Temporal Interference for Brain Activity in Healthy Subjects

(TITAN Trial)

Overseen By Sean Prahl

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

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

Disqualifiers: Neurological disorders, Psychiatric hospitalization, Seizures, others

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if temporal interference stimulation, a type of electrical brain stimulation, can alter communication between different brain regions. Participants will receive this stimulation both while awake and during sleep, with MRIs used to observe any changes. The trial seeks healthy adults aged 18-50 without a history of neurological disorders or other specific medical conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative approach.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that can affect seizure thresholds, like ADHD stimulants, some antidepressants, antipsychotics, bronchodilators, certain antibiotics, antivirals, and over-the-counter antihistamines. It's best to discuss your specific medications with the trial team.

What prior data suggests that this technique is safe for brain activity modulation?

Research has shown that temporal interference transcranial electrical stimulation (TI-TES) is generally safe. Studies have found that TI-TES is usually well-tolerated, with most side effects being mild, such as tingling or itching during treatment.

Further research suggests that TI-TES can safely reach deep brain areas without causing major issues. This indicates that the treatment does not pose significant risks to brain or mental functions.

Overall, current research supports the safety of TI-TES, making it a promising area for further study in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Temporal Interference Transcranial Electrical Stimulation (TI-TES) because it offers a unique approach to modulating brain activity. Unlike traditional brain stimulation techniques that can be invasive or limited in targeting specific areas, TI-TES uses non-invasive electrical fields that can focus deeper in the brain without affecting surrounding tissues. This method could lead to more precise control over brain activity during sleep and wakefulness, potentially paving the way for novel treatments for neurological conditions. By exploring how TI-TES affects healthy brain function, scientists hope to unlock new therapeutic strategies that are both safe and effective.

What evidence suggests that temporal interference stimulation is effective for altering brain activity?

Research has shown that temporal interference transcranial electrical stimulation (TI-TES) effectively reaches and influences deep brain regions. Studies have found that TI-TES can improve reaction time and assist in learning new movements, indicating changes in brain activity. Importantly, TI-TES has proven safe and tolerable for individuals. Although this approach is new, its ability to target specific brain areas without surgery is promising. These findings suggest that TI-TES might help temporarily adjust brain communication. Participants in this trial will experience TI-TES during two phases: overnight during non-rapid eye movement (NREM) sleep and during quiet wakefulness. ^{3 5 6 7 8}

Who Is on the Research Team?

Larissa Albantakis, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for healthy individuals interested in participating in a study to explore how a non-invasive brain stimulation technique affects brain communication. Specific eligibility details are not provided, but typically participants must meet certain health standards and have no contraindications for MRI.

Inclusion Criteria

U.S. citizen or holding permanent resident status

English-speaking

I am between 18 and 50 years old.

Exclusion Criteria

I have no history of neurological disorders or brain injuries.

History of inpatient psychiatric hospitalization

Possible pregnancy or plan to become pregnant in the next 6 months (self-reported)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stimulation Phase 1: Overnight TI-TES

Participants undergo repeated overnight TI-TES during NREM sleep, with resting-state fMRI and hdEEG assessments

Up to 2 weeks

2 sessions

Washout

A washout period to allow return to baseline thalamocortical functional connectivity

≥4 weeks

Stimulation Phase 2: Wakefulness TI-TES

Participants undergo repeated TI-TES during quiet wakefulness, with resting-state fMRI and hdEEG assessments

Up to 2 weeks

2 sessions

Follow-up

Participants are monitored for sustained changes in thalamocortical functional connectivity and other secondary outcomes

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Temporal Interference Transcranial electrical stimulation (TI-TES)

Trial Overview The trial tests Temporal Interference Transcranial Electrical Stimulation (TI-TES) during two phases: while awake and overnight. The effect on brain network communication is monitored using MRI scans before and after each stimulation phase.

How Is the Trial Designed?

Group I: Stimulation Experimental Treatment 1 Intervention

Participants will complete two stimulation phases-overnight TI-TES during non-rapid eye movement (NREM) sleep and TI-TES during quiet wakefulness

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12162641/

Advances in the application of temporal interference stimulation The study found that 70 Hz TIS enhanced reaction time and motor cortex excitability, while 20 Hz TIS significantly facilitated motor learning ...

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

Non-invasive temporal interference electrical stimulation of ... We demonstrate the safety and tolerability of TI stimulation in humans, the ability to focally target the stimulation locus to the hippocampus, ...

3. 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 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03747601

NCT03747601 | Temporal Interference Brain Stimulation The primary aim of this study is to translate temporal interference (TI) stimulation methodology into humans and examine its safety, feasibility, ...

5. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1661049/full

a review of transcranial temporal interference stimulation ... Invasive TI approaches, such as epicranial cortical stimulation, can improve e-field targeting, enhancing its intensity by up to 3.8 times and ...

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

Safety Evaluation of Employing Temporal Interference ... These results support that TI-tACS is safe and tolerable in terms of neurological and neuropsychological functions and adverse effects for use ...

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

Recommendations for the Safe Application of Temporal ... Temporal interference stimulation (TIS) is a new non-invasive brain stimulation method capable of targeting deep brain structures, unlike ...

8. frontiersin.org frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2024.1484593/full

The safety and efficacy of applying a high-current temporal ... Conclusion: The proposed high-current TI electrical stimulation is both safe and effective for stimulating the human brain. Moreover, the ...