Evaluation of a Wearable EEG-tFUS System for REM Sleep Modulation in Healthy Adults and Individuals With Subclinical Sleep Disturbances
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Change in Total REM Sleep Time
研究概览
简要总结
This study evaluates a wearable system (NEUSleeP) that combines overnight EEG recording with transcranial focused ultrasound (tFUS) targeted to deep brain structures involved in REM sleep regulation (e.g., subthalamic nucleus). The primary objective is to assess safety and estimate effects on REM sleep quantity and architecture; secondary objectives include changes in stress-related measures.
Healthy adults aged 18-50, with or without subclinical sleep or stress complaints, will complete two consecutive overnight recordings: Night 1 (baseline, no stimulation) and Night 2 (tFUS, EEG-guided and timed to REM). Participants will complete stress questionnaires. fMRI is conducted using two paradigms: in an imaging-validation subset, pre- and post-stimulation scans are acquired in the same MRI-FUS session; in the two-night cohorts, scans are acquired the morning before and the morning after the FUS night to assess BOLD responses.
Outcomes include REM time, REM percentage, number of REM periods, REM latency, safety/tolerability, and exploratory neuroimaging and self-reported stress measures. Findings will inform the feasibility of a wearable EEG-tFUS approach to modulate REM sleep and stress adaptation.
详细描述
This study evaluates the safety, feasibility, and preliminary signals of effect of NEUSleeP, a wearable neural interface for closed-loop modulation of REM sleep using transcranial focused ultrasound (tFUS) targeted to the subthalamic nucleus (STN). The system integrates a flexible ultrasound transducer with bioadhesive hydrogel EEG electrodes in a patch designed for repeated overnight use. REM sleep is implicated in emotional regulation, memory processes, and stress adaptation. Existing noninvasive approaches have focused largely on NREM modulation; this study examines a REM-focused, target-directed approach to determine whether tFUS delivered during sleep can alter REM architecture and related outcomes.
The study comprises four phases:
Phase 1 (device functionality) enrolls four healthy volunteers for repeated bench and on-body checks (EEG signal quality, contact impedance stability, usability) over four weeks, with comparisons to standard clinical electrodes.
Phase 2 (STN stimulation and imaging validation) uses structural MRI and acoustic modeling to configure STN targeting for both a reference research system (BrainSonix Pulsar 1002) and NEUSleeP. In up to 20 healthy volunteers, functional MRI is acquired immediately before and immediately after the same MRI-FUS session to characterize BOLD responses in STN and stress-related networks (e.g., amygdala, insula), using identical imaging protocols across platforms.
Phase 3 (REM modulation in healthy volunteers) enrolls 16 adults for two consecutive overnight recordings: Night 1 baseline (no stimulation) and Night 2 tFUS (closed-loop stimulation time-locked to REM using EEG). Primary sleep outcomes include REM time, REM percentage, number of REM periods, and REM latency; safety and tolerability are recorded throughout.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for Healthy Volunteers:
- •- Adults aged 18-50, willing and able to undergo MRI, EEG, and FUS experiments.
- •Inclusion Criteria for Healthy Volunteers with Non-Clinical Sleep Disturbances:
- •Adults aged 18-50, willing and able to undergo EEG and FUS experiments.
- •Pittsburgh Sleep Quality Index (PSQI) score between 5 and
- •Perceived Stress Scale (PSS) score between 16 and 21.
排除标准
- •for Both Groups:
- •Current or past history of psychopathology, epilepsy, or other seizure disorders.
- •Inability to provide informed consent to undergo EEG recording, FUS stimulation, and MRI.
- •Diagnosed sleep disorders (e.g., insomnia, obstructive sleep apnea).
- •Contraindications to FUS or MRI, including but not limited to: history of stroke, brain tumors, brain hemorrhages, internal wires, electrodes, pacemakers, implants, irremovable ferromagnetic objects in the head that are unsafe for MRI and/or cause large imaging artifacts, brain surgery, moderate-to-severe head injury, any penetrating head injury, or uncontrolled thyroid disorder.
- •Pregnant individuals or those attempting to become pregnant (due to unknown MRI-related risks to fetuses).
- •Serious medical illnesses likely to interfere with study participation.
