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.
Highlights
METHODSUltrasonic stimulation is a form of mechanical energy like sound, but at frequencies above auditory threshold, i.e., 20,000 HZ to several 100 MHZ, which offers deep penetration (10 to 15 cm or more) with high anatomic specificity (Bystritsky et al, 2011)
Studies meeting all of the following inclusion criteria were selected for this review: (1) Population (P): Studies using animals or human subjects as their experimental subjects; (2) Intervention (I): Studies using low-intensity Transcranial Ultrasound Stimulation (TUS), either focused or unfocused TUS, to modulate the brain functions; (3) Outcomes (O): Studies providing at least one outcome measurement evaluating the neuromodulatory effects of TUS on the brain, including but not limited to neurophysiological measurements, neuroimaging examinations, neurobehavioral changes in sensory, motor, cognition or other domains, and self-report mental state; and (4) Published in the English language
A total of 156 articles were subjected to fulltext review, of which 121 articles were removed for the following reasons: review or commentary (n = 52), study regarding the application of ultrasound in neurosurgery (n = 7), technique papers regarding the design of ultrasound system, stimulation protocol, parameter optimization and properties improvement (n = 39), computational modeling or simulation study (n = 4), ultrasonic stimulation targeting peripheral or cranial nerves rather than cortical and subcortical structures (n = 4), study with surrogate biomarkers as outcomes exclusively (n = 14), study regarding seizure control (n = 1) and study using mixed ultrasound magnetic stimulation (n = 1)
Summary
A literature search for published studies in the past 10 years was conducted. Two authors independently reviewed the relevant articles. Quality of studies was assessed by the SYRCLE’s risk of bias tool for preclinical studies or the PEDro scale for clinical studies
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