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

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

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).

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)