Transcranial direct current stimulation over the left inferior frontal gyrus improves sentence comprehension

Background The left inferior frontal gyrus (IFG) has been shown to be involved in sentence comprehension in many studies through its involvement in both semantic and syntactic computations. However, causal evidence for its involvement in sentence comprehension is scarce. We used transcranial direct current stimulation (tDCS) to test the causal involvement of the left IFG in sentence comprehension in a group of individuals with primary progressive aphasia (PPA). These individuals participated in a tDCS study targeting lexical retrieval only, not sentence comprehension, therefore in the present study we report on far-transfer effects of tDCS in sentence comprehension. Objective We sought to determine whether tDCS over the left inferior frontal gyrus (IFG) coupled with lexical retrieval treatment may improve sentence comprehension in PPA. Method Within a sham-controlled, double-blind design, we tested whether 15 daily sessions of anodal tDCS over the left IFG may improve sentence comprehension in 27 people with PPA, and whether the tDCS effects were sustained up to two months post-treatment. Results We found that immediately post-treatment, and up to 2-months post-treatment, there was significantly larger improvement of sentence comprehension in the tDCS condition compared to sham. There were, however, differential effects of tDCS in each PPA variant and sentence-type. Importantly, participants with the epicenter of atrophy over the stimulated area (non-fluent PPA) benefited most from tDCS. Conclusion TDCS over the left IFG induces far-transfer effects and may improve sentence comprehension in PPA. We provide causal evidence that left IFG is a critical area for sentence comprehension. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT02606422 ### Funding Statement This work was supported by grants from the Science of Learning Institute at Johns Hopkins University and by the National Institutes of Health (National Institute of Deafness and Communication Disorders) through award R01 DC014475 to Dr. Kyrana Tsapkini. ### 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: All participants provided informed consent to participate in the clinical trial (ClinicalTrials.gov Identifier: [NCT02606422][1]), in compliance with the Johns Hopkins Hospital Institutional Review Board. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. 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 Data sharing agreement: We will make the data and associated documentation available to users only under a data-sharing agreement that provides for: (1) a commitment to using the data only for research purposes and not to identify any individual participant; (2) a commitment to securing the data using appropriate computer technology; (3) proper acknowledgment of data source; and (4) a commitment to destroying or returning the data after analyses are completed. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02606422&atom=%2Fmedrxiv%2Fearly%2F2020%2F09%2F10%2F2020.09.08.20190744.atom