Electrical Stimulation for Sleep and Emotional Health

(REM-REST Trial)

Overseen By Stephanie G Jones

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Wisconsin, Madison

Must not be taking: ADHD stimulants, Antidepressants, Antipsychotics, others

Disqualifiers: Neurological disorders, Seizures, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores boosting sleep and emotional health by applying electrical currents to the brain during naps. Researchers aim to determine if this stimulation, known as Transcranial Electrical Stimulation with Temporal Interference (TES-TI), can enhance brain activity during sleep, potentially aiding emotional balance and stress management. Participants will undergo sessions both with and without brain stimulation. Individuals who nap regularly, are medically healthy, and have no metal in their body may be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on sleep and emotional health.

Do I need to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications that can affect seizure thresholds, such as ADHD stimulants, some antidepressants, antipsychotics, bronchodilators, certain antibiotics, antivirals, and some over-the-counter antihistamines.

What prior data suggests that this method is safe for improving sleep and emotional health?

Research has shown that transcranial electrical stimulation with Temporal Interference (TES-TI) is generally safe. Studies have found TES-TI to be a non-invasive method for brain stimulation without major side effects. Although it is a newer technique, current evidence suggests it is well-tolerated.

In one study, participants who received TES-TI did not experience significant negative effects during or after treatment, indicating its safety. However, as this method is still under investigation, more research is necessary to fully confirm its long-term safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for sleep and emotional health issues rely on medications or cognitive therapies, which can take time to show results and may have side effects. But the use of transcranial electrical stimulation with Temporal Interference (TES-TI) is different because it aims to directly influence brain activity through non-invasive electrical currents. This method is unique as it potentially offers immediate effects during a nap, targeting brain regions involved in sleep and mood regulation without the need for drugs. Researchers are excited about TES-TI because it could provide a fast-acting, non-pharmacological alternative to existing treatments, minimizing side effects and offering flexibility in treatment timing.

What evidence suggests that this trial's treatments could be effective for improving sleep and emotional health?

Research has shown that transcranial electrical stimulation with Temporal Interference (TES-TI) can reach deep brain areas without surgery. This method may enhance certain brain activities during sleep, which are linked to better emotional health. Early results suggest that TES-TI can safely boost slow wave activity, a type of brain wave important for restful sleep. In this trial, participants will experience TES-TI during one visit and no stimulation during another, allowing researchers to compare the effects. Other studies have used similar techniques to improve mood and reduce stress. Importantly, these benefits were achieved without surgery, making TES-TI a non-invasive option worth exploring. ^{1 2 5 6 7}

Who Is on the Research Team?

Giulio Tononi, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for healthy, English-speaking adults aged 18-50 who are regular nappers and either citizens or permanent residents. It's not suitable for those with a history of significant head trauma, neurological disorders, metal in the body, seizures, certain medical conditions or devices, dental implants with metal, claustrophobia, night-shift workers, back issues preventing lying flat or unstable medical conditions.

Inclusion Criteria

English-speaking (able to provide consent and complete questionnaires)

Citizen or holding permanent resident status

Regular napper (1 or more naps per week)

Exclusion Criteria

I have had a severe head injury or more than 3 mild concussions.

I suffer from severe headaches or migraines that are hard to control.

I have no history of neurological disorders or brain injuries.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I

Participants undergo multiple naps with varied parameters to identify optimal conditions for enhancing REM sleep

Varies per participant

Multiple visits

Phase II

Participants undergo two 90-minute naps with sham or non-sham stimulation conditions, completing questionnaires and emotion regulation tasks

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for changes in sleep quality, mood, and emotional response

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial electrical stimulation with Temporal Interference (TES-TI)

Trial Overview The study tests if brain stimulation using Transcranial electrical stimulation with Temporal Interference (TES-TI) during naps can enhance sleep-related brain activity and improve emotional health and stress resilience. Participants will have up to three visits involving wearing an hdEEG cap while taking a nap.

How Is the Trial Designed?

Group I: Stimulation followed by no stimulation Experimental Treatment 1 Intervention

Phase 2 participants will receive stimulation during their nap at the first visit, and no stimulation during their nap at the second visit.

