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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.

SUBMITTER: Kim T

PROVIDER: S-EPMC8079725 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Traumatic brain injury (TBI) is a kind of severe brain injury characterized with a high incidence rate and a high disability rate. Low-intensity transcranial ultrasound stimulation (LITUS) is a promising neuroprotective method for improving the functional prognosis of TBI. The fractional anisotropy (FA) value and mean diffusivity (MD) value can be sensitive to abnormal brain structure and function and can thus be used to evaluate the effect of LITUS on TBI. Our purpose was to evaluate the therapeutic effect of LITUS in a moderate TBI rat model with FA and MD values. For our method, we used 45 male Sprague Dawley rats (15 sham normal, 15 TBI, and 15 LITUS treatment rats). We used single-shot spin echo echo-planar imaging sequences at 3.0T to obtain the DTI parameters. Parameters of FA and MD on the treated side of the injury cortex were measured to evaluate the therapeutic effect of LITUS in a TBI rat model. For FA and MD values, groups were compared by using a two-way analysis of variance for repeated measures, and this was followed by Tukey's post hoc test. Differences were considered significant at P < 0.05. The results were that the FA value in the LITUS treatment group at 1 day after TBI was significantly higher than that in the control group (adjusted P = 0.0422) and significantly lower than that in the TBI group at 14, 21, and 35 days after TBI (adjusted P = 0.0015, 0.0064, and 0.0173, respectively). At the end of the scan time point, the differences between the two groups were not significant (adjusted P = 0.3242). The MD values in the LITUS treatment group were significantly higher in the early stage than that in the TBI group (adjusted P = 0.0167) and significantly lower at the following time points than in the TBI group. In conclusion, daily treatment with LITUS for 10 min effectively improved the brain damage in the Controlled Cortical Impact (CCI)-caused TBI model. FA and MD values can serve as evaluation indicators for the neuro-protective effect of LITUS.

Project description:BackgroundLow-intensity transcranial focused ultrasound (tFUS) has gained considerable attention as a promising noninvasive neuromodulatory technique for human brains. However, the complex morphology of the skull hinders scholars from precisely predicting the acoustic energy transmitted and the region of the brain impacted during the sonication. This is due to the fact that different ultrasound frequencies and skull morphology variations greatly affect wave propagation through the skull.PurposeAlthough the acoustic properties of human skull have been studied for tFUS applications, such as tumor ablation using a multielement phased array, there is no consensus about how to choose a single-element focused ultrasound (FUS) transducer with a suitable frequency for neuromodulation. There are interests in exploring the magnitude and dimension of tFUS beam through human parietal bone for modulating specific brain lobes. Herein, we aim to investigate the wave propagation of tFUS on human skulls to understand and address the concerns above.MethodsBoth experimental measurements and numerical modeling were conducted to investigate the transmission efficiency and beam pattern of tFUS on five human skulls (C3 and C4 regions) using single-element FUS transducers with six different frequencies (150-1500 kHz). The degassed skull was placed in a water tank, and a calibrated hydrophone was utilized to measure acoustic pressure past it. The cranial computed tomography scan data of each skull were obtained to derive a high-resolution acoustic model (grid point spacing: 0.25 mm) in simulations. Meanwhile, we modified the power-law exponent of acoustic attenuation coefficient to validate numerical modeling and enabled it to be served as a prediction tool, based on the experimental measurements.ResultsThe transmission efficiency and -6 dB beamwidth were evaluated and compared for various frequencies. An exponential decrease in transmission efficiency and a logarithmic decrease of -6 dB beamwidth with an increase in ultrasound frequency were observed. It is found that a >750 kHz ultrasound leads to a relatively lower tFUS transmission efficiency (<5%), whereas a <350 kHz ultrasound contributes to a relatively broader beamwidth (>5 mm). Based on these observations, we further analyzed the dependence of tFUS wave propagation on FUS transducer aperture size.ConclusionsWe successfully studied tFUS wave propagation through human skulls at different frequencies experimentally and numerically. The findings have important implications to predict tFUS wave propagation for ultrasound neuromodulation in clinical applications, and guide researchers to develop advanced ultrasound transducers as neural interfaces.

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

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