PDF(Pubmed)
Abstract：
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.
摘要：
经颅聚焦超声刺激（tFUS）已成为一种有前途的神经调制技术，可提供具有高空间分辨率的声能，以诱导长期增强（LTP）或抑郁（LTD）样可塑性。tFUS诱导的可塑性的主要影响的可变性可能是由于不同的刺激模式，例如间歇性与连续性，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来评估间歇性和连续性tFUS在应用tFUS前后对运动皮质可塑性的神经调节作用.三组大鼠暴露于间歇性，连续,或假tFUS。我们通过检查经颅磁刺激（TMS）引起的运动诱发电位（MEP）的变化，分析了对运动皮层兴奋性的神经调节作用。我们还研究了不同刺激模式对兴奋性和抑制性神经生物标志物的影响，使用免疫组织化学染色检查c-Fos和谷氨酸脱羧酶（GAD-65）的表达。此外,我们通过分析胶质纤维酸性蛋白（GFAP）的表达来评估tFUS的安全性。目前的结果表明，间歇性tFUS对电机兴奋性产生了促进作用，而连续tFUS显著抑制运动兴奋性。此外，tFUS方法均未对大鼠的刺激部位造成损伤。免疫组织化学染色显示，间歇性tFUS后c-Fos增加，GAD-65表达减少。相反，连续tFUS下调c-Fos并上调GAD-65表达。总之,我们的研究结果表明,间歇性和连续性tFUS均能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。这些效果被认为是安全和耐受性良好的，强调在未来的临床神经调节应用中使用不同模式的tFUS的潜力。
