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

描述（由申请人提供）：此K 01应用程序旨在为申请人提供必要的技能，以建立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致发现小脑激活，但该结构在疼痛中的作用尚不清楚。在这些研究中，关于小脑在疼痛事件中的功能的推测通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。这位候选人已经发表的工作表明，小脑对健康受试者和神经性疼痛患者的实验性疼痛的反应方式存在功能二分法。这表明小脑作为一个潜在的疼痛处理区域一直被忽视，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。该项目的假设是，小脑作为厌恶刺激和适应性运动行为的整合器，并可能调节情感和认知体验，将疼痛的感知与无害的感官刺激的欣赏区分开来。将使用实验性疼痛的人类三叉神经模型，因为所有涉及的疼痛相关回路可以与小脑一起沿着成像。具体目标是（1）利用功能磁共振成像（fMRI）和扩散张量成像（DTI）来绘制与伤害性刺激的感觉编码相关的小脑激活图，并将功能活动与解剖连接性相关联;（2）基于小脑反应和连接性来区分疼痛和其预期;以及（3）确定身体疼痛和令人厌恶的图像是否在小脑中参与了类似的回路。为了实现这些目标，候选人将需要扩展他在皮层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，并学习小脑与白色物质的连接。姆克林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，这些疼痛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.