Causal Role of Delta-beta Coupling for Goal-directed Behavior in Anhedonic Depression

Anhedonia, the inability to seek-out and experience pleasure, is a common symptom in depression that predicts treatment-resistance and is sometimes exacerbated by first-line antidepressants. In our previous research, we found that anhedonia decreases goal-directed behavior and its related neural activity. In this study, we will investigate target engagement from five-consecutive days of stimulation for participants that are within a unipolar major depressive episode and also have high symptoms of anhedonia.

The experiment comprises eight sessions total. People that request to be in the experiment will first complete demographic and self-report clinical assessments. People that meet our eligibility criteria will be invited to participate in the study. In the first session, clinical assessment are administered to determine eligibility for the full study. In the second session, participants complete a functional magnetic resonance imaging (MRI) session in which they complete three different reward-based decision-making tasks. After the MRI session, participants are randomized into one of three parallel arms to receive five consecutive days of cross-frequency transcranial alternating current stimulation (CF-tACS) in either delta-beta, control-frequency (theta-gamma), or placebo (sham) CF-tACS. In the third through seventh session, participants receive 40 minutes of CF-tACS while completing goal-setting and action planning worksheets. Before the first session of CF-tACS (the third session overall) and the last session of CF-tACS (the seventh session overall), participants complete brief self-report clinical assessments. On the third and seventh session (the first and fifth day of CF-tACS), the participant will complete the reward-based decision-making tasks prior to stimulation while EEG is recorded. In these two sessions, resting-state EEG is acquired before and after stimulation. The first and fifth session of tACS (third and seventh session overall) will take approximately three hours to complete. The second through fourth session of tACS (fourth through sixth session overall) will take approximately one hour to complete. In the follow-up session, visit 8, (approximately two weeks after the end of the five-days of stimulation), participants return for an in-person session that includes self-report clinical assessments and EEG during the reward-based decision-making tasks.

Eligibility Criteria:
Inclusion Criteria:

* Between the ages of 18 and 65
* Able to provide informed consent
* Have normal to corrected vision
* Willing to comply with all study procedures and be available for the duration of the study
* Speak and understand English
* Mild suicide risk as determined by the Hamilton Depression Rating Scale (HAM-D; less than 3 for the suicidality item) and non-existent or mild risk according to the Depression Symptom Index Suicidality Subscale (DSI-SS).
* Patient Health Questionnaire (PHQ-8) greater than or equal to 8 prior to the first session
* Snaith Hamilton Pleasure Scale (SHAPS) greater than 33 at the first session
* A diagnosis of major depressive disorder on the Mini International Neuropsychiatric Interview for the DSM-V (MINI)

Exclusion Criteria:

* ADHD (currently under treatment)
* Neurological disorders and conditions including, but not limited to history of epilepsy; seizures, except childhood febrile seizures; dementia; history of stroke; Parkinson's disease, multiple sclerosis, cerebral aneurysm; brain tumors
* Medical or neurological illness or treatment for a medical disorder that could interfere with study participation. For example, unstable cardiac disease, HIV/AIDS, malignancy, liver or renal impairment
* Prior brain surgery
* Any brain devices/implants including cochlear implants and aneurysm clips, cardiac pacemaker, or any other implanted electronic device
* History of current traumatic brain injury
* Pregnancy (for females)
* Current severe substance use disorder
* Claustrophobia
* Based on the use of MRI, additional exclusion/inclusion criteria are considered. Note that many contraindications for stimulation are common with MRI and thus are not repeated. Participants must not have metal in the body that is ferrous, will be required to remove all jewelry, must not have tattoos on the face or neck, must refrain from wearing metal in clothing (underwire) or active gear (possibility of metallic microparticle technology), must not be a metal worker or have an eye injury involving metal.
* 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
* DSM-V diagnosis of present moderate or severe substance use disorder or alcohol use disorder, and past severe substance use disorder or alcohol use disorder, or psychotic disorder within the last 12 months