Stroke and traumatic brain injury often involve the cerebral cortex and are leading causes of functional disability collectively affecting greater than 2 million people per year in the United States. The negative personal, social and economic impacts of these disorders are staggering. In clinical practice, variable levels of motor recovery are commonly observed and occur following damage of the motor cortex or its descending pathways. Although there appears to be considerable functional plasticity in the adult brain, the mechanisms underlying motor recovery following subtotal brain injury remain poorly understood. Our major goal is to test the hypothesis that a central mechanism of functional recovery of arm movement occurs through reorganization of the corticospinal projection from intact frontal motor areas located ipsilateral to a subtotal brain lesion and that forced use therapy enhances the corticospinal linkage. At clinically significant time intervals and under different durations of forced use therapy, we will test this hypothesis by studying neuroplastic adaptations of the corticospinal projection from the arm area of the supplementary motor cortex (M2) following isolated resection of the ipsilateral arm areas of: a) the primary motor cortex (M1) + the dorsolateral premotor cortex (LPMCd) and;b) M1 + LPMCd + the primary somatosensory cortex (S1). Both of these lesion categories involve part of the motor cortex that is typically involved in the most common form of human stroke, namely middle cerebral artery infarction. Hand recovery will be tracked by analyzing 3-D hand and digit motion during reaching and grasping, force control during grasping and lifting, and bimanual coordination using 3 specialized testing methods. This project will lead to a greater understanding of the role of the frontal motor cortices in the recovery process of arm movement following cortical injury and will determine the effect that short and long-term forced use therapy has on recovery outcome and its accompanying neuroplastic response. This research will also assess whether the integrity of spared corticospinal projections from intact motor areas positioned ipsilateral to a lesion of the cerebral cortex underlie functional restitution of hand movement control and whether long-term reorganization of intact corticospinal terminals accompany the recruitment of parallel cortical motor areas after subtotal brain injury. This information will assist in establishing predictors to identify a large patient population that may recover favorably after brain injury with appropriate therapy. Furthermore, it will assist in guiding creative rehabilitative interventions aimed at enhancing frontal cortical participation in the recovery process.

Public Health Relevance

Stroke and traumatic brain injury often involve the cerebral cortex and are leading causes of functional disability collectively affecting greater than 2 million people a year in the United States. This project will lead to a greater understanding of the role of the frontal motor cortices in the recovery process of arm movement following cortical injury and will determine the effect that short and long-term forced use therapy has on recovery outcome and its accompanying neuroplastic response. This information will assist in establishing predictors to identify a large patient population that may develop favorably after brain injury and will assist in guiding creative rehabilitative interventions aimed at enhancing frontal cortical participation in the recovery process.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS046367-08
Application #
8269688
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Hicks, Ramona R
Project Start
2003-07-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
8
Fiscal Year
2012
Total Cost
$375,299
Indirect Cost
$79,142
Name
University of South Dakota
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
929930808
City
Vermillion
State
SD
Country
United States
Zip Code
57069
Darling, Warren G; Pizzimenti, Marc A; Rotella, Diane L et al. (2016) Sensorimotor cortex injury effects on recovery of contralesional dexterous movements in Macaca mulatta. Exp Neurol 281:37-52
Morecraft, R J; Ge, J; Stilwell-Morecraft, K S et al. (2016) Frontal and frontoparietal injury differentially affect the ipsilateral corticospinal projection from the nonlesioned hemisphere in monkey (Macaca mulatta). J Comp Neurol 524:380-407
Morecraft, R J; Ge, J; Stilwell-Morecraft, K S et al. (2015) Vulnerability of the medial frontal corticospinal projection accompanies combined lateral frontal and parietal cortex injury in rhesus monkey. J Comp Neurol 523:669-97
Morecraft, R J; Stilwell-Morecraft, K S; Ge, J et al. (2015) Cytoarchitecture and cortical connections of the anterior insula and adjacent frontal motor fields in the rhesus monkey. Brain Res Bull 119:52-72
Morecraft, Robert J; Stilwell-Morecraft, Kimberly S; Solon-Cline, Kathryn M et al. (2014) Cortical innervation of the hypoglossal nucleus in the non-human primate (Macaca mulatta). J Comp Neurol 522:3456-84
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
Darling, Warren G; Helle, Nicole; Pizzimenti, Marc A et al. (2013) Laterality affects spontaneous recovery of contralateral hand motor function following motor cortex injury in rhesus monkeys. Exp Brain Res 228:9-24
Morecraft, Robert J; Ge, Jizhi; Stilwell-Morecraft, Kimberly S et al. (2013) Terminal distribution of the corticospinal projection from the hand/arm region of the primary motor cortex to the cervical enlargement in rhesus monkey. J Comp Neurol 521:4205-35
Morecraft, R J; Stilwell-Morecraft, K S; Cipolloni, P B et al. (2012) Cytoarchitecture and cortical connections of the anterior cingulate and adjacent somatomotor fields in the rhesus monkey. Brain Res Bull 87:457-97
Darling, Warren G; Pizzimenti, Marc A; Morecraft, Robert J (2011) Functional recovery following motor cortex lesions in non-human primates: experimental implications for human stroke patients. J Integr Neurosci 10:353-84

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