Augmenting Single-session Behavioral Activation (BA) With Delta-beta Transcranial Alternating Current Stimulation (tACS) for the Treatment of Depression

Study Overview
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Brief Summary
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Investigating whether delta-beta cross-frequency transcranial alternating current stimulation can augment the effects of a single session of behavioral activation in participants with major depressive disorder.

Detailed Description
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The purpose of this study is to examine whether concurrent transcranial alternating current stimulation (tACS) augments the effects of a single session behavioral activation (BA) treatment of depression. Following a series of clinical assessments, participants will perform a reward-based decision-making task while electroencephalography (EEG) is collected. Then, all participants will take part in a single-session 90-minute BA intervention; half of the participants will receive delta-beta tACS during the final 30 minutes of the session and half will receive an active sham stimulation. Participants will return two weeks later for another task-based EEG. Four weeks after the intervention session, they will receive self-report questionnaires via email to complete online.

Official Title
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Augmenting Single-session Behavioral Activation (BA) With Delta-beta Transcranial Alternating Current Stimulation (tACS) for the Treatment of Depression

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: Delta-beta cross-frequency transcranial alternating current stimulation via the NeuroConn DC-STIMULATOR MC
* Behavioral: Single-session behavioral activation
* Device: Active sham cross-frequency transcranial alternating current stimulation via the NeuroConn DC-STIMULATOR MC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old or order Able to provide informed consent Willing to comply with all study procedures and be available for the duration of the study Speak and understand English DSM-5 diagnosis of major depressive disorder (MDD) as assessed by the MINI Exclusion Criteria: Participants must not have active suicide intent as determined by the Columbia Suicide Severity Rating Scale (C-SSRS). Active suicide intent will be captured in responses to items 4 and/or 5 on the C-SSRS. Participants must not meet criteria for current severe substance use disorder, anorexia nervosa, or active psychosis as captured by the MINI. Participants may not currently be in psychotherapy and have not received any other psychotherapy and/or stimulation (ECT, TMS) within the last 4 weeks. Any participants taking psychotropic medication must be on a stable dose for at least 4 weeks with no planned dose changes within the next 4 weeks. (for female participants) Participants must not be pregnant or breastfeeding. Participants may not have any medical or neurological illness for which symptom presentation or treatment could interfere with study participation Participants may not have undergone prior brain surgery Participants may not have any brain devices/implants, including cochlear implants and aneurysm clips Participants may not have had brain injury or concussion within the last three months Participants may not have a history of brain injury requiring current treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will take part in a single-session behavioral activation (BA) intervention. To examine the effects of neurostimulation on treatment response, participants will be randomized to receive either delta-beta cross-frequency transcranial alternating current stimulation (tACS) or an active sham.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delta-beta tACS<br>Participants will receive a single session intervention of behavioral activation (BA) psychotherapy. Stimulation will be delivered via the NeuroConn DC-STIMULATOR MC at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. The tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz). | Device: Delta-beta cross-frequency transcranial alternating current stimulation via the NeuroConn DC-STIMULATOR MC<br>* Delta-beta stimulation will be delivered via the NeuroConn DC-STIMULATOR MC, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.<br>Behavioral: Single-session behavioral activation<br>* Participants will take part in a single-session behavioral activation (BA) intervention. This intervention was adapted from standard BA protocols for the treatment of depression to be completed in a single, 90-minute session. This intervention will have 4 main components based on prior protocols: Treatment overview and rationale Tracking of daily activities Exploration of values Planning/scheduling activities<br>|
| Sham Comparator: Active-sham tACS<br>Participants will receive a single session intervention of behavioral activation (BA) psychotherapy. The active sham condition includes brief stimulation, mimicking the skin sensations associated with tACS, assisting with blinding the participant's assignment. | Behavioral: Single-session behavioral activation<br>* Participants will take part in a single-session behavioral activation (BA) intervention. This intervention was adapted from standard BA protocols for the treatment of depression to be completed in a single, 90-minute session. This intervention will have 4 main components based on prior protocols: Treatment overview and rationale Tracking of daily activities Exploration of values Planning/scheduling activities<br>Device: Active sham cross-frequency transcranial alternating current stimulation via the NeuroConn DC-STIMULATOR MC<br>* Active sham stimulation will be delivered via the NeuroConn DC-STIMULATOR MC, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clinician-rated depressive symptoms | Treatment response will be calculated as the change in clinician rated depression symptom scores using the Hamilton Depression Rating Scale (HDRS). Items are scaled either from 0 - 2 to 0 - 4, and each item is summed for a total score. Benchmarks suggested at: 0-7 normal; 8 - 13 mild depression; 14-18 moderate depression; 19-22 severe depression; >=23 very severe depression. | Baseline up to follow-up 2 weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in phase-amplitude coupling between delta-beta oscillations during task performance of the Streamlined Expenditure of Effort for Reward Task (S-EEfRT) | In the Streamlined Expenditure of Effort for Reward Task (S-EEfRT), participants choose to complete a HARD task requiring many button presses or an EASY task with fewer button presses for variable monetary incentives. Number of button presses is individualized for each participant. Delta-beta coupling during the HARD/EASY decision will be calculated between the phase of delta oscillations (2-3Hz) in prefrontal electrodes (FCz and surrounding electrodes) and the amplitude of beta oscillations (15-25Hz) in left motor electrodes (C3 and surrounding electrodes). The instantaneous phase and amplitude of these oscillations will be calculated by averaging the signal in these two regions, band-filtering the signal to the specified range, and then performing the Hilbert transform on the signal. Phase-amplitude coupling (PAC) is calculated by creating a hybrid signal using the beta oscillation amplitude in left motor electrodes and the delta oscillation phase in prefrontal electrodes. | Baseline up to follow-up 2 weeks post treatment | 
| Change in percentage of hard trials chosen during the S-EEfRT | In the Streamlined Expenditure of Effort for Reward Task (S-EEfRT), participants choose to complete a HARD task requiring many button presses or an EASY task with fewer button presses for variable monetary incentives. Number of button presses is individualized for each participant. Goal-directed behavior will be calculated as the average decision to perform the HARD task across trials. | Baseline up to follow-up 2 weeks post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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behavioral activation, transcranial alternating current stimulation, cross-frequency coupling