An interventional study of Transcranial focused ultrasound delivered to the dentate nucleus using the NeuroFUS Pro by Brainbox and Transcranial focused ultrasound delivered to the ventricles (control) using the NeuroFUS Pro by Brainbox in Essential Tremor, sponsored by KU Leuven. Not yet recruiting at 1 site in Belgium. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-04-02.
Sponsored by KU Leuven · Not applicable, Interventional, and Basic science
Experiment 1: Modulation of Physiological Tremor in Healthy Volunteers Thirty healthy volunteers will undergo TUS targeting the dentate nucleus in a randomized, double-blinded crossover design. Tremor amplitude, induced by a 15 g weight, will be measured using an accelerometer, and EEG will assess neural oscillations and cerebello-thalamo-cortical connectivity.
Stimulation will include short-term (1 minute on/off for 12 minutes) and long-term (30 minutes) protocols, as well as closed-loop TUS for phase-specific effects. This experiment aims to optimize stimulation parameters and explore the dentate nucleus's role in tremor generation.
Experiment 2: Tremor Modulation in Essential Tremor Patients Thirty ET patients will receive TUS targeting the dentate nucleus with optimized parameters from Experiment 1 in a randomized crossover design. The best protocol from previous experiment will be tested here. Tremor amplitude and EEG will be recorded to assess short- and long-term effects of TUS on pathological tremor.
Experiment 1: Modulation of Physiological Tremor in Healthy Volunteers This is a randomized, double-blinded, crossover study involving 30 healthy volunteers. Healthy volunteers will be recruited from campus with a flyer and using social media platforms. Each participant will undergo two conditions: on-target transcranial focused ultrasound stimulation (TUS) to the dentate nucleus and off-target (sham) stimulation. Initial screening will be performed via phone, after which an informed consent will be signed. The full experiment will consist of four separate visit days, of which only the first one will take place at the UZ Leuven department of Radiology. Visit days 2-4 will entirely be performed at the KU Leuven Brainshub facility in gebouw De Nayer.
Experiment 2: Tremor Modulation in Essential Tremor Patients Building on the results from Experiment 1, 30 ET patients will participate in a similar crossover design. Patients will be recruited by a neurologist collaborating on this project. The optimized TUS parameters from Experiment 1 will be used to target the dentate nucleus. The most optimal protocol for tremor reduction will be selected during this experiment. Thus, experiment 2 will exist of one visit day for imaging and another visit day to test the most optimal TUS protocol. Similarly, tremor amplitude will be measured using an accelerometer, and EEG will monitor neural activity during stimulation.
Experiment 1: Healthy Volunteers
Experiment 2: ET Patients
Exclusion Criteria:
Experiment 1: Healthy volunteers
Experiment 2: ET Patients
Participants in this arm will receive on-target stimulation first, followed by the sham condition
Device: Transcranial focused ultrasound delivered to the dentate nucleus using the NeuroFUS Pro by Brainbox · Device: Transcranial focused ultrasound delivered to the ventricles (control) using the NeuroFUS Pro by Brainbox
Participants in this arm will receive sham stimulation first, followed by the on-target stimulation
Device: Transcranial focused ultrasound delivered to the dentate nucleus using the NeuroFUS Pro by Brainbox · Device: Transcranial focused ultrasound delivered to the ventricles (control) using the NeuroFUS Pro by Brainbox
This study will look at both physiological tremor in healthy volunteers and pathological tremor in ET patients. A set of parameters will be tested in healthy volunteers and the optimal combination of pulse repetition frequency (PRF) and pulse duration (PD) will be selected. A closed-loop system will also be tested where the timing of the ultrasound pulses is locked to the peak or the trough of the measured tremor and can adjust in real-time.
This condition will serve as the active control (sham stimulation).
Tremor amplitude
Extracted from accelerometer data. The PCA component will be calculated by combining data from all three accelerometer axis (x, y and z). The power spectral density average of this PCA component will be calculated before (1min), during and after (1 min) stimulation. The primary outcome is the change in tremor amplitude (m/s²) across pre-, during-, and post-TUS conditions.
Time frame: Experiment 1 (short-term effects): 1-minute recording segments up to 10 minutes after stimulation, Experiment 1(long-term effects): Up to 30 minutes after stimulation Experiment 2 (Essential tremor): Up to 30 minutes after stimulation
Tremor frequency
Tremor frequency will be derived from the same one-dimensional signal obtained via principal component analysis (PCA) of the triaxial accelerometer data. The power spectral density (PSD) will be estimated using Welch's method for each recording segment (pre-TUS, during TUS, post-TUS). The dominant tremor frequency will be defined as the frequency corresponding to the maximum PSD value within the predefined tremor band (e.g., 4-12 Hz) (expressed in Hz)
Time frame: Experiment 1 (short-term effects): 1-minute recording segments up to 10 minutes after stimulation, Experiment 1 (long-term effects): Up to 30 minutes after stimulation Experiment 2 (Essential tremor): Up to 30 minutes after stimulation
EEG oscillatory activity
Absolute and relative power change per band (post-TUS vs baseline, and vs sham/off-target). Power spectral density will be calculated and band-limited power will be extracted: Alpha (8-12 Hz), beta (13-30 Hz),Theta (4-8 Hz) and gamma (\>30 Hz).
Time frame: Experiment 1 (short-term effects): 1-minute segments of on/off stimulation from 10 minutes before stimulation up until 10 minutes after stimulation Experiment 1 (long-term effects) & 2: 10 minutes before stimulation up until 30 minutes after stimulation
EEG Phase
EEG phase (radians) using Hilbert transform at the tremor frequency will be extracted per channel.
Time frame: Experiment 1 (short-term): During 1-minute segments of ON-stimulation Experiment 1 (long-term): During full 30-minute stimulation session. Experiment 2 (essential tremor): During full 30-minute stimulation session.
Phase-Locking Value
Alignment of the instantaneous phase of the EEG signal to TUS pulses (PRF). range 0-1 with 0 = random phase, 1 = perfect alignment
Time frame: Experiment 1 (short-term): During 1-minute segments of ON-stimulation Experiment 1 (long-term): During full 30-minute stimulation session. Experiment 2 (essential tremor): During full 30-minute stimulation session.
Plan to share: No
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