Department of Radiology, Stanford University, Stanford, CA, USA.
Department of Bioengineering, Stanford University, Stanford, CA, USA.
Brain Stimul. 2019 Jul-Aug;12(4):901-910. doi: 10.1016/j.brs.2019.03.005. Epub 2019 Mar 6.
Recent studies in a variety of animal models including rodents, monkeys, and humans suggest that transcranial focused ultrasound (tFUS) has considerable promise for non-invasively modulating neural activity with the ability to target deep brain structures. However, concerns have been raised that motor responses evoked by tFUS may be due to indirect activation of the auditory pathway rather than direct activation of motor circuits.
In this study, we sought to examine the involvement of peripheral auditory system activation from tFUS stimulation applied to elicit motor responses. The purpose was to determine to what extent ultrasound induced auditory artifact could be a factor in ultrasound motor neuromodulation.
In this study, tFUS-induced electromyography (EMG) signals were recorded and analyzed in wild-type (WT) normal hearing mice and two strains of genetically deaf mice to examine the involvement of the peripheral auditory system in tFUS-stimulated motor responses. In addition, auditory brainstem responses (ABRs) were measured to elucidate the effect of the tFUS stimulus envelope on auditory and motor responses. We also varied the tFUS stimulation duration to measure its effect on motor response duration.
We show, first, that the sharp edges in a tFUS rectangular envelope stimulus activate the peripheral afferent auditory pathway and, second, that smoothing these edges eliminates the auditory responses without affecting the motor responses in normal hearing WT mice. We further show that by eliminating peripheral auditory activity using two different strains of deaf knockout mice, motor responses are the same as in normal hearing WT mice. Finally, we demonstrate a high correlation between tFUS pulse duration and EMG response duration.
These results support the concept that tFUS-evoked motor responses are not a result of stimulation of the peripheral auditory system.
最近的研究在各种动物模型中,包括啮齿动物、猴子和人类,表明经颅聚焦超声(tFUS)具有很大的潜力,可以非侵入性地调节神经活动,能够靶向深部脑结构。然而,人们担心 tFUS 诱发的运动反应可能是由于听觉通路的间接激活,而不是运动回路的直接激活。
在这项研究中,我们试图研究 tFUS 刺激引发运动反应时外周听觉系统激活的参与情况。目的是确定超声诱导的听觉伪影在多大程度上可能成为超声运动神经调节的一个因素。
在这项研究中,记录并分析了野生型(WT)正常听力小鼠和两种遗传性耳聋小鼠的 tFUS 诱导肌电图(EMG)信号,以研究外周听觉系统在 tFUS 刺激运动反应中的参与情况。此外,还测量了听觉脑干反应(ABR),以阐明 tFUS 刺激包络对听觉和运动反应的影响。我们还改变了 tFUS 刺激持续时间,以测量其对运动反应持续时间的影响。
我们首先表明,tFUS 矩形包络刺激的锐边激活了外周传入听觉通路,其次表明,平滑这些边缘可以消除听觉反应,而不影响正常听力 WT 小鼠的运动反应。我们进一步表明,通过使用两种不同的耳聋敲除小鼠消除外周听觉活动,运动反应与正常听力 WT 小鼠相同。最后,我们证明了 tFUS 脉冲持续时间和 EMG 响应持续时间之间存在高度相关性。
这些结果支持 tFUS 诱发的运动反应不是刺激外周听觉系统的结果的概念。