Is cortical reorganization following limb amputation functionally relevant and re

肢体截肢后的皮质重组是否与功能相关并重新组织？

• 批准号: 8613515
• 负责人: SCOTT H FREY
• 金额: $ 31.4万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8613515
• 关键词: Address; Affect; Amputation; Amputees; Behavior; Body Regions; Brain; Chronic; Communication; Data; Esthesia; Exhibits; Face; Functional Magnetic Resonance Imaging; Goals; Hand; 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; experience; limb amputation; neuroimaging; neuroprosthesis; nonhuman primate; painful neuropathy; public health relevance; 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，感觉和运动皮层内的戏剧性重组，从而破坏了手和大脑之间的通信。这些发现得到了人类截肢者广泛重组的非侵入性神经影像学演示的认可。这些观察结果共同构成了普遍观点的基础，即皮质表征是活动依赖性的，其组织是通过竞争性相互作用维持的。大量数据表明，增加刺激（练习）会引起皮质组织的功能相关变化。相比之下，目前尚不清楚完整大脑中损伤相关活动减少后的重组变化是适应性的、适应不良的还是功能上无关的。我们的首要目标是解决当前和以前接受手部再植的手部截肢者的这一基本科学且广泛临床相关的问题。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，并进行行为测试以确定其功能相关性。目标 1：评估截肢者以前手部区域内皮质地图重组的功能相关性。问题 A）面部图扩展到以前的手部区域与神经性（“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以前的手部区域与感性之间有什么关系？问题 C) 皮质重组是否是所提及的无痛触觉的基础 从触摸其他身体部位到缺失的肢体？目标 2：建立截肢者完整手部长期强迫使用后皮质表征重组变化的功能相关性。问题 A) 长期强迫使用非惯用手会如何影响表现？问题 B) 使用完整手时前手区域的募集与表现之间有什么关系？问题 C) 前手区域内的活动增加是否与完整的非惯用手的表现有关？目标 3：确定手再植后与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)：功能恢复是否与在以前的手部区域内重新建立手部地图有关？问题 B) 前手领域内重组变革的逆转是否与恢复有关？