An interventional study of Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 and Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 in Major Depressive Disorder and Anhedonia, sponsored by Florida State University. Recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-08-31.
Sponsored by Florida State University · Not applicable, Interventional, and Basic science
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.
The experiment comprises eight sessions total. People that request to be in the experiment will first complete demographic and self-report clinical assessments. People that meet our eligibility criteria will be invited to participate in the study. In the first session, clinical assessment are administered to determine eligibility for the full study. In the second session, participants complete a functional magnetic resonance imaging (MRI) session in which they complete three different reward-based decision-making tasks. After the MRI session, participants are randomized into one of three parallel arms to receive five consecutive days of cross-frequency transcranial alternating current stimulation (CF-tACS) in either delta-beta, control-frequency (theta-gamma), or placebo (sham) CF-tACS. In the third through seventh session, participants receive 40 minutes of CF-tACS while completing goal-setting and action planning worksheets. Before the first session of CF-tACS (the third session overall) and the last session of CF-tACS (the seventh session overall), participants complete brief self-report clinical assessments. On the third and seventh session (the first and fifth day of CF-tACS), the participant will complete the reward-based decision-making tasks prior to stimulation while EEG is recorded. In these two sessions, resting-state EEG is acquired before and after stimulation. The first and fifth session of tACS (third and seventh session overall) will take approximately three hours to complete. The second through fourth session of tACS (fourth through sixth session overall) will take approximately one hour to complete. In the follow-up session, visit 8, (approximately two weeks after the end of the five-days of stimulation), participants return for an in-person session that includes self-report clinical assessments and EEG during the reward-based decision-making tasks.
Exclusion Criteria:
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
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
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
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.
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.
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.
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.
Time frame: 1 week
Change in Symptoms of anhedonia
Anhedonia is measured using the Snaith Hamilton Pleasure Rating Scale (SHAPS) which ranges from 14 to 56 where a larger value reflects greater symptoms of anhedonia.
Time frame: 4 weeks
Plan to share: Yes — 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 FSU.
Supporting information: Study protocol, Sap, Icf
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