The purpose of this study is to test the efficacy of 1-Hz repetitive transcranial magnetic stimulation (TMS) over the pre-supplementary motor area as a treatment for obsessive compulsive disorder. Additionally, this study aims to identify the mechanisms of action of TMS and potential biomarkers and predictors of treatment response.

This treatment study examines the use of transcranial magnetic stimulation (TMS) in treating people with OCD and investigates what areas of the brain are involved during emotional learning. TMS is a noninvasive method in which a magnetic "coil" is placed near an individual's head and delivers small magnetic pulses into the brain, which produce small electrical currents in the brain, stimulating brain cells that may relieve OCD symptoms. TMS has been FDA approved since 2008 and Health Canada approved since 2002 as a treatment for depression. Our hope is to demonstrate that TMS is a successful treatment option for individuals struggling with OCD symptoms, and to identify the specific areas of the brain that are targeted through TMS.

Patients will be randomized (like the flip of a coin) to one of two groups: 6 weeks of daily active TMS, or 6 weeks of daily placebo (sham) TMS sessions. During phase I, participation in this study will last about 8 weeks and patients will be asked to make about 36 visits to our clinics at the MGH main campus and the MGH Charlestown Navy Yard campus. Patients will also participate in MRI scanning sessions and clinical assessments.

If patients' symptoms do not improve after phase I, they will be invited to participate in phase II. During phase II, patients receive 30 active TMS sessions over 6 weeks, as well as MRI scans and clinical assessments.

Part of the MRI scanning sessions will include participating in a task that uses mild, half-second electric shocks to fingers. The electric current will be generated from a 9V battery (e.g., battery in a smoke alarm), and is much less annoying than a static shock. In order to set the level of the current to be used during the study, we will begin at a level below what patients will be able to feel, and then increase in gradual steps with permission. Patients will be asked to stop the increase at a level of the current that they find highly annoying but not painful. The level of current that patients select during this trial procedure, and no higher level, will be used during the study so that they will not receive any painful electric shocks. The purpose of the electric shock is to create a situation in which emotional learning may occur. Patients will receive no more than ten of these electric shocks.

Compensation is provided for clinical assessments and MRI scan sessions.

Inclusion Criteria:

1. 18-65 years of age.
2. Proficient in English.
3. A diagnosis of primary OCD (as determined by SCID).
4. Yale-Brown Obsessive Compulsive Scale total score ≥ 16.
5. Normal (or corrected) vision.
6. Stable medication regimen or medication free for ≥ 12 weeks prior to study; benzodiazepine free ≥ 2 weeks.
7. Right-handed (Edinburgh Handedness Inventory - Short Form total score ≥ 61)
8. Able to give informed consent.

Exclusion Criteria:

1. Current or history of neurologic or psychiatric disease (e.g., mental retardation, dementia, brain damage, or other cognitive impairment) that would interfere with ability to engage in TMS
2. Psychopathology not appropriate for the treatment (e.g., manic episode or psychosis)
3. Substance abuse or dependence that is current or within the last six months or use of an illicit drug that is not prescribed, as indicated by a urine drug screen and/or clinical inference.
4. Use of benzodiazepines or anticonvulsants within 2 weeks prior to study (to be ruled out by a urine drug screen).
5. Use of Tricyclic Antidepressants (e.g. Clomipramine).
6. Use of other psychotropic medications (e.g., SSRIs) will be allowed provided the dose has been stable for > 12 weeks.
7. Documented resistance to 4 or more valid pharmacological trials of 2 or more different medication classes (e.g. SSRIs and TCAs).
8. Previous exposure to TMS.
9. Major/chronic medical conditions.
10. History of head injury resulting in prolonged loss of consciousness and/or neurological sequelae.
11. Prior neurosurgical procedure.
12. Metal in the body, metal injury to the eyes.
13. History of seizures.
14. Implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, or ventriculo-peritoneal shunt
15. Pregnancy; breastfeeding or nursing; for women of childbearing a pregnancy test (to be ruled out by urine β-HCG) will be conducted prior to study.
16. Currently in Cognitive Behavioral Therapy (CBT).
17. Diagnosis of primary sleep disorder such as primary insomnia, narcolepsy, sleep apnea, shift work sleep disorder and others. Sleep disorders such as insomnia or hypersomnia that are secondary to depression or OCD are permitted.

Adverse event data was assessed during clinician assessments every 2 weeks from baseline (week 0) through week 6 (phase I and phase II), and once more at the end of the 3-month follow-up after phase I (for those not continuing to phase II) or after phase II.