Is cortical reorganization following limb amputation functionally relevant and re

描述(申请人提供)：在现代神经科学中，感觉和运动皮质的功能组织是动态的--随着刺激的增加或减少而变化的概念是不言而喻的。这已成为神经康复的指导原则。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，手部和大脑之间的沟通中断后，感觉和运动皮质内的戏剧性重组的演示。这些发现得到了人类截肢者广泛重组的非侵入性神经成像演示的称赞。总而言之，这些观察结果为主流观点奠定了基础，即皮层表征是依赖活动的，其组织结构通过竞争性相互作用来维持。大量数据表明，增加刺激(练习)会导致大脑皮层组织功能上的相关变化。相比之下，尚不清楚完整大脑中与损伤相关的活动减少后的重组变化是适应性的、不适应性的，还是功能无关的。我们的首要目标是解决这一基本的科学和广泛的临床相关问题，在接受手部再植的现在和以前的手截肢患者中。我们的方法结合了功能磁共振成像(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内皮质地图重组的功能相关性。问题A)脸部地图扩展到前手区域与神经病理性(“幻觉”)疼痛之间有什么关系？问题B)面部、残肢和完整手的地图扩展到前手区域和感觉之间有什么关系？问题C)所提及的非痛性触觉是否以皮质重组为基础 从身体其他部位的接触到失去的肢体？目的2：建立慢性强迫使用后截肢者完整手的皮质表现中重组变化的功能相关性。问题A)长期强迫使用非优势手对成绩有何影响？问题B)在使用完好的手的过程中招募前手领地与成绩之间有什么关系？问题C)前手区域内的活动增加是否与完整的非优势手的表演有关？目的3：确定手部再植后截肢相关的皮质重组逆转的程度，并阐明这些变化与功能恢复的相关性。问题A)：功能的恢复是否与在以前的手持领土内重新建立手绘地图有关？问题B)前手领域内重组变化的逆转是否与复苏有关？

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?