Is Cortical Reorganization Following Limb Amputation Functionally Relevant and Reversible?

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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?