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) in different disease stages.

Background: TUS is a non-invasive neuromodulation technique, which in theta burst mode (tbTUS) can increase cortical excitability up to 60 minutes, likely due to LTP-plasticity, in PD patients while on dopaminergic medication, but not in the off-medication state. The effects of tbTUS in denovo (untreated) PD patients is not known.

Method: We studied 7 denovo PD patients (3F, 66.4 ± 8.7 years), 19 PD patients OFF dopaminergic medication (4F, 59.6 ± 8.2 years), and 17 controls (6F, 63.7±9.2 years). tbTUS was applied for 80 seconds at M1 at intensity of 20W/cm2. Motor evoked potential (MEP) from transcranial magnetic stimulation 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 a rater blinded to the condition.

Results: A linear mixed model on the squared roots of the MEP amplitudes comparing controls to PD-OFF and denovo PD showed a significant effect of time ( F=6.15, p<0.001), interaction (group x time) (F=2.49, p=0.026), with no effect of group. Post-hoc analysis for time showed higher MEP amplitude at T30 compared to baseline (p=0.001) and at T30 compared to T60 (p=0.002). Post-hoc analysis showed higher MEP amplitudes at T30 compared to baseline in the control (p=0.001) and denovo PD groups (p=0.002), but not in the PD-OFF group (P=0.524) (Figure 1). There was a significant difference in mUPDRS bradykinesia score with lower values at T60 compared to baseline in denovo PD (Wilcoxon W, p = 0.041) 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 denovo PD or PD-OFF.

Conclusion: The tbTUS induced motor cortical plasticity in older healthy controls and denovo PD patients, but not in OFF medication state. The denovo PD patients also showed mild improvement of the motor symptoms. The differences between denovo PD and PD-OFF suggest that disease duration

and severity affect cortical plasticity. Dopamine likely plays an important role in tbTUS plasticity in PD patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evaluation-of-theta-burst-transcranial-ultrasound-stimulation-on-motor-cortex-in-parkinsons-denovo-patients/