Combined Neuromodulation and Cognitive Training for Post-mTBI Depression

The primary goal of this clinical trial is to evaluate whether Personalized Augmented Cognitive Training (PACT) plus intermittent theta burst stimulation (iTBS) is effective for treating depression in Service Members, Veterans, and civilians who have sustained a mild TBI. Participants will receive PACT plus 20 sessions of iTBS or sham iTBS over 4 weeks. Assessments will occur at baseline, 2 weeks, 4 weeks, and 8 weeks. Researchers will compare the PACT+iTBS group to the PACT+sham iTBS group to see if PACT+iTBS is associated with more depression improvement.

Inclusion Criteria:Male or femaleAll racial and ethnic groupsAges 18 to 65Military service members receiving treatment at NMCSD or civilians receiving treatment at UCSD HealthHistory of mild TBI (as defined by the DoD/VA criteria used in conjunction with the OSU TBI-ID method) over 3 months prior to study entryMeets criteria for current Major Depressive Episode within the context of Major Depressive Disorder, per MINIScore of 18 or higher on the HAMD-17, indicating moderate to severe depressive symptomsStable on psychiatric medications for 6 weeks, with no changes to psychiatric medications expected during the study periodNo contraindications to TMS (passes the TMS Adult Safety Screening questionnaire)No contraindications to MRI (passes MRI safety screening questionnaire)Able to commit to the treatment scheduleAble to complete assessment procedures in EnglishIntact decision-making capacity and ability to provide voluntary informed consentExclusion Criteria:History of moderate, severe, or penetrating TBIHistory of other neurological condition unrelated to TBI, including but not limited to: conditions associated with increased intracranial pressure; space occupying brain lesions; cerebral aneurysm; stroke; transient ischemic attack within past two years; Parkinson's disease; Huntington's disease; dementia; multiple sclerosis; history of brain surgery; epilepsy; seizure except those therapeutically induced by electroconvulsive therapy (ECT) or a febrile seizure of infancyImplanted medical devices including cardiac pacemaker, medication pump, aneurysm clip, shunt, stimulator, cochlear implant, electrodes, or any other metal object within or near the head (excluding the mouth) that cannot be safely removedActive manic or psychotic illness per MINICurrent substance use disorder per MINICurrent active suicidal or homicidal ideationPregnant or intending to become pregnant within the study period; breastfeedingOther sensory conditions or illnesses precluding participation in assessments or treatmentCurrent dose of lorazepam 2 mg or greater daily (or benzodiazepine equivalent) or any anticonvulsant due to the potential to limit iTBS efficacyTaking medication that lowers seizure thresholdPrevious failed treatment with rTMS, iTBS, or ECTCompleted >4 sessions of cognitive rehabilitation within the last 3 years