RTMS for Military TBI-related Depression

Inclusion Criteria:

• Age 18-55 at the time of consent. Older individuals will not be enrolled in thisinitial trial for reasons of safety and expected reduced efficacy.

• Current or former US military service member eligible for care at a MilitaryTreatment Facility (MTF) or Veterans Administration Medical Center (VAMC.)

• Able to provide written, informed consent in English .

• Self-reported or medically diagnosed history of concussion (synonymous with "mildTBI.") >6 months, but <26 years prior to consent, defined based on the DoD/VAdefinition:

1. Positive Loss of Consciousness of <30 minutes as confirmed by the TBI Screenerand/or medical records and/or;

2. Positive Alteration of Consciousness of <24 hours as confirmed by the TBIScreener and/or medical records and/or;

3. Positive Post-traumatic Amnesia of 0 to 1 day as confirmed by the TBI Screenerand/or medical records.

• Note: Neuroimaging data or documentation from medical records is notrequired.

• Baseline MADRS >13 at the time of screening indicating at least mild-moderatedepressive symptoms.

• Maintained a steady psychotropic medication regimen for six weeks and a steadybehavioral therapy regimen for twelve weeks prior to enrollment in the study.

• Female participants with child-bearing potential must agree to use an effectivemethod of birth control during the course of the study.

• Under the care of a primary care and/or behavioral health provider.

Exclusion Criteria:

• Elevated risk of seizures at the time of rTMS including any of the following:

1. History of unprovoked seizures.

2. History of seizure within 24 hours of sustaining a concussion(s) or other headinjury regardless of whether it was determined to have been related toconcussion.

3. Family history of two or more unprovoked seizures in a first degree relative (parent, sibling, or child).

4. History of Moderate, Severe, or Penetrating TBI based on TBI Screener and/ormedical records.

5. Intracranial lesion (such as intracranial tumor or intraparenchymal hemorrhage)that, in the opinion of the investigators, would increase seizure risk.

6. Currently taking medication or other substances (such as tricyclicantidepressants or neuroleptics) that, in the opinion of the investigator,lowers the seizure threshold.

• Contraindications to awake 3T MRI without contrast at the time of the Baseline MRIaccording to site radiology department criteria.

• Severe claustrophobia interfering with medication/sedation-free 3T closed-bore MRI.

• Intracranial lesion that would produce an artifact that would compromise theintegrity of rsfMRI data.

• History of severe or recent uncontrolled heart disease.

• Presence of a cardiac pacemaker or intracardiac lines.

• Any implant, prosthesis or other permanent alteration of the body (such as implantedneurostimulators and medication pumps) that, in the opinion of the investigator,would be unsafe with MRI or TMS or that would produce an artifact that wouldcompromise the integrity of data.

• Presence of rapidly progressive illnesses such as late-stage cancer,neurodegenerative conditions, major organ failure, etc.

• History of Bipolar Disorder or Schizophrenia Spectrum Disorders.

• Current evidence of substance-induced mood disorder, active psychosis, or depressionsecondary to general medical illness other than TBI.

• Severe or uncontrolled substance use.

• Concomitant or lifetime history of receiving open-label TMS, due to issuespreserving blinding.

• Concomitant or recent history (within 12 weeks prior to enrollment) of receivingother neurostimulatory treatment, including but not limited to transcranial directcurrent (tDCS), transcranial alternating current (tACS), alpha stim, orelectroconvulsive therapy.

• Suicide attempt within six months prior to enrollment.

• Right upper extremity amputation or other condition precluding left motor thresholdcalibration.

• Unable to complete timeline of study (e.g., planned hospitalization partway throughthe study period.)

• Prisoner, or other legally restricted freedom of movement and participation.

• Any other considerations that, in the opinion of the investigators, may adverselyaffect participant safety, participation, or the scientific validity of the databeing collected (e.g., erratic or unreliable responses, inconsistent communication,inability to remain on a steady neurotropic medication and/or behavioral therapyregimen over the course of the Randomization phase of the study.)