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

Not Applicable

Completed

• Conditions: Major Depressive Disorder; Anhedonia
• Interventions: Device: Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus

• Registration Number: NCT05084924
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2021-10-06
• Study First Submitted QC: 2021-10-06
• Study First Posted: 2021-10-20
• Study Start: 2021-11-02
• Primary Completion: 2023-07-31
• Study Completion: 2023-07-31
• Status Verified: 2023-09
• Results First Submitted: 2024-05-01
• Results First Submitted QC: 2024-05-30
• Last Update Submitted: 2024-05-30
• Results First Posted: 2024-06-25
• Last Update Posted: 2024-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

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)

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active-sham tACS	Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus	For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 10 seconds and then returns to baseline. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset of stimulation, assisting with blinding the participant's assignment.
Delta-beta tACS	Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus	The study is investigating the use of transcranial alternating current stimulation (tACS). The stimulation is delivered at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. For the experimental arm, the tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz).
Theta-gamma tACS	Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus	This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz).

Primary Outcome Measures

Name	Time	Method
Change in the Percentage of Trials That the Participant Chooses to Perform the Hard Task	Baseline (Hour 1), Stimulation (Hours 2 through 3)	In the Expenditure of Effort for Reward Task, participants are faced with a decision on every trial: to choose an easy task with a low effort exertion for a chance at winning a low amount of money or a hard task with a high effort exertion for a chance at winning a greater amount of money. The incentive for the high effort exertion is changed on each trial and the participant gets physically tired from repeated effort exertion. Goal-directed behavior was calculated as the percentage of trials in which the participant decides to perform the high effort exertion. The average of the 4 blocks prior to stimulation served as a baseline (1st hour). The effect of the intervention was the average of the next 8 blocks during stimulation (hours 2 through 3).

Secondary Outcome Measures

Name	Time	Method
Change in Coupling Strength Between Low-frequency Prefrontal Signals and High-frequency Posterior Signals	Baseline (Hour 1), Stimulation (Hours 2 through 3)	Coupling strength was estimated using the Mean Vector Length calculation between the phase of low-frequency electrical activity in prefrontal electrodes and amplitude of high-frequency activity in posterior cortex. A hybrid signal was created using high-frequency amplitude and low-frequency phase. The magnitude of the average of this signal over time is the coupling strength. Coupling strength was normalized using a z-transformation relative to a null distribution generated by randomly time-shifting the high-frequency data relative to the low-frequency data (z-score). A value of zero represents no coupling. A higher value represents greater coupling strength, which is generally associated with better cognition. Values range from -3 to 3 and a score greater than 1.6 means the coupling is present. The average of the 4 blocks prior to stimulation served as a baseline (1st hour). The effect of the intervention was the average of the next 8 blocks during stimulation (hours 2 through 3).

Trial Locations

Locations (1)

University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States