Modulation of Cerebellar Activity by Electrical and Focused Ultrasound Stimulation

通过电刺激和聚焦超声刺激调节小脑活动

• 批准号: 10429656
• 负责人: ERIC J LANG
• 金额: $ 286.79万
• 依托单位: NEW JERSEY INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10429656
• 关键词: Acoustics; Acute; Address; Affect; Anatomy; Animal Experiments; Animal Model; Animals; Area; Automobile Driving; Axon; Basal Ganglia; Beds; Behavioral; Brain; Cerebellar Cortex; Cerebellar Diseases; Cerebellar Nuclei; Cerebellum; Chronic; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Data; Deep Brain Stimulation; Disease; Efferent Pathways; Electric Stimulation; Electrodes; Emotional; Emotions; Equipment; Fertilization; Focused Ultrasound; Frequencies; Functional Imaging; Goals; Grant; Harmaline; Image; Lateral; Lead; Learning; Mental disorders; Methodology; Methods; Modality; Modeling; Modification; Motivation; Motor; Neurons; Operative Surgical Procedures; Output; Pathway interactions; Patients; Pattern; Population; Process; Prosencephalon; Protocols documentation; Rattus; Reporting; Research; Resolution; Risk; Role; Site; Stimulus; Structure; Techniques; Testing; Thalamic structure; Therapeutic; Ultrasonics; awake; behavior test; clinical application; crystallinity; design; experience; experimental study; implantation; improved; insight; integrated circuit; interest; knowledge base; motor learning; nervous system disorder; neural circuit; neuroregulation; new technology; noninvasive brain stimulation; novel; optogenetics; prototype; psychiatric symptom; tool; ultrasound

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, which 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, reviving interest in cerebellar stimulation as a therapeutic tool. However, direct stimulation of the CN requires surgical implantation of deep brain stimulation leads into the cerebellum. Research Opportunity: Focused Ultrasound (FUS) 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. 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 CN. Thus, we have novel tools and the knowledge base to develop effective protocols both for direct stimulation of the CN and indirect modulation of them via stimulation of the cerebellar cortex. Current Proposal: The overarching goal of this proposal is to develop effective modulation paradigms of cerebellar output both by direct stimulation of the CN using FUS and indirect CN modulation via electrical stimulation of the cerebellar cortex. Optimal stimulation parameters will be investigated for selective stimulation of neuronal subtypes in the cortex and the CN. Novel mechanisms of neuromodulation will also be investigated that can emerge from combined application of the two methods on the cerebellar circuits. The modulation paradigms developed should generalize to numerous motor and non-motor functions in which the cerebellum is involved.

几十年来，小脑因其神经调节的潜力而被忽视。传统上，人们认为对运动协调，解剖学，临床和成像证据至关重要，这表明小脑在认知和情感中也具有核心作用，小脑功能障碍会影响这些功能。与这些小脑涉及运动和非运动功能的发现，小脑核（CN）靶标的投影，通过丘脑，皮质的运动和非运动区域和基底神经节。因此，小脑输出的调节应该能够影响整个前脑的区域，因此有可能治疗多种疾病。先前研究中的差距：小脑皮层的刺激在近五十年前的临床试验中产生了混杂的结果，这阻止了进一步的尝试。尽管CN的刺激是在小脑皮层融合的FRERENT轴突中，最近已证明对患者和动物模型具有临床益处，从而恢复了对小脑刺激的兴趣作为治疗工具。但是，直接刺激CN需要手术植入深脑刺激会导致小脑。研究机会：聚焦超声（FUS）和经颅电刺激（TES）是两种非侵入性大脑刺激方法，具有临床应用的巨大潜力，并为小脑刺激提供了理想的工具。 FUS具有直接刺激CN的优质聚焦和转向能力的潜力。 TE将是刺激小脑皮层的首选方法，因为它的易于应用和涉及廉价设备。在过去的二十年中，在功能成像和解剖图映射方面的进步提供了对小脑皮层电路及其与CN的连接的改进理解。因此，我们拥有新的工具和知识库来开发有效方案，既可以通过刺激小脑皮质来直接刺激CN和间接调节它们。目前的建议：该建议的总体目标是通过使用FUS直接刺激CN和间接CN调制小脑皮层来开发小脑输出的有效调制范式。将研究最佳刺激参数，以选择性刺激皮质和CN中的神经元亚型。还将研究神经调节的新机制，可以从两种方法在小脑回路上的联合应用中出现。开发的调制范例应推广到涉及小脑的众多电动机和非运动功能。

项目成果

Modulation of cerebellar cortical, cerebellar nuclear and vestibular nuclear activity using alternating electric currents.

• DOI: 10.3389/fnsys.2023.1173738
• 发表时间: 2023
• 期刊: FRONTIERS IN SYSTEMS NEUROSCIENCE
• 影响因子: 3
• 作者: Avlar, Billur;Rahman, Ramia;Vendidandi, Sai;Cetinkaya, Esma;Asan, Ahmet S.;Sahin, Mesut;Lang, Eric J.
• 通讯作者: Lang, Eric J.