Noninvasive modulation of essential tremor with focused ultrasonic waves

Thomas S Riis, Adam J Losser, Panagiotis Kassavetis, Paolo Moretti, Jan Kubanek

Journal of Neural Engineering 2024, 21, 016033 · 10.1088/1741-2552/ad27ef

human patientessential tremorbehaviourclinical scale

Abstract

Objective : Transcranial focused low-intensity ultrasound has the potential to noninvasively modulate confined regions deep inside the human brain, which could provide a new tool for causal interrogation of circuit function in humans. However, it has been unclear whether the approach is potent enough to modulate behavior. Approach : To test this, we applied low-intensity ultrasound to a deep brain thalamic target, the ventral intermediate nucleus, in three patients with essential tremor. Main results : Brief, 15 s stimulations of the target at 10% duty cycle with low-intensity ultrasound, repeated less than 30 times over a period of 90 min, nearly abolished tremor (98% and 97% tremor amplitude reduction) in 2 out of 3 patients. The effect was observed within seconds of the stimulation onset and increased with ultrasound exposure time. The effect gradually vanished following the stimulation, suggesting that the stimulation was safe with no harmful long-term consequences detected. Significance : This result demonstrates that low-intensity focused ultrasound can robustly modulate deep brain regions in humans with notable effects on overt motor behavior.

Abstract via europepmc.

Specieshuman

Subjects3 participants

Sessions per subject1

Randomisedyes

Blindingnot reported

Sham / controlinactive transducer

Auditory controlmasking sound

Readout timingboth

Anaesthesianot applicable

Readoutsbehaviour, clinical scale — Hand-worn triaxial accelerometer (TSD109C2, Biopac Systems) tremor amplitude; Fahn-Tolosa-Marin Tremor Rating Scale

Direction of effectinhibitoryUltrasound to the VIM nearly abolished tremor amplitude (98% and 97% reduction) in 2 of 3 subjects; the third subject showed no significant tremor reduction (a non-significant increase).

Adverse eventsnone observedWe found that repeated stimulation of the VIM with focused ultrasound was well tolerated. The tremor amplitude returned to pre-stimulation state within about 20 minutes following the last stimulation, as judged by neurological examination (Methods). No adverse events were noted and subjects did not note any side effects in the 24 h post experiment they were monitored for.

Exposures

Exposure 1: Ultrasound to VIM of thalamus in essential tremor patients

Target: ventral intermediate nucleus — “ventral intermediate nucleus (VIM)”
Device: custom-built · two 126-element phased arrays (650 kHz), driven by a Vantage256 (Verasonics) system ✓

Pulse timing
Waveform	pulsed
Fundamental frequency (kHz)	650	✓✓✓
Pulse duration (ms)	10	✓✓✓
Pulse repetition frequency (Hz)	10	✓✓✓
Duty cycle (%)	10pulse duration × PRF gives 10%	✓✓✓
Sonication duration (s)	15	✓✓✓

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	measurementsingle value
In-situ pressure (kPa)	720	✓✓✓
In-situ Isppa (W/cm²)	16.12	✓✓✓
In-situ Ispta (W/cm²)	1.61	✓✓✓

Protocol, in the paper’s words

Brief, 15 s stimulations of the target at 10% duty cycle with low-intensity ultrasound, repeated less than 30 times (an average of 23 trials per subject) over a period of 90 min. Each 45 s trial consisted of a 15 s pre-sonication baseline, 15 s of ultrasound delivery, and a 15 s post-sonication window, with about 2 min rest between trials and a 15 min break in the middle of the 90 min session. Sham sonications, where no ultrasound was delivered within the trial, were interleaved randomly.

Flags from extraction

n_sessions_per_subject — Paper describes a single continuous 90-minute experimental session per subject but does not explicitly state 'one session'; coded as 1 based on the described single-session design.
exposures[0].device.family — Transducer arrays are the same custom-built (PMN-PT elements) system described in Riis et al. 2024, driven by a commercial Verasonics Vantage256 system; classified as custom_or_research for the transducer itself.