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: 9339873
• 负责人: SCOTT H FREY
• 金额: $ 34.67万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9339873
• 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的概念是不言自明的。这已成为神经康复的指导原则。这种可塑性的最早和最有影响力的证据来自非人类灵长类动物的感觉和运动皮层在截肢（或周围神经或脊髓的其他损伤）中断手和大脑之间的通信后发生的戏剧性重组。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证明的补充。总之，这些观察结果是流行观点的基础，即皮层表征是活动依赖性的，它们的组织通过竞争性相互作用来维持。有大量数据表明，增加刺激（练习）会引起皮层组织的功能相关变化。相比之下，目前还不清楚是否重组的变化，以下损伤相关的活动减少在完整的大脑是适应性，适应不良，或功能无关。我们的首要目标是解决这个基本的科学，广泛的临床相关，在当前和以前的手截肢者谁接受了手移植的问题。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其功能相关性。目的1：评价截肢者前手部区域皮质地图重组的功能相关性。问题A）面部地图扩展到以前的手部区域与神经性（“幻肢”）疼痛之间的关系是什么？问题B）面部、残肢和完好手的地图扩展到以前的手区域与感觉之间的关系是什么？问题C）皮层重组是否是非疼痛性触觉的基础 从触摸身体其他部位到失去的肢体目标二：建立截肢者在长期强迫使用后完整手的皮质表征的重组变化的功能相关性。问题A：长期强迫使用非惯用手如何影响表现？问题B）在使用完整手的过程中，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优势手的表现有因果关系？目标三：确定在何种程度上截肢相关的皮质重组逆转后，手再植，并阐明这些变化的功能恢复的相关性。问题A）：功能恢复是否与在前手区域内重建手地图相关？问题B）在前手区域内的重组变化的逆转是否与恢复有关？

项目成果

Changes in Primary Somatosensory Cortex Following Allogeneic Hand Transplantation or Autogenic Hand Replantation.

同种异体手移植或自体手再植后初级体感皮层的变化。

• DOI: 10.3389/fnimg.2022.919694
• 发表时间: 2022
• 期刊: Frontiers in neuroimaging
• 作者: Philip,BA;Valyear,KF;Cirstea,CM;Baune,NA;Kaufman,C;Frey,SH
• 通讯作者: Frey,SH

Maturation and experience in action representation: Bilateral deficits in unilateral congenital amelia.

• DOI: 10.1016/j.neuropsychologia.2015.05.018
• 发表时间: 2015-08
• 期刊: Neuropsychologia
• 影响因子: 2.6
• 作者: Philip BA;Buckon C;Sienko S;Aiona M;Ross S;Frey SH
• 通讯作者: Frey SH

Cortical Neurochemical Profile Depends on the Origin and the Site of the Central Nervous System Injury.

皮质神经化学特征取决于中枢神经系统损伤的起源和部位。

• DOI: 10.1016/j.pmrj.2016.07.035
• 发表时间: 2016
• 期刊: PM & R : the journal of injury, function, and rehabilitation
• 作者: Cirstea,CarmenM;Burris,JosephE;Peng,Huiling;Nanda,Ashish;Singh,Niranjan;Craciunas,SorinC
• 通讯作者: Craciunas,SorinC

Brain Morphometry on Congenital Hand Deformities based on Teichmüller Space Theory.

基于 Teichmüller 空间理论的先天性手部畸形的脑形态测量。

• DOI: 10.1016/j.cad.2014.08.024
• 发表时间: 2015
• 期刊: Computer aided design
• 作者: Peng,Hao;Wang,Xu;Duan,Ye;Frey,ScottH;Gu,Xianfeng
• 通讯作者: Gu,Xianfeng

Microstructural integrity of corticospinal and medial lemniscus tracts: insights from diffusion tensor tractography of right-hand amputees.

皮质脊髓和内侧丘系束的微观结构完整性：来自右手截肢者扩散张量束成像的见解。

• DOI: 10.1152/jn.00316.2018
• 发表时间: 2019
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Peng,Huiling;Cirstea,CarmenM;Kaufman,ChristinaL;Frey,ScottH
• 通讯作者: Frey,ScottH