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Suppression of pathological oscillations with transcranial focused ultrasound in Parkinson’s disease

John Eraifej, Jake Toth, Jeremy Hanemaaijer, Shenghong He, Xinghao Cheng, Amir Puyan Divanbeighi Zand, Max E. Stewart, James J. FitzGerald, Christopher R. Butler, Timothy Denison, Alexander L. Green, Robin O. Cleveland

Nature Communications 2026 · 10.1038/s41467-026-70714-7

human patientparkinsons diseaseinvasive electrophysiologyeeg megbehaviourclinical scale

Abstract

Transcranial ultrasound stimulation (TUS) is an emerging method for non-invasive neuromodulation of deep brain structures. However, to date, there is no evidence that TUS can directly modulate disease-related pathological oscillations in the same direction as known therapies. Inspired by clinical deep brain stimulation, in this randomised controlled cross-over study we probed the effects of pallidal TUS pulsed at 130 Hz on subthalamic beta-band activity, a biomarker in Parkinson's Disease (PD) in four male participants with PD. Beta-band power reduced in the ipsilateral subthalamic nucleus (STN) by 10.34% (95% CI:3.81% to 16.87%, p 2 = 0.980, p < 0.05, FDR adjusted), but not contralateral, STN and primary motor cortex. Bradykinesia, as measured by change in reaction time, was also reduced by 17.70% (95% CI:8.95% to 26.41%, p < 0.05, FDR adjusted). In this proof of concept study, we demonstrate that TUS can suppress pathological oscillations, potentially opening the door for therapeutic TUS (NCT06932185).

Abstract via europepmc.

Specieshuman
Subjects4 participants
Sessions per subject2
Randomisedyes
Blindingdouble
Sham / controlundescribed, active control site
Auditory controlmasking sound
Readout timingonline
Anaesthesianot applicable
Readoutsinvasive electrophysiology, eeg meg, behaviour, clinical scale — STN local field potentials (Medtronic Percept); EEG; random dot-motion reaction time; stop-signal task; abbreviated UPDRS-III
Direction of effectinhibitoryGPi-TUS versus ventricle-TUS reduced ipsilateral STN beta power by 10.34% and median reaction time by 17.70%; abbreviated UPDRS-III not significantly changed.
Adverse eventsnot reportedThermal simulations gave a mean maximum temperature rise of 0.47 ± 0.37 °C; no clinical adverse-event report given.

Exposures

Exposure 1: 130 Hz GPi-TUS

Target: globus pallidus internus — “globus pallidus internus (GPi)”
Device: Sonic Concepts · Sonic Concepts Inc · H294 single element planar transducer, 64 mm diameter, with personalised PDMS acoustic lens ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)500✓✓✓
Pulse duration (ms)0.09✓✓✓
Pulse repetition frequency (Hz)130✓✓✓
Duty cycle (%)1.17pulse duration × PRF gives 1.17%✓✓✓
Sonication duration (s)0.8✓✓✓
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 estimatesimulationsingle value
In-situ pressure (kPa)600✓✓✓⚑
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

800 ms pulse trains repeated every 2.5 s; within each train 90 µs pulses at 130 Hz PRF (duty cycle 1.17%); five 5-minute active blocks per day, after a sham block, with an auditory masking signal.

Flags from extraction

  • exposures[0].in_situ.pressure_kpa — 600 kPa is the maximum of the simulated colour scale in brain tissue, not an explicitly stated delivered pressure; 600 kPa also used in the phantom artefact tests.
  • n_sessions_per_subject — Two study days (GPi and ventricle on separate consecutive days, each with sham block then TUS block); number of days inferred from the two targets.
  • sham_type — A sham block preceded each active block, mechanism not described; the ventricle was the active control site. Ventricle sonication is not recorded as a separate exposure.
  • exposures[0].free_field.pressure_kpa — Lens validation in water used 500 kHz, 20 cycles per pulse, but no pressure value is stated.