MAGNETS is a prospective, randomized, parallel-design, sham-controlled clinical trial of accelerated, functional magnetic resonance imaging (fMRI)-guided intermittent theta burst stimulation (iTBS) to the right dorsolateral prefrontal cortex (dlPFC) for chronic symptoms of posttraumatic stress disorder (PTSD) in a comorbid Veteran population.

In MAGNETS, sixty-four participants will be recruited from the NMVAHCS PTSD programs, Polytrauma services, and outpatient mental health clinics. At study entry (Visit #1), participants will undergo baseline demographic, behavioral, and cognitive assessment, and fMRI and diffusion tensor imaging (DTI). The data analysis team will then determine the image-based target in the right hemisphere. Participants will be randomized to either the active (n=32) or sham (n=32) group and undergo 50 sessions of iTBS (10x/day, five days). At end of treatment (Visit #2), they will repeat all baseline tests, including fMRI. One-, three- and six-month symptom levels will be obtained through phone visits (Visits #3-5) to establish longevity and stability of benefit. Repeated measures analyses will be performed on behavioral and connectivity variables, with clinical (age, duration, head injury history) and imaging (white matter fiber counts) features as covariates.

Inclusion Criteria:

• Veterans will be enrolled in this study if they:

  1. are aged 18-80;
  2. have a documented diagnosis of PTSD with evidence of ongoing symptoms as demonstrated by score of "31" or higher on the PCL-5, a measure of posttraumatic stress symptoms;
  3. are fluent in English (as the neuropsychological testing tools used are only available in English) and
  4. have been on stable doses of psychotropic medications for the past month.

Exclusion Criteria:

• Veterans will be excluded from participation in this study if there is:

  1. a prior history of other neurological disease beyond mild TBI, as determined by VA/DoD criteria for TBI severity;
  2. any history of seizures beyond immediate posttraumatic seizure or childhood febrile seizure, so as to reduce risk of exacerbation of epilepsy or other neurological symptoms;
  3. history of a psychotic disorder, such as schizophrenia or bipolar disorder, so as to reduce risk of psychiatric decompensation;
  4. active substance/alcohol dependence without ongoing treatment, to reduce confounding effects on diagnosis and brain imaging;
  5. presence of any implanted electrical device (e.g., pacemaker), to reduce risk of device malfunction from rTMS;
  6. recent medical hospitalization (within four weeks), to reduce risk of medical decompensation during the study;
  7. any condition that would prevent the subject from completing the protocol;
  8. appointment of a legal representative or inability to provide informed consent, to avoid coercion of a vulnerable population;
  9. any ongoing litigation related to PTSD, TBI, disability determination, or service connection, to prevent interference with legal proceedings;
  10. any contraindication to MRI;
  11. pregnant women, so as to prevent complications;
  12. membership in an identified vulnerable population, including minors and prisoners, so as to prevent coercion;
  13. Cognitively impaired adults who lack capacity to consent.