Is Cortical Reorganization Following Limb Amputation Functionally Relevant and Reversible?

截肢后的皮质重组在功能上相关且可逆吗？

• 批准号: 9138225
• 负责人: SCOTT H FREY
• 金额: $ 31.71万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-05 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9138225
• 关键词: Address; Affect; Amputation; Amputees; Behavior; Body Regions; Brain; Chronic; Communication; Data; Esthesia; Exhibits; Face; Functional Magnetic Resonance Imaging; Goals; Hand; Health; Human; Influentials; Injury; Intervention; Knowledge; Limb structure; Maps; Motor; Motor Cortex; Movement; Neuropathy; Neurorehabilitation; Neurosciences; Operative Surgical Procedures; Painless; Performance; Peripheral Nerves; Phantom Limb Pain; Recovery; Recovery of Function; Rehabilitation therapy; Residual state; Sensory; Site; Spinal Cord; Stimulus; Surgical Replantation; Tactile; Touch sensation; Transcranial magnetic stimulation; Writing; behavior test; clinically relevant; cortex mapping; experience; limb amputation; neuroimaging; neuroprosthesis; nonhuman primate; painful neuropathy; residual limb; response; sensory cortex; success

DESCRIPTION (provided by applicant): In modern neuroscience, the notion that the functional organization of sensory and motor cortex is dynamic-- changing in response either to increases or decreases in stimulation, is axiomatic. This has become a guiding principle of neurorehabilitation. Some of the earliest and most influential evidence for this plasticity comes from demonstrations of dramatic reorganization within the sensory and motor cortices of non-human primates following amputations (or other injuries to the peripheral nerves or spinal cord) that disrupt communications between the hand and brain. These findings are complimented by non-invasive neuroimaging demonstrations of extensive reorganization in human amputees. Together these observations are foundational to the prevailing view that cortical representations are activity-dependent, with their organization maintained through competitive interactions. Data indicating that increased stimulation (practice) induces functionally relevant changes in cortical organization are plentiful. By contrast, it remains unclear whether the reorganizational changes that follow injury-related decreases in activity in the intact brain are adaptive, maladaptive, or functionally irrelevant. Our overarching goal is to address this fundamental scientific, and broadly clinically relevant, issue in current and former hand amputees who have received hand replants. Our approach combines functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) to determine changes occurring within the former hand territory, and behavioral testing to establish their functional relevance. Aim 1: Evaluate the functional relevance of cortical map reorganization within amputees' former hand territories. Issue A) What is the relationship between the expansion of the face map into the former hand territory and neuropathic ("phantom") pain? Issue B) What is the relationship between the expansion of maps of the face, residual limb and intact hand into the former hand territory and sensibility? Issue C) Does cortical reorganization underlie non-painful tactile sensations referred from touch on other body regions to the missing limb? Aim 2: Establish the functional relevance of reorganizational changes in the cortical representation of amputees' intact hands following chronic forced use. Issue A) How does chronic forced use of the non-dominant hand affect performance? Issue B) What is the relationship between recruitment of the former hand territory during use of the intact hand and performance? Issue C) Is increased activity within the former hand territory causally involved in performances of the intact non-dominant hand? Aim 3: Determine the extent to which amputation-related cortical reorganization is reversed following hand replantation and elucidate the relevance of these changes to recovery of function. Issue A): Is recovery of function associated with re-establishing the hand map within the former hand territory? Issue B) Is the reversal of reorganizational changes within the former hand territory related to recovery?

描述（由申请人提供）：在现代神经科学中，感觉和运动皮层的功能组织是动态的——随着刺激的增加或减少而变化，这一概念是不言自明的。这已经成为神经康复的指导原则。关于这种可塑性的一些最早和最有影响力的证据来自于非人类灵长类动物在截肢（或周围神经或脊髓的其他损伤）后感觉和运动皮层的戏剧性重组，这破坏了手和大脑之间的交流。这些发现被非侵入性神经影像学证明在人类截肢者中广泛重组。总的来说，这些观察结果是主流观点的基础，即皮层表征是活动依赖的，它们的组织通过竞争相互作用来维持。大量数据表明，增加的刺激（练习）会引起皮质组织的功能相关变化。相比之下，在完整的大脑中，损伤相关的活动减少所导致的重组变化是适应性的、不适应性的还是功能无关的，目前尚不清楚。我们的首要目标是解决这一基础科学和广泛临床相关的问题，目前和以前的手部截肢者接受了手部再植。我们的方法结合了功能性磁共振成像（fMRI）和经颅磁刺激（TMS）来确定前手区域内发生的变化，并通过行为测试来确定它们的功能相关性。目的1：评估截肢者前手区域皮质图谱重组的功能相关性。问题A)面部图谱扩展到前手区域与神经性（“幻像”）疼痛之间的关系是什么？问题B)面部，残肢和完整手的地图扩展到前手领域与敏感性之间的关系是什么？问题C)所提到的非疼痛性触觉的基础是皮层重组吗