Objective: Evaluate the neurophysiological and clinical effects of low-intensity transcranial ultrasound stimulation (TUS) of motor cortex (M1) in patients with Parkinson’s disease (PD).

Background: TUS is a non-invasive neuromodulation technique, which in theta burst mode (tbTUS) can increase cortical excitability, likely due to LTP-plasticity. PD has altered cortical excitability and plasticity of M1 and benefit from non-invasive stimulation in previous studies.

Method: We studied 17 PD patients (4F, 57.8 ± 8.6 years) in ON and OFF dopaminergic medication states, and 16 controls (5F, 62.9±9.2 years) were evaluated. tbTUS was applied for 80 seconds at M1 with 20W/cm². Motor evoked potential (MEP) was recorded at baseline, at 5-minutes (T5), T30, and T60 after tbTUS. Motor (m)UPDRS was evaluated in PD at baseline and T60 and scored by two blinded raters

Results: A linear mixed model on MEP amplitudes comparing controls to PD-ON showed  a significant effect of time ( F=5.30, p=0.002), with no effect of group (F=0.07, p=0.789) or interaction (group x time) ( F=0.88, p=0.454). Posthoc analysis of time showed differences between baseline and T30 (p=0.009) and T30 compared to T60 (p=0.004). When comparing controls with PD-OFF there was significant an effect of time (F = 33.48, p<0.001), with significant interaction between time and group (F = 3.20, p=0.027), and no effect of group (F = 2.92, p=0.098).  Posthoc analysis of time showed difference between T30 and T60 (p=0.04). The groups were compared at the different timepoints, there was a significant effect at T30 (p=0.012). The effect of the tbTUS was higher in controls than PD-OFF at T30. When comparing PD-ON with PD-OFF, there was a significant effect of group ( F= 4.41, p=0.038), with no effect of time (F = 0.445, p=0.721) or the interaction between time and group (F=0.741, p=0.530) (Figure 1). There was a significant difference in mUPDRS bradykinesia score between baseline and T60 in PD-ON  (Wilcoxon W, p = 0.043) but not in PD-OFF (p= 0.779). The total score and the other sub scores were not different when comparing baseline and T60 in PD-ON or PD-OFF (Figure 2).

Conclusion: The tbTUS induced motor cortical plasticity in older healthy controls and PD patients in ON, but not in OFF state. The PD-ON patients showed improvement of the motor symptoms, highlighting that tbTUS may have a symptomatic effect and could be further explored in future studies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-theta-burst-transcranial-ultrasound-stimulation-on-motor-cortex-excitability-in-parkinsons-disease/