Wearable Neural Interfacing System for REM Sleep Restoration and Enhancement

NCT ID: NCT07190287

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-15
• Study Completion Date: 2025-10-03

Brief Summary

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.

Detailed Description

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.

Phase 4 (REM modulation in participants with non-clinical sleep disturbance) enrolls 12 adults with elevated sleep complaints and perceived stress for the same two-night protocol; exploratory outcomes include self-reported stress measures collected around the FUS night.

Two fMRI paradigms are used across phases. In Phase 2, a same-session MRI-FUS visit includes pre-stimulation and post-stimulation fMRI acquisitions in the same session (healthy imaging-validation subset). In Phases 3 and 4, participants complete morning-before (pre-FUS night) and morning-after (post-FUS night) fMRI sessions to assess changes around the overnight REM-timed stimulation.

Safety procedures include MRI screening where applicable, continuous adverse event capture, stop rules for stimulation, and post-visit follow-up. Ultrasound exposure is controlled within established diagnostic ultrasound limits (e.g., MI <= 1.9 and derated time-averaged intensity within applicable FDA limits), with device-level acoustic verification prior to use. Data monitoring is performed by the study team with predefined criteria for pausing or discontinuation. Findings will inform the feasibility of a wearable EEG-tFUS approach for REM-related modulation and guide parameters for future controlled trials.

Conditions

Sleep Disturbance; Stress, Psychological; REM Sleep Measurement

Keywords

Transcranial Focused Ultrasound (tFUS); Wearable EEG; Sleep Modulation; REM Sleep; Subthalamic Nucleus; Closed-Loop Neuromodulation; Non-invasive Brain Stimulation; Stress Adaptation; Neural Interface

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

NEUSleeP system (FUS-EEG wearable device)

Intervention Type: DEVICE

The NEUSleeP system is a wearable FUS-EEG device integrating hydrogel-based EEG and focused ultrasound neuromodulation. The intervention includes:

1. Device testing in 4 healthy volunteers to assess EEG signal and impedance over 4 weeks vs. wet electrodes;

2. STN targeting validation in up to 20 participants using MRI-guided tFUS with NEUSleeP and BrainSonix Pulsar 1002, with fMRI analysis of BOLD activation in stress-related areas (amygdala, insula);

3. REM sleep modulation in 16 healthy participants across two nights, evaluating REM sleep architecture and stress-related fMRI changes following STN stimulation during REM;

4. A similar protocol in 12 individuals with self-reported poor sleep and moderate stress, assessing subjective stress (PSS), sleep dynamics, and connectivity changes post-tFUS.

BrainSonix Pulsar 1002

Intervention Type: DEVICE

The BrainSonix Pulsar 1002 is a research-grade focused ultrasound device used to evaluate STN targeting in up to 20 healthy participants. COMSOL 2D acoustic simulations and structural MRI are used to localize the STN. The BrainSonix system is tuned and installed for STN stimulation during fMRI scanning. Pre- and post-stimulation fMRI is conducted to verify BOLD signal changes in the STN and related regions. These responses are compared with those from NEUSleeP stimulation, using identical imaging protocols. Ultrasound parameters are iteratively adjusted to optimize targeting while adhering to FDA diagnostic ultrasound safety limits. A linear mixed model is used to assess stimulation-induced changes.

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.

Group Type: EXPERIMENTAL

NEUSleeP system (FUS-EEG wearable device)

Intervention Type: DEVICE

The NEUSleeP system is a wearable FUS-EEG device integrating hydrogel-based EEG and focused ultrasound neuromodulation. The intervention includes:

1. Device testing in 4 healthy volunteers to assess EEG signal and impedance over 4 weeks vs. wet electrodes;

2. STN targeting validation in up to 20 participants using MRI-guided tFUS with NEUSleeP and BrainSonix Pulsar 1002, with fMRI analysis of BOLD activation in stress-related areas (amygdala, insula);

3. REM sleep modulation in 16 healthy participants across two nights, evaluating REM sleep architecture and stress-related fMRI changes following STN stimulation during REM;

4. A similar protocol in 12 individuals with self-reported poor sleep and moderate stress, assessing subjective stress (PSS), sleep dynamics, and connectivity changes post-tFUS.

Interventions

NEUSleeP system (FUS-EEG wearable device)

The NEUSleeP system is a wearable FUS-EEG device integrating hydrogel-based EEG and focused ultrasound neuromodulation. The intervention includes:

1. Device testing in 4 healthy volunteers to assess EEG signal and impedance over 4 weeks vs. wet electrodes;

2. STN targeting validation in up to 20 participants using MRI-guided tFUS with NEUSleeP and BrainSonix Pulsar 1002, with fMRI analysis of BOLD activation in stress-related areas (amygdala, insula);

3. REM sleep modulation in 16 healthy participants across two nights, evaluating REM sleep architecture and stress-related fMRI changes following STN stimulation during REM;

4. A similar protocol in 12 individuals with self-reported poor sleep and moderate stress, assessing subjective stress (PSS), sleep dynamics, and connectivity changes post-tFUS.

Intervention Type: DEVICE

BrainSonix Pulsar 1002

The BrainSonix Pulsar 1002 is a research-grade focused ultrasound device used to evaluate STN targeting in up to 20 healthy participants. COMSOL 2D acoustic simulations and structural MRI are used to localize the STN. The BrainSonix system is tuned and installed for STN stimulation during fMRI scanning. Pre- and post-stimulation fMRI is conducted to verify BOLD signal changes in the STN and related regions. These responses are compared with those from NEUSleeP stimulation, using identical imaging protocols. Ultrasound parameters are iteratively adjusted to optimize targeting while adhering to FDA diagnostic ultrasound safety limits. A linear mixed model is used to assess stimulation-induced changes.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Adults aged 18-50, willing and able to undergo MRI, EEG, and FUS experiments.

• Adults aged 18-50, willing and able to undergo EEG and FUS experiments.
• Pittsburgh Sleep Quality Index (PSQI) score between 5 and 10.
• Perceived Stress Scale (PSS) score between 16 and 21.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Texas at Austin

OTHER

Sponsor Role: lead

Responsible Party

Evan (Huiliang) Wang

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Huiliang (Evan) Wang, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The University of Texas at Austin

Locations

UT Austin, Biomedical Engineering Department

Austin, Texas, United States

Countries

United States

References

Summers J, Nowicki M. Managing organizational improvement in a resource-challenged environment. Healthc Financ Manage. 2002 Jul;56(7):60-2. No abstract available.

Reference Type: BACKGROUND

PMID: 12119832 (View on PubMed)

Cicolin A, Lopiano L, Zibetti M, Torre E, Tavella A, Guastamacchia G, Terreni A, Makrydakis G, Fattori E, Lanotte MM, Bergamasco B, Mutani R. Effects of deep brain stimulation of the subthalamic nucleus on sleep architecture in parkinsonian patients. Sleep Med. 2004 Mar;5(2):207-10. doi: 10.1016/j.sleep.2003.10.010.

Reference Type: BACKGROUND

PMID: 15033145 (View on PubMed)

Legon W, Sato TF, Opitz A, Mueller J, Barbour A, Williams A, Tyler WJ. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat Neurosci. 2014 Feb;17(2):322-9. doi: 10.1038/nn.3620. Epub 2014 Jan 12.

Reference Type: BACKGROUND

PMID: 24413698 (View on PubMed)

Other Identifiers

HR00112490328

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

STUDY00005703

Identifier Type: -

Identifier Source: org_study_id