A Study on the Efficacy and Safety of Accelerated Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder and Its Underlying Neurological Mechanisms
Phase: NA
Conditions: Obsessive Compulsive Disorder (OCD), Obsessive - Compulsive Disorder
Sponsor: Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University

1
Research Proposal
Title: A Study on the Efficacy and Safety of Accelerated Transcranial
Magnetic Stimulation for Obsessive-Compulsive Disorder and Its
Underlying Neurological Mechanisms
Principal Investigator: Yi-jie Zhao
Protocol Number: 2.0
Protocol Version/Date: 2.0/17 June 2025
I.
Research Background
Obsessive-Compulsive Disorder (OCD) is a refractory psychiatric disorder primarily
characterised by obsessive thoughts (persistent rumination or doubt concerning an
event) and/or compulsive behaviours (repetitive actions, often undertaken to
repeatedly verify a particular matter). Its lifetime prevalence ranges from 0.8% to
2.5%1. The primary treatment approaches for OCD are pharmacotherapy and
cognitive behavioural therapy, though their efficacy rates remain approximately 40%–
65%. Physical therapies constitute secondary treatment options.
Among these, invasive physical therapies primarily involve anterior capsulotomy and
deep brain stimulation. Deep brain stimulation (DBS) is a neurosurgical intervention
involving electrode implantation at specific brain locations to deliver therapeutic
electrical pulses. The ventral capsule/ventral striatum (VC/VS), subthalamic nucleus,
and nucleus accumbens are currently common DBS targets for OCD, effectively
alleviating symptoms in patients with severe, treatment-resistant OCD. Multiple
randomised controlled trials targeting VC/VS demonstrate approximately 76%
response rates in treatment-resistant OCD patients2,3. However, the surgical risks and

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financial burden render this approach inaccessible for most individuals. Consequently,
non-invasive neuromodulation offers greater universal applicability.
The US Food and Drug Administration (FDA) has approved the H7 coil for deep
transcranial magnetic stimulation (dTMS) targeting the medial prefrontal
cortex/anterior cingulate cortex for OCD treatment. Following treatment, the response
rate (defined as a 30% or greater reduction in symptom severity) among 42 patients
receiving active stimulation was 38%, rising to 45% at the one-month follow-up4,5,6.
Evidently, existing targets and treatment protocols for rTMS in OCD remain
suboptimal.
The inferior frontal cortex (IFC) is closely associated with OCD's characteristic
functions of response inhibition, conflict resolution, and uncertainty processing.
Research indicates that cognitive behavioural therapy (CBT) can alter IFC volume.
This study aims to explore the efficacy of repetitive transcranial magnetic stimulation
(rTMS) using novel, individualized IFC targeting combined with symptom-induction
techniques.
Reference
1
Hirschtritt, M. E., Bloch, M. H. & Mathews, C. A. Obsessive-Compulsive Disorder:
Advances in Diagnosis and Treatment. Jama 317, 1358-1367, doi:10.1001/jama.2017.2200
(2017).
2
Sinai, A. et al. Focused Ultrasound Thalamotomy in Tremor Dominant Parkinson's
Disease: Long-Term Results. J Parkinsons Dis 12, 199-206, doi:10.3233/JPD-212810 (2022).
3
Yamamoto, K. et al. Focused Ultrasound Thalamotomy for Tremor-dominant
Parkinson's Disease: A Prospective 1-year Follow-up Study. Neurol Med Chir (Tokyo) 61,
414-421, doi:10.2176/nmc.oa.2020-0370 (2021).
4
Grant, J. E. Clinical practice: Obsessive-compulsive disorder. N Engl J Med 371,
646-653, doi:10.1056/NEJMcp1402176 (2014).

