Overnight Thalamic TES-TI to Modulate Sleep Spindles in Individuals With Schizophrenia Spectrum Disorders and Matched Healthy Controls (ONSETS)

A Pilot Feasibility Study of Overnight Thalamic TES-TI to Modulate Sleep Spindles in Individuals With Schizophrenia Spectrum Disorders and Matched Healthy Controls

This study to find out whether a type of non-invasive electrical brain stimulation called transcranial electrical stimulation with temporal interference (TES-TI) can temporarily change brain activity during sleep-especially sleep spindles (brain rhythms in the ~8-16 Hz range). The investigators are focusing on the thalamus, a deep brain region that helps coordinate brain activity during non-REM sleep. Sleep spindles are often reduced in schizophrenia, so this study is to see whether TES-TI can change spindle activity in individuals with schizophrenia spectrum disorders (SSD) and in healthy adults. To study this, a structural MRI scan will be used to customize where the stimulation electrodes are placed, and then TES-TI will be applied during one of two overnight sleep lab visits while brain activity is recorded with high-density EEG and standard sleep sensors. The other overnight is a baseline/control night during which only sham stimulation is delivered. The goal is to determine whether TES-TI during sleep can increase spindle-frequency activity in this population.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia
• Intervention / Treatment: Device: TES-TI; Device: Sham TES-TI

Detailed Description

This single-site, single-blind, proof-of-concept feasibility study will evaluate the feasibility of overnight thalamic transcranial electrical stimulation with temporal interference (TES-TI) to modulate sleep spindle activity during N2 sleep in individuals with schizophrenia spectrum disorders (SSD) and matched healthy controls (HC).

The study is investigational and is not designed or intended to provide therapeutic benefit; no treatment effect is claimed. After screening, consent, and clinical interview for individuals with SSD, participants will complete an MRI visit (T1, T2, DWI, and 10 min resting-state fMRI) for individualized montage optimization and two overnight hdEEG/PSG sessions in randomized, counterbalanced order, separated by at least two weeks: one baseline/control night with ramp-sham stimulation only, and one stimulation night. During the stimulation night, TES-TI will be delivered during stable N2 sleep in 3-minute epochs separated by 6-minute intervals, with up to 20 protocols per night, using randomized 10 Hz, 14 Hz, and carrier-only control conditions under continuous sleep-technician monitoring.

Primary physiological outcomes will assess changes in spindle-frequency activity and related spindle measures relative to baseline and carrier-only control. Exploratory analyses will compare baseline spindle deficits and TES-TI responsiveness across groups and examine whether stimulation-related changes are associated with cognitive performance, assessed using the Boston Cognitive Assessment (BoCA).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: ONSETS Study; Phone Number: 608-263-4313; Email: onsets@psychiatry.wisc.edu

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53719
      • Recruiting
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria (all participants):

• U.S. citizen or holding permanent resident status
• English-speaking

Inclusion Criteria (Participants with SSD):

• DSM-5 schizophrenia spectrum disorder (SSD) diagnosis, defined as schizophrenia, schizoaffective disorder, or schizophreniform disorder (confirmed by clinical interview and/or chart review)
• Chronic illness, defined as diagnosis of SSD for at least 1 year
• Clinically stable outpatient (no psychiatric hospitalization in past 6 months; no change in antipsychotic medication in the past 6 weeks)

Inclusion Criteria (Healthy Controls):

• Medically healthy (based on self-report and study team review)
• Matched to SSD participants on age (±5 years) and sex

Exclusion Criteria (all participants):

