fMRI and DTI of Cerebellar Responses to Pain in the Human Trigeminal System

人类三叉神经系统小脑对疼痛反应的 fMRI 和 DTI

• 批准号: 8034369
• 负责人: Eric Alan Moulton
• 金额: $ 12.94万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034369
• 关键词: Anger; Animals; Anterior; Area; Aversive Stimulus; Behavior; Brain Stem; Capsaicin; Cerebellum; Code; Cognitive; Complex Regional Pain Syndromes; Cream; Data; Diffusion Magnetic Resonance Imaging; Emotional; Environment; Event; Experimental Models; Face; Fiber; Functional Imaging; Functional Magnetic Resonance Imaging; Goals; Hospitals; Human; Image; Image Analysis; Insula of Reil; Lead; Learning; Maps; Motor; Pain; Patients; Pattern; Perception; Physiological; Physiology; Process; Property; Publishing; Recovery; Research; Resources; Rest; Role; Sensory; Somatosensory Cortex; Stimulus; Structure; System; Thalamic structure; Time; Trigeminal System; Visual; Work; base; chronic neuropathic pain; chronic pain; design; experience; insight; medical schools; painful neuropathy; programs; relating to nervous system; response; skills; somatosensory; white matter

DESCRIPTION (provided by applicant): This K01 application is designed to prepare the applicant with the skills necessary to establish an independent research program on pain-related processing in the cerebellum. Although pain studies using functional imaging in humans consistently find cerebellar activation, the role of this structure during pain is unknown. In such studies, speculation regarding the cerebellum's function during a painful event is often influenced by its reputation as a coordinator of motor function, though animal studies have indicated that it may also modulate the neural encoding of noxious stimuli. The candidate has published work that indicates a functional dichotomy in the way the cerebellum responds to experimental pain in healthy subjects and neuropathic pain patients. This suggests that the cerebellum has been overlooked as a potential pain processing area, and research into this area could lend invaluable insight into the basic physiological circuitry involved with pain and its modulation. The hypothesis of this project is that the cerebellum serves as an integrator of aversive stimuli and adaptive motor behavior, and may modulate the emotional and cognitive experience that distinguishes the perception of pain from the appreciation of innocuous sensory stimulation. A human trigeminal model of experimental pain will be used, as all the pain-related circuitry involved can be imaged along with the cerebellum at the same time. The specific aims are (1) to map cerebellar activations related to sensory coding of noxious stimuli and to correlate functional activity with anatomical connectivity using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI); (2) to distinguish between pain and its anticipation based on cerebellar responses and connectivity; and (3) to determine whether physical pain and aversive images engage similar circuitry in the cerebellum. To accomplish these aims, the candidate will need to expand his background in fMRI of cortical and brainstem pain processing to encompass cerebellar physiology, become proficient in DTI analysis, and learn the white matter connectivity to and from the cerebellum. The research environment at McLean Hospital and the other affiliates of the Harvard Medical School system will provide the candidate with the resources to reach his aims within 4 years. Enhanced understanding of cerebellar pain processing may lead to new treatments for chronic neuropathic pain conditions, which can have altered cerebellar functionality.

描述（由申请人提供）：本 K01 申请旨在帮助申请人具备建立小脑疼痛相关处理的独立研究项目所需的技能。尽管使用功能成像对人类进行的疼痛研究一致发现小脑激活，但这种结构在疼痛期间的作用尚不清楚。在此类研究中，关于小脑在痛苦事件期间的功能的推测常常受到其作为运动功能协调器的声誉的影响，尽管动物研究表明它也可能调节有害刺激的神经编码。该候选人发表的论文表明，小脑对健康受试者和神经性疼痛患者的实验疼痛的反应方式存在功能二分法。这表明小脑作为潜在的疼痛处理区域被忽视了，对该区域的研究可以为了解与疼痛及其调节有关的基本生理回路提供宝贵的见解。该项目的假设是，小脑充当厌恶刺激和适应性运动行为的整合器，并且可以调节情感和认知体验，从而区分疼痛的感知和无害的感官刺激的欣赏。将使用实验性疼痛的人体三叉神经模型，因为所有涉及的疼痛相关电路都可以与小脑同时成像。具体目标是（1）绘制与有害刺激的感觉编码相关的小脑激活图，并使用功能磁共振成像（fMRI）和扩散张量成像（DTI）将功能活动与解剖连接相关联； （2）根据小脑反应和连通性区分疼痛及其预期； （3）确定身体疼痛和厌恶图像是否与小脑中的类似回路有关。为了实现这些目标，候选人将需要扩展其在皮质和脑干疼痛处理的功能磁共振成像方面的背景，以涵盖小脑生理学，精通 DTI 分析，并了解与小脑之间的白质连接。麦克莱恩医院和哈佛医学院系统其他附属机构的研究环境将为候选人提供在 4 年内实现其目标的资源。 增强对小脑疼痛处理的理解可能会导致慢性神经性疼痛的新治疗方法，这种疼痛可能会改变小脑的功能。