3
5
Banks, G. P., Heilbronner, S. R., Goodman, W. & Sheth, S. A. A population-
normalized tractographic fiber atlas of the anterior limb of the internal capsule: relevance to
surgical neuromodulation. J Neurosurg 137, 1278-1288, doi:10.3171/2022.1.JNS211935
(2022).
6
Bonelli, R. M. & Cummings, J. L. Frontal-subcortical circuitry and behavior.
Dialogues Clin Neurosci 9, 141-151, doi:10.31887/DCNS.2007.9.2/rbonelli (2007).
II.
Research Objectives and Anticipated Outcomes
(1) To validate the efficacy of 20Hz rTMS targeting the right IFC in treating
treatment-resistant obsessive-compulsive disorder (OCD);
(2) To investigate whether provocation techniques for obsessive symptoms can
enhance treatment efficacy;
(3) To explore the effects of transcranial magnetic stimulation on cognitive function
in OCD patients and its potential physiological mechanisms.
III.
Research Content and Methods
3.1 Overall Study Design and Plan
This study constitutes an open-label, prospective, single-centre investigation.
The intervention employs 20Hz repetitive transcranial magnetic stimulation (rTMS)
targeting the right inferior frontal cortex (rIFC). To shorten the treatment cycle,
reduce dropout rates, and ensure efficacy, the study will employ the following design:
six stimulation sessions per day for five consecutive days, totalling 30 therapeutic
stimulation sessions. Magnetic resonance imaging (MRI) scans, cognitive function
assessments, and symptom evaluations will be conducted before and after the
intervention. Symptom follow-up assessments will occur at two weeks post-treatment,
with both symptom and cognitive function follow-ups at four weeks post-treatment.
Symptom assessments will be completed by psychiatrists (psychiatrists/psychologists),
while the intervention will be administered by trained research assistants.
The study aims to investigate the cognitive regulatory effects of non-invasive
interventions. Participants will undergo tailored cognitive assessments based on

4
individual clinical profiles, with all tasks completed via computer using keyboard or
mouse input. These tasks primarily evaluate working memory whilst also assessing
attention, learning and memory, executive control, reasoning ability, risk decision-
making, affective decision-making, and emotional awareness. Additionally,
neuroimaging techniques will be employed to investigate the neural mechanisms
underlying cognitive function in OCD patients. Participants will undergo task-related
functional magnetic resonance imaging (fMRI) before and after electrical stimulation,
performing a series of cognitive tasks related to executive function and affective
decision-making during scanning. This will enable comparison of rTMS intervention
effects on cognitive function and associated imaging mechanisms.
Data to be recorded for the study include:
Behavioural data: Task-specific behavioural metrics such as accuracy rates and
reaction times.
Magnetic resonance imaging data: Acquisition sequences encompass structural
imaging, task-state imaging, resting-state imaging, and diffusion tensor imaging.
3.2 Case Numbers and Grouping Methodology
The study anticipates enrolling 20 subjects with obsessive-compulsive disorder
(OCD), all of whom will be assigned to the intervention group for treatment. This is
an exploratory clinical study conducted as an open-label trial.
Sample size calculation was performed using G-Power 3.1 with the following
parameters:
Effect size d: 1.0
Significance level α: 0.05 (two-tailed)
Power (1-β): 0.95
The calculated minimum sample size required is approximately 16. Considering a
20% clinical attrition rate, 20 participants are planned for enrolment.

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IV.
Inclusion and Exclusion Criteria
4.1 Inclusion Criteria
1)
Volunteer subjects with Obsessive Compulsive Disorders (OCD) according to
the Diagnostic and Statistical Manual of Mental Disorders (DSM V) criteria;
2)
Age 18–60 years, right-handed;
3)
Disease severity: Yale-Brown Obsessive Compulsive Scale score ≥16 for OCD
patients;
4)
Medication stable for at least 4 weeks;
5)
Resistant patients to standard treatments: partial but insufficient response
(reduction of Y-BOCS score < 35%) or lack of response to previous well conducted
treatment including: optimal tolerated dose and adequate duration (> 12 weeks) of at
least 2 Serotonin Reuptake Inhibitors (selective serotonin reuptake inhibitors,
clomipramine), or 1 Serotonin Reuptake Inhibitors + 1 augmentation strategy
(adjunction of an antipsychotic - such as risperidone or olanzapine or aripiprazole - or
lithium or buspirone)
6)
No systematic rTMS therapy in the past six months;
7)
Signature of informed consent form;
8)
Normal vision or corrected vision;
9)
Capacity to complete protocol-specified tests.
4.2 Exclusion Criteria
1)
Abnormal cognitive status (assessed using MoCA with score <24);
2)
Other primary diagnosis than OCD (comorbid mild depression is tolerated)
3)
Comorbid diagnosis of schizophrenia/ psychotic disorder, bipolar disorder,
substance abuse or dependance3)
4)
Significant self-harm intent or severe suicidal tendencies within the past year;

