Efficacy and mechanisms underlying MRI-guided high-definition transcranial direct current stimulation for depression among university students: study protocol for a stepped wedge cluster randomized controlled trial

Abstract

Background: In worldwide, the prevalence of depression among university students raises year by year. Although current interventions for depression may be effective, only about one-third experiencing complete response. There is a critical need for more effective, precision, and personalized approaches for depression. High-definition transcranial direct current stimulation (HD-tDCS) shows promise as a potential intervention in depression, yet its optimal stimulation parameters and neural mechanisms remain unclear. In this study, we aim to evaluate the effectiveness of magnetic resonance imaging (MRI)-guided HD-tDCS in depression among university students and explore its neural mechanisms.

Method: In this stepped-wedge cluster randomized controlled trial, all participants will be randomly assigned to four groups. During the intervention, all groups will receive sham stimulation at week 1. With each subsequent week, one group will transition to active intervention. All groups will be receiving active intervention in week 5. Structural MRI data for each participant will be acquired to select the optimal electrode placement and correct for individual anatomical differences. The central anodal electrode will be positioned over the left dorsolateral prefrontal cortex (DLPFC), and four return electrodes will be placed 3.5 cm from the central electrode to form a circular current loop. The HD-tDCS will be delivered at a current intensity of 2 mA for 30 min per day, 5 days per week. Psychological assessment will conduct at week 0 (baseline), 1-5, and 9. MRI measurements will be performed before and after HD-tDCS. The primary outcome measures are changes in the Hamilton Rating Scale for Depression (HAMD) and Patient Health Questionnaire-9 (PHQ-9). Secondary outcomes are severity of anxiety, insomnia, and stress. Furthermore, we will employ functional near-infrared spectroscopy (fNIRS) and MRI to explore the neural mechanisms underlying the effects of HD-tDCS on depression.

Discussion: This study will facilitate the development of precision interventions for depression at an individual level. Multi-modal imaging approaches will provide a deepened insight into the role of MRI-guided HD-tDCS in depression and may ultimately improve intervention strategies among university students.

Trial registration: This study is registered in https://www.chictr.org.cn/ under protocol registration number ChiCTR2400094235 (date of registration: 19. December. 2024). Recruitment will start in March 2025.

Keywords: Depression; Functional Near-Infrared spectroscopy; High-Definition transcranial direct current stimulation; Magnetic resonance imaging; Stepped wedge cluster design; University students.

Fig. 1

Study schedule for the participants in the stepped wedge cluster randomized trial. Study schedule and overview. At the beginning of the study, participants will undergo assessments of psychological and multimodal imaging. Then, they will be randomly assigned to one of four groups. Initially, all groups will receive sham stimulation. With each subsequent week, one group will transition to active intervention. All groups will be receiving active HD-tDCS intervention at week 5. Psychological assessment and functional near-infrared spectroscopy (fNIRS) will be conducted at week 0 (baseline), week 1–5, and week 9 (follow-up in 4 weeks after the intervention). MRI measurements will be performed before and after HD-tDCS. fNIRS: Functional Near-Infrared Spectroscopy; GAD-7: Generalized Anxiety Disorder-7; HAMD: Hamilton Depression Rating Scale; HD-tDCS: High-definition transcranial direct current stimulation. ISI: Insomnia Severity Index; MRI: Magnetic Resonance Imaging; PHQ-9: Patient Health Questionnaire-9; PSS: Perceived Stress Scale

Fig. 2

Flowchart of the study design. All participants will be randomly assigned to four groups, each containing an equal number of individuals. Different intervention arrangement will be implemented across the groups, with assessments conducted on a weekly basis throughout the duration of the intervention

Fig. 3

Flow diagram and time point of the study. Assessments will be conducted on a weekly basis throughout the study. First, all groups will receive sham stimulation. Then, additional groups will transition to active stimulation, with all groups receive active stimulation by the end of the intervention period. fNIRS: Functional Near-Infrared Spectroscopy; HD-tDCS: High-definition transcranial direct current stimulation; MRI: Magnetic Resonance Imaging

Fig. 4

Electrode configuration and HD-tDCS montage. Electrode montage and simulated distribution of the electrical field during 4 × 1 HD-tDCS are based on the standard 10–20 electroencephalography system. The central electrode is depicted by the yellow point, whereas the four return electrodes are shown as blue points. The SimNIBS software will be utilized to model the field intensity and current flow for anodal HD-tDCS. HD-tDCS: High-definition transcranial direct current stimulation

Fig. 5

Functional near-infrared spectroscopy measurement. a fNIRS probe positioning and measurement points. b Schematic of fNIRS channel and optode arrangement. c The paradigm for VFT adopted for fNIRS. Each trial comprised a 30-second pre-task rest period, a 60-second task period (divided into three 20-second blocks), and a 60-second post-task rest period. The pre-task baseline duration is set between 20 and 30 s, while the post-task baseline duration is set between 110 and 115 s. fNIRS: Functional near-infrared spectroscopy; VFT: verbal fluency test