tDCS Plus Virtual Reality for PTSD

PTSD is highly prevalent in Veterans and is associated with significant psychiatric and
medical comorbidity, as well as poor quality of life. Despite its prevalence and impact, the
success of currently available treatments is mixed, highlighting the need for novel
approaches that aim to reduce symptoms and improve outcomes. Prior research has demonstrated
that reduced activity in a part of the brain, the ventromedial prefrontal cortex (VMPFC), is
associated with an inability to regulate fear responses, preventing the generation of safety
memories and allowing PTSD symptoms to persist. Targeting the VMPFC with non-invasive
electrical brain stimulation may therefore alleviate these symptoms.

Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation
that may enhance the likelihood of neuronal activity in the VMPFC. In doing so, tDCS prepares
the brain to respond to external stimuli and to facilitate learning and memory. Because
therapeutic success from exposure to trauma-related content - as used in exposure-based
therapy for PTSD - is thought to be based on an adaptive learning process, applying tDCS in
combination with exposure to trauma cues may effectively boost exposure-based learning. To do
this, investigators at the Providence VA Medical Center will use a standardized virtual
reality (VR) setting to deliver trauma-related content. The virtual reality setting involves
three, 8-minute driving scenarios, which consist of VR stimuli (sights, sounds, smells, etc.)
often encountered in combat training and in theater.

Eligible participants will be randomized to receive six sessions of either active tDCS plus
virtual reality (tDCS+VR) or sham tDCS+VR. Clinical and self-report assessments will be
completed at baseline, midpoint, and endpoint, as well as 1 and 3 months following the final
tDCS+VR session. Participants will also undergo a MRI before and after completion of all six
tDCS+VR sessions.

Inclusion Criteria:

- Must be a Veteran

- Located in the greater Providence and Boston areas

- Have a diagnosis of chronic PTSD, meeting DSM-5 criteria

- If in treatment, symptomatic despite ongoing stable treatment regimens for at least 6
weeks prior to study procedures.

- Willing and able to comply with all study related procedures and visits

- Capable of independently reading and understanding study materials and providing
informed consent.

Exclusion Criteria:

Contraindications to MRI or tDCS, including:

- Implanted device (e.g., deep brain stimulation) or metal in the brain, cervical spinal
cord, or upper thoracic spinal cord.

- Skin lesions at the site of stimulation that may increase conductance (e.g., vascular
moles or angiomas)

- Pregnancy/lactation, or planning to become pregnant during the study

- Lifetime history of moderate or severe traumatic brain injury (TBI)

- Current unstable medical conditions

- Current (or past if appropriate) significant neurological disorder, or lifetime
history of a) seizure disorder b) primary or secondary CNS tumors c) stroke or d)
cerebral aneurysm.

Other exclusions:

- Primary psychotic disorder

- Bipolar I disorder

- Active moderate/severe substance use disorders (within the last month, excluding
nicotine/caffeine)

- Active suicidal intent or plan as detected on screening instruments or in the
investigative team's judgment is likely to attempt suicide within 6 months

- Other conditions or circumstances that, in the opinion of the investigator team, have
the potential to prevent completion and/or have a confounding effect on outcome
assessments.