Location- and Frequency-Dependent Effects of Thalamic Temporal Interference Stimulation During Sleep

University of Wisconsin, Madison24 enrolled

Overview

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.

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).

Interventions

Magnetic Resonance Imaging (MRI)OTHER

MRI is to optimize placement of uni- or multipolar TI-TES

Broad thalamic stimulation (TI-TES)DEVICE

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

Carrier only SHAM stimulationDEVICE

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

Anterior thalamic stimulation (TI-TES)DEVICE

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

Posterior thalamic stimulation (TI-TES)DEVICE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)