Human Studies of Transcranial Ultrasound neuromodulation: A systematic review of effectiveness and safety

Can Sarica; Jean-François Nankoo; Anton Fomenko; Talyta Cortez Grippe; Kazuaki Yamamoto; Nardin Samuel; Vanessa Milano; Artur Vetkas; Ghazaleh Darmani; Mehmet N Cizmeci; Andres M Lozano; Robert Chen

doi:10.1016/j.brs.2022.05.002

Human Studies of Transcranial Ultrasound neuromodulation: A systematic review of effectiveness and safety

Brain Stimul. 2022 May-Jun;15(3):737-746. doi: 10.1016/j.brs.2022.05.002. Epub 2022 May 6.

Authors

Affiliations

¹ Krembil Research Institute, University Health Network, Toronto, ON, Canada; Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.
² Krembil Research Institute, University Health Network, Toronto, ON, Canada.
³ Division of Neurosurgery, Department of Surgery, University of Manitoba, Winnipeg, MB, Canada.
⁴ Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada.
⁵ Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, Canada; Department of Neurosurgery, Tartu University Hospital, University of Tartu, Tartu, Estonia.
⁶ Department of Neonatology, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
⁷ Krembil Research Institute, University Health Network, Toronto, ON, Canada; Edmond J. Safra Program in Parkinson's Disease, University Health Network, Toronto, ON, Canada; Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: Robert.chen@uhn.ca.

PMID: 35533835
DOI: 10.1016/j.brs.2022.05.002

Abstract

Background: Transcranial ultrasound stimulation (TUS) is gaining traction as a safe and non-invasive technique in human studies. There has been a rapid increase in TUS human studies in recent years, with more than half of studies to date published after 2020. This rapid growth in the relevant body of literature necessitates comprehensive reviews to update clinicians and researchers.

Objective: The aim of this work is to review human studies with an emphasis on TUS devices, sonication parameters, outcome measures, results, and adverse effects, as well as highlight future directions of investigation.

Methods: A systematic review was conducted by searching the Web of Science and PubMed databases on January 12, 2022. Human studies of TUS were included.

Results: A total of 35 studies were identified using focused/unfocused ultrasound devices. A total of 677 subjects belonging to diverse cohorts (i.e., healthy, chronic pain, dementia, epilepsy, traumatic brain injury, depression) were enrolled. The stimulation effects vary in a sonication parameter-dependant fashion. Clinical, neurophysiological, radiological and histological outcome measures were assessed. No severe adverse effects were reported in any of the studies surveyed. Mild symptoms were observed in 3.4% (14/425) of the subjects, including headache, mood deterioration, scalp heating, cognitive problems, neck pain, muscle twitches, anxiety, sleepiness and pruritis.

Conclusions: Although increasingly being used, TUS is still in its early phases. TUS can change short-term brain excitability and connectivity, induce long-term plasticity, and modulate behavior. New techniques should be used to further elucidate its underlying mechanisms and identify its application in novel populations.

Keywords: Brain stimulation; Clinical trials; Complication; Focused ultrasound; Outcome measures; Sonication parameters.

Publication types

Review
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Affect
Brain / physiology
Chronic Pain*
Epilepsy*
Humans
Ultrasonography / methods