Stage-Specific Multimodal Imaging–Guided Non-Invasive BrainStimulation for Post-Stroke Aphasia: A Structured Narrative Review

Liting Chen; Zhenye Luo; Xiaoling Wu; Wenying Chen; Xiaole Fan

doi:10.71321/sxgrxh75

Authors

Liting Chen Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
Zhenye Luo Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
Xiaoling Wu Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China
Wenying Chen Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, China
Xiaole Fan Department of Ultrasound, The First Affiliated Hospital of Jinan University, Guangzhou 510000, China

DOI:

https://doi.org/10.71321/sxgrxh75

Keywords:

Non-invasive brain stimulation, Post-stroke aphasia, Functional magnetic resonance imaging

Abstract

Non-invasive brain stimulation (NIBS) modalities—including transcranial magnetic stimulation (TMS), theta-burst stimulation (TBS), and transcranial direct current stimulation (tDCS)—have emerged as promising approaches to promote language recovery in post-stroke aphasia by engaging both functional and structural neuroplasticity. This structured narrative review integrates recent multimodal evidence from functional magnetic resonance imaging (fMRI), DTI, and connectome analyses to delineate the stage-dependent mechanisms underlying NIBS-induced modulation of language networks. Findings across studies suggest a dynamic pattern of reorganization: acute-phase hypoactivation of left-hemisphere language areas and diffuse right-hemisphere disinhibition give way to bilateral upregulation in the subacute phase, followed by gradual restoration of left-dominant connectivity during the chronic stage, which may be limited by persistent contralesional hyperactivity. Low-frequency TMS or continuous TBS targeting right-hemisphere homologues can suppress maladaptive overcompensation, whereas high-frequency TMS or intermittent TBS applied to residual left-hemisphere sites enhances excitability and network centrality. Bilateral or neuronavigation-guided tDCS, particularly when combined with language training, rebalances interhemispheric excitability and supports sustained gains in naming and fluency. DTI-derived increases in arcuate and uncinate fasciculi integrity correlate with clinical improvement, while contralesional temporoparietal cortical thickening reflects concurrent structural remodeling.

References

[1] Jane B. Allendorfer, Judd M. Storrs, and Jerzy P. Szaflarski. 2012. Changes in white matter integrity follow excitatory rTMS treatment of post-stroke aphasia. Restorative neurology and neuroscience 30, 2: 103–113. https://doi.org/10.3233/RNN-2011-0627

[2] Guangtao Bai, Liang Jiang, Qi Li, and Peiju Qiu. 2025. Study on intermittent theta burst stimulation improves expression function and mechanism in patients with aphasia after stroke. The Neurologist 30, 4: 204–211. https://doi.org/10.1097/NRL.0000000000000622

[3] Zhongfei Bai, Jiaqi Zhang, and Kenneth N. K. Fong. 2022. Effects of transcranial magnetic stimulation in modulating cortical excitability in patients with stroke: a systematic review and meta-analysis. Journal of NeuroEngineering and Rehabilitation 19, 1: 24. https://doi.org/10.1186/s12984-022-00999-4

[4] M. Bikson, Abhishek Datta, Asif Rahman, and Jen Scaturro. 2010. Electrode montages for tDCS and weak transcranial electrical stimulation: role of “return” electrode’s position and size. Clinical Neurophysiology 121, 12: 1976–1978. https://doi.org/10.1016/j.clinph.2010.05.020

[5] L.J. Boddington and J.N.J. Reynolds. 2017. Targeting interhemispheric inhibition with neuromodulation to enhance stroke rehabilitation. Brain Stimulation 10, 2: 214–222. https://doi.org/10.1016/j.brs.2017.01.006

[6] Won Kee Chang, Jihong Park, Ji-Young Lee, Sungmin Cho, Jongseung Lee, Won-Seok Kim, and Nam-Jong Paik. 2022. Functional network changes after high-frequency rTMS over the most activated speech-related area combined with speech therapy in chronic stroke with non-fluent aphasia. Frontiers in Neurology 13: 690048. https://doi.org/10.3389/fneur.2022.690048

[7] Jing Cheng, Yijing Jiang, Ting Rao, Yihan Yang, Yanping Liu, Ying Zhan, and Shanli Yang. 2024. Repetitive transcranial magnetic stimulation for post-stroke non-fluent aphasia: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Neurology 15: 1348695. https://doi.org/10.3389/fneur.2024.1348695

