Location- and Frequency-Dependent Effects of Thalamic Temporal Interference Stimulation During Sleep (CAP-TI)

This study is to find out whether a type of non-invasive electrical brain stimulation called temporal interference transcranial electrical stimulation (TI-TES) can temporarily change brain activity during sleep, especially sleep spindles (brain rhythms in the ~8-16 Hz range). Up to 24 healthy participants in Dane County, Wisconsin will be enrolled for 3 overnight study visits. Participants can expect to be on study for approximately 5 weeks, depending on scheduling availability.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Participants; Healthy Adult Participants
• Intervention / Treatment: Other: Magnetic Resonance Imaging (MRI); Device: Broad thalamic stimulation (TI-TES); Device: Carrier only SHAM stimulation; Device: Anterior thalamic stimulation (TI-TES); Device: Posterior thalamic stimulation (TI-TES)

Detailed Description

This single-site, single-blind, experimental study will test whether thalamic temporal interference transcranial electrical stimulation (TI-TES) delivered during Non-Rapid Eye Movement (NREM) sleep can enhance spindle-frequency activity (SFA) in healthy adults and identify optimal stimulation parameters across frequency and thalamic target location.

After screening/consent, participants will complete a structural MRI for personalized montage optimization, then undergo three overnight High-Density Electroencephalography (hdEEG) and Polysomnography (PSG) sleep sessions (10-12 hours each) in a randomized, counterbalanced crossover design, one session per stimulation location (broad thalamic, anterior thalamic, posterior thalamic). During stable N2 sleep, TI-TES will be delivered in 3-minute epochs separated by 6-minute intervals, for up to 24 epochs per night, under real-time sleep-technician monitoring. The study uses a two-phase frequency plan: Phase 1 (~10 participants) will test 10 Hz, 14 Hz, and matched carrier-only SHAM; contingent on feasibility/sensitivity, Phase 2 (~10 participants) will expand frequencies across 8-16 Hz. Primary outcomes quantify stimulation-related increases in 8-16 Hz spectral power (SFA) and spindle characteristics comparing active TI-TES versus SHAM and across stimulation locations/frequencies.

Primary Objectives:

1. Determine whether active thalamic TI-TES increases 8-16 Hz spindle-frequency activity (SFA) relative to carrier-only SHAM (evaluated using STIM-PRE and POST-PRE contrasts).
2. Identify the most effective TI-TES stimulation parameters across stimulation frequencies and stimulation locations (broad thalamic, anterior, posterior) by comparing SFA changes across parameter combinations.

3. Characterize stimulation-related changes in spindle characteristics (density, amplitude, duration, topography) for slow and fast spindle subtypes.

   Secondary Objectives:

4. Evaluate stimulation-related changes in slow (8-12 Hz) and fast (13-16 Hz) spindle spectral power.
5. Evaluate stimulation-related changes in slow wave (0.5-4.0 Hz) spectral power.
6. Characterize stimulation-related changes in slow-wave characteristics (density, amplitude, duration).
7. Evaluate stimulation-related changes in SO-spindle coupling (phase-amplitude coupling) for slow and fast spindles.
8. (Exploratory) Evaluate stimulation-related changes in hdEEG functional connectivity between channels using the phase slope index (PSI).

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sean Prahl; Phone Number: 608-263-4313; Email: capti@psychiatry.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53719
      • Wisconsin Institute for Sleep and Consciousness

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Medically healthy (based on self-report and study team review)
• U.S. citizen or holding permanent resident status
• English-speaking (able to provide consent and complete questionnaires)

Exclusion Criteria:

• Any current or past history of neurological disorders or acquired neurological disease (e.g. stroke, traumatic brain injury), including intracranial lesions (including clinically significant findings identified in first MRI)
• History of inpatient psychiatric hospitalization
• History of head trauma resulting in prolonged loss of consciousness; or a history of greater than 3 grade I concussions
• Current history of poorly controlled headaches including intractable or poorly controlled migraines
• Any systemic illness or unstable medical condition that may cause a medical emergency in case of a provoked seizure (cardiac malformation, cardiac dysrhythmia, asthma, etc.)
• History of seizures, diagnosis of epilepsy, history of abnormal (epileptiform) EEG, or family history of treatment resistant epilepsy except for a single seizure of benign etiology (e.g. febrile seizures) in the judgment of a board-certified neurologist
• Possible pregnancy or plan to become pregnant in the next 6 months (self reported)
• Any metal in the head
• Any medical devices or implants (i.e. cardiac pacemaker, medication infusion pump, cochlear implant, vagal nerve stimulator)
• Dental implants
• Permanent retainers
• Any hair braid, dreadlocks, hair pieces, or extensions which cannot be taken out before the study sessions
• Any head coverings or headdress that participant feels uncomfortable removing for the purposes of study sessions
• Any medication that may alter seizure threshold taken during the study i.e., ADHD stimulants (Adderall, amphetamine); Tricyclic/atypical antidepressants (amitriptyline, doxepine, imipramine, maprotiline, nortriptyline, bupropion); SSRIs (Escitalopram, Fluoxetine, Sertraline); Antipsychotics (chlorpromazine, clozapine), Bronchodilators (theophylline, aminophylline); Antibiotics (fluoroquinolones, imipenem, penicillin, cephalosporins, metronidazole, isoniazid); Antivirals (valacyclovir, ritonavir); OTC antihistamines (diphenhydramine, Benadryl)
• Claustrophobia (a fear of small or closed places)
• Back problems that would prevent lying flat for up to two hours
• Regular night-shift work (second or third shift)
• Sleep apnea or other sleep disorder (self-reported)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: All Participants; Participants will complete three overnight stimulation sessions with simultaneous 256-channel hdEEG and PSG, in a randomized, counterbalanced crossover design, with each overnight session using a distinct personalized montage targeting one of three thalamic locations (broad thalamic, anterior thalamic, posterior thalamic), and sessions spaced at least three days apart.

