Abstract
Non-invasive focused ultrasound stimulation (FUS) is a non-ionising neuromodulatory technique that employs acoustic energy to acutely and reversibly modulate brain activity of deep-brain structures. It is currently being investigated as a potential novel treatment for Parkinson’s disease (PD). This scoping review was carried out to map available evidence pertaining to the provision of FUS as a PD neuromodulatory tool. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews, a search was applied to Ovid MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials on 13 January 2022, with no limits applied. In total, 11 studies were included: 8 were from China and 1 each from Belgium, South Korea and Taiwan. All 11 studies were preclinical (6 in vivo, 2 in vitro, 2 mix of in vivo and in vitro and 1 in silico). The preclinical evidence indicates that FUS is safe and has beneficial neuromodulatory effects on motor behaviour in PD. FUS appears to have a therapeutic role in influencing the disease processes of PD, and therefore holds great promise as an attractive and powerful neuromodulatory tool for PD. Though these initial studies are encouraging, further study to understand the underlying cellular and molecular mechanisms is required before FUS can be routinely used in PD.
Highlights
Parkinson’s disease (PD) is a common and progressive neurodegenerative condition, characterised by the degeneration and death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and reduced dopamine biosynthesis from surviving neurons [1]
Many hypotheses have been proposed for the mechanisms by which Deep brain stimulation (DBS) generates improvements in motor symptoms, but prevailing theories have focused on stimulation-induced disruption of pathological brain circuit activity [9,10], which occur at the ionic, protein, cellular and network levels [11]
The literature has consistently proven that focused ultrasound stimulation (FUS) is capable of eliciting various behavioural responses in various PD models [40,43,47,49,50,72,73,74,75], inducing protein expression changes in glial cell line-derived neurotrophic factor (GDNF) [41,43], tyrosine hydroxylase (TH) [40,41,43,46] and dopamine levels [46] in the SNpc, which are implicated in the disease pathology of PD
Summary
Parkinson’s disease (PD) is a common and progressive neurodegenerative condition, characterised by the degeneration and death of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and reduced dopamine biosynthesis from surviving neurons [1]. PD patients can experience motor manifestations typically starting with tremor, progressing to bradykinesia and typical “cogwheel” rigidity, postural instability and gait disorders [2]. These manifestations significantly impact the activities of daily living and health-related quality of life of these patients [2,3,4]. Many hypotheses have been proposed for the mechanisms by which DBS generates improvements in motor symptoms, but prevailing theories have focused on stimulation-induced disruption of pathological brain circuit activity [9,10], which occur at the ionic, protein, cellular and network levels [11]. It is effective and in aggregate it is a safe approach [12,13,14,15], just like any surgical
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