Investigating the Causal Role of Prefrontal Control in Decision-making in Patients With Anhedonia

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

Investigating whether delta-beta cross-frequency transcranial alternating current stimulation can increase goal-directed behavior in participants with major depressive disorder and elevated symptoms of anhedonia.

The purpose of this clinical trial is to investigate the causal role that delta-beta coupling plays in goal-directed behavior in participants with major depressive disorder (MDD) and symptoms of anhedonia. The participants will perform a reward-based decision-making task. During the task, cross-frequency transcranial alternating current stimulation (tACS) will be delivered at delta-beta frequency, a control-frequency, or an active sham. Electroencephalography will be collected in intermittent resting-state periods. Structural and functional magnetic resonance imaging (MRI) will be collected during the resting-state and during performance of the task.

Inclusion Criteria:

• 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
• Low suicide risk as determined by the Columbia Suicide Severity Rating Scale (C-SSRS), and by the Hamilton Depression Rating Scale (HAM-D; less than 3 for the suicidality item).
• Negative pregnancy test for female participants
• Patient Health Questionnaire (PHQ) with 9 items greater than or equal to 10 and a diagnosis of major depressive disorder on the Mini International Neuropsychiatric Interview (MINI)

Exclusion Criteria:

• Attention deficit (hyperactivity) disorder (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 (e.g., unstable cardiac disease, HIV/AIDS, malignancy, liver or renal impairment)
• Prior brain surgery
• Any brain devices/implants, including cochlear implants and aneurysm clips
• History of current traumatic brain injury
• (For females) Pregnant or breast feeding
• 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
• Diagnostic and Statistical Manual of Mental Disorders version 5 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
• Not taking medications for attention deficit (hyperactivity) disorder or benzodiazepines as these medications often produce specific EEG activity that may disrupt our interpretation of the findings
• If major depressive disorder is experienced in episode, the participant must currently be within a depressive episode.
• Contraindications for magnetic resonance imaging (MRI): ferrous metal inside the body, jewelry must be removable, pacemaker or cochlear implant.