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

描述(由申请人提供)：这份K01申请旨在为申请人准备必要的技能，以建立一个关于小脑疼痛相关处理的独立研究计划。虽然在人类中使用功能成像的疼痛研究一直发现小脑激活，但这种结构在疼痛中的作用尚不清楚。在这样的研究中，关于小脑在痛苦事件中的功能的猜测通常会受到它作为运动功能协调者的声誉的影响，尽管动物研究表明，它也可能调节有害刺激的神经编码。这位候选人发表的研究表明，在健康受试者和神经病理性疼痛患者中，小脑对实验性疼痛的反应方式存在功能性二分法。这表明，小脑被认为是一个潜在的疼痛处理区域，对这一区域的研究可以为了解与疼痛及其调制有关的基本生理回路提供宝贵的见解。这个项目的假设是，小脑作为厌恶刺激和适应性运动行为的积分器，可能调节区分疼痛感知和无害感觉刺激欣赏的情绪和认知体验。将使用实验性疼痛的人类三叉神经模型，因为所有涉及到的疼痛相关回路都可以与小脑一起同时成像。其具体目标是(1)利用功能磁共振成像(FMRI)和扩散张量成像(DTI)技术绘制与伤害性刺激感觉编码相关的小脑激活图谱，并将功能活动与解剖连通性联系起来；(2)根据小脑的反应和连通性区分疼痛及其预期；以及(3)确定身体疼痛和厌恶图像是否参与小脑的类似回路。为了实现这些目标，应聘者需要扩大他在皮质和脑干疼痛处理功能磁共振方面的背景，以涵盖小脑生理学，熟练掌握DTI分析，并学习与小脑之间的白质连接。麦克莱恩医院和哈佛医学院系统的其他附属机构的研究环境将为候选人提供资源，以在4年内实现他的目标。加强对小脑疼痛过程的理解可能会导致慢性神经病理性疼痛的新治疗方法，这可能会改变小脑功能。

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.