Electrical and Ultrasonic Modulation of Lateral Cerebellar Nucleus

小脑外侧核的电和超声调制 摘要 几十年来，小脑因其神经调节的潜力而被忽视。传统上 被认为是运动协调的关键，解剖学，临床和成像证据现在表明， 小脑在认知和情感方面也起着中心作用，小脑功能障碍会影响这些功能。 功能协调发展的与小脑参与运动和非运动功能的这些发现一致， 来自小脑核（CN）的投射通过丘脑靶向小脑的运动区和非运动区。 皮层和基底神经节。因此，小脑输出的调制应该能够影响整个区域， 前脑，因此具有治疗多种疾病的潜力。 先前研究的差距：在临床试验中，小脑皮层的刺激产生了混合的结果，几乎 50年前，他曾试图阻止进一步的尝试。然而，刺激CN，传出轴突 从小脑皮质会聚，最近已被证明有临床效益，在病人和动物 模型然而，直接刺激CN需要手术植入深部脑刺激电极导线 进入小脑 当前技术的新解决方案：聚焦超声（FUS）刺激和经颅电刺激 电刺激（tES）是两种无创性脑刺激方法，具有很大的临床应用潜力 应用并为小脑刺激提供理想的工具。FUS有可能刺激CN 直接与其优越的上级聚焦和转向能力。tES将是刺激的优选方法， 小脑皮层，因为它易于应用和所涉及的廉价设备。小脑 到目前为止，任何其他小组都没有报道过超声刺激，小脑的tES是 严重缺乏了解潜在机制的动物数据。过去二十年的进展 功能成像和解剖标测提供了一个更好的了解电路的 小脑皮质及其与小脑核的连接。因此，我们有了新的工具和知识， 基地开发有效调制小脑输出的协议。 当前提案：该提案的总体目标是开发一种非侵入性和有效的调制方法， 小脑外侧核（Lateral Cerebellar Nucleus，LCN）。最佳的刺激参数 将研究LCN中神经元亚型的选择性刺激。新的机制 将研究电和超声波联合应用可能产生的神经调节 方法.在这个项目中开发的调制范例应该推广到许多电机和非电机。 小脑参与的大脑运动功能。

Electrical and Ultrasonic Modulation of Lateral Cerebellar Nucleus Abstract The cerebellum has been overlooked for its potential for neuromodulation for decades. Traditionally thought of as critical for motor coordination, anatomical, clinical and imaging evidence now indicate that the cerebellum also has central roles in cognition and emotion, and that cerebellar dysfunction impacts these functions. Consistent with these findings of cerebellar involvement in motor and non-motor functions, projections from the cerebellar nuclei (CN) target, via the thalamus, both motor and non-motor areas of the cortex and the basal ganglia. Thus, modulation of cerebellar outputs should be able to affect areas throughout the forebrain, and therefore has the potential to treat numerous disorders. Gap in Prior Research: Stimulation of the cerebellar cortex produced mixed results in clinical trials, almost fifty years ago, and discouraged further attempts. Whereas stimulation of the CN, where the efferent axons from the cerebellar cortex converge, has recently been shown to have clinical benefits in patients and animal models. However, direct stimulation of the CN requires surgical implantation of deep brain stimulation leads into the cerebellum. Novel Solution by Current Technology: Focused Ultrasound (FUS) Stimulation and Transcranial Electrical Stimulation (tES) are two non-invasive brain stimulation methods that have great potentials for clinical applications and provide ideal tools for cerebellar stimulation. FUS has the potential to stimulate the CN directly with its superior focusing and steering capabilities. tES would be the preferred method for stimulation of the cerebellar cortex due to its ease of application and the inexpensive equipment involved. Cerebellar stimulation with ultrasound has not been reported by any other group to date and tES for the cerebellum is severely lacking animal data for understanding of underlying mechanisms. Advances in the past two decades on functional imaging and anatomical mapping provide an improved understanding of the circuitry of the cerebellar cortex and its connections to the cerebellar nuclei. Thus, we have novel tools and the knowledge base to develop protocols for effective modulation of the cerebellar outputs. Current Proposal: The overarching goal of this proposal is to develop a non-invasive and effective modulation paradigm for one of the cerebellar nuclei, the lateral cerebellar nucleus (LCN). Optimal stimulation parameters will be investigated for selective stimulation of neuronal subtypes in the LCN. Novel mechanisms of neuromodulation will be investigated that can emerge from combined application of the electrical and ultrasonic methods. The modulation paradigms developed in this project should generalize to numerous motor and non- motor brain functions in which the cerebellum is involved.