Schizophrenia
Conditions
Keywords
schizophrenia spectrum disorders, sleep spindles, transcranial electrical stimulation with temporal interference
Brief summary
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.
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).
Interventions
DEVICETES-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.
DEVICESham TES-TI
ramp-sham stimulation only
Sponsors
University of Wisconsin, Madison
Alkermes, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
This is an experimental study using a within-subject, randomized, counterbalanced crossover design in which each participant serves as their own control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in spindle topography | data collected over two overnight visits separated by at least 2 weeks during stable N2 sleep | 8-16 Hz spectral power |
| 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 | data collected over two overnight visits separated by at least 2 weeks during stable N2 sleep | 8-16 Hz spectral power |
| Change in spindle amplitude | data collected over two overnight visits separated by at least 2 weeks during stable N2 sleep | 8-16 Hz spectral power |
| Change in spindle duration | data collected over two overnight visits separated by at least 2 weeks during stable N2 sleep | 8-16 Hz spectral power |
Countries
United States
Contacts
CONTACTONSETS Study
PRINCIPAL_INVESTIGATORLarissa Albantakis, PhD
University of Wisconsin, Madison
Outcome results
None listed