Testing the safety of non-invasive transcranial ultrasound stimulation in people with essential tremor

INTERVENTION: Participants receive a single session of low‐intensity transcranial ultrasound stimulation (TUS), delivered with the Meridian device and targeting the ventral intermediate nucleus (VIM) of the thalamus in one hemisphere (left or right, randomised 1:1 using a computer‐generated sequence). The session comprises four stimulation conditions, one of which is a sham (control) condition; participants are not told which condition is the sham. Hand tremor is measured by accelerometers during the session and for up to 60 minutes afterwards. Participants attend a screening visit including a brain MRI scan (Visit 1), the stimulation session lasting approximately 2.5 to 3 hours (Visit 2), and a telephone follow‐up approximately 24 hours later (Visit 3); total participation is approximately 2 to 4 weeks. CONDITION: Essential tremor ; Nervous System Diseases PRIMARY OUTCOME: Safety measured using adverse event and device deficiency recording (incidence, nature, severity, and relationship to device or procedure) at each study contact from consent to the 24‐hour follow‐up (Visit 3) Target engagement (tremor modulation) measured using log‐transformed accelerometer‐derived tremor band power (3‐12 Hz) in the hand contralateral to the stimulated hemisphere, comparing the pre‐stimulation baseline with the active stimulation and post‐stimulation periods, pooled across the active conditions and compared with sham at the single intervention session (Visit 2) SECONDARY OUTCOME: Clinical tremor severity measured using the TETRAS Performance Subscale and Archimedes spiral drawing at baseline and post‐intervention (TETRAS), and after each stimulation condition and at 30 and 60 minutes during follow‐up (spirals) (Visit 2) Laterality of effect measured using accelerometer‐derived tremor amplitude in the ipsilateral hand (within‐subject control) compared with the contralateral hand at the intervention session (Visit 2) Participant experience and tolerability measured using participant‐reported sensations, a tolerability questionnaire, and the Patient Global Impression of Change at the end of each stimulation condition and the end of the session (Visit 2), and the 24‐hour telephone follow‐up (Visit 3) Time course and durability of tremor modulation measured using accelerometer‐derived tremor amplitude at 5‐minute intervals for up to 60 minutes during the post‐stimulation follow‐up (Visit 2) INCLUSION CRITERIA: 1. Adults aged 18‐80 years 2. Clinical diagnosis of essential tremor according to Movement Disorder Society consensus criteria 3. Tremor affecting both upper limbs, defined as TETRAS Performance Subscale item 4 (upper limb tremor) score >=1.5 in both upper limbs 4. Tremor duration of at least 3 years 5. Suboptimal response to, intolerance of, contraindication to, or preference not to use at least one first‐line medication (propranolol, primidone) 6. Stable dose of tremor medication for at least 2 weeks prior to screening, or medication‐naive 7. Able to maintain a postural hold position for tremor assessment (repeated blocks of 30 seconds) 8. Able to provide written informed consent, comply with study procedures, and communicate in English