6
5)
Irreversible visual or auditory impairment preventing completion of scales or
related assessments;
6)
Presence of metallic implants, such as pacemakers or stents;
7)
Any current or potential medical, psychological, social, or geographical factors
compromising patient safety or study participation;
8)
Poor compliance;
9)
Claustrophobia;
10)
History of epilepsy or familial epilepsy
11)
Pregnant or lactating women (women of childbearing potential must obtain a
negative pregnancy test result prior to study commencement and employ medically
approved contraceptive measures);
12)
Deterioration or failure of vital organ function (cardiac, pulmonary, hepatic,
renal, etc.); or unstable vital signs;
13)
Conditions unsuitable for this stimulation site, such as increased intracranial
pressure, elevated intraocular pressure, or glaucoma
14)
History of or concomitant neurological disorders: cerebrovascular disease,
central nervous system infections, Creutzfeldt-Jakob disease, Huntington's disease
and Parkinson's disease, Lewy body dementia, traumatic brain injury dementia, other
physical/chemical factors (drugs, alcohol, CO, etc.), significant somatic diseases
(hepatic encephalopathy, pulmonary encephalopathy, etc.), intracranial space-
occupying lesions (subdural haematoma, brain tumours), endocrine system disorders
(thyroid disease, parathyroid disease), and dementia caused by vitamin deficiency or
any other cause
V.
Endpoints
5.1 Primary Endpoint

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Obsessive-compulsive symptom severity: Yale-Brown Obsessive Compulsive Scale
(Y-BOCS)
5.2 Secondary Endpoints
Clinical Global Impression Scale (CGI)
Depressive Symptom Severity: Hamilton Depression Rating Scale (HAMD-17 items)
Anxiety Symptom Severity: Hamilton Anxiety Rating Scale (HAMA-14 items)
Impulse Control Scale (UPPS-P)
Short-Form Parenting Behaviour Questionnaire (s-EMBU-C)
5.3 Safety Endpoints
Severity of Clinical Symptoms
5.4 Exploratory Endpoints
Beck Depression Inventory (BDI)
Chinese Version State-Trait Anxiety Inventory (STAI-S, STAI-T)
Chinese Version of the Obsessive-Compulsive Inventory (Revised) (OCI-R)
Intolerance of Uncertainty Scale (IUS-12)
Intolerance of Uncertainty Questionnaire (IUI-A, IUI-B)
Stress Perception Scale
Snaith-Hamilton Pleasure Scale (SHAPS)
Aphasia Evaluation Scale (Self-Report Version) (AES-S)
Physiological Data: Imaging and EEG require signal-to-noise ratios within acceptable
ranges. Excessive head motion and motion artefacts may compromise data quality.
Data significantly affected (e.g., imaging head motion impacting image clarity,
electrophysiological artefacts exceeding 20% of data) will be excluded.
Cognitive Behavioural Data.

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All behavioural data exceeding three standard deviations above or below the mean
will be excluded to prevent statistical bias.
VI.
Adverse Event Collection and Reporting
6.1 Definition of Adverse Events
Adverse Event (AE): An undesirable medical occurrence in a patient or clinical trial
subject following treatment, not necessarily causally related to the treatment. An
adverse event may therefore be an undesirable and unexpected sign, symptom, or
time-related condition associated with use, irrespective of causality to the treatment.
Serious Adverse Event (SAE):
1)
Resulting in death;
2)
Resulting in a serious deterioration in the subject's health:
a)
Life-threatening illness or injury, or
b)
Permanent impairment of a bodily structure or bodily function, or
c)
Hospitalisation or prolongation of hospitalisation, or
d)
Medical or surgical intervention to avert a life-threatening illness or injury, or to
prevent permanent impairment of a bodily structure or bodily function
e)
Fetal distress, foetal death, congenital malformation, or birth defect
Note: Hospitalisation previously planned for the current medical condition or steps
required by the clinical study protocol, without significant deterioration in health,
shall not be considered a serious adverse event.
When completing the adverse event form, the investigator shall use mild, moderate, or
severe to describe the intensity of the adverse event. To standardise criteria, the
grading of event intensity is as follows:
Mild: Subjective discomfort not requiring symptomatic treatment or intervention
suspension. Examples include mild headache, fatigue, slight itching or tingling at the

