Repetitive Transcranial Magnetic Stimulation Equipment Testing and Pilot Study

* INCLUSION CRITERIA: Subjects must: 1. Be able to give valid informed consent 2. Be 18 55 years of age. 1. Justification: Many neural processes change with age, and these changes could introduce unwanted variability in both behavioral and MRI signals. In addition, the risk of difficult-to-detect medical abnormalities such as silent cerebral infarcts increases with age. 2. Screening tool: History. Government-issued forms of identification (e.g. driver s license, birth certificate) will be required when participant appears to be out of age range. 3. Be in good health. 1. Justification: Many illnesses may alter neural functioning as well as fMRI signals. 2. Screening tools: Medical Assessment, Medical History and Physical Examination. Medical assessments include: Vital Signs, EKG, oral HIV test, height/weight measurements, urinalysis and blood sample. Tests on the blood sample include complete blood count (CBC), complete metabolic profile, thyroid-stimulating hormone (TSH), erythrocyte sedimentation rate (ESR), Serologic Test For Syphilis (STS) and HIV (if needed to confirm a positive salivary test for HIV). The following individual laboratory results will independently disqualify individuals: Cholesterol \>250 mg/dl, Hemoglobin \< 10.5 g/dl, white blood cell count (WBC) \< 2400/microl, liver function tests (LFTs) \> 3x normal, Human chorionic gonadotropin (HCG) positive, Casual serum glucose \> 200 mg/dl, Urine protein \> 1+. The medically accountable investigator (MAI) will retain discretion to exclude at less extreme values, depending on the clinical presentation. (Serum glucose over 140 mg/dl will be followed up with a fasting serum glucose assessment. Those with fasting glucose below 100 mg/dl may be considered for the protocol. Others will be rejected and referred for work-up.) MAI will make the final judgment on any questionable lab results. 4. Right-handed. 1. Justification: Using right-handed individuals will reduce variability in BOLD MRI data. 2. Screening tool: Edinburgh Handedness Inventory. 5. Estimated intelligence quotient (IQ) greater than or equal to 85 1. Justification: Subjects must be able to perform a cognitively challenging task to a high standard. 2. Screening tool: Wechsler Abbreviated Scale of Intelligence. EXCLUSION CRITERIA: 1. Personal history of stroke, brain lesions, previous neurosurgery, any personal history of seizure or fainting episode of unknown cause, or head trauma resulting in loss of consciousness, lasting over 30 minutes or with sequela lasting longer than two days. Justification: Stroke or head trauma can lower the seizure threshold, and are therefore contra-indications for TMS. Fainting episodes or syncope of unknown cause could indicate an undiagnosed condition associated with seizures. Screening tool: TMS adult safety questionnaire, Medical History. 2. First-degree family history of any neurological disorder with a potentially hereditary basis, including migraines, epilepsy, or multiple sclerosis. 1. Justification: Neurological disorders can lower the seizure threshold, and are therefore contra-indications for TMS. First-degree family history of certain neurological disorders with a hereditary component increases the risk of the subject having an undiagnosed condition that is associated with lowered seizure threshold. 2. Screening tool: TMS adult safety screening, Medical History. 3. Cardiac pacemakers, neural stimulators, implantable defibrillator, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head that precludes MRI scanning. 1. Justification: Any metal around the head is a contraindication for both MRI and TMS, as both methods involve exposure to a relatively strong magnetic field. 2. Screening tool: TMS adult safety screening, MRI safety screening, Medical History. 4. Noise-induced hearing loss or tinnitus. 1. Justification: individuals with noise-induced hearing problems may be particularly vulnerable to the acoustic noise generated by TMS and MRI equipment. 2. Screening tools: TMS adult safety screening. 5. Current use (any use in the past 4 weeks, chronic use within 6 past six months) of any investigational drug or of any medications with psychotropic, anti or pro-convulsive action. 1. Justification: The use of certain medications or drugs can lower seizure threshold and is therefore contra-indicated for TMS. 2. Screening tools: MRI safety screening questionnaire, Medical history, Medical Assessments: Urine toxicology analyzes for presence of a broad range of prescription and nonprescription drugs. 6. Lifetime history of major depressive disorder, schizophrenia, bipolar disorder, mania, or hypomania. 1. Justification: The population of interest here is a healthy control population with no psychiatric disorders. In subjects with depression, bipolar disorder, mania or hypomania, there is a small chance that TMS can trigger (hypo)manic symptoms. 2. Screening tools: Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID) Screen Patient Questionnaire. Potential diagnoses will be further evaluated by a counsellor. 7. Meet current Diagnostic and Statistical Manual (DSM) V criteria for moderate to severe substance use disorder (excluding nicotine), smoke daily, or urine toxicology positive for any illicit substance inconsistent with history given. 1. Justification: The population of interest here is a healthy control population with no substance use disorder. Current use of illicit substances could impact on seizure threshold and is therefore contra-indicated for TMS. 2. Screening tools: SCID Screen Patient Questionnaire. Potential diagnoses will be further evaluated by a counsellor, Drug Use Survey (DUS), Substance Use Disorder Evaluation, Medical Assessments: urine qualitative drug screen is performed for methadone, benzodiazepines, cocaine, amphetamine/methamphetamine, opiates, barbiturates, and tetrahydrocannabinol. 8. Have met DSM V criteria for moderate to severe substance use disorder (excluding nicotine, alcohol and cannabis) in the past, or have met DSM V criteria for moderate to severe substance use disorder for cannabis or alcohol in the past 5 years. 1. Justification: the population of interest here is a healthy control population with no present or past substance use disorder. 2. Screening tools: SCID Screen Patient Questionnaire. Potential diagnoses will be further evaluated by a counselor. Drug Use Survey (DUS), Substance Use Disorder Evaluation. 9. History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or any heart condition currently under medical care. 1. Justifications: the risk of TMS for individuals with a heart condition is unknown. 2. Screening tool: physical assessment (EKG), medical history. 10. Pregnant women or women with reproductive potential who are sexually active and not using an acceptable form of contraception. 1. Justification: it is unknown whether TMS poses a risk to fetuses. 2. Screening tool: Medical assessments (urine pregnancy test) at the beginning of each visit that involves TMS or MRI. 11. History of learning disability or current attention deficit hyperactivity disorder (ADHD) 1. Justification: Subjects should be able to perform cognitive tasks to a high degree of accuracy, both in the MRI scanner and outside the scanner. Subjects with ADHD/LD may engage different neural circuitry even if they can perform the tasks. 2. Screening tool: Wechsler Abbreviated Scale of Intelligence, Medical history, Adult ADHD Self-Report Scale. 12. Participation in an rTMS session less than two weeks ago. 1. Justification: in order to limit exposure to TMS, we will not enroll subjects who have received TMS less than two weeks ago. 2. Screening tool: TMS safety screening questionnaire.