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

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.

Study Overview

• Status: Completed
• Conditions: Anhedonia; Major Depressive Disorder
• Intervention / Treatment: Device: Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus

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 Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delta-beta tACS; 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).	Device: Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus; Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.
Active Comparator: Theta-gamma tACS; This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz).	Device: Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus; Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.
Sham Comparator: Active-sham tACS; 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.	Device: Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus; Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Percentage of Trials That the Participant Chooses to Perform the Hard Task	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).	Baseline (Hour 1), Stimulation (Hours 2 through 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Coupling Strength Between Low-frequency Prefrontal Signals and High-frequency Posterior Signals	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).	Baseline (Hour 1), Stimulation (Hours 2 through 3)

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Flavio Frohlich, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: October 6, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: May 30, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: transcranial Alternating Current Stimulation; Goal-directed behavior; Cross-frequency coupling; Reward-based decision-making
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Mood Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Depressive Disorder; Anhedonia; Depressive Disorder, Major
• Other Study ID Numbers: 21-1321; 1K99MH126161-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
• IPD Sharing Time Frame: from 9 to 36 months following publication
• IPD Sharing Access Criteria: Deidentified individual data that supports the results will be shared provided the investigator who proposes to use the data has approval from an IRB, IEC, or REB and an executed data use/sharing agreement with UNC.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No