Novel and Conventional Interventions for Cognitive and Emotional Flexibility in Patient Trauma

This study is testing whether combining a rapid form of transcranial magnetic stimulation (TMS), an oral medication called d-cycloserine (DCS), and therapy can improve brain flexibility and emotional control in adults experiencing moderate-to-severe depression, anxiety, or trauma symptoms. TMS is a non-invasive treatment that uses gentle magnetic pulses to stimulate specific areas of the brain. In this phase of the study, all participants receive active accelerated TMS (delivering multiple brief sessions in a single day) along with DCS, a medication that helps enhance brain learning and plasticity. Participants will be randomly assigned to have TMS directed at one of two brain targets: a region called the precuneus (identified using personalized brain scans) or the dorsolateral prefrontal cortex (a standard area for mood treatment). Afterward, participants are randomly assigned to complete three weeks of either therapist-led talk therapy (a modified Unified Protocol) or self-guided educational videos and readings. The main goals are to determine which brain stimulation target works best and to see whether therapist-led therapy leads to more lasting symptom relief and brain changes compared to self-guided education.

Inclusion Criteria: * Can safely receive TMS and study drugs * Stable medication regimen for one month prior to study participation, and for the duration of the study * Not currently receiving TMS, ECT, or ketamine * No active safety concerns related to suicidality * Moderate to severe Major Depressive Disorder as indicated by the Patient Health Questionnaire or Quick Inventory of Depressive Symptomatology Exclusion Criteria: * History of seizures or epilepsy * History of intracranial pathology or lesions from any etiology * History of traumatic brain injury including prolonged loss of consciousness more than 15 min * Signs of increased intracranial pressure * Any major neurological conditions (ex: recent stroke, tumor, neurodegenerative disorders, etc.) * Major medical conditions that may cause a medical emergency in case of a - provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.) * Severe migraines that may result in treatment intolerance. * Inability to tolerate MRI. * Pregnancy * Known allergy to D-cycloserine