9
stimulation site, photopsia, or minor facial muscle twitching. Such events cease upon
intervention cessation.
Moderate: Subjective discomfort requiring intervention suspension but not special
symptomatic treatment, as such adverse events cease shortly after intervention
cessation. Examples include severe headache, significant stinging sensation or muscle
twitching at the stimulation site, and other adverse events reported as intolerable.
Severe: Risk of disability or death requiring emergency treatment and immediate
intervention cessation. Examples include epileptic seizures.
6.2 Recording and Reporting of Adverse Events
Adverse events occurring during clinical research must be reported by research
personnel to the clinical research sponsor and the principal investigator's institution
within 24 hours of becoming aware of the event. For mild or moderate adverse events,
the study physician may document the event in detail and report it to the principal
investigator within three days, provided the event has been adequately resolved and
the subject's condition has improved and recovered. For serious adverse events, the
investigator shall notify within 24 hours of becoming aware of the event and
immediately complete an adverse event form, documenting the time of occurrence,
severity, duration, measures taken, and outcome.
For any SAE occurring during the clinical trial (regardless of whether related to the
trial or investigational device), the investigator shall immediately provide appropriate
treatment to the subject while completing an SAE report form and submitting a
written report to the principal investigator. The SAE must also be recorded in the AE
report section of the Case Report Form (CRF).
The Principal Investigator shall submit a written report to the relevant Ethics
Committee within 24 hours of receiving the SAE report form. For any fatality, the
investigator shall provide all required documentation to both the Ethics Committee
and the sponsor.
Adverse events (AEs) in this study specifically refer to any unfavourable medical
events occurring in clinical research subjects during the intervention period, which
need not necessarily have a causal relationship with the treatment. To ensure the

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completeness of safety data collection, all adverse events occurring during the study
must be recorded on the CRF, including those occurring during treatment and during
the protocol-specified period after treatment. This encompasses all AEs not yet
present prior to the initial visit and all AEs that recur or worsen after the initial visit.
Subjects may report AEs spontaneously. When documenting AEs, the investigator
should use comprehensive diagnostic or standard medical terminology to describe
symptoms, rather than recording individual signs or symptoms. The CRF and source
documentation must be consistent. Any discrepancies between lay language in subject
records (e.g., subject diaries) and corresponding medical terminology should be
clarified in the source documentation.
AEs should be followed up until resolution, stabilisation, or when the investigator
deems them no longer clinically significant, or until loss to follow-up. For a subject
where an AE persists at the end of the study, follow-up should continue until
resolution, stabilisation, or when the investigator deems it no longer clinically
significant, or until loss to follow-up. If follow-up is not conducted, the investigator
must provide justification. Follow-up shall typically continue for 30 days after the
subject ceases intervention treatment. Where necessary, the investigator may be
requested to conduct examinations to obtain supplementary measurements and/or
assessments.
6.3 Risks and Adverse Reactions
To date, among tens of thousands of subjects globally who have undergone
transcranial magnetic stimulation, no cases of permanent brain damage attributable to
its use have been reported. However, a small proportion of subjects may experience
mild headaches and fatigue during stimulation; mild tingling or itching may occur at
the stimulation site; and depending on the stimulation location, photopsia or facial
muscle twitching may also occur. These symptoms can be managed by adjusting
stimulation parameters and are transient adverse reactions, resolving upon cessation
of stimulation.
Beyond mild headaches, safety considerations for TMS encompass other factors
documented in the literature. For instance, epileptic seizures may occur, typically in
individuals with pre-existing brain disorders, those using medications that lower the

11
seizure threshold, or those with a history of alcohol abuse. Therefore, in addition to
screening criteria requiring the absence of any neurological or psychiatric conditions
and no family history of epilepsy, this study will also exclude any individuals at risk
of seizure induction due to epilepsy medications or alcohol consumption, thereby
minimising the likelihood of epileptic seizures.
The transcranial magnetic stimulation apparatus currently in our possession allows for
parameter adjustment, fully conforming to the aforementioned specifications and
constituting a highly safe device. Professional medical personnel will be present
throughout the stimulation period. Should any participant experience a seizure during
transcranial magnetic stimulation, we shall implement the following procedures:
1)
Disconnect the power supply to the transcranial magnetic stimulator and
immediately remove the stimulation coil from the participant's head.
2) Medical personnel will administer emergency treatment.
3)
Family members will be notified.
4)
Staff will accompany the subject to the nearest medical facility.
5)
Medical expenses will be advanced by trial personnel and covered by the
research organisation.
6)
Referral to another hospital will be determined based on clinical necessity.
VII. Withdrawal Criteria
Subjects may withdraw from the study at any time for any reason. Investigators may
withdraw subjects from the study at any time for any reason. If any medical condition
or circumstance arises that renders continued participation in the study not in the
subject's best interests, the research subject may withdraw from the study. Withdrawal
from the study shall not prejudice any benefit to the subject. Following termination,
no further data collection shall be conducted from the subject. Reasons for
termination or withdrawal shall be documented on the Case Report Form (CRF).
Reasons for study termination include, but are not limited to:

