Stroke is the leading cause of functional disability affecting greater than 780,000 people a year in the United States. The negative personal, social and economic impacts of this disease are staggering. In clinical practice, it is a common observation that variable levels of motor recovery 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. In adult rhesus monkeys, 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 cingulate motor areas located ipsilateral to a subtotal brain lesion. At clinically significant time intervals, we will test this hypothesis by studying neuroplastic adaptations of the corticospinal projection from the arm areas of the rostral (M3) and caudal (M4) cingulate motor cortices following isolated resection of the ipsilateral arm areas of a) the primary motor cortex (M1); b) M1 and dorsolateral area 6 (LPMCd) and; c) M1, LPMCd and the supplementary motor cortex (M2). The first two lesion categories model the most common form of stroke, namely middle cerebral artery infarction. Hand recovery will be carefully tracked by analyzing 3-D hand trajectory during reaching, force control during grasping and lifting, and monitoring functional hand performance using 2 specialized assessment methods. This project will lead to a greater understanding of the role of the cingulate motor cortices in the recovery process of arm movement following ipsilateral damage to the frontal motor cortices. This work 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. We will determine the type of motor/premotor cortical lesion that activates natural (i.e., non-therapeutic) recruitment of the cingulate corticospinal system, the timing of the activation process and how this affects the reaching and grasping process. This information will assist in establishing predictors to identify a large patient population that may develop favorably after stroke since the origin of the cingulate corticospinal projection is supplied by the anterior cerebral artery (ACA) and the ACA is spared in greater than 97% of all first time ischemic stroke victims. Furthermore, it will assist in guiding creative rehabilitative intervention approaches aimed at enhancing anterior cingulate participation in the recovery process. ? ? ?

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1-CNNT (02))
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Hicks, Ramona R
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University of South Dakota
Other Basic Sciences
Schools of Medicine
United States
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Darling, Warren G; Ge, Jizhi; Stilwell-Morecraft, Kimberly S et al. (2018) Hand Motor Recovery Following Extensive Frontoparietal Cortical Injury Is Accompanied by Upregulated Corticoreticular Projections in Monkey. J Neurosci 38:6323-6339
Morecraft, Robert J; Ge, Jizhi; Stilwell-Morecraft, Kimberly S et al. (2018) New Corticopontine Connections in the Primate Brain: Contralateral Projections From the Arm/Hand Area of the Precentral Motor Region. Front Neuroanat 12:68
Morecraft, R J; Binneboese, A; Stilwell-Morecraft, K S et al. (2017) Localization of orofacial representation in the corona radiata, internal capsule and cerebral peduncle in Macaca mulatta. J Comp Neurol 525:3429-3457
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; 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, 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
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
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
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

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