Displacement-Guided Focused Ultrasound of the Median Nerve Modulates Somatosensory Evoked Potentials in Humans

Erica P. McCune, Samuel G. Blackman, Hermes A. S. Kamimura, Ethan V. Bendau, Talia D. Sachs, Seongyeon Kim, Stephen A. Lee, Christopher J. Winfree, Elisa E. Konofagou

IEEE Transactions on Biomedical Engineering 2026 · 10.1109/tbme.2025.3602291

human healthyhuman patienthealthyothereeg megclinical scale

Abstract

Objective This study investigated the attenuation of somatosensation in healthy subjects (n = 18) and subjects with carpal tunnel syndrome (CTS) (n = 6) via displacement-guided median nerve focused ultrasound (FUS). Somatosensory evoked potentials (SSEPs), pain, stiffness, and numbness were used as markers of sensation. Methods Electroencephalography (EEG) was used to evaluate changes in electrically-induced SSEPs when paired with FUS. Subjects underwent 1000 (healthy population) or 500 (CTS population) surface electrical pulses at a maximum rate of 1 Hz to the median nerve to invoke a thumb twitch. Half of these pulses were paired with 5 ms of upstream median nerve sonication from a 1.1 MHz transducer at 1.8 or 2.9 MPa derated peak-positive pressure. Results On-nerve sonication reduced the amplitude of SSEPs at both pressures. Reductions in beta and low-gamma frequency power occurred in healthy subjects and increases in alpha power occurred in CTS subjects. CTS subjects who received on-nerve sonication reported an average pain reduction of 40.6%. Off-nerve sonication did not reduce SSEP amplitudes or CTS symptoms. Median nerve displacement was correlated with SSEP reductions. Conclusion Sonication of the median nerve can attenuate SSEPs, potentially in a displacement dose-driven manner. Symptom reduction in CTS subjects lasted 1-3 days post-procedure. Nerve targeting is essential to ensure therapeutic efficacy. Significance This study is the first to demonstrate that peripheral nerve FUS modulates somatosensory-evoked potentials in humans. FUS attenuated neuropathic pain and stiffness related to median nerve entrapment, illustrating the potential analgesic effects of the procedure.

Abstract via europepmc.

Specieshuman

Subjects18, 6swept participants

Sessions per subject1

Randomisedyes

Blindingdouble

Sham / controlinactive transducer, active control site

Auditory controlnot reported

Readout timingboth

Anaesthesianot applicable

Readoutseeg meg, clinical scale — N20-P30 somatosensory evoked potential peak-to-peak amplitude (64-channel EEG); verbal pain rating (1-10 scale) and symptom description in CTS subjects

Direction of effectinhibitoryOn-nerve median nerve FUS reduced N20-P30 SSEP amplitude at both 1.8 and 2.9 MPa in healthy subjects and at 2.9 MPa in CTS subjects, and reduced verbal pain ratings by 40.6% on average in CTS subjects; off-nerve (active) control sonication instead slightly increased SSEP amplitude and produced no symptom change.

Adverse eventsnone observedNo inertial cavitation was detected at either sonication pressure, and room-temperature chicken breast sonicated at the higher dose (2.9 MPa, 1.1 MHz, 1 Hz PRF, 5 ms PD, 1000 pulses) produced only a 0.12°C peak temperature increase; no adverse events were reported by subjects.

Exposures

Exposure 1: Median nerve FUS (on-nerve), healthy and CTS subjects, 1.8 vs 2.9 MPa

Target: median nerve — “median nerve”
Device: Sonic Concepts · Sonic Concepts Inc. ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	1,100	✓✓✓
Pulse duration (ms)	5	✓✓✓
Pulse repetition frequency (Hz)	1, 0.5swept	✓✓✓
Duty cycle (%)	0.5, 0.25swept	✓✓✓
Sonication duration (s)	not reported	⚑

Pressure and intensity, by domain
Free-field pressure (kPa)	not reported
Free-field Isppa (W/cm²)	not reported
Free-field Ispta (W/cm²)	not reported
In-situ estimate	deratingsingle value
In-situ pressure (kPa)	1,800, 2,900swept	✓✓✓⚑
In-situ Isppa (W/cm²)	not reported
In-situ Ispta (W/cm²)	not reported

Protocol, in the paper’s words

Single 5 ms FUS pulses were triggered simultaneously with each median-nerve electrical stimulation pulse. Healthy subjects received 1000 electrical/FUS pulse pairs at 1 Hz (0.5% duty cycle); CTS subjects received 500 pairs at 0.5 Hz (0.25% duty cycle) to reduce discomfort. Non-randomized healthy subjects were sonicated at 1.8 MPa derated PPP; randomized healthy subjects and all CTS subjects were sonicated at 2.9 MPa derated PPP. A separate off-nerve (transducer moved ~3 cm laterally) active-control group was tested for each pressure/population.

Flags from extraction

n_subjects — Paper states group sizes separately (18 healthy, 6 CTS); no explicit combined total of 24 is given, so recorded as a list per the group-sizes rule.
exposures[0].in_situ.pressure_kpa — Pressures are stated as 'derated' peak-positive pressure; classified as in_situ/derating rather than free_field since the paper does not report a separate water-tank (free-field) value.
sham_type — Off-nerve sonication used real ultrasound output moved ~3 cm laterally from the nerve, classified as active_control_site; the paper describes it as an 'active sham'.
randomised — Design was mixed: the 1.8 MPa healthy group used a non-randomized order (single-blind), while the 2.9 MPa healthy and CTS groups used randomized order (double-blind); majority (15/24) were randomized so 'true' was chosen, with blinding set to 'double' for the same majority.
exposures[0].timing.sonication_duration_s — Total duration of the pulse train session is not stated directly in seconds (only pulse counts and repetition rates); left not_reported to avoid computing it.