Plasticity‐Induced Effects of Theta Burst Transcranial Ultrasound Stimulation in Parkinson's Disease
Talyta Grippe, Yazan Shamli‐Oghli, Ghazaleh Darmani, Jean‐François Nankoo, Nasem Raies, Can Sarica, Tarun Arora, Carolyn Gunraj, Mandy Yi Rong Ding, Cricia Rinchon, Daniel G. DiLuca, Samuel Pichardo, Francisco Cardoso, Andres M. Lozano, Robert Chen
Movement Disorders 2024, 39, 1364-1374 · 10.1002/mds.29836
Abstract
Background Low-intensity transcranial ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) technique with high spatial specificity. Previous studies showed that TUS delivered in a theta burst pattern (tbTUS) increased motor cortex (MI) excitability up to 30 minutes due to long-term potentiation (LTP)-like plasticity. Studies using other forms of NIBS suggested that cortical plasticity may be impaired in patients with Parkinson's disease (PD). Objective The aim was to investigate the neurophysiological effects of tbTUS in PD patients off and on dopaminergic medications compared to healthy controls. Methods We studied 20 moderately affected PD patients in on and off dopaminergic medication states (7 with and 13 without dyskinesia) and 17 age-matched healthy controls in a case-controlled study. tbTUS was applied for 80 seconds to the MI. Motor-evoked potentials (MEP), short-interval intracortical inhibition (SICI), and short-interval intracortical facilitation (SICF) were recorded at baseline, and at 5 minutes (T5), T30, and T60 after tbTUS. Motor Unified Parkinson's Disease Rating Scale (mUPDRS) was measured at baseline and T60. Results tbTUS significantly increased MEP amplitude at T30 compared to baseline in controls and in PD patients on but not in PD patients off medications. SICI was reduced in PD off medications compared to controls. tbTUS did not change in SICI or SICF. The bradykinesia subscore of mUPDRS was reduced at T60 compared to baseline in PD on but not in the off medication state. The presence of dyskinesia did not affect tbTUS-induced plasticity. Conclusions tbTUS-induced LTP plasticity is impaired in PD patients off medications and is restored by dopaminergic medications. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Abstract via europepmc.
Exposures
Exposure 1: tbTUS to primary motor cortex (M1)
Target: primary motor cortex — “primary motor cortex (M1), FDI hot spot”
Device: Sonic Concepts · Sonic Concepts Inc., Bothell, WA · custom 2-element annular array transducer (500 kHz, 38 mm diameter, 10 mm thickness) ✓
| 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) | 20 | ✓?⚑ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 2.93 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.29 | ✓✓✓ |
One pulse train of 80 seconds delivered to M1 (theta-burst pattern, tbTUS), pulse duration 20 ms, repetition interval 200 ms (PRF 5 Hz), fundamental frequency 500 kHz, duty cycle 10%, power setting 20 W/cm2; sonication depth set to 30 mm to approximate scalp-to-cortex distance; white noise masking delivered through earphones during the 80-s sonication.
Flags from extraction
n_subjects— Paper reports two distinct groups (20 PD patients, 17 healthy controls) rather than a single sweep; recorded as a list.exposures[0].free_field.isppa_w_cm2— The 20 W/cm2 'power setting' used to measure ISPPA/ISPTA in free water is not unambiguously stated as the measured free-field ISPPA value itself; interpreted as such because the derated in-situ values are given immediately afterward.blinding— No sham condition was used; only the video rater for mUPDRS was blinded. Classified as 'single' blinding (rater) but this does not reflect blinding of the TUS intervention itself, which was open (all groups received active tbTUS).n_sessions_per_subject— PD patients attended two sessions (on/off medication); number of sessions for healthy controls is not explicitly stated.
Notes: Case-control study (PD-on, PD-off, healthy controls); no sham TUS condition. Free-field vs in-situ (skull-derated, 75% attenuation assumption) intensities both reported for the same exposure.