STUDY PROTOCOL article
Front. Psychiatry
Sec. Schizophrenia
This article is part of the Research TopicCognitive impairments in schizophrenia, bipolar disorder, and major depression: Dissecting common and divergent featuresView all 17 articles
Efficacy and mechanisms underlying MRI-guided HD-tDCS combined with aerobic exercise to ameliorate cognitive impairment associated with schizophrenia
Provisionally accepted
Yange Wei
Zengyuan Shen
Peng Luo
Shanyuan HeHanshuo SuRongxun LiuYanran Wu
Juan WangJingdan ZhangGuangjun Ji
Fei Wang
Chuansheng Wang*- Peking University Sixth Hospital, Beijing, China
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Background: The primary treatment for schizophrenia currently relies on medication. Nevertheless, the efficacy of medication for Cognitive Impairment Associated with Schizophrenia (CIAS) is constrained, and it is also accompanied by side effects. Consequently, the investigation of novel non-pharmacological strategies is essential. High-definition transcranial direct current stimulation (HD-tDCS) and aerobic exercise (AE) have emerged as promising approaches for cognitive enhancement in individuals with schizophrenia. This study aims to evaluate the efficacy of integrating HD-tDCS with AE for CIAS and to elucidate the underlying mechanisms of this synergistic intervention. Methods: A randomized, double-blind, controlled trial will be conducted. The CIAS will be randomly allocated to one of four groups: MRI-guided HD-tDCS + AE, MRI-guided HD-tDCS alone, AE alone, and a control group. Structural magnetic resonance imaging (MRI) data will be obtained to determine the optimal electrode placement. The central electrode will be positioned over the medial prefrontal cortex (mPFC). Both HD-tDCS and AE will be administered five times per week over a four-week period, resulting in a total of 20 sessions. The primary outcome measure will be the change in cognitive function, evaluated using the MATRICS Consensus Cognitive Battery. Secondary outcomes will include changes assessed by the Repeatable Battery for the Assessment of Neuropsychological Status and the Wisconsin Card Sorting Test which are designed to evaluate global and executive functions. The Facial Emotion Perception Test and the Voice Emotion Perception Test will be utilized to assess social cognition. The severity of clinical symptoms will be quantified through the Positive and Negative Syndrome Scale and the Brief Psychiatric Rating Scale. This study will incorporate functional near-infrared spectroscopy, MRI, electroencephalography, P300 event-related potential, eye movement examination and plasma brain-derived neurotrophic factor (BDNF) levels to investigate the underlying mechanisms. Assessments will be evaluated at baseline (T0), after 2 weeks (T1), after 4 weeks (T2), and after 6 months (T3). Discussion: The integration of MRI-guided HD-tDCS targeting the mPFC and AE presents an efficacious and individualized treatment strategy for CIAS. This proof-of-concept study may provide a multi-dimensional view of biological mechanisms underlying HD-tDCS combined with AE in precision psychiatry.
Keywords: aerobic exercise, Cognitive Function, high-definition transcranial direct current stimulation, Schizophrenia, study protocol
Received: 09 Nov 2025; Accepted: 21 Jan 2026.
Copyright: © 2026 Wei, Shen, Luo, He, Su, Liu, Wu, Wang, Zhang, Ji, Wang and Wang. 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: Chuansheng Wang
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