Effects of non-invasive brain stimulation on spontaneous neural activity in post-stroke aphasia: a protocol for a coordinate-based meta-analysis of fALFF studies.

Abstract

Introduction: Post-stroke aphasia (PSA) is a common and debilitating sequela of stroke that severely impairs quality of life. Non-invasive brain stimulation (NIBS), particularly repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has increasingly emerged as a promising adjunctive approach for language recovery in patients with PSA. Although accumulating evidence supports the beneficial effects of NIBS on language outcomes, the neural mechanisms underlying these clinical improvements remain incompletely elucidated. Previous meta-analyses in PSA and stroke have synthesized multiple resting-state functional magnetic resonance imaging (rs-fMRI) indices, but no meta-analysis has specifically examined treatment-related fractional amplitude of low-frequency fluctuations (fALFF) changes after NIBS in PSA. This protocol describes a coordinate-based meta-analysis designed to quantitatively synthesize rs-fMRI data, aiming to investigate how NIBS modulates intrinsic neural activity-indexed by fALFF-in patients with PSA.

Methods and analysis: Two independent reviewers will conduct a systematic search of the PubMed, Web of Science, Embase, and Cochrane databases for studies published from database inception to December 1, 2025. Eligible studies evaluating the effects of NIBS on fALFF in patients with PSA will be selected based on pre-defined criteria. Only whole-brain voxel-wise fALFF studies reporting stereotactic peak coordinates in standard space will be entered into the primary quantitative AES-SDM analysis; ROI-only studies or studies without usable coordinates will be retained for narrative synthesis. Any discrepancies arising during study selection or data extraction will be resolved through consultation with a third independent reviewer. Neuroimaging reporting quality will be assessed with a customized 20-point checklist, and risk of bias will be evaluated with design-specific tools (RoB 2 for randomized trials and ROBINS-I for non-randomized intervention studies). We will also record studies using other rs-fMRI indices (e.g., ALFF, ReHo, and functional connectivity) during screening to describe the broader evidence base. The primary outcome measures will focus on alterations in specific intrinsic regional neuronal activity assessed via rs-fMRI. The meta-analysis of neuroimaging data will be conducted using Anisotropic Effect Size Seed-Based d Mapping (AES-SDM, version 5.15), while clinical outcome analyses will be performed using RevMan 5.4 software (The Cochrane Collaboration). The reporting of this study will strictly adhere to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

Conclusion: This study will quantitatively synthesize findings from independent neuroimaging studies to provide comprehensive evidence for identifying the modulation patterns of intrinsic brain activity induced by NIBS in patients with PSA.

Systematic review registration: Identifier CRD420251275236. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251275236.