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

Sponsor

University of North Carolina, Chapel Hill (Other)

Overall Status

Recruiting

CT.gov ID

NCT05084924

Collaborator

National Institute of Mental Health (NIMH) (NIH)

Enrollment

Location

Arms

Anticipated Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder Anhedonia	Device: Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Participants are randomized into one of three arms of the study: delta-beta tACS, control tACS in theta-gamma, or active sham. Randomization is stratified by SHAPS level such that there are an equal number of participants that are high anhedonia (SHAPS > 33) and low anhedonia (SHAPS <=33).Participants are randomized into one of three arms of the study: delta-beta tACS, control tACS in theta-gamma, or active sham. Randomization is stratified by SHAPS level such that there are an equal number of participants that are high anhedonia (SHAPS > 33) and low anhedonia (SHAPS <=33).

Masking:

Double (Participant, Investigator)

Masking Description:

This study is designed to be double-blind. Participants and the researchers are unaware of each participant's assignment until the completion of all data collection. This is accomplished using randomization codes. Furthermore, this study utilizes an active sham stimulation. This means that the active sham condition includes some stimulation, mimicking the skin sensations associated with tACS. In a previously concluded trial, participants in the delta-beta tACS, theta-gamma tACS, and active sham groups responded similarly to the blinding questionnaire, indicating that the active sham stimulation successfully blinded the participants.

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Nov 2, 2021

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

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.

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

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

Outcome Measures

Primary Outcome Measures

Percentage of trials that the participant chooses to perform the hard task [3 hours]
Goal-directed behavior will be calculated as the percentage of trials in which the participant decides to perform the most difficult effort exertion task in the Expenditure of Effort for Reward Task. The average for the four blocks prior to stimulation serve as a baseline and the eight blocks during stimulation will be calculated and the difference from baseline will be investigated.

Secondary Outcome Measures

Coupling strength between low-frequency prefrontal signals and high-frequency posterior signals [3 hours]
Phase-amplitude coupling strength is calculated between the phase of low-frequency activity in prefrontal electrodes and amplitude of high-frequency in posterior cortex. These signals are extracted from eyes-open resting-state periods after stimulation is turned off following each task block. Instantaneous phase and amplitude will be calculated by averaging electrodes in the regions, band-filtering to the specified range, and performing the Hilbert transform. Next, a hybrid signal is created using the high-frequency amplitude and low-frequency phase. Coupling strength is the magnitude of the average of this signal over time. Finally, coupling strength is normalized using a z-transformation with respect to a null distribution generated by randomly time-shifting the high-frequency time-series.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.