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?

Public Health Relevance

The results of this project have the potential to fundamentally reshape our understanding of the relationship between behavior and experience-dependent decrease- or increase-related changes in the organization of the mature human brain. This knowledge will have a significant impact on how we approach the challenge of optimizing the long-term success of rehabilitative, surgical, and neuroprosthetic interventions for a broad range of injuries that affect the limbs, spinal cord and brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS083377-05
Application #
9052232
Study Section
Motor Function, Speech and Rehabilitation Study Section (MFSR)
Program Officer
Chen, Daofen
Project Start
2015-09-05
Project End
2016-08-31
Budget Start
2016-05-01
Budget End
2016-08-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Washington University
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Valyear, Kenneth F; Mattos, Daniela; Philip, Benjamin A et al. (2017) Grasping with a new hand: Improved performance and normalized grasp-selective brain responses despite persistent functional changes in primary motor cortex and low-level sensory and motor impairments. Neuroimage :
Randerath, Jennifer; Valyear, Kenneth F; Philip, Benjamin A et al. (2017) Contributions of the parietal cortex to increased efficiency of planning-based action selection. Neuropsychologia 105:135-143
Valyear, Kenneth F; Frey, Scott H (2015) Human posterior parietal cortex mediates hand-specific planning. Neuroimage 114:226-38
Philip, B A; Buckon, C; Sienko, S et al. (2015) Maturation and experience in action representation: Bilateral deficits in unilateral congenital amelia. Neuropsychologia 75:420-30
Randerath, Jennifer; Valyear, Kenneth F; Hood, Anna et al. (2015) Two routes to the same action: an action repetition priming study. J Mot Behav 47:142-52
Frey, Scott H; Hansen, Marc; Marchal, Noah (2015) Grasping with the Press of a Button: Grasp-selective Responses in the Human Anterior Intraparietal Sulcus Depend on Nonarbitrary Causal Relationships between Hand Movements and End-effector Actions. J Cogn Neurosci 27:1146-60
Peng, Hao; Wang, Xu; Duan, Ye et al. (2015) Brain Morphometry on Congenital Hand Deformities based on Teichm├╝ller Space Theory. Comput Aided Des 58:84-91
Frey, Scott H; Chen, Pin-Wei (2015) The mirror neuron analogy: implications for rehabilitation neuroscience: comment on ""Grasping synergies: a motor-control approach to the mirror neuron mechanism"" by A. D'Ausilio et al. Phys Life Rev 12:106-7
Shigaki, Cheryl L; Frey, Scott H; Barrett, A M (2014) Rehabilitation of poststroke cognition. Semin Neurol 34:496-503
Philip, Benjamin A; Frey, Scott H (2014) Compensatory changes accompanying chronic forced use of the nondominant hand by unilateral amputees. J Neurosci 34:3622-31

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