Brain Modulatory Effects by Low-Intensity Transcranial Ultrasound Stimulation (TUS): A Systematic Review on Both Animal and Human Studies

Abstract

Background and objective: Low Intensity Transcranial Ultrasound Stimulation (TUS) is a new form of non-invasive brain modulation with promising data; however, systematic reviews on the brain modulatory effects of TUS on both animals and humans have not been well-conducted. We aimed to conduct a systematic review on the studies using the TUS to modulate the brain functions and associated behavioral changes in both animals and humans. Methods: A literature search for published studies in the past 10 years was conducted. Two authors independently reviewed the relevant articles. Data were extracted and qualitatively summarized. Quality of studies was assessed by the SYRCLE's risk of bias tool for preclinical studies or the PEDro scale for clinical studies. Results: A total of 24 animal studies (506 animals) and 11 human studies (213 subjects) were included. Findings based on most animal studies demonstrated the excitatory or suppressive modulatory effects of ultrasonic stimulations on motor cortex, somatosensory cortex, thalamus, prefrontal cortex, auditory, and visual areas. Brain modulatory effects also were found among healthy human subjects in seven studies and two clinical studies suggested TUS may result in potential benefits on patients with disorder of consciousness or chronic pain. The safety concerns of TUS seem to be minor based on the human studies. Conclusions: TUS appears to be a viable technique in modulating the brain functions; however, research on TUS is still in its early stages, especially in human studies. Parameters need to be optimized before launching systematic investigations in humans.

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

“…Furthermore, Yuan et al (2020) reported a monotonic dose-response parametric relationship with the cerebral blood flow peak value increasing as a function of stimulation intensity [0.20, 0.40, 0.80, and 1.10 W/cm 2 (I SPPA )] and SD (50, 100, 200, 300, and 400 ms), while DC (10, 20, 30, and 40%) only had a weak effect on peak response. These findings demonstrated the permutations of LI-TUS parameters that can manipulate modulatory function that is reflected as changes in the excitability of neuronal activity in M1 of healthy mice (Wang et al, 2019b).…”

“…Language limitations were not imposed to ensure the inclusion of published manuscripts in other languages. In addition, two recently published systematic review articles were reviewed to exclude studies that already reviewed by Wang et al (2019b) and Di Biase et al (2019).…”

“…Compared to other NIBS modalities, LI-TUS offers greater spatial resolution and focused penetration depth, which potentially opens access to subcortical brain structures (Di Biase et al, 2019). Evidence of LI-TUS induced neuromodulation of cortical and deep structures of the brain relies heavily on data obtained from animal studies (Wang et al, 2019b). In human studies, LI-TUS has been administered primarily in the primary somatosensory (S1) and primary motor (M1) cortices with limited success (Legon et al, 2014(Legon et al, , 2018.…”

“…The field of LI-TUS is rapidly progressing with numerous publications publishing every quarter, it is critical to summarize emerging evidence on the status of this brain modulatory tool. In this review, we aim to provide an updated overview of initial version of systematic review regarding the LI-TUS for neuromodulation in both human and animal research since our initial review on this topic that summarized the finding prior to 2019 (Wang et al, 2019b).…”

Effects of Transcranial Ultrasound Stimulation on Trigeminal Blink Reflex Excitability

“…TUS can be transmitted through the skull and may exert direct modulation of neurons at low intensities [ 2 , 3 , 4 ]. The putative mechanism of TUS relates to the mechanical energy of ultrasound, which produces changes in cell membrane proteins and bioelectrical properties, including activation of voltage-dependent sodium and potassium, and calcium channels [ 5 , 6 , 7 ].…”