[8] Leora R. Cherney, Edna M. Babbitt, Xue Wang, and Laura L. Pitts. 2021. Extended fMRI-Guided Anodal and Cathodal Transcranial Direct Current Stimulation Targeting Perilesional Areas in Post-Stroke Aphasia: A Pilot Randomized Clinical Trial. Brain sciences 11, 3. https://doi.org/10.3390/brainsci11030306

[9] Bruce Crosson, Amy D Rodriguez, David Copland, Julius Fridriksson, Lisa C Krishnamurthy, Marcus Meinzer, Anastasia M Raymer, Venkatagiri Krishnamurthy, and Alexander P Leff. 2019. Neuroplasticity and aphasia treatments: new approaches for an old problem. Journal of Neurology, Neurosurgery and Psychiatry 90, 10: 1147–1155. https://doi.org/10.1136/jnnp-2018-319649

[10] Robert Darkow, Andrew Martin, Anna Würtz, Agnes Flöel, and Marcus Meinzer. 2017. Transcranial direct current stimulation effects on neural processing in post-stroke aphasia. Human brain mapping 38, 3: 1518–1531. https://doi.org/10.1002/hbm.23469

[11] Andrew T. DeMarco, Elizabeth Dvorak, Elizabeth Lacey, Catherine J. Stoodley, and Peter E. Turkeltaub. 2021. An exploratory study of cerebellar transcranial direct current stimulation in individuals with chronic stroke aphasia. Cognitive and Behavioral Neurology 34, 2: 96–106. https://doi.org/10.1097/WNN.0000000000000270

[12] Bernhard Elsner (ed.). 2013. Transcranial direct current stimulation (tDCS) for improving function and activities of daily living in patients after stroke. In Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, Chichester, UK. https://doi.org/10.1002/14651858.cd009645.pub2

[13] Sarah Feil, Peter Eisenhut, Frauke Strakeljahn, Sarah Müller, Claude Nauer, Jens Bansi, Stefan Weber, Alexandra Liebs, Jean-Pascal Lefaucheur, Jürg Kesselring, Roman Gonzenbach, and Veit Mylius. 2019. Left shifting of language related activity induced by bihemispheric tDCS in postacute aphasia following stroke. Frontiers in Neuroscience 13: 295. https://doi.org/10.3389/fnins.2019.00295

[14] Zi-Jian Feng, Xin-Ping Deng, Na Zhao, Jing Jin, Juan Yue, Yun-Song Hu, Ying Jing, Hong-Xiao Wang, Thomas R Knösche, Yu-Feng Zang, and Jue Wang. 2022. Resting-state fMRI functional connectivity strength predicts local activity change in the dorsal cingulate cortex: a multi-target focused rTMS study. Cerebral Cortex 32, 13: 2773–2784. https://doi.org/10.1093/cercor/bhab380

[15] Agnes Flöel. 2014. tDCS-enhanced motor and cognitive function in neurological diseases. Neuroimage 85: 934–947. https://doi.org/10.1016/j.neuroimage.2013.05.098

[16] Julius Fridriksson, Jessica D. Richardson, Julie M. Baker, and Chris Rorden. 2011. Transcranial direct current stimulation improves naming reaction time in fluent aphasia: a double-blind, sham-controlled study. Stroke 42, 3: 819–821. https://doi.org/10.1161/STROKEAHA.110.600288

[17] Ivor B. Gartside. 1968. Mechanisms of sustained increases of firing rate of neurones in the rat cerebral cortex after polarization: role of protein synthesis. Nature 220, 5165: 383–384. https://doi.org/10.1038/220383a0

[18] Roy H. Hamilton, Linda Sanders, Jennifer Benson, Olufunsho Faseyitan, Catherine Norise, Margaret Naeser, Paula Martin, and H. Branch Coslett. 2010. Stimulating conversation: enhancement of elicited propositional speech in a patient with chronic non-fluent aphasia following transcranial magnetic stimulation. Brain and Language 113, 1: 45–50. https://doi.org/10.1016/j.bandl.2010.01.001

[19] Yue Han, Yuanyuan Jing, Yanmin Shi, Hongbin Mo, Yafei Wan, Hongwei Zhou, and Fang Deng. 2024. The role of language-related functional brain regions and white matter tracts in network plasticity of post-stroke aphasia. Journal of Neurology 271, 6: 3095–3115. https://doi.org/10.1007/s00415-024-12358-5

