Effect of Low Intensity Transcranial Ultrasound Stimulation on Neuromodulation in Animals and Humans: An Updated Systematic Review

Abstract

Background: Although low-intensity transcranial ultrasound stimulation (LI-TUS) has received more recognition for its neuromodulation potential, there remains a crucial knowledge gap regarding the neuromodulatory effects of LI-TUS and its potential for translation as a therapeutic tool in humans.Objective: In this review, we summarized the findings reported by recently published studies regarding the effect of LI-TUS on neuromodulation in both animals and humans. We also aim to identify challenges and opportunities for the translation process.Methods: A literature search of PubMed, Medline, EMBASE, and Web of Science was performed from January 2019 to June 2020 with the following keywords and Boolean operators: [transcranial ultrasound OR transcranial focused ultrasound OR ultrasound stimulation] AND [neuromodulation]. The methodological quality of the animal studies was assessed by the SYRCLE's risk of bias tool, and the quality of human studies was evaluated by the PEDro score and the NIH quality assessment tool.Results: After applying the inclusion and exclusion criteria, a total of 26 manuscripts (24 animal studies and two human studies) out of 508 reports were included in this systematic review. Although both inhibitory (10 studies) and excitatory (16 studies) effects of LI-TUS were observed in animal studies, only inhibitory effects have been reported in primates (five studies) and human subjects (two studies). The ultrasonic parameters used in animal and human studies are different. The SYRCLE quality score ranged from 25 to 43%, with a majority of the low scores related to performance and detection bias. The two human studies received high PEDro scores (9/10).Conclusion: LI-TUS appears to be capable of targeting both superficial and deep cerebral structures to modulate cognitive or motor behavior in both animals and humans. Further human studies are needed to more precisely define the effective modulation parameters and thereby translate this brain modulatory tool into the clinic.

Meta‐analytic evidence for downregulation of the amygdala during working memory maintenance

“…This could be a potential explanation why amygdala downregulation and changes in self‐report do not always co‐occur. Future studies could focus on a potential causal relationship between the amygdala and changes in self‐report during cognitive reappraisal, for example, using novel neuromodulatory techniques such as transcranial focused ultrasound stimulation that are currently emerging (e.g., Folloni et al, 2019; Kim et al, 2021).…”

Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels

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Ultrasound has been used to non-invasively manipulate neuronal functions in humans andother animals 1-4 . However, this approach is limited as it has been challenging to target specific cells within the brain or body [5][6][7][8] . Here, we identify human Transient Receptor Potential A1 (hsTRPA1) as a candidate that confers ultrasound sensitivity to mammalian cells.

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Radiomics-Informed Modeling for Transcranial Ultrasound Stimulation: Age Matters

“…As the most commonly used target in TUS studies (Kim et al, 2021 ), primary motor cortex (M1) was selected to demonstrate the transcranial features in individuals at different stages of life ( Figure 1 ). With the same measurement scale (i.e., mm), the skull thickness, scalp-to-cortex distance and cortical thickness varied between children, young adult, middle-aged adult and old adult ( Figure 1D ).…”