{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:34:41Z","timestamp":1760060081460,"version":"build-2065373602"},"reference-count":28,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T00:00:00Z","timestamp":1754179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Foundation for Science and Technology","award":["UID\/01662"],"award-info":[{"award-number":["UID\/01662"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Transcranial direct current stimulation (tDCS) has emerged as a promising neuromodulatory tool for language rehabilitation in chronic aphasia. However, the effects of bi-hemispheric, multisite stimulation remain largely unexplored, especially in people with chronic and treatment-resistant language impairments. The goal of this study is to look at the effects on behavior and brain activity of an individualized language training program that combines bi-hemispheric multisite anodal tDCS with personalized language training for Albert, a patient with long-standing, treatment-resistant non-fluent aphasia. Methods: Albert, a right-handed retired physician, had transcortical motor aphasia (TCMA) subsequent to a left-hemispheric ischemic stroke occurring more than six years before the operation. Even after years of traditional treatment, his expressive and receptive language deficits remained severe and persistent despite multiple rounds of traditional therapy. He had 15 sessions of bi-hemispheric multisite anodal tDCS aimed at bilateral dorsal language streams, administered simultaneously with language training customized to address his particular phonological and syntactic deficiencies. Psycholinguistic evaluations were performed at baseline, immediately following the intervention, and at 1, 2, 3, and 6 months post-intervention. Resting-state fMRI was conducted at baseline and following the intervention to evaluate alterations in functional connectivity (FC). Results: We noted statistically significant enhancements in auditory sentence comprehension and oral reading, particularly at the 1- and 3-month follow-ups. Neuroimaging showed decreased functional connectivity (FC) in the left inferior frontal and precentral regions (dorsal stream) and in maladaptive right superior temporal regions, alongside increased FC in left superior temporal areas (ventral stream). This pattern suggests that language networks may be reorganizing in a more efficient way. There was no significant improvement in phonological processing, which may indicate reduced connectivity in the left inferior frontal areas. Conclusions: This case underscores the potential of combining individualized, network-targeted language training with bi-hemispheric multisite tDCS to enhance recovery in chronic, treatment-resistant aphasia. The convergence of behavioral gains and neuroplasticity highlights the importance of precision neuromodulation approaches. However, findings are preliminary and warrant further validation through controlled studies to establish broader efficacy and sustainability of outcomes.<\/jats:p>","DOI":"10.3390\/jpm15080352","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T15:30:06Z","timestamp":1754321406000},"page":"352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Personalized Language Training and Bi-Hemispheric tDCS Improve Language Connectivity in Chronic Aphasia: A fMRI Case Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1759-5146","authenticated-orcid":false,"given":"Sandra","family":"Carvalho","sequence":"first","affiliation":[{"name":"Psychological Neuroscience Laboratory, Centro de Investiga\u00e7\u00e3o em Psicologia (CIPsi), Department of Basic Psychology, School of Psychology, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9497-0707","authenticated-orcid":false,"given":"Augusto J.","family":"Mendes","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroimaging of Aging (LANVIE), University of Geneva, 1205 Geneva, Switzerland;<email>augusto.martinsmendes@unige.ch<\/email>"},{"name":"Geneva Memory Center, Department of Rehabilitation and Geriatrics, Geneva University Hospitals, 1205 Geneva, Switzerland"}]},{"given":"Jos\u00e9 Miguel","family":"Soares","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal"}]},{"given":"Adriana","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Psychological Neuroscience Laboratory, Centro de Investiga\u00e7\u00e3o em Psicologia (CIPsi), Department of Basic Psychology, School of Psychology, University of Minho, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0323-9012","authenticated-orcid":false,"given":"Jorge","family":"Leite","sequence":"additional","affiliation":[{"name":"RISE-Health, CINTESIS.UPT, Portucalense University, Rua Dr. Ant\u00f3nio Bernardino de Almeida, 541, 4200-072 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1162\/nol_a_00025","article-title":"Neuroplasticity in post-stroke aphasia: A systematic review and meta-analysis of functional imaging studies of reorganization of language processing","volume":"2","author":"Wilson","year":"2021","journal-title":"Neurobiol. Lang. (Camb.)"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Nasios, G., Dardiotis, E., and Messinis, L. (2019). From Broca and Wernicke to the Neuromodulation Era: Insights of Brain Language Networks for Neurorehabilitation. Behav. Neurol., 9894571.","DOI":"10.1155\/2019\/9894571"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3109\/17549507.2010.520090","article-title":"Delivering for aphasia","volume":"13","author":"Code","year":"2011","journal-title":"Int. J. Speech Lang. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1093\/brain\/awac129","article-title":"Recovery from aphasia in the first year after stroke","volume":"146","author":"Wilson","year":"2023","journal-title":"Brain"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1212\/WNL.0b013e31821a44c1","article-title":"Are networks for residual language function and recovery consistent across aphasic patients?","volume":"76","author":"Turkeltaub","year":"2011","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Barbati, S.A., Podda, M.V., and Grassi, C. (2022). Tuning brain networks: The emerging role of transcranial direct current stimulation on structural plasticity. Front. Cell Neurosci., 16.","DOI":"10.3389\/fncel.2022.945777"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105459","DOI":"10.1016\/j.bandl.2024.105459","article-title":"Transcranial direct stimulatiojpm-15-00352-revision-r1-2n over left inferior frontal gyrus improves language production and comprehension in post-stroke aphasia: A double-blind randomized controlled study","volume":"257","author":"Zheng","year":"2024","journal-title":"Brain Lang."