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Sponsor: University of Pennsylvania
Conditions: PTSD, Post Traumatic Stress Disorder (PTSD)
Interventions: Active Transcranial Magnetic Stimulation (TMS), Sham Transcranial Magnetic Stimulation (TMS)
The goal of this clinical trial is to learn how transcranial magnetic stimulation (TMS) affects brain circuits involving the amygdala in adults with posttraumatic stress disorder (PTSD). The main questions it aims to answer are: * Can MRI-guided TMS engage the amygdala by stimulating an individualized brain target connected to the amygdala? * Does stimulation of this individualized target engage the amygdala differently than stimulation of control sites? * Does a 6-week course of active TMS, compared with sham TMS, change amygdala responses and physiological responses to fear? Researchers will compare active TMS with sham TMS to evaluate changes in the targeted brain circuit and fear-related responses. Participants will: * Receive active or sham TMS every weekday for 6 weeks * Undergo MRI scans with TMS before and after the 6-week intervention to measure brain responses to stimulation * Participate in fear learning and memory tasks while physiological responses are measured * Undergo additional MRI scans, clinical assessments, questionnaires, and cognitive testing * Complete remote follow-up assessments at 1, 6, and 12 months after the intervention
Sex: ALL
Age: 18 Years to 65 Years
Healthy volunteers: No
Study type: INTERVENTIONAL
INCLUSION CRITERIA In order to participate in this study, potential participants must meet all of the following eligibility criteria: 1. 18-65 years old 2. Current diagnosis of PTSD based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria, as assessed by the Clinician-Administered PTSD Scale-5. 3. Patient Health Questionnaire (PHQ-9) score = or \> than 10 4. Comprehension of instructions in the English language. 5. Capacity to provide informed consent and follow study procedures. 6. Availability for the duration of the study. EXCLUSION CRITERIA Any individual who meets any of the following criteria at the time of enrollment will be excluded from participation: 1. Implanted medical devices, metallic implants, or drug infusion pumps that are not MRI-safe (e.g., aneurysm clips, defibrillators, or cochlear implants) 2. History of significant medical events (e.g., stroke, seizures, brain scarring) or neurological/neurodevelopmental conditions (e.g., epilepsy) that are contraindications for TMS and MRI or may adversely affect brain function and data interpretation. 3. Current substance use disorder. 4. History of a psychotic or bipolar disorder, including manic or hypomanic episodes. 5. Prior failed response to full rTMS or Electroconvulsive Therapy (ECT)/Magnetic Seizure Therapy (MST) trial. Any successful prior treatments are acceptable and support a prognosis that a new rTMS treatment would be worth attempting. 6. Inability to complete an MRI scan (e.g., claustrophobia, inability to remain still for extended periods). 7. Inability to tolerate TMS administration 8. Significant handicaps that would interfere with testing procedures 9. Acute systemic infection, high fever 10. Acute sleep deprivation or medication/substance intoxication or withdrawal (TMS seizure risk) 11. Current use of cyclosporine, tacrolimus, or others that can cause leukoencephalopathy. 12. Pregnancy 13. Dialysis 14. Suicide attempt in past 6 months (safety precaution); similarly, if ideation is particularly pronounced, Drs. Oathes and Sheline will decide with the patient whether the benefit of participating in a sham controlled (all patients given the option to receive active treatment eventually) study outweighs the risks. If the patient has a mental health provider and acquiesces, consultation with the provider will also be instrumental in this decision. 15. Current use of Bupropion (Wellbutrin) above 300 mg, benzodiazepines, lithium, monoamine oxidase inhibitors (MAOIs), and/or high doses of stimulant medication is exclusionary. Note: Exclusionary dosages or medications may be reduced or discontinued under the supervision of a medical provider. 16. Transportation limits or physical limits to attending daily M-F treatment sessions. 17. Per study physician discretion medications likely to interfere with blood flow or otherwise compromise functional imaging measures. 18. Any other factor that in the investigators' judgment may affect patient safety or compliance (e.g. distance greater than 100 miles from procedure site; unlikely to be able to schedule daily treatment sessions, etc.) DURING STUDY REQUIREMENTS During this study, participants will be asked to: 1. Refrain from substance use (including marijuana and illicit drugs) for the duration of the study (self-attestation alone) 2. Abstain from alcohol for 24 hours before study visits (self-attestation alone) 3. Maintain a consistent level of caffeine consumption throughout the study period and avoid any significant increases (self-attestation). 4. Not initiate, discontinue, or adjust any psychiatric medications or therapy treatments during the study period. 5. Inform the study team of any new medical treatments or prescribed medications (e.g., antibiotics) to allow for safety review and determination of continued eligibility for the study.