Leveraging behavioral state to enhance specificity of non-invasive brain stimulation on motor circuits

利用行为状态增强运动回路非侵入性脑刺激的特异性

• 批准号: 10217389
• 负责人: Michael Vesia
• 金额: $ 42.9万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217389
• 关键词: Address; Adult; Area; Behavior; Behavior Control; Behavior Therapy; Behavioral; Biologic Development; Biological; Brain; Brain region; Cerebral Palsy; Data; Dependence; Development; Electrophysiology (science); Foundations; Functional Magnetic Resonance Imaging; Future; Goals; Growth; Human; Impairment; Individual; Influentials; Intervention; Knowledge; Light; Manuals; Measures; Methods; Motor; Motor Cortex; Motor Pathways; Movement; Neuronal Plasticity; Neurons; Neurosciences; Outcome; Parietal; Parietal Lobe; Pathway interactions; Patients; Pattern; Performance; Protocols documentation; Reporting; Residual state; Site; Specificity; Stroke; Techniques; Testing; Therapeutic; Time; Traumatic Brain Injury; Treatment Efficacy; Work; base; behavior measurement; behavioral outcome; brain behavior; clinical application; clinical practice; dexterity; disability; experimental group; functional MRI scan; grasp; hand rehabilitation; improved; innovation; interest; magnetic field; mind control; motor control; motor disorder; motor function improvement; nervous system disorder; neural circuit; neural patterning; neurological rehabilitation; neuromechanism; neurophysiology; neuroregulation; noninvasive brain stimulation; novel; parietal-frontal circuits; post stroke; relating to nervous system; repetitive transcranial magnetic stimulation; response; stroke patient; tool

Project Summary The last two decades have seen an exponential growth in the use of noninvasive brain stimulation techniques, including repetitive transcranial magnetic stimulation (rTMS), in both basic neuroscience and clinical practice. rTMS holds promise for the study and treatment of neurological disorders. Yet, there is a limited understanding of the effects of rTMS on brain and behavior. We will examine a particular type of rTMS, known as theta burst stimulation (TBS), which induces longer lasting effects than other forms of rTMS, making TBS an important tool for therapeutic applications. While TBS provides relatively focal stimulation, effects on the brain occur through interconnected networks in ways that are poorly understood. Moreover, stimulation is highly state-dependent, and the use of rTMS in most therapeutic settings, such as the treatment of motor disorders, leaves the behavioral state uncontrolled. Augmenting rTMS by pairing it with behavioral interventions is an attractive idea for improving therapeutic rTMS, but its efficacy and mechanisms remain unknown. To address this critical gap, this exploratory R21 proposal will examine the effects of TBS and behavioral state on brain and behavior. Our overall objectives in the proposed work are to (i) elucidate the neural mechanism by which TBS paired with a motor task leads to improvements in hand function and (ii) develop more targeted network-modulatory rTMS interventions to enhance motor function. We will focus on the posterior parietal cortex (PPC), and associated parietal-motor circuits, which subserve skilled grasp control, an ability known to be impaired in stroke, traumatic brain injury, cerebral palsy, and other motor disorders. We will collect functional magnetic resonance imaging (fMRI), electrophysiological measures with TMS, and behavioral measures in the same subjects. Five consecutive daily TBS sessions will be applied to 65 healthy subjects assigned to one of three groups, each followed by two assessments to evaluate the effects of stimulation. In Aim 1, we will demonstrate improvement in action performance by manipulating the behavioral state during PPC stimulation. In Aim 2, we will demonstrate modulation of neurophysiological aftereffects of PPC stimulation by manipulating behavioral state. In Aim 3, we will assess the relationship between brain connectivity, neural plasticity and behavior in response to the behavioral state during brain stimulation. Impact: The methods reported here potentially can be modified to more incisively treat motor disorders after stroke by targeting residual higher motor areas to improve impaired cortical pathways. Results will lay a mechanistic foundation for future studies to show how controlling behavioral state during rTMS can improve therapeutic efficacy after stroke.

项目摘要 在过去的二十年里，非侵入性脑刺激技术的使用呈指数级增长， 包括重复经颅磁刺激(RTMS)，在基础神经科学和临床实践中都是如此。 RTMS为神经系统疾病的研究和治疗带来了希望。然而，人们对此的理解是有限的 RTMS对大脑和行为的影响。我们将研究一种特殊类型的rTMS，称为theta Burst 刺激(TBS)，比其他形式的rTMS产生更持久的影响，使TBS成为重要工具 用于治疗应用。虽然TBS提供相对局部的刺激，但对大脑的影响通过 以鲜为人知的方式互连网络。此外，刺激高度依赖于国家， 而rTMS在大多数治疗环境中的使用，如运动障碍的治疗， 行为状态失控。通过将rTMS与行为干预相结合来增强rTMS是一个有吸引力的想法 用于改善治疗性rTMS，但其疗效和机制尚不清楚。为了解决这一关键差距， 这项探索性的R21提案将研究TBS和行为状态对大脑和行为的影响。我们的 这项拟议工作的总体目标是：(I)阐明TBS与 运动任务导致手功能的改善和(Ii)开发更有针对性的网络调制rTMS 增强运动功能的干预措施。我们将专注于后顶叶皮质(PPC)，并与 顶端运动回路，辅助熟练的抓握控制，这是一种已知在中风时受损的能力， 创伤性脑损伤、脑瘫和其他运动障碍。我们将收集功能性磁共振 在同一受试者中进行成像(FMRI)、电生理测量(TMS)和行为测量。五 对65名健康受试者进行连续的每日TBS治疗，每组被分配到三组中的一组 随后进行两次评估，以评估刺激的效果。在目标1中，我们将展示改进 通过在PPC刺激过程中操纵行为状态来进行动作表现。在目标2中，我们将 通过操纵行为状态，展示PPC刺激对神经生理后效的调节作用。 在目标3中，我们将评估大脑连通性、神经可塑性和反应行为之间的关系 大脑刺激时的行为状态。影响：此处报告的方法可能会被修改 更深入地治疗中风后运动障碍，靶向残存的较高运动区以改善 皮质通路受损。这些结果将为未来的研究奠定机制基础，以显示如何控制 RTMS中的行为状态可提高卒中后的治疗效果。

项目成果

The behavioral and neural effects of parietal theta burst stimulation on the grasp network are stronger during a grasping task than at rest.

• DOI: 10.3389/fnins.2023.1198222
• 发表时间: 2023
• 期刊: FRONTIERS IN NEUROSCIENCE
• 影响因子: 4.3
• 作者: Goldenkoff, Elana R.;Deluisi, Joseph A.;Destiny, Danielle P.;Lee, Taraz G.;Michon, Katherine J.;Brissenden, James A.;Taylor, Stephan F.;Polk, Thad A.;Vesia, Michael
• 通讯作者: Vesia, Michael