STUDY PROTOCOL article
Front. Psychiatry
Sec. Schizophrenia
Augmented Intermittent Theta-Burst Stimulation of the Left Dorsolateral Prefrontal Cortex for Cognitive Dysfunction in Stable-Phase Schizophrenia: Protocol for a Randomized, Double-Blind, Sham-Controlled Trial
Provisionally accepted
Yuke He1Mei Yu1
Hao Wu1Wenzhong Liu1Yang Fan1Wei Xu1Han Deng1Shanshan Long1
Bo Liu2*Kezhi Liu1
Youguo Tan1- 1Southwest Medical University, Luzhou, China
- 2Zigong City Mental Health Center, Zigong, China
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Background: Schizophrenia is a severe mental disorder affecting approximately 1% of the global population, characterized by three core symptom domains: positive symptoms, negative symptoms, and cognitive dysfunction. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising intervention for both positive and negative symptoms in schizophrenia. However, its therapeutic potential for cognitive dysfunction remains inconclusive. Methods: This randomized, double-blind, sham-controlled trial will enroll 70 medication-stable patients meeting DSM-5 criteria for schizophrenia. Participants will be randomly allocated (1:1) to receive either active or sham augmented intermittent theta-burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC). The treatment protocol consists of 600 pulses per session, three sessions per day, for 10 consecutive weekdays. Clinical symptoms will be evaluated with the Positive and Negative Syndrome Scale (PANSS), cognitive function will be assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and neural activity will be measured via functional near-infrared spectroscopy (fNIRS) during a semantic verbal fluency task. All patients will be assessed at baseline and post-intervention. Ethics and dissemination: The trial protocol complies with the principles of the Declaration of Helsinki and has been approved by the Ethics Committee of Zigong Mental Health Center (approval number: 20250802). The findings of this trial will be published and made publicly accessible in a peer-reviewed journal. Discussion: This study aims to provide strong evidence supporting the therapeutic potential of augmented iTBS for improving cognitive functioning in schizophrenia, offering a potential new treatment option for patients with schizophrenia. Trial registration: Chinese Clinical Trials Register, ChiCTR2500107943. Registered on 21 August 2025, https://www.chictr.org.cn/index.html.
Keywords: cognitive dysfunction, DLPFC, functionalnear-infrared spectroscopy, iTBS, rTMS, Schizophrenia
Received: 22 Oct 2025; Accepted: 05 Dec 2025.
Copyright: © 2025 He, Yu, Wu, Liu, Fan, Xu, Deng, Long, Liu, Liu and Tan. 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: Bo Liu
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