The capacity for individuals to recover motor function after stroke or traumatic brain injury is thought to be largely dependent upon adaptive plasticity mechanisms in uninjured regions of the brain. Over the past 20+ years, investigators have demonstrated a remarkable array of neurophysiological and neuroanatomical changes after focal cortical injury in animal models, especially in spared cortical areas. Many of these changes have been correlated with functional motor recovery. Also, neuroimaging and noninvasive stimulation studies in human stroke survivors have shown changes in both the injured and the intact (or contralesional) hemisphere. However, a focus of continuing debate is whether contralesional plasticity is adaptive, maladaptive, or epiphenomenal. From a clinical perspective, this is a critical topic, since many investigators are now employing non-invasive stimulation techniques to modulate activity in the intact hemisphere after stroke to improve motor function. Our long-term goal is to provide a comprehensive understanding of the neural mechanisms underlying recovery of function after brain injury. The objective of this application is to assess the behavioral significance of post-injury neuronal plasticity, especially within the intact hemisphere. To this end, we will utilize our extensive experience in neurophysiological recording, neuroanatomical tract-tracing and behavioral approaches in mammalian models of injury and recovery to describe in detail the role of neuronal plasticity in recovery of motor skills. Our central hypothesis is that spared cortical motor areas in the injured and uninjured hemispheres play evolving and interdependent roles in the execution of motor tasks during functional recovery (Aim 1), and that the participation of the intact hemisphere is dependent upon task complexity (Aim 2), lesion anatomy (Aim 3), and post-injury behavioral experience (Aim 4). We also propose that post-injury plasticity is associated with altered interhemispheric neuroanatomical connections (Aim 5). With this new and unique information, investigators will be better able to design evidence-based interventions to help restore function after cortical injuries. The application of chronic microelectrode recording techniques to the question of neural network plasticity after cortical injury is quite novel. While motor output maps in anesthetized animals have revealed behaviorally-relevant changes after injury, neuronal activity patterns (task- related spike activity, local field potentials, interhemispheric communication) after injury in ambulatory animals is largely unknown. At the conclusion of the proposed five-year project, we expect to have contributed in a unique and substantial way to understanding cortical network dynamics after injury, significantly advancing our ability to design future therapeutic interventions based on a firm mechanistic footing.

Public Health Relevance

The proposed studies address fundamental questions regarding how the remaining parts of the brain reorganize after focal brain injury, as might occur in stroke or trauma. They will provide critical information needed to design future therapeutic interventions to restore function after brain injury.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-BDCN-Y (02)M)
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Bellgowan, Patrick S F
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University of Kansas
Physical Medicine & Rehab
Schools of Medicine
Kansas City
United States
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Plautz, Erik J; Barbay, Scott; Frost, Shawn B et al. (2016) Effects of Subdural Monopolar Cortical Stimulation Paired With Rehabilitative Training on Behavioral and Neurophysiological Recovery After Cortical Ischemic Stroke in Adult Squirrel Monkeys. Neurorehabil Neural Repair 30:159-72
Andrews, Brian T; Lydick, Anna; Barbay, Scott et al. (2016) Reversibility of Murine Motor Deficits Following Hemi-Craniectomy and Cranioplasty. J Craniofac Surg 27:1875-1878
Nishibe, Mariko; Urban 3rd, Edward T R; Barbay, Scott et al. (2015) Rehabilitative training promotes rapid motor recovery but delayed motor map reorganization in a rat cortical ischemic infarct model. Neurorehabil Neural Repair 29:472-82
Murphy, Maxwell D; Guggenmos, David J; Bundy, David T et al. (2015) Current Challenges Facing the Translation of Brain Computer Interfaces from Preclinical Trials to Use in Human Patients. Front Cell Neurosci 9:497
Darling, Warren G; Morecraft, Robert J; Rotella, Diane L et al. (2014) Recovery of precision grasping after motor cortex lesion does not require forced use of the impaired hand in Macaca mulatta. Exp Brain Res 232:3929-38
Barbay, Scott; Guggenmos, David J; Nishibe, Mariko et al. (2013) Motor representations in the intact hemisphere of the rat are reduced after repetitive training of the impaired forelimb. Neurorehabil Neural Repair 27:381-4
Milliken, Garrett W; Plautz, Erik J; Nudo, Randolph J (2013) Distal forelimb representations in primary motor cortex are redistributed after forelimb restriction: a longitudinal study in adult squirrel monkeys. J Neurophysiol 109:1268-82
Dancause, Numa; Nudo, Randolph J (2011) Shaping plasticity to enhance recovery after injury. Prog Brain Res 192:273-95
Nishibe, Mariko; Barbay, Scott; Guggenmos, David et al. (2010) Reorganization of motor cortex after controlled cortical impact in rats and implications for functional recovery. J Neurotrauma 27:2221-32
Guggenmos, David J; Barbay, Scott; Bethel-Brown, Crystal et al. (2009) Effects of tongue force training on orolingual motor cortical representation. Behav Brain Res 201:229-32

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