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Updated: Jun 25, 2026

Utilizing Repetitive Transcranial Magnetic Stimulation to Improve Language Function in Stroke Patients with Chronic Non-fluent Aphasia
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Baseline Functional Connectivity Predicts Who Will Benefit From Neuromodulation: Evidence From Primary Progressive

Zeyi Wang1,2, Jessica Gallegos3, Donna Tippett3,4,5

  • 1Department of Biostatistics, Johns Hopkins School of Public Health, Baltimore, MD, USA.

Neurorehabilitation and Neural Repair
|January 9, 2026
PubMed
Summary
This summary is machine-generated.

Functional connectivity predicts language improvement in primary progressive aphasia (PPA) patients undergoing transcranial direct current stimulation (tDCS). Higher baseline connectivity in specific brain regions indicates greater benefit from tDCS for naming and fluency.

Keywords:
electrical stimulation (tES)heterogeneityinferior frontal gyrusneuromodulationprecision medicinepredictionprimary progressive aphasiasemantic fluencysemantic retrievaltranscranial direct current stimulation (tDCS)verbal fluency

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Area of Science:

  • Neuroscience
  • Neurology
  • Medical Imaging

Background:

  • Personalized treatment strategies require understanding individual variability in treatment response.
  • Predicting treatment response in heterogeneous conditions like primary progressive aphasia (PPA) is challenging.
  • This study investigates predictors of language response to transcranial direct current stimulation (tDCS) in PPA.

Purpose of the Study:

  • To identify predictors of individual language response to tDCS of the left inferior frontal gyrus (IFG).
  • To compare the predictive value of demographic, clinical, volumetric, and functional connectivity data.
  • To utilize a novel analytic approach focusing on treatment effect heterogeneity.

Main Methods:

  • 36 PPA patients received active or sham tDCS over 3 weeks.
  • Predictive abilities of demographic/clinical data and volumetric fMRI were compared against resting-state functional connectivity (FC).
  • Outcome measures included generalization (semantic fluency) and main outcome (written naming).

Main Results:

  • Functional connectivity was the strongest predictor, explaining 62% of semantic fluency variance and 75% of written naming variance.
  • Demographic/clinical data and volumetric data predicted <15% and <23% of variance, respectively.
  • Higher baseline FC within the left IFG predicted greater benefit in naming and generalization; higher FC between temporal regions predicted generalization.

Conclusions:

  • Baseline functional connectivity is crucial for predicting tDCS outcomes in PPA.
  • This highlights the potential of a precision medicine approach in neuromodulation.
  • Findings have implications for clinical trials, enabling accurate prediction and enrollment of likely responders.