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.rehab.2019.01.003","article-title":"Transcranial direct current stimulation in post-stroke aphasia rehabilitation: A systematic review","volume":"62","author":"Biou","year":"2019","journal-title":"Ann. Phys. Rehabil. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/ijnp\/pyaa051","article-title":"Evidence-Based Guidelines and Secondary Meta-Analysis for the Use of Transcranial Direct Current Stimulation in Neurological and Psychiatric Disorders","volume":"24","author":"Fregni","year":"2021","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yoon, M.J., Park, H.J., Yoo, Y.J., Oh, H.M., Im, S., Kim, T.W., and Lim, S.H. (2024). Electric field simulation and appropriate electrode positioning for optimized transcranial direct current stimulation of stroke patients: An in Silico model. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-52874-y"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.12786\/bn.2024.17.e21","article-title":"The Optimized Transcranial Direct Current Stimulation With Simulation Using MRI","volume":"17","author":"Yoon","year":"2024","journal-title":"Brain Neurorehabil."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bandl.2011.05.002","article-title":"Cathodal transcranial direct current stimulation of the right Wernicke\u2019s area improves comprehension in subacute stroke patients","volume":"119","author":"You","year":"2011","journal-title":"Brain Lang."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1080\/13554794.2024.2349327","article-title":"Functional neuroimaging and behavioral correlates of multisite tDCS as an add-on to language training in a person with post-stroke non-fluent aphasia: A year-long case study","volume":"30","author":"Mendes","year":"2024","journal-title":"Neurocase"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.bandl.2019.01.001","article-title":"Roles of ventral versus dorsal pathways in language production: An awake language mapping study","volume":"191","author":"Ries","year":"2019","journal-title":"Brain Lang."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2105646118","DOI":"10.1073\/pnas.2105646118","article-title":"The neural architecture of language: Integrative modeling converges on predictive processing","volume":"118","author":"Schrimpf","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","unstructured":"Castro, S.L., Cal\u00f3, S., and Gomes, I. (2007). PALPA: Provas de Avalia\u00e7\u00e3o da Linguagem e da Afasia, Cegoc-Tea."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1037\/0022-006X.59.1.12","article-title":"Clinical significance: A statistical approach to defining meaningful change in psychotherapy research","volume":"59","author":"Jacobson","year":"1991","journal-title":"J. Consult. Clin. Psychol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.3758\/s13428-016-0767-4","article-title":"The Minho Word Pool: Norms for imageability, concreteness, and subjective frequency for 3,800 Portuguese words","volume":"49","author":"Soares","year":"2017","journal-title":"Behav. Res. Methods"},{"key":"ref_19","unstructured":"Correa, N., Adali, T., Li, Y.O., and Calhoun, V.D. (2005, January 18\u201323). Comparison of blind source separation algorithms for FMRI using a new MATLAB toolbox: GIFT. Proceedings of the ICASSP\u201905, IEEE International Conference on Acoustics, Speech, and Signal Processing\u2014Proceedings, Philadelphia, PA, USA."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1093\/cercor\/bhr099","article-title":"Decoding subject-driven cognitive states with whole-brain connectivity patterns","volume":"22","author":"Shirer","year":"2012","journal-title":"Cereb. Cortex"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neulet.2015.01.045","article-title":"Effects of transcranial direct current stimulation on naming and cortical excitability in stroke patients with aphasia","volume":"589","author":"Wu","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Godoi, D.C., Pandi\u00e1, E., Rodrigues, M.E., Ara\u00fajo, L., Barbosa, M., Alhwaishel, K., Godoi, A., and McGonigle, D.J. (2025). Linguistic effects of transcranial Direct Current Stimulation (tDCS) in patients with primary progressive aphasia: A systematic review and meta-analysis of randomised controlled trials. Neurosci. Biobehav. Rev., 176.","DOI":"10.1016\/j.neubiorev.2025.106264"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lomi, F., Simonelli, I., Cappa, S., Pasqualetti, P., and Rossi, S. (2025). Noninvasive Brain Stimulation in Primary Progressive Aphasia with and Without Concomitant Speech and Language Therapy: Systematic Review and Meta-analysis. Neuropsychol. Rev., in press.","DOI":"10.1007\/s11065-025-09659-5"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e17144","DOI":"10.7717\/peerj.17144","article-title":"Tailoring transcranial alternating current stimulation based on endogenous event-related P3 to modulate premature responses: A feasibility study","volume":"12","author":"Mendes","year":"2024","journal-title":"PeerJ"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1044\/1058-0360(2008\/025)","article-title":"Principles of motor learning in treatment of motor speech disorders","volume":"17","author":"Maas","year":"2008","journal-title":"Am. J. Speech Lang. Pathol."},{"key":"ref_26","first-page":"CD000425","article-title":"Speech and language therapy for aphasia following stroke","volume":"2016","author":"Brady","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_27","unstructured":"REhabilitation and recovery of peopLE with Aphasia after StrokE (RELEASE) Collaborators (2022). Dosage, Intensity, and Frequency of Language Therapy for Aphasia: A Systematic Review-Based, Individual Participant Data Network Meta-Analysis. Stroke, 53, 956\u2013967."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Zhang, L., Lin, B., Huang, Y., Wang, M., Ni, J., Song, J., and Huang, J. (2024). Speech and Language Therapy Plus Electroacupuncture or Non-Invasive Brain Stimulation for Post-Stroke Aphasia: A Systematic Review and Network Meta-Analysis. Neurorehabilit. Neural Repair, in press.","DOI":"10.1177\/10538135241312600"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/8\/352\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:22:18Z","timestamp":1760034138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/15\/8\/352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,3]]},"references-count":28,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["jpm15080352"],"URL":"https:\/\/doi.org\/10.3390\/jpm15080352","relation":{},"ISSN":["2075-4426"],"issn-type":[{"type":"electronic","value":"2075-4426"}],"subject":[],"published":{"date-parts":[[2025,8,3]]}}}