Skin-attached bioadhesive patch enabling ultrasound deep brain stimulation and real-time electrophysiological monitoring for REM sleep enhancement
Kai Wing Kevin Tang, Benjamin Baird, William D. Moscoso-Barrera, Mengxia Yu, Mengmeng Yao, Jinmo Jeong, Ilya Pyatnitskiy, Anakaren Romero Lozano, Jiachen Wang, Ju-Chun Hsieh, Tony Sungjin Chae, Daniel Song, Julieta Garcia, Rithvik Mittapalli, Adam Bush, Wynn Legon, Vincent Mysliwiec, Gregory A. Fonzo, Huiliang Wang
Nature Communications 2026 · 10.1038/s41467-026-73787-6
Abstract
Wearable bioelectronic interfaces capable of simultaneous neural sensing and targeted deep brain modulation remain limited by the lack of non-invasive technologies with sufficient spatial precision and mechanical stability for continuous operation. Here we report NEUSLeeP, a flexible skin-attached bioadhesive patch integrating electrophysiological sensing with transcranial focused ultrasound neuromodulation. The system incorporates a tunable concentric-ring ultrasound array, conformal hydrogel electrophysiological electrodes, and compliant interconnects within a soft substrate optimized for stable overnight operation. This integrated architecture enables spatially selective modulation and concurrent electrophysiological monitoring of deep brain structures, specifically the subthalamic nucleus during natural sleep. In a 28-participant study, NEUSLeeP demonstrated robust monitoring of sleep performance with precise-targeted neuromodulation of STN resulting in an increase in REM duration by 4.6% and reducing REM latency by 24%. This work establishes an ultrasound bioelectronic platform for non-invasive, spatiotemporally precise modulation and monitoring of deep neural circuits for neuroscience and bioelectronic medicine. ClinicalTrials.gov identifier: NCT07190287.
Abstract via europepmc.
Exposures
Exposure 1: STN-FUS with NEUSLeeP/CRUTA (target engagement study and overnight REM sleep study)
Target: subthalamic nucleus — “left subthalamic nucleus (STN)”
Device: custom-built · Concentric Ring Ultrasound Transducer Array (CRUTA)
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓⚑ |
| Sonication duration (s) | 30 | ✓✓✓⚑ |
| Free-field pressure (kPa) | 900 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 26.9 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 0.674 | ✓✓✓ |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | 680 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 15.4 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.385 | ✓✓✓ |
In an initial single-session target-engagement study (n=16), participants received 10 min of FUS delivered as 10 blocks of 30 s ON / 30 s OFF (Pressure 0.90 MPa, PRF 100 Hz, pulse duration 0.5 ms), before/after resting-state fMRI. In the subsequent overnight sleep study, participants underwent two consecutive overnight sessions (sham night 1, FUS night 2); on the FUS night, stimulation (30 s ON/30 s OFF for 5 min) was delivered per block every 90 min for five blocks overnight. Table 1 also reports a 'Burst Duty' of 50% (the 30 s ON/30 s OFF cycling) in addition to the 5% 'Pulse Duty' derived from the 0.5 ms pulse within the 10 ms PRF period. A separate preliminary pilot study (cited as ref 68, fMRI-compatible BrainSonix device) tested 10 Hz vs 100 Hz PRF at 5% duty cycle and ~719 mW/cm2 derated ISPTA, finding a PRF-dependent bimodal (excitatory at 10 Hz, inhibitory at 100 Hz) effect; frequency and other parameters for that pilot device are not given in the main text.
Flags from extraction
n_subjects— 28 subjects were recorded (healthy n=16, insomnia n=12) but 2 were excluded from analysis for excessive noise (subjects #1 and #25), leaving 26 analysed ('the observed effects of NEUSLeeP enabled STN-FUS in 26 subjects'); enrolled/recorded total (28) is reported here per convention. It is also unclear whether the 16 healthy participants overlap with the separately described 16-participant STN target-engagement sub-study (mean age reported as 25.7±6.3 years there vs. 22.7±5.4 years for the healthy REM-study group).n_sessions_per_subject— the value of 2 reflects the two consecutive overnight sessions (sham + FUS) of the main REM sleep study; a subset of participants may have also undergone an earlier single-session STN target-engagement scan (10 min FUS with pre/post fMRI), which would add a session not counted here.exposures[0].timing.sonication_duration_s— the paper reports the sonication structure at several nested timescales (30 s ON/OFF block cycling; 5 or 10 min per experimental block; 10 min total for the engagement study); 30 s (the length of one uninterrupted ON period) was recorded as sonication_duration_s per the definition, with the other durations placed in protocol_description.exposures[0].timing.duty_cycle_pct— Table 1 reports both a 'Pulse Duty' of 5% (matching 0.5 ms pulse duration at 100 Hz PRF) and a separate 'Burst Duty' of 50% (the 30 s ON/30 s OFF block cycling); 5% (Pulse Duty) was recorded as duty_cycle_pct and the 50% Burst Duty is described in protocol_description.exposures[0].device.manufacturer— CRUTA is described as a custom-made transducer array built by the authors; no external manufacturer is named for the transducer itself (the driving electronics, Vantage 64LE, are from Verasonics).condition_other— the insomnia subgroup was screened by PSQI score only and explicitly described as not having received a formal clinical diagnosis; classified under 'other' rather than as a distinct clinical condition.