Explore Neural Mechanism of Obsessive-Compulsive Disorder (OCD) by Intervention of Repetitive Transcranial Magnetic Stimulation With Symptom Provocation

The purpose of this study is to investigate the differences in therapeutic efficacy of different deep Transcranial Magnetic Stimulation (deep TMS) treatment coils and different brain stimulation targets on obsessive-compulsive symptoms, and to explore the neural mechanisms of obsessive-compulsive disorder using functional neuroimaging analysis.

1. Inclusion Criteria:

Adults aged 18-65 years. Patients diagnosed with obsessive-compulsive disorder according to DSM-5 criteria. 2. Study Design: Double-blind, randomized assignment. 3. Number of Participants:

Sham group: 32 participants Active H7 group: 32 participants Active H1 group: 32 participants Total: 96 participants 4. Study Procedures:

- Participant Screening and Baseline Assessment (Week 0) Determine eligibility for enrollment, including diagnostic confirmation, symptom assessment, screening for contraindications, and whether the participant has previously experienced adverse effects following TMS treatment. Participants with high suicide risk within the past year will be excluded.

Develop a personalized symptom provocation procedure for obsessive-compulsive symptoms.

Complete baseline symptom severity assessments and brain positron emission tomography/magnetic resonance imaging (PET/MRI). Participants with structural brain abnormalities will be excluded.

Participants will be randomly assigned (1:1:1) into three groups, with a planned total enrollment of 96 participants.

Participants currently taking medication may continue their existing regimen, but no medication changes will be allowed during the study period.

- Treatment Phase (Week 1 to Week 6; duration: 6 weeks) Before each TMS session, participants will remove their shoes and socks, rest both hands flat on their thighs, keep their eyes looking straight ahead, and undergo measurement of resting motor threshold (RMT).

Approximately 3-5 minutes before each TMS session, trained personnel with Exposure and Response Prevention (ERP) experience will assist participants in symptom provocation and record the participant's subjective level of distress.

The deep TMS treatment schedule consists of five sessions per week, one session per day, for six consecutive weeks. Adverse effects will be assessed and monitored at each session.

After completing the first treatment session, participants will be asked to guess which group they were assigned to, in order to evaluate the effect of treatment expectations on outcomes.

Symptom severity interviews will be conducted every two weeks.

- Post-treatment Assessment and Follow-up (Week 7 and after; duration: 2 weeks, then 6 months later) Within one week after completion of the deep TMS treatment course (within Week 7), participants will undergo follow-up brain PET/MRI.

At the end of Week 8 (two weeks after treatment completion), symptom severity will be reassessed. Subsequent treatment plans will be discussed with participants, and outpatient follow-up will be arranged within six months.

Subsequent treatment options may include cognitive behavioral therapy, pharmacotherapy, and figure-8 rTMS. 5. Statistical Analysis

* Expected Outcomes:

The H7 coil may improve obsessive-compulsive symptoms. Both the H7 and H1 coils may improve mood symptoms.

- Descriptive and Inferential Statistics: Analysis of covariance (ANCOVA) will be used to compare differences among the three groups in Montgomery-Asberg Depression Rating Scale (MADRS), Yale-Brown obsessive compulsive scale (Y-BOCS), Hamilton Anxiety Scale (HAM-A), Hamilton Depression Scale (HDRS), and Clinical Global Impression (CGI-S) scores.

The percentage of responders (% responders) will be calculated and compared among groups.

Repeated-measures ANOVA will be used to examine within-group and between-group differences in symptom improvement before and after deep TMS treatment.

Pearson correlation analysis will be used to assess the association between symptom improvement and changes observed in PET/MRI neuroimaging measures.

- PET/MRI Neuroimaging Analysis: Functional MRI analyses will include ROI-to-ROI functional connectivity and seed-based functional connectivity analyses.

Changes in PET glucose uptake within specific regions of interest (ROIs) will also be examined to evaluate alterations in neural networks and brain function before and after deep TMS treatment.