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1)
Death of the subject.
2)
Loss to follow-up.
3)
Refusal by the subject to receive further treatment and/or follow-up,
accompanied by withdrawal of informed consent.
4)
Investigator termination of the subject's participation.
5)
Adverse events (e.g., occurrence of intolerable adverse events or adverse event
treatment necessitating withdrawal).
6)
Serious protocol deviation.
7)
Subject meeting exclusion criteria (newly emerging or confirmed).
Management of withdrawn subjects:
1) All original data for withdrawn subjects shall be retained. If withdrawal occurs
due to reason 2, the investigator shall endeavour to contact the subject via multiple
channels (e.g., telephone, text message) to ascertain the reason, conducting at least
three attempts at follow-up and re-enrolment.
2) The timing and reason for trial discontinuation shall be documented in detail on
the CRF.
3) For subjects withdrawing due to reason 5, adverse events must be appropriately
managed, with follow-up continuing until the adverse event (AE) is resolved or
stabilised.
VIII. Data Management
This project will utilise Case Report Forms (CRFs) for data recording. The CRF cover
page shall display the clinical trial name, study site, subject name abbreviation and
code, study start and end dates, and date of each interview to facilitate collation and
organisation. The initial interview shall cover: demographic characteristics (pinyin
initials, gender, age, ethnicity, etc.), general disease status (diagnosis, duration, etc.),
past medical history, prior treatments (medication names, duration, dosage, etc.),

13
physical examination, and vital signs. Interviews shall occur during the baseline
period, treatment completion period, and follow-up period. The CRF shall include
clinical scales required by the study, to be assessed by a clinician. Except during the
baseline period, each assessment requires recording the occurrence of adverse events
on the case report form. If present, the adverse event report form must be completed
in detail. Upon completion of the case report form, the investigator must enter the data
into the study computer. Magnetic resonance imaging data and cognitive task data are
stored on the study computer, named using the subject identification number and
interview period, and saved in a specific format. Data entered into the computer may
not be modified by any person during the study period.
This study protocol and data shall be accessible only to medical and statistical experts
involved in this trial, participating investigators, and other trial personnel, as well as
relevant institutions such as the healthcare facility conducting the trial and the ethics
committee. Participants' personal information shall be strictly confidential, with data
stored in encrypted computers using participant identification numbers. Data transfer
shall be conducted by researchers via encrypted portable hard drives.
Findings from this project may be published in medical journals. Patient information
shall remain confidential in accordance with legal requirements and shall not be
disclosed unless mandated by relevant legislation. Where necessary, governmental
regulatory bodies, hospital ethics committees, and their authorised personnel may
access patient records as prescribed.
IX.
Statistical Analysis
9.1 Definition and Selection of Statistical Analysis Datasets
All statistical tests shall employ two-tailed procedures, with p < 0.05 indicating
statistically significant differences.
Quantitative indicators shall be described by calculating mean, standard deviation,
maximum, minimum, and median values. Categorical indicators shall be described by
case numbers and percentages within each category. All data processing shall be
conducted using SPSS professional statistical software.

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Comparisons between groups for general characteristics were analysed using
appropriate methods according to indicator type. Inter-group comparisons for
quantitative data employed paired t-tests (assuming equal variance and normal
distribution) or Wilcoxon signed-rank tests based on data distribution; intra-group
comparisons used paired t-tests (assuming normal distribution) or Wilcoxon signed-
rank tests. Categorical data will be analysed using chi-square tests or exact probability
methods (where chi-square is inappropriate); ordinal data will be analysed using
Wilcoxon signed-rank tests or Cochran-Mantel-Haenzel (CMH) tests.
9.2 Statistical Analysis of Research Data
Magnetic resonance data will be analysed using the SPM toolkit based on MATLAB.
Electrophysiological data will be analysed using the fieldtrip toolkit based on
MATLAB. Behavioural data will be analysed using MATLAB. Statistical methods
will be selected according to research hypotheses and experimental requirements.
Statistical software utilised will include MATLAB and SPSS. The primary focus of
the study is to compare changes in brain activity (magnetic resonance,
electrophysiological) and behaviourally measured cognitive alterations before and
after transcranial magnetic stimulation or electrical stimulation.
X.
Conflict of Interest
There are no relevant conflicts of interest for this study.
XI.
Privacy and Confidentiality
This study will implement stringent privacy protection policies. All information
pertaining to this project and its collaborations will be securely safeguarded. No
personally identifiable information concerning participants will be disclosed to any
external parties under any circumstances. Even if study results are published,
participants' personal details will remain confidential.