• Current or past history of clinically significant neurological disorder or acquired neurological disease (e.g., stroke, traumatic brain injury), including intracranial lesions (including clinically significant findings identified on the structural MRI)
• Active suicidal ideation, plan, or intent (assessed via PHQ-9 item 9 and follow-up Columbia-Suicide Severity Rating Scale (C-SSRS) Screener; see Safety Response Procedure)
• Inability to provide informed consent, including inadequate decisional capacity in the judgment of the study team and/or study psychiatrist
• History of head trauma resulting in prolonged loss of consciousness; or a history of >3 grade I concussions
• Current poorly controlled headaches, including intractable or frequent 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
• Current use of medications known to substantially lower seizure threshold, specifically chlorpromazine, clozapine, bupropion, clomipramine, or maprotiline; or other medications at doses known to substantially lower seizure threshold in the judgment of the PI or Study Psychiatrist
• Current use of medications known to directly and substantially enhance sleep spindle activity, including benzodiazepines; non-benzodiazepine "Z-drug" hypnotics (zolpidem, eszopiclone, zaleplon); barbiturates; and gabapentin or pregabalin, within 2 weeks of the overnight study visits. Other sedating medications used as sleep aids (e.g., trazodone, hydroxyzine, mirtazapine) are permitted provided the regimen is stable across the two overnight visits; dose and timing will be recorded as covariates
• Current moderate-to-severe alcohol or other substance use disorder (DSM-5) other than nicotine or caffeine
• Active scalp lesions, broken skin, or skin conditions at planned electrode sites that would preclude safe electrode application
• 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)

Exclusion Criteria (Healthy Controls):

• Self-reported history of inpatient psychiatric hospitalization
• Self-reported current or past diagnosis of schizophrenia or any other psychotic disorder
• Self-reported first-degree relative with schizophrenia or any other psychotic disorder
• Self-reported current or past diagnosis of bipolar disorder or major depressive disorder with psychotic features, or current treatment for any psychiatric disorder other than depression or anxiety (handled via the medication rule below)
• Current use of any psychotropic medication, with the exception of a single SSRI or SNRI taken at a stable dose for at least 6 weeks for depression or anxiety. Current use of antipsychotics, tricyclic antidepressants, mirtazapine, trazodone, lithium or other mood stabilizers, benzodiazepines, non-benzodiazepine hypnotics, other anxiolytics, or stimulants will result in exclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Controls	Device: TES-TI; During the stimulation night, TES-TI will be delivered during stable N2 sleep in 3-minute epochs separated by 6-minute intervals, with up to 20 protocols per night, using randomized 10 Hz, 14 Hz, and carrier-only control conditions under continuous sleep-technician monitoring.; Other Names: transcranial electrical stimulation with temporal interference; Device: Sham TES-TI; ramp-sham stimulation only
Experimental: Participants with SSD	Device: TES-TI; During the stimulation night, TES-TI will be delivered during stable N2 sleep in 3-minute epochs separated by 6-minute intervals, with up to 20 protocols per night, using randomized 10 Hz, 14 Hz, and carrier-only control conditions under continuous sleep-technician monitoring.; Other Names: transcranial electrical stimulation with temporal interference; Device: Sham TES-TI; ramp-sham stimulation only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in spindle-frequency activity (8-16 Hz spectral power)		data collected over two overnight visits separated by at least 2 weeks during stable N2 sleep
Change in spindle density	8-16 Hz spectral power	data collected over two overnight visits separated by at least 2 weeks during stable N2 sleep
Change in spindle amplitude	8-16 Hz spectral power	data collected over two overnight visits separated by at least 2 weeks during stable N2 sleep
Change in spindle duration	8-16 Hz spectral power	data collected over two overnight visits separated by at least 2 weeks during stable N2 sleep
Change in spindle topography	8-16 Hz spectral power	data collected over two overnight visits separated by at least 2 weeks during stable N2 sleep

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Alkermes, Inc.
• Investigators: Principal Investigator: Larissa Albantakis, PhD, University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 25, 2026
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 27, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: sleep spindles; schizophrenia spectrum disorders; transcranial electrical stimulation with temporal interference
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: 2026-0751; SMPH | Psychiatry (Other Identifier: UW Madison); Protocol Version 1 (Other Identifier: UW Madison)

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.: Yes