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

NCT06132581 | Recruiting DMC FDA Device

• 2 other identifiers: STUDY000045034R00MH126161-03
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Anhedonia, the inability to seek-out and experience pleasure, is a common symptom in depression that predicts treatment-resistance and is sometimes exacerbated by first-line antidepressants. In our previous research, we found that anhedonia decreases goal-directed behavior and its related neural activity. In this study, we will investigate target engagement from five-consecutive days of stimulation for participants that are within a unipolar major depressive episode and also have high symptoms of anhedonia.

Conditions

Anhedonia; Major Depressive Disorder

Keywords

Transcranial alternating current stimulation; Goal-directed behavior; Cross-frequency coupling

Outcome Measures

Primary Outcomes (1)

• Change in coupling strength between prefrontal and posterior cortex

  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 the S-EEfRT during the decision period. 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.

  1 week

Secondary Outcomes (1)

• Change in Symptoms of anhedonia

  4 weeks

Study Arms (3)

Delta-beta tACS

EXPERIMENTAL

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: Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4

Theta-gamma tACS

ACTIVE COMPARATOR

This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz).

Device: Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4

Active-sham tACS

SHAM COMPARATOR

For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 15 seconds only at the beginning and end of the stimulation period. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset and offest of stimulation, assisting with blinding the participant's assignment.

Device: Sham tACS via the Neurocare Direct Current Stimulator Multi-Channel 4

Interventions

Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 DEVICE

Stimulation will be delivered via the Neurocare Direct Current Stimulator Multi-Channel 4, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research. The electrical waveform for stimulation was designed to mimic theta-gamma coupling in the brain and is used as an active comparator.

Theta-gamma tACS

Sham tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 DEVICE

Stimulation will be delivered via the Neurocare Direct Current Stimulator Multi-Channel 4, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research. The electrical waveform is randomly selected to be the theta-gamma or delta-beta waveform, but the stimulation is delivered for only a brief period of time of approximately 30 seconds, which is not sufficient to produce a meaningful dose to the brain. This placebo, or sham, stimulation is designed to mimic the sensation of receiving stimulation.

Active-sham tACS

Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 DEVICE

Stimulation will be delivered via the Neurocare Direct Current Stimulator Multi-Channel 4, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research. The electrical waveform for stimulation was designed to mimic delta-beta coupling in the brain.

Delta-beta tACS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 18 and 65
• 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
• Mild suicide risk as determined by the Hamilton Depression Rating Scale (HAM-D; less than 3 for the suicidality item) and non-existent or mild risk according to the Depression Symptom Index Suicidality Subscale (DSI-SS).
• Patient Health Questionnaire (PHQ-8) greater than or equal to 8 prior to the first session
• Snaith Hamilton Pleasure Scale (SHAPS) greater than 33 at the first session
• A diagnosis of major depressive disorder on the Mini International Neuropsychiatric Interview for the DSM-V (MINI)

You may not qualify if:

• ADHD (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. For example, unstable cardiac disease, HIV/AIDS, malignancy, liver or renal impairment
• Prior brain surgery
• Any brain devices/implants including cochlear implants and aneurysm clips, cardiac pacemaker, or any other implanted electronic device
• History of current traumatic brain injury
• Pregnancy (for females)
• Current severe substance use disorder
• Claustrophobia
• 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
• DSM-V 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

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): collaborator
• Florida State University: lead

Study Sites (1)

Florida State University

Tallahassee, Florida, 32306, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Anhedonia

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Justin M Riddle, PhD

CONTACT

850-645-2389; jriddle@fsu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Participants are randomized into one of three arms of the study: delta-beta tACS, control tACS in theta-gamma, or active sham tACS.

Study Record Dates

• First Submitted: November 7, 2023
• First Posted: November 15, 2023
• Study Start: January 24, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: from 9 to 36 months following publication
• 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 FSU.

Locations

US (1)