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Participants retain the right to access their personal information and the final research
findings. Personal data will be protected throughout all stages of collection, storage,
and application (including analysis and comparison).
PI's Signature:
Date:

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Informed Consent Form
Title：A Study on the Efficacy and Safety of Accelerated Transcranial Magnetic Stimulation for
Obsessive-Compulsive Disorder and Its Underlying Neurological Mechanisms
Research Institution: Shanghai Pudong New Area Mental Health Centre
Protocol Number/Version: 2.0
Informed Consent Form Version/Date: 2.0/17 June 2025
Principal Investigator: Yi-jie Zhao
You have been invited to participate in a study investigating the neural mechanisms in the brains
of patients with obsessive-compulsive disorder undergoing a novel transcranial magnetic
stimulation treatment protocol. This research is supported by the Pudong New Area Mental Health
Centre. Please read this informed consent form carefully and consider your decision to participate
in this study. Participation is entirely voluntary. As a subject, you must provide written consent
before joining the clinical trial. Should any part of the informed consent form be unclear during
discussion with your study doctor or researcher, you may ask them to explain it to you. We
encourage you to discuss your decision to participate thoroughly with your family and friends
before making a choice. You have the right to decline participation in this study or withdraw at
any time without penalty or loss of rights. Should you be participating in another study, please
inform your study doctor or researcher. The background, purpose, procedures, and other important
information regarding this study are as follows:
I. Research Background
Obsessive-Compulsive Disorder (OCD) is a refractory psychiatric disorder primarily
characterised by obsessive thoughts (persistent rumination or doubt concerning an
event) and/or compulsive behaviours
(repetitive actions
often
undertaken
to
repeatedly verify a particular matter), with a lifetime prevalence of 0.8%–2.5%.
First-line treatments for OCD comprise pharmacotherapy and cognitive behavioural
therapy, yet their efficacy rates remain approximately 40%–65%. Physical therapies
constitute second-line interventions, with invasive approaches primarily involving
anterior insular lobotomy and deep brain stimulation. Deep brain stimulation involves
neurosurgical implantation of electrodes into specific brain locations to deliver
therapeutic electrical pulses. However, for most patients, the associated surgical risks
and financial burden render this approach prohibitive. Consequently, non-invasive

2 / 8
neuromodulation protocols offer greater accessibility.
The US Food and Drug Administration (FDA) has approved the H7 coil of deep
transcranial magnetic stimulation (TMS) for treating OCD by stimulating the medial
prefrontal cortex/anterior cingulate cortex. Following treatment, the response rate
(defined as a 30% or greater reduction in symptoms) among 42 patients receiving
active stimulation was 38%, rising to 45% at the one-month follow-up. Evidently,
existing targets and treatment protocols for TMS in OCD remain suboptimal. The
inferior frontal cortex (IFC) is closely associated with OCD's characteristic functions
of response inhibition, conflict resolution, and uncertainty processing. Research
indicates that cognitive behavioural therapy (CBT) can alter IFC volume. This study
aims to explore the efficacy of repetitive transcranial magnetic stimulation (rTMS)
using
a
novel,
individualised
IFC
target
combined
with
symptom-induction
techniques.
II. Study Objectives
The primary objective is to validate the efficacy of 20Hz rTMS targeting the right
inferior frontal cortex (rIFC) in alleviating OCD symptoms. Additionally, the study
aims to investigate rTMS's effects on brain and cognitive functions, elucidating
underlying neural mechanisms to provide evidence-based support for its clinical
application in neurological and psychiatric disorders.
III. Research Process
1. How many individuals will participate in this study?
It is anticipated that 20 participants will be recruited for this study.
The study will recruit individuals aged 18–60 years with a primary diagnosis of
obsessive-compulsive disorder who have not previously undergone any physical
therapy. To ensure safety, the following individuals will be excluded: pregnant or
breastfeeding women; those with a personal or family history of epilepsy; individuals
with a history of or concomitant neurological disorders; those experiencing increased
intracranial pressure, elevated intraocular pressure, or glaucoma; individuals with
comorbid psychiatric disorders; and those exhibiting abnormal cognitive status.
2.
Study Procedures
You will undergo baseline data collection, transcranial electrical stimulation
intervention, and post-treatment assessment. During the baseline phase, you will