- •Current active suicidal or homicidal ideation (or suicide attempt within the past 3 months).
- •Current substance use disorder.
- •Current or recent (within the past 3 months) psychotic symptoms.
- •Currently meeting diagnostic criteria for a manic episode.
- •Currently engaged in evidence-based or experimental treatments (e.g., weekly cognitive behavioral therapy, transcranial magnetic stimulation, ketamine/esketamine treatment) other than psychiatric medications that have been on a stable dosage and regimen for at least 3 months (including antidepressants, mood stabilizers, atypical antipsychotics, and sedatives/hypnotics), in order to avoid confounding therapeutic effects.
研究组 & 干预措施
Healthy Volunteers - NEUSleeP Validation and Modulation
Participants will undergo three phases: (1) NEUSleeP device validation through biweekly EEG and impedance testing over 4 weeks (subset of participants); (2) STN targeting validation using BrainSonix and NEUSleeP with structural MRI and fMRI to assess BOLD response in the STN; and (3) overnight REM sleep modulation with NEUSleeP including EEG/EMG/EOG recordings and pre/post fMRI scans to assess stress-related brain activity and REM sleep outcomes.
干预措施: NEUSleeP system (FUS-EEG wearable device) (Device)
Healthy Volunteers - NEUSleeP Validation and Modulation
Participants will undergo three phases: (1) NEUSleeP device validation through biweekly EEG and impedance testing over 4 weeks (subset of participants); (2) STN targeting validation using BrainSonix and NEUSleeP with structural MRI and fMRI to assess BOLD response in the STN; and (3) overnight REM sleep modulation with NEUSleeP including EEG/EMG/EOG recordings and pre/post fMRI scans to assess stress-related brain activity and REM sleep outcomes.
干预措施: BrainSonix Pulsar 1002 (Device)
Subclinical Sleep Disturbance Group - NEUSleeP REM Modulation
Participants with non-clinical sleep and stress disturbances (PSQI 5-10, PSS 16-21) will undergo baseline overnight EEG/EMG/EOG recording followed by a second night of NEUSleeP-guided FUS stimulation targeting the STN. Pre- and post-intervention fMRI scans and stress questionnaires will assess neural and behavioral effects.
干预措施: NEUSleeP system (FUS-EEG wearable device) (Device)
结局指标
主要结局
Change in Total REM Sleep Time
时间窗: Night 1 (Baseline) and Night 2 (FUS); consecutive nights.
This measure evaluates the difference in total time (minutes) spent in rapid eye movement (REM) sleep between the baseline and stimulation nights, as recorded via EEG during overnight polysomnography. The goal is to assess whether STN-targeted tFUS delivered by NEUSLeeP enhances REM sleep duration.
Change in REM Sleep Percentage of Total Sleep Time
时间窗: Night 1 (Baseline) and Night 2 (FUS); consecutive nights.
Percentage of total sleep time spent in REM sleep will be compared between the baseline and stimulation nights to determine whether NEUSLeeP tFUS enhances REM architecture.
Change in STN BOLD Signal Following Ultrasound Stimulation
时间窗: pre-FUS (≤15 minutes before) and post-FUS (≤15 minutes after).
This outcome measures the change in blood-oxygen-level-dependent (BOLD) signal in the subthalamic nucleus (STN) before and after transcranial focused ultrasound (tFUS) stimulation using NEUSleeP and BrainSonix devices. Functional MRI will be used to assess activation in the STN and related regions (e.g., amygdala, insula). The goal is to evaluate device efficacy in modulating STN activity.
次要结局
- Change in Number of REM Sleep Cycles(Night 1 (Baseline) and Night 2 (FUS); consecutive nights.)
- Change in REM Sleep Latency(Night 1 (Baseline) and Night 2 (FUS); consecutive nights.)
- Change in Subjective Stress Levels (PSQ Score)(Night 2 (FUS): pre (≤24 hours before) and post (≤24 hours after).)
- Change in Stress-Related Brain Connectivity and Activation (fMRI)(Day 2 morning (pre-FUS night) and Day 3 morning (post-FUS night).)
研究者
Evan (Huiliang) Wang
Assistant Professor
University of Texas at Austin