Project number:** 1R01AG075404-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Kyrana Tsapkini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $828,275
- **Award type:** 1
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522359

## Citation

> US National Institutes of Health, RePORTER application 10522359, Targeting language-specific and executive-control networks with transcranial direct current stimulation in aphasic AD (1R01AG075404-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10522359. Licensed CC0.

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