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complete
clinical
symptom
evaluations,
cognitive
function
assessments,
electroencephalogram (EEG) recordings, and magnetic resonance imaging (MRI)
scans. Clinical symptom assessment comprises self-report questionnaires and
clinician evaluations. Cognitive function assessments will be conducted on tablets and
computers, requiring you to complete a series of tasks following verbal instructions.
During
MRI
scanning,
you
must
remove
all
metallic
accessories,
wear
noise-cancelling earplugs, and lie on the MRI scanner bed for head imaging. Please
keep your head as still as possible throughout the scan. Researchers will communicate
with you via microphone for two-way voice interaction during the procedure. Should
you require assistance or experience discomfort, please communicate with the
researcher by pressing the alarm ball. During functional MRI, you will be asked to
press buttons as instructed to complete a series of cognitive tasks.
Subsequently, you will undergo five consecutive days of transcranial magnetic
stimulation (TMS) intervention. Prior to stimulation, the researcher will elicit your
symptoms using visual stimuli. This process may cause discomfort; however, for the
intervention's efficacy, we kindly request your patience. During the intervention, you
will be required to remove all hair accessories and sit in the chair. The researcher will
administer stimulation according to the predefined protocol. Please endeavour to keep
your head still throughout the stimulation. Should you experience any discomfort
during the stimulation, you may immediately inform the researcher. Transcranial
magnetic stimulation must be conducted consecutively for five days, with six
repetitions per day. Each stimulation session lasts three minutes, with intervals of at
least one hour between sessions.
A rest area equipped with tables, chairs, and a television will be provided adjacent to
the treatment room for your use during waiting periods.
Following the intervention, you will undergo clinical symptom assessment, cognitive
function evaluation, electroencephalogram (EEG) recording, and magnetic resonance
imaging (MRI) scans, mirroring the pre-intervention protocol. An online follow-up
will be conducted at 2 weeks, with a further assessment of clinical symptoms and

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cognitive function at 4 weeks. Additional online follow-ups will be scheduled at 3 and
6 months post-treatment completion.
3. Trial Duration
The overall study is planned to last three years. For your individual participation, the
study comprises a baseline period, treatment intervention period, and post-treatment
follow-up phase. During baseline data collection, clinical symptom assessment takes
approximately 30 minutes, cognitive function assessment approximately 1 hour, and
brain MRI scanning approximately 2 hours, totalling about 3.5 hours. The treatment
intervention period requires five consecutive days, with six daily sessions. Each
stimulation session lasts three minutes, with intervals of at least one hour between
sessions, equating to approximately six hours per day. Post-treatment assessments
comprise a one-hour cognitive function evaluation and a 70-minute MRI scan. The
two-week follow-up will be conducted online, while the four-week follow-up mirrors
the post-treatment assessment format.
IV. Risks and Benefits
1. What are the risks of participating in this study?
To date, among tens of thousands of participants worldwide who have undergone
transcranial magnetic stimulation, no cases of permanent brain damage resulting from
its use have been reported. However, a small proportion of subjects may experience
mild headaches and fatigue during stimulation. A slight tingling sensation or mild
itching may occur at the stimulation site. Depending on the location of stimulation,
photopsia (flashes of light) or facial muscle twitching may also occur. These
symptoms can be managed by adjusting stimulation parameters and are transient
adverse reactions that resolve upon cessation of stimulation.
Beyond mild headaches, safety considerations for TMS include other factors
documented in the literature. For instance, the risk of epileptic seizures typically
arises in individuals with pre-existing brain disorders, those using medications that
lower the seizure threshold, or those with a history of alcohol abuse. Therefore,

