The effect of transcranial direct current stimulation combined with working memory training on working memory deficits in schizophrenic patients: study protocol for a randomized controlled trial.

Background: Working memory deficits are one of the core and most characteristic clinical features of cognitive impairment in schizophrenia. Cognitive training can improve the cognitive function of patients with schizophrenia. However, the overall and transfer effects of working memory treatment (WMT) require improvement. Numerous studies have confirmed that transcranial direct current stimulation (tDCS) enhances neuroplasticity in the brain, providing a new treatment approach for cognitive impairment in patients with schizophrenia. We hypothesize that a training mode combining "preheating" (tDCS, which changes the neural activity of working memory-related brain regions) and "ironing" (WMT) affords greater cognitive improvements than WMT alone. In addition, this study aims to examine the mechanisms underlying the superiority of tDCS combined with WMT in improving cognitive function in patients with schizophrenia.

Methods: This study will include 120 patients with schizophrenia aged 18-60 years. The patients will be randomized into four groups: the study group (tDCS + WMT), tDCS group (tDCS + simple response training, SRT), WMT group (sham tDCS + WMT), and control group (sham tDCS + SRT). Patients will receive 20-min, 2 mA sessions of active or sham tDCS twice a day on weekdays for 2 weeks. Each stimulation will be immediately followed by a 1 - 2-min rest and 40 min of WMT or SRT. The primary outcome is cognitive function, measured using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and some subscales of the MATRICS Consensus Cognitive Battery (MCCB). The secondary outcomes are other behavioral measures, variations in brain imaging, and serum levels of brain-derived neurotrophic factor (BDNF). All outcomes will be measured at baseline, post-treatment, and 3-month follow-up, except for brain imaging and BDNF levels, which will be measured at baseline and post-treatment only.

Discussion: If tDCS combined with WMT results in significant improvements and prolonged effects on working memory, this method could be considered as a first-line clinical treatment for schizophrenia. Moreover, these results could provide evidence-based support for the development of other approaches to improve cognitive function in patients with schizophrenia, especially by enhancing WMT effects.

Trial Registration: Chictr.org.cn; ChiCTR2200063844. Registered on September 19, 2022.