[20] Takatoshi Hara and Masahiro Abo. 2021. New treatment strategy using repetitive transcranial magnetic stimulation for post-stroke aphasia. Diagnostics 11, 10: 1853. https://doi.org/10.3390/diagnostics11101853

[21] Denise Y. Harvey, Joely A. Mass, Priyanka P. Shah-Basak, Rachel Wurzman, Olufunsho Faseyitan, Daniela L. Sacchetti, Laura DeLoretta, and Roy H. Hamilton. 2019. Continuous theta burst stimulation over right pars triangularis facilitates naming abilities in chronic post-stroke aphasia by enhancing phonological access. Brain and language 192: 25–34. https://doi.org/10.1016/j.bandl.2019.02.005

[22] Denise Y. Harvey, Jamie Podell, Peter E. Turkeltaub, Olufunsho Faseyitan, H. Branch Coslett, and Roy H. Hamilton. 2017. Functional Reorganization of Right Prefrontal Cortex Underlies Sustained Naming Improvements in Chronic Aphasia via Repetitive Transcranial Magnetic Stimulation. Cognitive and Behavioral Neurology: Official Journal of the Society for Behavioral and Cognitive Neurology 30, 4: 133–144. https://doi.org/10.1097/WNN.0000000000000141

[23] W.-D. Heiss and A. Thiel. 2006. A proposed regional hierarchy in recovery of post-stroke aphasia. Brain and language 98, 1: 118–123. https://doi.org/10.1016/j.bandl.2006.02.002

[24] Tingting Jiang, Xiupan Wei, Mingzhu Wang, Jiang Xu, Nan Xia, and Min Lu. 2024. Theta burst stimulation: what role does it play in stroke rehabilitation? A systematic review of the existing evidence. BMC Neurology 24, 1: 52. https://doi.org/10.1186/s12883-023-03492-0

[25] Zafer Keser, Rajani Sebastian, Khader M. Hasan, and Argye E. Hillis. 2020. Right hemispheric homologous language pathways negatively predicts poststroke naming recovery. Stroke 51, 3: 1002–1005. https://doi.org/10.1161/STROKEAHA.119.028293

[26] Swathi Kiran and Cynthia K. Thompson. 2019. Neuroplasticity of language networks in aphasia: advances, updates, and future challenges. Frontiers in Neurology 10. https://doi.org/10.3389/fneur.2019.00295

[27] Trevor A. Low, Kevin Lindland, Adam Kirton, Helen L. Carlson, Ashley D. Harris, Bradley G. Goodyear, Oury Monchi, Michael D. Hill, Miranda L. Rose, and Sean P. Dukelow. 2025. Transcranial magnetic stimulation combined with multimodality aphasia therapy for chronic poststroke aphasia: a randomized clinical trial. Neurology 104, 6: e213424. https://doi.org/10.1212/WNL.0000000000213424

[28] Paola Marangolo, Valentina Fiori, Umberto Sabatini, Giada De Pasquale, Carmela Razzano, Carlo Caltagirone, and Tommaso Gili. 2016. Bilateral transcranial direct current stimulation language treatment enhances functional connectivity in the left hemisphere: preliminary data from aphasia. Journal of Cognitive Neuroscience 28, 5: 724–738. https://doi.org/10.1162/jocn_a_00927

[29] Jared Medina, Catherine Norise, Olufunsho Faseyitan, H. Branch Coslett, Peter E. Turkeltaub, and Roy H. Hamilton. 2012. Finding the right words: transcranial magnetic stimulation improves discourse productivity in non-fluent aphasia after stroke. Aphasiology 26, 9: 1153–1168. https://doi.org/10.1080/02687038.2012.710316

[30] Marcus Meinzer, Robert Darkow, Robert Lindenberg, and Agnes Flöel. 2016. Electrical stimulation of the motor cortex enhances treatment outcome in post-stroke aphasia. Brain : a journal of neurology 139, Pt 4: 1152–1163. https://doi.org/10.1093/brain/aww002

