Accelerated Transcranial Ultrasound Neuromodulation in Parkinson's Disease: A Pilot Study
Nardin Samuel, Mandy Yi Rong Ding, Can Sarica, Ghazaleh Darmani, Irene E. Harmsen, Talyta Grippe, Xingyu Chen, Andrew Yang, Negar Nasrkhani, Ke Zeng, Robert Chen, Andres M. Lozano
Movement Disorders 2023, 38, 2209-2216 · 10.1002/mds.29622
Abstract
Objective Low-intensity transcranial focused ultrasound (TUS) is a novel method for neuromodulation. We aimed to study the feasibility of stimulating the bilateral primary motor cortices (M1) with accelerated theta-burst TUS (a-tbTUS) on neurophysiologic and clinical outcomes in Parkinson's disease (PD). Methods Patients were randomly assigned to receive active or sham a-tbTUS for the first visit and the alternate condition on the second visit, at least 10 days apart. a-tbTUS was administered in three consecutive sonications at 30-minute intervals. We used an accelerated protocol to produce an additive effect of stimulation. Patients were studied in the OFF-medication state. Transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) were used to assess motor cortical excitability before and after TUS. Clinical outcomes after a-tbTUS administration were assessed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS)-III. Results A total of 20 visits were conducted in 10 PD patients. Compared to the baseline, TMS-elicited MEP amplitudes significantly increased following active but not sham sonication (P = 0.0057). MEP amplitudes were also higher following a-tbTUS than sham sonication (P = 0.0064). There were no statistically significant changes in MDS-UPDRS-III scores with active or sham a-tbTUS. Conclusions a-tbTUS increases motor cortex excitability and is a feasible non-invasive neuromodulation strategy in PD. Future studies should determine optimal dosing parameters and the durability of neurophysiologic and clinical outcomes in PD patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Abstract via europepmc.
Exposures
Exposure 1: Accelerated theta-burst TUS (a-tbTUS) to bilateral M1
Target: primary motor cortex — “bilateral primary motor cortex (M1), hand area”
Device: Sonic Concepts · Sonic Concepts Inc. · H246 ✓
| Waveform | theta burst | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 5 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | 80 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reportedsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 2.26 | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 0.23 | ✓✓✓ |
The tbTUS paradigm consisted of an 80 s train of pulses with a pulse repetition frequency of 5 Hz, pulse duration of 20 ms, ultrasonic stimulus duration of 200 ms, and duty cycle of 10%, for a total of 400 pulses. a-tbTUS was administered in three consecutive sonications at 30-minute intervals to bilateral M1, with the side sonicated first randomly assigned at each visit.
Flags from extraction
exposures[0].timing.protocol_description— The paradigm also states an 'ultrasonic stimulus duration of 200 ms' and a total of 400 pulses, which do not map cleanly onto the four timing fields (though duty cycle/PRF is self-consistent with the stated 20 ms pulse duration); recorded in protocol_description.exposures[0].in_situ.isppa_w_cm2— Paper describes these as 'estimated ... at the M1 target' (in-brain) intensities from a prior calibration study, but does not state whether this was simulation, derating, or measurement; domain (in_situ vs free_field) inferred from 'at the M1 target' wording.