Low-intensity transcranial ultrasound effects on the ventral intermediate nucleus and zona incerta in Parkinson's disease tremor

Maggie Q. Vuong, Varsha Sreenivasan, Soojin Lee, Ben Quinn, Martin S. Keung, Michael Grundy, Juana Ayala Castañeda, Hongchae Baek, Martin J. McKeown

Brain Stimulation 2026, 19, 103025 · 10.1016/j.brs.2026.103025

human patientparkinsons diseasefmribehaviourclinical scale

Abstract

Background Tremor in Parkinson's disease (PD) is a disabling symptom that often persists despite pharmacological treatment. High-intensity focused ultrasound (HIFU) targeting the ventral intermediate nucleus (VIM) alleviates Essential Tremor, but recent evidence suggests the zona incerta (ZI) may be a superior target for Parkinsonian tremor. This study compared the effects of transcranial ultrasound stimulation (TUS) to the VIM and ZI on postural and rest tremor, and examined related neural correlates using resting-state fMRI (rs-fMRI). Methods In this within-subject, crossover study, 19 participants with PD and right-hand tremor received both left VIM- and ZI-TUS on the same day in randomized order, separated by a 4-h washout period. Tremor severity and rs-fMRI data were collected before and after each session. Normalized changes in tremor intensity, resting-state functional connectivity (Δrs-FC), and fractional amplitude of low-frequency fluctuations (ΔfALFF) within the cerebello-thalamo-cortical network were analysed. Results TUS effects differed by target and tremor type. VIM-TUS significantly reduced postural tremor (p Conclusion ZI-TUS modulates tremor more robustly than VIM-TUS, suggesting that ZI may be a promising target for treatment of Parkinsonian tremor.

Abstract via europepmc.

Specieshuman

Subjects20 participants

Sessions per subject2

Randomisedyes

Blindingsingle

Sham / controlnone

Auditory controlnot reported

Readout timingoffline

Anaesthesianot applicable

Readoutsfmri, behaviour, clinical scale — UPDRS Part III; tri-axial accelerometer tremor recording (index finger, wrist, elbow) during postural/rest tremor and cognitive-motor exacerbation tasks; post-TUS phone survey (CGI-like 7-point quality-of-life scale, % tremor improvement, side effects)

Direction of effectmixed or unclearVIM-TUS significantly improved postural tremor but not rest tremor; ZI-TUS improved both postural and rest tremor in participants who received it first, but effects were order-dependent and could be exacerbated when a target was stimulated second (after prior stimulation of the other target on the same day).

Adverse eventsnone observedThere were no TUS-related side effects or adverse events; in a 1-week follow-up survey, most participants reported no change in overall symptoms and one participant reported feeling worse.

Exposures

Exposure 1: VIM-TUS

Target: ventral intermediate nucleus — “left ventral intermediate nucleus (VIM)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-500-4CH-042B (driver: NeuroFUS TPO-203-47) ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	500	✓✓✓
Pulse duration (ms)	0.5	✓✓✓
Pulse repetition frequency (Hz)	100	✓✓✓
Duty cycle (%)	5pulse duration × PRF gives 5%	✓✓✓
Sonication duration (s)	30	✓✓✓

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	simulation
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	not reported
In-situ Ispta (W/cm²)	not reported

Protocol, in the paper’s words

Each session comprised 30 s of stimulation followed by a 30 s inter-stimulus interval, repeated for a total stimulation duration of 10 min. Tremor assessment and resting-state fMRI were acquired once before and once immediately after TUS in each session.

Exposure 2: ZI-TUS

Target: zona incerta — “left zona incerta (ZI)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-500-4CH-042B (driver: NeuroFUS TPO-203-47) ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	500	✓✓✓
Pulse duration (ms)	0.5	✓✓✓
Pulse repetition frequency (Hz)	100	✓✓✓
Duty cycle (%)	5pulse duration × PRF gives 5%	✓✓✓
Sonication duration (s)	30	✓✓✓

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	simulation
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	not reported
In-situ Ispta (W/cm²)	not reported

Protocol, in the paper’s words

Flags from extraction

n_subjects — 20 participants were enrolled but one withdrew (19 completed the study); enrolled number (20) reported here per convention, flagged for the enrolled/completed discrepancy.
exposures[*].in_situ.reported_as — individual-specific stimulation intensities/pressures were simulated via k-Plan (Table S1, Fig. 1C) but the actual numeric pressure/intensity values are only shown in a supplementary table and a figure, not stated as numbers in the main text, so pressure_kpa/isppa/ispta are left not_reported despite method being described as simulation.
direction_of_effect — effects were target- and tremor-type-specific and also depended on stimulation order (exacerbation when a target was stimulated second), so a single excitatory/inhibitory label does not capture the full pattern; classified as mixed_or_unclear.