Efficacy of MRI-guided rTMS for post-traumatic stress disorder by modulating amygdala activity: study protocol for a randomised controlled trial.

INTRODUCTION: Post-traumatic stress disorder (PTSD) is a prevalent and severe psychiatric disorder. Repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex provides limited relief for symptoms of PTSD. This study will be conducted to validate the efficacy of MRI-guided rTMS in targeting the sites most closely associated with the amygdala for patients with PTSD. We hypothesise that the intervention will improve clinical symptoms by decreasing amygdala activity in patients. METHODS AND ANALYSIS: A randomised, double-blind, sham-controlled trial will be conducted. Forty-eight eligible patients with PTSD will be randomly assigned to receive either active or sham MRI-guided rTMS for 10 consecutive days after the initial MRI scans. MRI scans will be recollected at the end of the intervention. Clinical assessments will be performed at baseline, treatment day 5, treatment day 10, and 2 weeks, 4 weeks, 8 weeks after completion of the intervention to monitor changes in clinical symptoms. The primary assessment outcome is the change in PTSD symptoms between baseline and treatment day 10, as measured by the PTSD Checklist for DSM-5. Repeated measures analysis of variance will be performed using statistical software SPSS V.26.0. The significance level will be set at 0.05. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Xijing Hospital in Xi'an, China (KY20222176-X-1), and the trial has been registered on ClinicalTrials.gov. The findings of this trial will be disseminated at academic conferences or published in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05544110.

Efficacy of functional magnetic resonance imaging-guided personalized repetitive transcranial magnetic stimulation (fMRI-rTMS) in depressive patients with emotional blunting: study protocol for a randomized controlled trial.

BACKGROUND: Emotional blunting is a symptom that has always been present in depressed patients. Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective supplementary therapy for treating depression. However, the effectiveness and brain imaging processes of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) in the treatment of depression with emotional blunting have not been observed in randomized controlled trials. METHODS: This study is a randomized, controlled, double-blind, and single-center clinical trial in which 80 eligible depressed patients with emotional blunting will be randomly assigned to two groups: a functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) group and a control group. Individuals in the fMRI-rTMS group (n = 40) will receive high-frequency rTMS (10 Hz, 120% MT). The main target of stimulation will be the area most relevant to the functional connectivity of the right medial prefrontal cortex (mPFC) and amygdala. The control group (n = 40) will receive sham stimulation, with a coil flipped to 90 degrees relative to the vertical scalp. All patients will receive 15 consecutive days of treatment, with each session lasting half an hour per day, followed by 8 weeks of follow-up. The primary outcome is the comparison of Oxford Depression Questionnaire (ODQ) scores between these two groups at different time points. The secondary outcomes include evaluating other clinical scales and assessing the differences in brain imaging changes between the two groups before and after treatment. DISCUSSION: This trial aims to examine the effects of functional magnetic resonance imaging-guided personalized rTMS (fMRI-rTMS) intervention on depressed patients experiencing emotional blunting and to elucidate the potential mechanism behind it. The results will provide new evidence for using fMRI-rTMS in treating depression with emotional blunting in the future. TRIAL REGISTRATION: ClinicalTrials.gov INCT05555940. Registered on 13 September 2022 at http://clinicaltrials.gov .

Active versus sham DLPFC-NAc rTMS for depressed adolescents with anhedonia using resting-state functional magnetic resonance imaging (fMRI): a study protocol for a randomized placebo-controlled trial.

BACKGROUND: Anhedonia, which is defined as the inability to feel pleasure, is considered a core symptom of major depressive disorder (MDD). It can lead to several adverse outcomes in adolescents, including heightened disease severity, resistance to antidepressants, recurrence of MDD, and even suicide. Specifically, patients who suffer from anhedonia may exhibit a limited response to selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT). Previous researches have revealed a link between anhedonia and abnormalities within the reward circuitry, making the nucleus accumbens (NAc) a potential target for treatment. However, since the NAc is deep within the brain, repetitive transcranial magnetic stimulation (rTMS) has the potential to modulate this specific region. Recent advances have enabled treatment technology to precisely target the left dorsolateral prefrontal cortex (DLPFC) and modify the functional connectivity (FC) between DLPFC and NAc in adolescent patients with anhedonia. Therefore, we plan to conduct a study to explore the safety and effectiveness of using resting-state functional connectivity magnetic resonance imaging (fcMRI)-guided rTMS to alleviate anhedonia in adolescents diagnosed with MDD. METHODS: The aim of this article is to provide a study protocol for a parallel-group randomized, double-blind, placebo-controlled experiment. The study will involve 88 participants who will be randomly assigned to receive either active rTMS or sham rTMS. The primary object is to measure the percentage change in the severity of anhedonia, using the Snaith-Hamilton Pleasure Scale (SHAPS). The assessment will be conducted from the baseline to 8-week post-treatment period. The secondary outcome includes encompassing fMRI measurements, scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17), the Montgomery Asberg Depression Rating Scale (MADRS), the Chinese Version of Temporal Experience of Pleasure Scale (CV-TEPS), and the Chinese Version of Beck Scale for Suicide Ideation (BSI-CV). The Clinical Global Impression (CGI) scores will also be taken into account, and adverse events will be monitored. These evaluations will be conducted at baseline, as well as at 1, 2, 4, and 8 weeks. DISCUSSION: If the hypothesis of the current study is confirmed, (fcMRI)-guided rTMS could be a powerful tool to alleviate the core symptoms of MDD and provide essential data to explore the mechanism of anhedonia. TRIAL REGISTRATION: ClinicalTrials.gov NCT05544071. Registered on 16 September 2022.