Cerebellar Research in Ultrasound Stimulation
ConditionEssential Tremor
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-75
SponsorKU Leuven
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Experiment 1: Healthy Volunteers
Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
Participants aged 18-55 years
Male of female
Disqualifiers
Experiment 1: Healthy volunteers
Currently taking any psychotropic medication
Any head trauma resulting in loss of consciousness
Diagnosed with a serious mental illness
Trial design
Design model
Crossover
Treatments tested in this trial
Transcranial focused ultrasound delivered to the dentate nucleus using the NeuroFUS Pro by Brainbox
DeviceThis 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.
Transcranial focused ultrasound delivered to the ventricles (control) using the NeuroFUS Pro by Brainbox
DeviceThis condition will serve as the active control (sham stimulation).
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: On-target to shamExperimental treatment 2 interventions
Group B: Sham to on-targetExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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 stimulation2
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 stimulationSecondary outcomes
1
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 stimulation2
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.3
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. Source ClinicalTrials.gov
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