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

Major Depressive Disorder Clinical Trial

— DEBRA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05084924
• Other study ID #: 21-1321
• Secondary ID: 1K99MH126161-01A
• Status: Completed
• Phase: N/A
• Start date: November 2, 2021
• Est. completion date: July 31, 2023

Study information

• Verified date: September 2023
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: July 31, 2023
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anhedonia
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

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.

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of trials that the participant chooses to perform the hard task	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.	3 hours
Secondary	Coupling strength between low-frequency prefrontal signals and high-frequency posterior signals	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.	3 hours