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，小脑在神经调节方面的潜力一直被忽视。传统上讲 被认为对运动协调至关重要的解剖学、临床和成像证据现在表明 小脑在认知和情绪中也起着中心作用，小脑功能障碍会影响这些 功能。与小脑参与运动和非运动功能的这些发现一致， 小脑核(CN)靶通过丘脑的运动区和非运动区的投射 皮质和基底节。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。 先前研究中的差距：在临床试验中，刺激小脑皮质产生的结果喜忧参半，几乎 50年前，并阻止了进一步的尝试。而刺激CN，在那里传出轴突 从小脑皮质汇聚，最近已被证明在患者和动物身上具有临床益处 模特们。然而，直接刺激CN需要手术植入脑深部刺激导联 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 刺激(TES)是两种极具临床应用潜力的无创脑刺激方法 并为小脑刺激提供理想的工具。FUS有可能刺激CN 直接与其卓越的对焦和转向能力。经皮超声心动图是刺激心脏功能的首选方法。 小脑皮质，因为它易于应用和所涉及的廉价设备。小脑 到目前为止，还没有任何其他组织报道过用超声波刺激小脑的报道。 严重缺乏动物数据来了解潜在的机制。过去二十年的进步 功能成像和解剖标测提供了更好的理解 小脑皮质及其与小脑核团的联系。因此，我们有了新的工具和知识 基地，以开发有效调制小脑输出的方案。 当前建议：该建议的首要目标是开发一种非侵入性和有效的调制 小脑核团之一，小脑外侧核(LCN)的范例。最佳吞吐参数 将研究选择性刺激LCN中的神经元亚型。一种新的机制 我们将研究电和超声波的联合应用对神经调节的影响。 方法：研究方法。本项目中开发的调制范例应推广到许多电机和非 小脑参与的运动脑功能。

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.