Impact of neuromodulation on post-stroke aphasia: a multimodal randomized controlled study

Background Transcranial direct current stimulation (tDCS) combined with speech and language therapy (SLT) may increase the effectiveness of recovery in post-stroke aphasia. However, inconsistent responses have been observed, in part due to small sample sizes, limited comprehensive assessments, and poor mechanistic understanding of intervention related recovery. Methods Using a double-blind, randomized, sham-controlled design, we investigated the efficacy of anodal Broca’s tDCS combined with SLT over five 20-minute daily sessions in 45 chronic stroke patients. EEG and DTI were used to explore treatment-mediated neuroplastic mechanisms. The primary outcome measures were linguistic skills evaluated by the Western Aphasia Battery-Revised before and after the intervention. Results Compared to sham (SLT + placebo), tDCS patients improved significantly more in aphasia quotient, auditory verbal comprehension, and spontaneous speech. While tDCS improved both expressive and receptive domains, sham only improved expressive language. EEG showed recovery in both groups to rely predominantly on the contralesional side, particularly the right middle temporal area (T4). While tDCS induced recovery correlated with changes in the faster frequencies (e.g., alpha, beta), sham mediated recovery correlated with changes in the slower frequencies (e.g., theta, delta). Furthermore, reduced beta coherence between T3 and T4 was associated with repetition gains specific to tDCS. Furthermore, improved spontaneous speech in tDCS was associated with decreased mean diffusivity in superior cerebellar peduncle. Given this region’s connectivity with contralateral cortical regions, this finding extends and aligns with the EEG signatures of neuroplasticity in right-lateralized cortical regions, highlighting the role of cerebro-cerebellar connections in language recovery. Conclusions Our findings support the use of anodal Broca’s tDCS for enhancing both expressive and receptive language domains in chronic aphasia. To the best of our knowledge, this study represents the first multimodal neuroimaging (EEG, DTI) study to uncover mechanistic differences between tDCS and behavioral mediated aphasia recovery, and the first to identify a cerebellar white matter marker of language recovery following tDCS. Clinical Trial Registration [[NCT03699930][1]] ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT03699930 ### Funding Statement This study was funded by Ability Central. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Institutional Review Board at Casa Colina Hospital and Centers for Healthcare. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data underlying this article will be shared on reasonable request to the corresponding author. * AQ : Aphasia Quotient AVC : Auditory Verbal Comprehension DTI : Diffusion Tensor Imaging FA : Fractional Anisotropy MD : Mean Diffusivity NWF : Name and Word Finding REP : Repetition SLT : Speech and Language Therapy SOM : Secondary Outcome Measures SS : Spontaneous Speech TSI : Time Since Injury WAB-R : Western Aphasia Battery-Revised [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03699930&atom=%2Fmedrxiv%2Fearly%2F2023%2F02%2F16%2F2023.02.12.23285828.atom