Single Session of tACS in a Depressive Episode

Participants will report for a study visit and will review and sign a consent form.

Participants will complete several clinical assessments and also take a urine drug test and
urine pregnancy test (if applicable). Eligibility will be re-assessed by the investigators
before the participant moves on to the next phase.

If the participant still qualifies, the participant will first be fitted with two 5x5cm
electrodes placed over F3/F4 (10-20 measurement system) and one 5x7cm electrode placed over
Cz. In addition, the participant will have a 128-channel EEG net placed on their head.
Participants will provide a saliva sample to assess for brain-derived neurotrophic factor
(BDNF), which may affect how the participant's brain responds to stimulation. Once the
participant is fitted with this equipment, the participant will complete two interactive EEG
tasks, then 2-minute resting state EEG with the participant's eyes closed, then a 5-minute
resting state EEG with the participant's eyes open.

Following these recordings, participants will respond to additional questionnaires.
Immediately following this, the participant will receive 40 minutes of stimulation (tACS or
sham tACS). During this stimulation, participants will sit comfortably upright and awake.

After stimulation has completed, participants will respond to additional questionnaires. Once
completed, participants will then complete an additional 5-minute resting state EEG with the
participant's eyes open, as well as complete one of the additional interactive EEG tasks.

Finally, participants will respond to a blinding questionnaire to assess if the participant
thought that the participant received stimulation. Once complete, the participant will leave.
This session is estimated to last about 4 hours.

Inclusion Criteria for individuals with depressed mood:

- Ages 18-65 years

- Hamilton Depression Rating Scale score >8

- Capacity to understand all relevant risks and potential benefits of the study
(informed consent)

- Low suicide risk which will be determined through the use of both the Structured
Clinical Interview for the DSM-5 and by scoring less than 3 (0,1, or 2) in the
Hamilton rating depression scale.

- Negative pregnancy test for female participants

Exclusion Criteria for individuals with depressed mood:

- DSM-5 diagnosis of alcohol of substance abuse (other than nicotine) within the 12
months

- DSM-5 diagnosis of alcohol or substance dependence (other than nicotine) within the
last 12 months

- DSM-5 diagnosis of personality disorder

- Eating disorder (current or within the past 3 months)

- Anything that, in the opinion of the investigator, would place the participant at
increased risk or preclude the participant's full compliance with or completion of the
study

- Neurological disorders, including but not limited to history of seizures (except
childhood febrile seizures and electro-convulsive therapy (ECT) induced seizures),
dementia, history of stroke, Parkinson's disease, multiple sclerosis, cerebral
aneurysm.

- Medical or neurological illness (unstable cardiac disease, AIDS, malignancy, liver or
renal impairment) or treatment for a medical disorder that could interfere with study
participation

- History of traumatic brain injury, reoccurring seizures or later cognitive
rehabilitation or causing cognitive sequelae

- History of childhood trauma (determined by the Childhood Trauma Questionnaire)

- Prior brain surgery

- Any brain devices/implants, including cochlear implants and aneurysm clips

- Co-morbid neurological condition (i.e. seizure disorder, brain tumor)

- Use of illicit drugs, confirmed by a drug test

- Non English speakers

- Pregnant or nursing females

- Current use of benzodiazepines or anti-epileptic drugs

Inclusion Criteria for healthy controls:

- Ages 18-65 years

- Hamilton Depression Rating Scale score ≤8

- Capacity to understand all relevant risks and potential benefits of the study
(informed consent)

- Negative pregnancy test for female participants

Exclusion Criteria for healthy controls:

- History of major neurological or psychiatric illness, including epilepsy

- Medication use associated with neurological or psychiatric illnesses

- Currently undergoing counseling or psychotherapy treatment for depression, anxiety,
eating disorders, PTSD or other behavioral conditions

- DSM-5 diagnosis of personality disorder

- First degree relative (parent, sibling, child) with major neurological or psychiatric
illness

- Prior brain surgery

- Major head injury

- Any brain devices/implants (including cochlear implants and aneurysm clips)

- History of childhood trauma (determined by the Childhood Trauma Questionnaire)

- Use of illicit drugs, confirmed by a drug test

- Braids or other hair styling that prevents direct access to the scalp (if removal not
possible)

- Skin allergies or very sensitive skin

- Non English speakers

- Pregnant or nursing females