[31] Alina Menichelli, Giovanni Furlanis, Arianna Sartori, Mariana Ridolfi, Marcello Naccarato, Paola Caruso, Valentina Pesavento, and Paolo Manganotti. 2019. Thrombolysis’ benefits on early post-stroke language recovery in aphasia patients. Journal of Clinical Neuroscience 70: 92–95. https://doi.org/10.1016/j.jocn.2019.08.064

[32] Alessia Monti, Roberta Ferrucci, Manuela Fumagalli, Francesca Mameli, Filippo Cogiamanian, Gianluca Ardolino, and Alberto Priori. 2013. Transcranial direct current stimulation (tDCS) and language. Journal of neurology, neurosurgery, and psychiatry 84, 8: 832–842. https://doi.org/10.1136/jnnp-2012-302825

[33] Jianxun Ren, Weijing Ren, Ying Zhou, Louisa Dahmani, Xinyu Duan, Xiaoxuan Fu, Yezhe Wang, Ruiqi Pan, Jingdu Zhao, Ping Zhang, Bo Wang, Weiyong Yu, Zhenbo Chen, Xin Zhang, Jian Sun, Mengying Ding, Jianting Huang, Liu Xu, Shiyi Li, Weiwei Wang, Wuxiang Xie, Hao Zhang, and Hesheng Liu. 2023. Personalized functional imaging-guided rTMS on the superior frontal gyrus for post-stroke aphasia: a randomized sham-controlled trial. Brain Stimulation 16, 5: 1313–1321. https://doi.org/10.1016/j.brs.2023.08.023

[34] Dorothee Saur, Rüdiger Lange, Annette Baumgaertner, Valeska Schraknepper, Klaus Willmes, Michel Rijntjes, and Cornelius Weiller. 2006. Dynamics of language reorganization after stroke. Brain : a journal of neurology 129, Pt 6: 1371–1384. https://doi.org/10.1093/brain/awl090

[35] Shannon M. Sheppard and Rajani Sebastian. 2021. Diagnosing and managing post-stroke aphasia. Expert Review of Neurotherapeutics 21, 2: 221–234. https://doi.org/10.1080/14737175.2020.1855976

[36] Laura M. Skipper-Kallal, Elizabeth H. Lacey, Shihui Xing, and Peter E. Turkeltaub. 2017. Right hemisphere remapping of naming functions depends on lesion size and location in poststroke aphasia. Neural Plasticity 2017: 1–17. https://doi.org/10.1155/2017/8740353

[37] Radwa K. Soliman, Chantal M. W. Tax, Noha Abo-Elfetoh, Ahmed A. Karim, Ayda Youssef, Doaa Kamal, and Eman M. Khedr. 2021. Effects of tDCS on Language Recovery in Post-Stroke Aphasia: A Pilot Study Investigating Clinical Parameters and White Matter Change with Diffusion Imaging. Brain sciences 11, 10. https://doi.org/10.3390/brainsci11101277

[38] Nico Sollmann and Petro Julkunen. 2022. Modern developments in transcranial magnetic stimulation: the editorial. Brain Sciences 12, 5: 628. https://doi.org/10.3390/brainsci12050628

[39] Ethan A. Solomon, Michael R. Sperling, Ashwini D. Sharan, Paul A. Wanda, Deborah F. Levy, Anastasia Lyalenko, Isaac Pedisich, Daniel S. Rizzuto, and Michael J. Kahana. 2021. Theta-burst stimulation entrains frequency-specific oscillatory responses. Brain Stimulation 14, 5: 1271–1284. https://doi.org/10.1016/j.brs.2021.08.014

[40] Shihui Xing, Elizabeth H. Lacey, Laura M. Skipper-Kallal, Xiong Jiang, Michelle L. Harris-Love, Jinsheng Zeng, and Peter E. Turkeltaub. 2016. Right hemisphere grey matter structure and language outcomes in chronic left hemisphere stroke. Brain : a journal of neurology 139, Pt 1: 227–241. https://doi.org/10.1093/brain/awv323

[41] Shuo Xu, Qing Yang, Mengye Chen, Panmo Deng, Ren Zhuang, Zengchun Sun, Chong Li, Zhijie Yan, Yongli Zhang, and Jie Jia. 2021. Capturing Neuroplastic Changes after iTBS in Patients with Post-Stroke Aphasia: A Pilot fMRI Study. Brain sciences 11, 11. https://doi.org/10.3390/brainsci11111451

