The primary purpose of this study is to investigate the effects of tDCS timing on extinction memory in PTSD. A total of 90 participants will be randomized equally across one of three groups:

1. One group receiving active stimulation during extinction followed by sham stimulation during consolidation
2. One group receiving sham stimulation during extinction followed by active stimulation during consolidation
3. One group receiving sham stimulation both during extinction and consolidation

This study also includes an online sub-study (Aim 2) focused on contextual processing along the PTSD spectrum. The online study tests if there is an association between threat and non-threat learning in contextual and non-contextual situations. A maximum of 500 participants will be recruited using an online, panel-based platform.

This is a three-arm study composed of four to five visits over an approximate period of three weeks. Up to ninety participants are exposed to a fear conditioning, extinction, and extinction memory paradigm at three separate study visits (day 3-5); one of these study visits will include active or sham transcranial direct current stimulation (tDCS) for a period of 15 minutes. Skin conductance reactivity during extinction memory (day 5) is the primary outcome. Additional study procedures include a screening period (day 1) and two optional MRI scans, one done on study day 2 and one done on study day 5. As the completion of MRI scans are an optional study component, MRI-related data is not reported here.

SUB-STUDY: The objective of this sub-study is to test performance differences between contextual and non-contextual processing in individuals across the PTSD spectrum using an online, panel-based platform. Following a within-subjects study design, up to 500 adult participants, 18-89 years, will be asked to complete experimental tasks that assess contextual (configural) and non-contextual (elemental) threat and non-threat learning. They will also provide demographic information (age, sex, ethnicity) and complete questionnaires assessing self-reported PTSD, anxiety, and depression severity. As this sub-study does not reflect a randomized clinical trial (no groups, no randomization, no intervention), no further information is reported here.

Inclusion Criteria:

1. Primary diagnosis of PTSD, assessed by the Structured Clinical Interview of DSM-5 (SCID);
2. aged 18-70;
3. ability to speak, read, write, and understand English sufficiently well to complete study procedures and provide informed consent;
4. Stable psychiatric medication use or treatment for at least 6 weeks.

Exclusion Criteria:

1. Lifetime history of psychotic or bipolar disorder;
2. Current moderate or severe substance use disorder; if mild, not under the influence at time of study participation;
3. Acute suicidal or homicidal ideation as detected on screening instruments or in the investigator team's opinion, is likely to attempt suicide within 6 months;
4. current (or past) significant neurological disorder, injury, or other intracranial pathology including severe traumatic brain injury or lifetime history of a) seizure disorder b) primary or secondary CNS tumors c) stroke or d) cerebral aneurysm;
5. lifetime history of moderate or, current unstable medical conditions;
6. Any problems that would interfere with study participation, including MRI- or tDCS-related contraindications (e.g., implanted metallic devices/substances, metallic tattoos, pregnancy, claustrophobia, holes in the skull, skin abnormalities under stimulation sites), or indication of colorblindness, or presence of any other condition or circumstance that, in the opinion of the investigator team, has the potential to prevent study completion and/or inability to schedule visit days within the allotted time, and/or to have a confounding effect on outcome assessments.

One day, following active tDCS or sham stimulation

A transcranial direct current stimulation side effects questionnaire was used following active tDCS or sham stimulation.

Enrollment disruptions due to COVID-19 pandemic resulted in a smaller size than planned (86%; n=62 across three groups out of n=72 planned) for primary outcome analysis and inadequate numbers (51%; n=37 across three groups out of n=72) for analyses of secondary MRI outcomes.