5 / 8
alongside screening criteria excluding neurological or psychiatric conditions and
familial epilepsy history, this study will also exclude individuals at risk of seizure
induction due to antiepileptic medication or alcohol use to minimise this possibility.
Our current TMS equipment allows full parameter adjustment, fully complying with
the above specifications and representing a highly safe device. Throughout
stimulation, professional medical personnel will be present at all times. Should any
participant experience an epileptic seizure during transcranial magnetic stimulation,
we will implement the following procedures:
1)
Immediately disconnect the power supply to the transcranial magnetic
stimulator and remove the stimulation coil from the participant's head.
2)
Medical personnel will administer emergency treatment.
3)
Notify family members.
4)
Escort the subject to the nearest medical facility.
5)
Study personnel will cover initial medical expenses, with the research team
assuming full treatment costs.
6)
Determine referral to another hospital based on clinical necessity.
2. What benefits does participation offer?
This study cannot guarantee direct, definitive medical benefits. While transcranial
magnetic stimulation may alleviate symptoms, efficacy varies significantly between
individuals.
Participation provides complimentary comprehensive brain MRI scans and cognitive
function assessments. Study physicians will offer free consultations regarding your
condition and clinical symptoms during follow-up visits.
This research investigates the underlying neurological mechanisms of the disease and
potential treatment approaches. We hope insights gained from your participation may
benefit you or others with similar conditions in the future.

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V. Alternative Treatment Options
This study will not affect your existing treatment regimen.
VI. Use of Research Findings and Confidentiality of Personal Information
With your understanding and that of other participants, findings from this research
project may be published in authoritative scientific journals. However, we shall
maintain the confidentiality of your research records in accordance with legal
requirements.
Personal
information
of
research
participants
will
be
strictly
confidential and shall not be disclosed unless required by relevant legislation. Where
necessary, government regulatory bodies, hospital ethics committees, and other
relevant researchers may access your records as prescribed.
VII. Research Costs and Related Compensation
1. Medications/devices and associated examination fees
All costs incurred by this study will be covered. Routine treatments and examinations
for any concurrent conditions will not be included in this complimentary provision.
2. Compensation for study participation
Reimbursement will be provided for travel expenses incurred due to study
participation (receipts required).
VIII. Rights of Participants and Relevant Considerations
1. Your Rights
Your participation throughout this study is entirely voluntary. Should you decide not
to participate, this will not affect other treatments you are entitled to receive. Should
you choose to participate, you will be asked to sign this written informed consent
form. You retain the right to withdraw from the trial at any stage without facing
discrimination or unfair treatment, and your corresponding medical care and rights
will remain unaffected.
2. Precautions

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As a participant, you must provide truthful information regarding your medical
history and current physical condition; inform the study physician of any discomfort
experienced during the study period and any medications currently taken; individuals
with a history of epilepsy, familial epilepsy, metallic implants, or claustrophobia are
ineligible for this study and should inform the physician in advance.
IX. Contact Information for Accessing Study Information
Should any significant new information arise during the study that may affect your
willingness to continue participation, your doctor will notify you promptly. If you
wish to access your research data or learn about the study's findings after its
conclusion, you may raise any questions regarding this research at any time and
receive appropriate responses. Please contact Zhao Yijie at 021-68306699 ext. 1311.
This study has been reviewed and approved by the Ethics Committee. Should you
have any concerns regarding your rights or interests, wish to report difficulties,
dissatisfaction, or anxieties encountered during participation, or wish to provide
feedback or suggestions concerning this study, please contact the Ethics Committee of
Shanghai Pudong New Area Mental Health Centre via email: pdjw_ec@shspdjw.com.
You have ample time to consider whether to participate in the study and sign the
informed consent form.
Each participant will be assigned a unique identification number and a file will
be created. All your information will be used solely for this research. Your test content
and personal details will be kept strictly confidential. Researchers are prohibited from
discussing your test content or personal circumstances with anyone outside the study.
Any research findings published will not disclose any of your personal information.

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Informed Consent Form - Signature Page
I have read this informed consent form.
I have had the opportunity to ask questions and all questions have been answered.
I understand that participation in this study is voluntary.
I may choose not to participate in this study, or withdraw at any time by
informing the researcher, without facing discrimination or reprisal, and my medical
care and rights will not be affected as a result.
I will receive a signed copy of this informed consent form.
Name of Participant: __________________________________
Signature of Participant: __________________________________
Date: __________________________________
I have accurately communicated this document to the respondent, who has
accurately read this informed consent form. I confirm that the respondent had the
opportunity to ask questions. I attest that his/her consent is voluntary.
Researcher's Name: __________________________________
Researcher's Signature: ________________________________________
Date: __________________________________