[42] Zhijie Yan, Shuo Xu, Dongshuai Wei, Xinyuan He, Chong Li, Yongli Zhang, Mengye Chen, Jingna Zhang, Xiaofang Li, Qing Yang, and Jie Jia. 2022. Comparison of three cognitive assessment methods in post-stroke aphasia patients. Frontiers in Psychology 13. https://doi.org/10.3389/fpsyg.2022.896095

[43] Woo-Kyoung Yoo, Marine Vernet, Jung-Hoon Kim, Anna-Katharine Brem, Shahid Bashir, Fritz Ifert-Miller, Chang-Hwan Im, Mark Eldaief, and Alvaro Pascual-Leone. 2020. Interhemispheric and Intrahemispheric Connectivity From the Left Pars Opercularis Within the Language Network Is Modulated by Transcranial Stimulation in Healthy Subjects. Frontiers in Human Neuroscience 14: 63. https://doi.org/10.3389/fnhum.2020.00063

[44] Juan Yue, Na Zhao, Yang Qiao, Zi‐Jian Feng, Yun‐Song Hu, Qiu Ge, Tian‐Qing Zhang, Zhu‐Qian Zhang, Jue Wang, and Yu‐Feng Zang. 2023. Higher reliability and validity of WAVELET‐ALFF of resting‐state FMRI : from multicenter database and application to RTMS modulation. Human Brain Mapping 44, 3: 1105–1117. https://doi.org/10.1002/hbm.26144

[45] Yuheng Zeng, Zujuan Ye, Wanxin Zheng, and Jue Wang. 2024. Efficacy of cerebellar transcranial magnetic stimulation for post-stroke balance and limb motor function impairments: meta-analyses of random controlled trials and resting-state fMRI studies. Cerebellum 23, 4: 1678–1696. https://doi.org/10.1007/s12311-024-01660-7

[46] Marina Zettin, Caterina Bondesan, Giulia Nada, Matteo Varini, and Danilo Dimitri. 2021. Transcranial Direct-Current Stimulation and Behavioral Training, a Promising Tool for a Tailor-Made Post-stroke Aphasia Rehabilitation: A Review. Frontiers in human neuroscience 15: 742136. https://doi.org/10.3389/fnhum.2021.742136

[47] Yi Zhao, Bronte Ficek, Kimberly Webster, Constantine Frangakis, Brian Caffo, Argye E. Hillis, Andreia Faria, and Kyrana Tsapkini. 2021. White matter integrity predicts electrical stimulation (tDCS) and language therapy effects in primary progressive aphasia. Neurorehabilitation and Neural Repair 35, 1: 44–57. https://doi.org/10.1177/1545968320971741

[48] Kai Zheng, Xinlei Xu, Yingying Ji, Hui Fang, Fanglan Gao, Guilan Huang, Bin Su, Li Bian, Guofu Zhang, and Caili Ren. 2023. Continuous theta burst stimulation-induced suppression of the right fronto-thalamic-cerebellar circuit accompanies improvement in language performance in poststroke aphasia: A resting-state fMRI study. Frontiers in Aging Neuroscience 14: 1079023. https://doi.org/10.3389/fnagi.2022.1079023

[49] Zhong Sheng Zheng, Jing Wang, Sharon Lee, Kevin Xing-Long Wang, Ben Zhang, Melissa Howard, Emily Rosario, and Caroline Schnakers. 2025. Cerebellar transcranial direct current stimulation improves quality of life in individuals with chronic poststroke aphasia. Scientific Reports 15, 1: 6898. https://doi.org/10.1038/s41598-025-90927-y

[50] Bingbing Zhou, Jiajia Qi, Kangjia Chen, Hong Li, Jiahui Liu, Qian Zhou, Zujuan Ye, and Jue Wang. 2025. Localizing Function-specific Targets for Transcranial Magnetic Stimulation in the Absence of Navigation Equipment. Journal of Visualized Experiments, 219: 67888. https://doi.org/10.3791/67888

[51] Wenwen Cheng, Yufeng Li, Bin Cheng, Ying Chen, Zhiwen Chen, Liyan Cui, et al. Effects of transcranial direct current stimulation over the right hemisphere on naming ability in patients with poststroke aphasia: a meta-analysis. Journal of Neurolinguistics 58: 100986. https://doi.org/10.1016/j.jneuroling.2021.100986