Group II: No stimulation followed by stimulation Experimental Treatment 1 Intervention

Phase 2 participants will not receive stimulation during their nap at the first visit, and receive stimulation during their nap at the second visit.

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

Transcranial Current Stimulation (tCS) is a safe and well-tolerated non-invasive technique that can effectively modulate sleepiness, sleep, and vigilance by applying weak electric currents to the scalp.

Recent studies indicate that tCS can influence sleep and arousal patterns, suggesting its potential as a therapeutic tool for treating sleep disorders and other clinical conditions related to sleep and arousal regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy of Transcranial Current Stimulation Techniques to Modulate Resting-State EEG, to Affect Vigilance and to Promote Sleepiness. Annarumma, L., D'Atri, A., Alfonsi, V., et al.[2020]

A study involving 25 participants showed that personalized transcranial alternating current stimulation (tACS) significantly increased sleep duration by an average of 22 minutes compared to a control condition, highlighting its potential as a non-invasive sleep intervention.

Personalized tACS also reduced the time taken to fall asleep by 28% compared to fixed stimulation, suggesting that tailoring stimulation to individual brain activity may enhance sleep quality, especially for those with insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized transcranial alternating current stimulation improves sleep quality: Initial findings. Ayanampudi, V., Kumar, V., Krishnan, A., et al.[2023]

In a study involving 38 healthy adults, temporal interference transcranial alternating current stimulation (TI-tACS) was found to be safe, with no significant adverse effects reported after active stimulation at 2 mA for 30 minutes.

The study showed no significant differences in neurological and neuropsychological measurements between the active TI-tACS group and the sham group, indicating that TI-tACS does not negatively impact brain function under the tested conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Employing Temporal Interference Transcranial Alternating Current Stimulation in Human Studies. Piao, Y., Ma, R., Weng, Y., et al.[2022]

In a study involving 1,019 participants across 4 sites, adverse events (AEs) following multiple sessions of transcranial electrical stimulation (tES) were found to be influenced more by factors like testing site and session number rather than the stimulation itself, suggesting a good safety profile for repeated use.

The effectiveness of blinding procedures was found to be less reliable for tDCS and tACS compared to tRNS, indicating a need for improved blinding methods, especially when using higher stimulation intensities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinding efficacy and adverse events following repeated transcranial alternating current, direct current, and random noise stimulation. Sheffield, JG., Ramerpresad, S., Brem, AK., et al.[2022]

Low intensity transcranial electrical stimulation (TES) is considered safe, with no serious adverse events reported in over 18,000 sessions across various populations, including healthy individuals and patients with neurological or psychiatric conditions.

While moderate adverse events like skin burns from tDCS are rare, mild adverse events such as headaches and fatigue are more common, and the safety profile is consistent across different age groups and vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Antal, A., Alekseichuk, I., Bikson, M., et al.[2023]

Transcranial Electrical Stimulation (tES) has been shown to modify brain oscillations during sleep, indicating its potential as a non-invasive tool for sleep modulation.

While the effects of tES on objective sleep patterns are inconsistent, subjective assessments of sleep quality consistently show improvements, suggesting that tES may enhance perceived sleep quality in both healthy individuals and patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Transcranial Electrical Stimulation of the Brain on Sleep: A Systematic Review. Dondé, C., Brunelin, J., Micoulaud-Franchi, JA., et al.[2021]

Cranial electrotherapy stimulation is an effective treatment for anxiety, depression, and insomnia, supported by over 40 years of research and more than 100 clinical studies.

The device has a very low incidence of adverse effects (less than 1%), which are generally mild and self-limiting, making it a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia. Kirsch, DL., Nichols, F.[2022]

Transcranial electrical stimulation (TES) can modulate brain activity using low-intensity currents, but the effects observed may not solely be due to the targeted brain region, as peripheral stimulation could also play a significant role.

