Accelerated Transcranial Ultrasound Neuromodulation in Parkinson's Disease: A Pilot Study

Abstract

ObjectiveLow‐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).MethodsPatients 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.ResultsA 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.Conclusionsa‐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.

Neuromodulation techniques – From non-invasive brain stimulation to deep brain stimulation

“…A recent advancement in the field demonstrated the safety of an accelerated theta burst protocol (a-tbTUS) in PD patients, involving three consecutive TUS sessions separated by 30-min intervals. While our pilot study confirmed the safety of a-tbTUS and observed changes in motor cortical excitability, clinical improvements, as assessed by the UPDRS score, did not reach statistical significance [ 127 , 128 ].…”

Low-intensity focused ultrasound to the insula and dorsal anterior cingulate has site-specific and pressure dependent effects on pain during measures of central sensitization

“…The Institutional Review Board at Virginia Tech approved all experimental procedures (IRB #21-796). N=16 healthy participants (25.7 years ± 3.4 years; range (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34); M/F 5/11), who met all inclusion/exclusion criteria provided written informed consent to all aspects of the study.…”

“…LIFU has been extensively studied in small [3][4][5] and large animals [6][7][8][9] including humans [10][11][12][13]. It has been demonstrated to produce safe [14,15] and reversible inhibition and excitation [8,16] in different parts of the cortex [12,13,17] and subcortical structures [1,18] including emerging clinical applications [19][20][21][22][23]. An additional promising clinical application for LIFU is pain as demonstrated in both primates [8,24] and humans [25,26].…”

A review of functional neuromodulation in humans using low-intensity transcranial focused ultrasound

“…This approach enhanced both motor and cognitive functions, along with increased perfusion at the substantia nigra. In another study, Samuel et al (2023) [71] delivered in stroke treatments, utilizing NIBS such as repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS) to normalize interhemispheric imbalances in stroke patients. In the case of tFUS, although not a study involving stroke patients, Ren et al (2023) [25] (listed in Table 2) observed that the excitatory effects of tFUS stimulation on the unilateral M1 in humans were accompanied by decreased excitability in the contralateral M1, suggesting the potential of tFUS in clinical interventions such as a rebalancing modality of the interhemispheric imbalances in stroke.…”

“…Furthermore, the interhemispheric inhibition (IHI) hypothesis is a concept of neurophysiological mechanism in which one hemisphere, when excited, inhibits the activity of the other, playing a role in the regulation of motor functions. The IHI hypothesis has been employed as an effective strategy [21] TMS hotspot Zeng K et al 2022 [26] TMS hotspot Samuel N et al 2022 [27] TMS hotspot Samuel N et al 2023 [71] TMS hotspot Shamli Oghli Y et al 2023 [33] TMS hotspot Thync Inc.…”