School of Physical Therapy, Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan 33302, Taiwan.
Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
Int J Mol Sci. 2024 May 23;25(11):5687. doi: 10.3390/ijms25115687.
Transcranial focused ultrasound stimulation (tFUS) has emerged as a promising neuromodulation technique that delivers acoustic energy with high spatial resolution for inducing long-term potentiation (LTP)- or depression (LTD)-like plasticity. The variability in the primary effects of tFUS-induced plasticity could be due to different stimulation patterns, such as intermittent versus continuous, and is an aspect that requires further detailed exploration. In this study, we developed a platform to evaluate the neuromodulatory effects of intermittent and continuous tFUS on motor cortical plasticity before and after tFUS application. Three groups of rats were exposed to either intermittent, continuous, or sham tFUS. We analyzed the neuromodulatory effects on motor cortical excitability by examining changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). We also investigated the effects of different stimulation patterns on excitatory and inhibitory neural biomarkers, examining c-Fos and glutamic acid decarboxylase (GAD-65) expression using immunohistochemistry staining. Additionally, we evaluated the safety of tFUS by analyzing glial fibrillary acidic protein (GFAP) expression. The current results indicated that intermittent tFUS produced a facilitation effect on motor excitability, while continuous tFUS significantly inhibited motor excitability. Furthermore, neither tFUS approach caused injury to the stimulation sites in rats. Immunohistochemistry staining revealed increased c-Fos and decreased GAD-65 expression following intermittent tFUS. Conversely, continuous tFUS downregulated c-Fos and upregulated GAD-65 expression. In conclusion, our findings demonstrate that both intermittent and continuous tFUS effectively modulate cortical excitability. The neuromodulatory effects may result from the activation or deactivation of cortical neurons following tFUS intervention. These effects are considered safe and well-tolerated, highlighting the potential for using different patterns of tFUS in future clinical neuromodulatory applications.
经颅聚焦超声刺激（tFUS）已成为一种很有前途的神经调控技术，它可以高空间分辨率传递声能，诱导长时程增强（LTP）或长时程抑制（LTD）样可塑性。tFUS 诱导可塑性的主要影响的可变性可能是由于不同的刺激模式，如间歇与连续，这是一个需要进一步详细探索的方面。在这项研究中，我们开发了一个平台，用于评估间歇和连续 tFUS 在 tFUS 应用前后对运动皮质可塑性的神经调节作用。三组大鼠分别暴露于间歇、连续或假 tFUS。我们通过检查经颅磁刺激（TMS）诱发的运动诱发电位（MEPs）的变化来分析运动皮质兴奋性的神经调节作用。我们还通过免疫组织化学染色检查 c-Fos 和谷氨酸脱羧酶（GAD-65）的表达，研究不同刺激模式对兴奋性和抑制性神经生物标志物的影响。此外，我们通过分析神经胶质纤维酸性蛋白（GFAP）的表达来评估 tFUS 的安全性。目前的结果表明，间歇 tFUS 对运动兴奋性产生易化作用，而连续 tFUS 显著抑制运动兴奋性。此外，两种 tFUS 方法都不会导致大鼠刺激部位受伤。免疫组织化学染色显示，间歇 tFUS 后 c-Fos 表达增加，GAD-65 表达减少。相反，连续 tFUS 下调 c-Fos 表达，上调 GAD-65 表达。总之，我们的研究结果表明，间歇和连续 tFUS 均可有效调节皮质兴奋性。神经调节作用可能是由于 tFUS 干预后皮质神经元的激活或失活所致。这些作用被认为是安全且耐受良好的，突出了在未来临床神经调节应用中使用不同模式 tFUS 的潜力。
