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一直被忽视。传统上认为小脑对运动协调至关重要，但现在解剖学、临床和影像学证据表明，小脑在认知和情感中也发挥着核心作用，而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）目标通过丘脑、皮层的运动和非运动区域以及基底神经节进行投射。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。先前研究的空白：近五十年前，刺激小脑皮质的临床试验产生了好坏参半的结果，这阻碍了进一步的尝试。而对中枢神经系统（小脑皮层传出轴突汇聚的地方）的刺激最近已被证明对患者和动物模型具有临床益处，重新燃起了人们对小脑刺激作为治疗工具的兴趣。然而，直接刺激中枢神经需要通过手术将深部脑刺激导线植入小脑。研究机会：聚焦超声（FUS）和经颅电刺激（tES）是两种非侵入性脑刺激方法，具有巨大的临床应用潜力，为小脑刺激提供了理想的工具。 FUS 凭借其卓越的聚焦和转向能力，有可能直接刺激 CN。由于其易于应用且所涉及的设备便宜，tES 将成为刺激小脑皮质的首选方法。过去二十年功能成像和解剖图谱方面的进展提高了人们对小脑皮层回路及其与 CN 的连接的理解。因此，我们拥有新颖的工具和知识库来开发有效的方案，既可以直接刺激中枢神经系统，也可以通过刺激小脑皮层来间接调节中枢神经系统。当前提案：该提案的总体目标是通过使用 FUS 直接刺激 CN 和通过电刺激小脑皮质间接 CN 调制来开发小脑输出的有效调制范例。将研究选择性刺激皮层和中枢神经元亚型的最佳刺激参数。还将研究两种方法在小脑回路上的联合应用所产生的神经调节新机制。开发的调制范式应该推广到小脑参与的众多运动和非运动功能。

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.