The review emphasizes the need for careful consideration of TES's biophysical properties and dose-response relationships, suggesting that researchers should control for peripheral effects and be cautious in attributing behavioral changes to specific brain areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Transcranial Electrical Stimulation Localize Brain Function? Karabanov, AN., Saturnino, GB., Thielscher, A., et al.[2023]

Non-invasive electrical neuromodulation techniques, particularly transcranial direct current stimulation (tDCS) and cerebral electrotherapy stimulation (CES), have shown significant efficacy in reducing symptoms of depression and anxiety, with tDCS demonstrating a moderate effect size for both conditions (Hedges' g = 0.544 for depression and g = 0.667 for anxiety).

The analysis of 58 studies indicates that active stimulation from these methods improves not only depression and anxiety but also sleep-related issues, suggesting that tDCS and CES can be effective treatment options across various populations and conditions, particularly for those with mild to moderate symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of non-invasive, non-convulsive electrical neuromodulation on depression, anxiety and sleep disturbance: a systematic review and meta-analysis. Cheng, YC., Kuo, PH., Su, MI., et al.[2022]

Sleep deprivation for 24 hours disrupts the functional connectivity of the brain, particularly affecting the bilateral posterior cingulate cortex and its connections with other brain regions like the thalamus and hippocampus.

Transcranial direct current stimulation (tDCS) can partially restore these disrupted connections, improving connectivity between the posterior cingulate cortex and the right precuneus, while also reducing connectivity with other areas affected by sleep deprivation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of transcranial direct current stimulation on dysfunction of bilateral posterior cingulate cortex after sleep deprivation: a preliminary study]. Meng, QQ., Li, JY., Guo, DL., et al.[2020]

Transcranial electrical stimulation (tES), including tDCS and MHF-tPCS, was found to be well tolerated in healthy subjects over a six-week period, with common side effects being mild skin sensations like tingling and itching, which were less frequent than in the sham-tDCS group.

The MHF-tPCS group showed significantly higher compliance in completing sessions compared to the sham-tDCS group, indicating that this waveform may be more acceptable for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Repeated Application of Transcranial Electrical Stimulation with Limited Outputs to Healthy Subjects. Paneri, B., Adair, D., Thomas, C., et al.[2018]

Cranial electrotherapy stimulation significantly improved depression and physical well-being in participants with subclinical insomnia, with 59 individuals using the device for 30 minutes twice daily over 2 weeks.

While both active and sham groups reported better sleep, only the active device group showed notable changes in brain activity, particularly in specific EEG patterns, suggesting potential benefits in psychological symptoms and brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cranial electrotherapy stimulation on mood and sense of well-being in people with subclinical insomnia. Hong, JK., Yoon, IY.[2023]

Citations

1. medrxiv.org medrxiv.org/content/10.1101/2025.08.11.25333452v1.full-text

Enhancement of Sleep Slow Wave Activity using ... The safety and efficacy of applying a high-current temporal interference electrical stimulation in humans. Front Hum Neurosci 18, 1484593 ...

2. nature.com nature.com/articles/s41593-023-01456-8

Non-invasive temporal interference electrical stimulation of ... Deep brain stimulation (DBS) via implanted electrodes is used worldwide to treat patients with severe neurological and psychiatric disorders ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11638170/

The safety and efficacy of applying a high-current temporal ... This study aimed to introduce a high-current TI electrical stimulation protocol to enhance its intensity and evaluate its safety and efficacy

4. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25003699

Human Applications of Transcranial Temporal Interference ... Transcranial temporal interference stimulation (tTIS) is a novel, non-invasive method developed to selectively modulate deep brain regions and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06896279

Study on the Effectiveness and Safety of Temporal ... Consequently, the objective of this study is to assess the therapeutic effect of temporal interference stimulation in awakening patients with severe disorders ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/bem.22542

Recommendations for the Safe Application of Temporal ... TIS is a new form of transcranial electrical stimulation (tES) that has been proposed as a method for targeted, non-invasive stimulation of deep brain ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9496688/

Safety Evaluation of Employing Temporal Interference ... It is necessary to verify the safety of TI-tACS before we apply TI-tACS to human participants and patients. Transcranial electric stimulation ( ...