Other: Magnetic Resonance Imaging (MRI); MRI is to optimize placement of multipolar TI-TES; Other Names: structural MRI; Device: Broad thalamic stimulation (TI-TES); Stimulation targeted at the whole thalamus. Within each overnight session, up to 24 stimulation protocols will be administered, randomized across frequencies (including SHAM). Stimulation will be initiated by trained sleep technicians during stable N2 sleep and delivered in 3-minute epochs separated by 6-minute intervals to enable comparison of PRE, STIM, and POST intervals; Device: Carrier only SHAM stimulation; Carrier only SHAM condition. Within each overnight session, up to 24 stimulation protocols will be administered, randomized across frequencies (including SHAM). Stimulation will be initiated by trained sleep technicians during stable N2 sleep and delivered in 3-minute epochs separated by 6-minute intervals to enable comparison of PRE, STIM, and POST intervals; Device: Anterior thalamic stimulation (TI-TES); Stimulation targeted at the anterior thalamus. Within each overnight session, up to 24 stimulation protocols will be administered, randomized across frequencies (including SHAM). Stimulation will be initiated by trained sleep technicians during stable N2 sleep and delivered in 3-minute epochs separated by 6-minute intervals to enable comparison of PRE, STIM, and POST intervals; Device: Posterior thalamic stimulation (TI-TES); Stimulation targeted at the posterior thalamus. Within each overnight session, up to 24 stimulation protocols will be administered, randomized across frequencies (including SHAM). Stimulation will be initiated by trained sleep technicians during stable N2 sleep and delivered in 3-minute epochs separated by 6-minute intervals to enable comparison of PRE, STIM, and POST intervals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Spectral Power (SFA) for Active TI-TES vs SHAM	Comparing active TI-TES vs carrier only SHAM, evaluated using both STIM-PRE and POST-PRE contrasts.	during each of the 3 overnight visits, 5 weeks
Change in SFA by Location	Changes in 8-16 Hz spectral power across frequency-location combinations (broad thalamic, anterior thalamic, posterior thalamic) for STIM-PRE and POST-PRE to identify the most effective parameters within the tested parameter space.	during each of the 3 overnight visits, 5 weeks
Spindle Density in slow (8-12 Hz) and fast (13-16 Hz) SFA	Changes in slow (8-12 Hz) and fast (13-16 Hz) spindle characteristics (density) using STIM-PRE and POST-PRE contrasts	during each of the 3 overnight visits, 5 weeks
Spindle Amplitude in slow (8-12 Hz) and fast (13-16 Hz) SFA	Changes in slow (8-12 Hz) and fast (13-16 Hz) spindle characteristics (amplitude) using STIM-PRE and POST-PRE contrasts	during each of the 3 overnight visits, 5 weeks
Spindle Duration in slow (8-12 Hz) and fast (13-16 Hz) SFA	Changes in slow (8-12 Hz) and fast (13-16 Hz) spindle characteristics (duration) using STIM-PRE and POST-PRE contrasts	during each of the 3 overnight visits, 5 weeks
Spindle Topography in slow (8-12 Hz) and fast (13-16 Hz) SFA	Changes in slow (8-12 Hz) and fast (13-16 Hz) spindle characteristics (topography) using STIM-PRE and POST-PRE contrasts	during each of the 3 overnight visits, 5 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Spectral Power (SFA) for SHAM during slow vs fast conditions	Changes in slow (8-12 Hz) and fast (13-16 Hz) spectral power relative to SHAM	during each of the 3 overnight visits, 5 weeks
Changes in slow-wave spectral power (0.5-4.0 Hz) relative to SHAM	Changes in slow-wave spectral power (0.5-4.0 Hz) relative to SHAM	during each of the 3 overnight visits, 5 weeks
Changes in Slow-wave Density	Changes in slow-wave characteristics (density) in STIM-PRE and POST-PRE contrasts.	during each of the 3 overnight visits, 5 weeks
Changes in Slow-wave Amplitude	Changes in slow-wave characteristics (amplitude) in STIM-PRE and POST-PRE contrasts.	during each of the 3 overnight visits, 5 weeks
Changes in Slow-wave Duration	Changes in slow-wave characteristics (duration) in STIM-PRE and POST-PRE contrasts.	during each of the 3 overnight visits, 5 weeks
Changes in Spindle and Slow Oscillation Coupling	Changes in SO-Spindle coupling, quantified via phase-amplitude coupling metrics	during each of the 3 overnight visits, 5 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in directed hdEEG functional connectivity	Changes in directed hdEEG functional connectivity measured using the phase slope index (PSI), with effects assessed over stimulation-related intervals (STIM-PRE and POST-PRE).	during each of the 3 overnight visits, 5 weeks

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Larissa Albantakis, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: March 23, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: sleep; neurobiology; brain stimulation; SSD; impairment; non-invasive stimulation; spindles; non-rapid eye movement
• Additional Relevant MeSH Terms: Investigative Techniques; Chemistry Techniques, Analytical; Spectrum Analysis; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: 2026-0034; SMPH | Psychiatry (Other Identifier: UW Madison); R21MH141540 (U.S. NIH Grant/Contract: NIMH); Protocol Version 4/9/26 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No