ORIGINAL RESEARCH article
Front. Rehabil. Sci.
Sec. Rehabilitation in Neurological Conditions
Volume 6 - 2025 | doi: 10.3389/fresc.2025.1589588
Dual-Target tDCS and Dual-Task Training Modulate Neuroinflammation and Neuroplasticity: Transcriptomic and Behavioral Evidence in Stroke Rehabilitation
Provisionally accepted
- The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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Background: Transcranial direct current stimulation (tDCS) combined with dual-task training (DTT) has shown potential in promoting neurorehabilitation. However, the transcriptomic mechanisms underlying the synergistic effects of dual-target tDCS remain unexplored. This study aims to evaluate the effects of tDCS+DTT on cognitive and motor functions and preliminarily explore its molecular basis through transcriptomic analysis. Methods: Fifty two chronic stroke patients were randomized to receive dual-target tDCS (anodal electrodes over affected primary motor cortex M1 and left dorsolateral prefrontal cortex DLPFC) combined with DTT (n=26) or sham stimulation with DTT (n=26). Behavioral assessments, including the Visual Cognitive Assessment Test (VCAT), Hamilton Depression Scale (HAMD), Fugl-Meyer Lower Limb Assessment (FMA-L), Timed Up and Go Test (TUG), and Modified Barthel Index (MBI), were conducted before and after the intervention. Peripheral blood transcriptomic analysis was performed on a subset of patients from the tDCS+DTT group to identify differentially expressed genes (DEGs) and enriched pathways. Results: Significant interactions were observed for VCAT (p < 0.001), MBI (p = 0.033), HAMD (p < 0.001), FM-L (p < 0.001), TUG-CMDT time (p < 0.001), and TUG-CMDT accuracy rate (p < 0.001). Transcriptomic analysis revealed 1,319 DEGs post-treatment, predominantly downregulating inflammation/apoptosis-related genes (1,155) and upregulating neuroplasticityassociated genes (164). KEGG pathway analysis highlighted suppressed NF-κB signaling and apoptosis pathways, alongside enhanced synaptic plasticity mechanisms. Key regulatory genes, such as PPP1R15A, BCL3, GADD45B, and NFKBIA, were identified as potential mediators of 2 tDCS-induced neuroprotection. Conclusion: Dual-target tDCS combined with DTT promotes functional recovery in stroke patients through transcriptomic reprogramming of inflammatory and neuroplastic pathways, offering a novel strategy for multi-modal neurorehabilitation.
Keywords: tDCS, Dual-task training, Neurorehabilitation, Transcriptomics, Inflammation, neuroplasticity
Received: 07 Mar 2025; Accepted: 26 Sep 2025.
Copyright: © 2025 Fu, Yan, Wang, Zhang, Wang and Liqing. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yutong Fu, 906363326@qq.com
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