Pediatric-onset hemiplegia (PH) causes movement impairments on one side of the body and accounts for more than a third of all cases of cerebral palsy, the most common motor disability in childhood. Motor impairments in this population include weakness, movement synergies, and coupling movements between limbs (between arms and between paretic arm and legs), all of which limit independence with functional mobility throughout the lifespan. Crucial tasks, such as reaching and grasping, required for countless daily activities including participating in the classroom, become limited or impossible. In the previous cycle of this R01, we discovered that the timing of brain injury during neurodevelopment impacted the expression of weakness, involuntary coupling of shoulder abduction with elbow, wrist, and finger flexion (flexion synergy), and involuntary coupling between upper limbs during isometric tasks. Our previous work uncovered the importance of the timing of the injury on the preservation of neural structures, expressed in the integrity of white matter, as they may be affected differently based on the stage of neurodevelopment when the injury occurs. During early injuries (PRE-natal), there may be preservation of direct ipsilateral corticospinal projections that are present as part of typical neural development. We hypothesize that this explains the reduced presence of the flexion synergy and the greater movement coupling between upper limbs. Conversely, in later injuries (PERI- and POST-natal) we hypothesize that the developmental pruning of these ipsilateral corticospinal projections is in process (PERI-natal) or has already occurred (POST-natal) leading to increased reliance in indirect ipsilateral corticoreticulospinal pathways to control movement of the paretic limbs. These indirect pathways branch significantly at the spinal cord, explaining the presence of the flexion synergy and abnormal involuntary coupling between the paretic leg and arm. In an effort to determine the effects of time of injury and limb loading on motor impairments during functional reaching-grasping tasks in PH and the link to neural microstructural morphology, we propose to: 1) quantify upper extremity reaching distance and hand opening/closing ability; 2) determine the expression of between-limb movement coupling; and 3) identify the changes in white and gray matter complexity of motor pathways in ipsilesional and contralesional hemispheres as well as the brainstem. As such, the proposed research will, for the first time, investigate the effect of time of brain injury on motor pathway complexity in individuals with pediatric-onset hemiplegic who express within-limb and between-limb coupling dysfunction. This will provide the foundation for the development of more effective targeted, time-of-injury specific interventions for the treatment of abnormal within- and between-limb coupling to improve functional capabilities in this population.

Public Health Relevance

The proposed study seeks to quantify the effect of time of brain injury on abnormal involuntary within limb and between limb movement coupling patterns in pediatric hemiplegia and its link to losses of motor pathways in the brain and brainstem. A more complete understanding of the timing of the injury on motor impairments is expected to lead to the development of more targeted, time of injury-specific and therefore effective rehabilitation interventions in this population.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Musculoskeletal Rehabilitation Sciences Study Section (MRS)
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Chen, Daofen
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Northwestern University at Chicago
Physical Medicine & Rehab
Schools of Medicine
United States
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Filatova, Olena G; Yang, Yuan; Dewald, Julius P A et al. (2018) Dynamic Information Flow Based on EEG and Diffusion MRI in Stroke: A Proof-of-Principle Study. Front Neural Circuits 12:79
Hurley, Donna S; Sukal-Moulton, Theresa; Gaebler-Spira, Deborah et al. (2015) Systematic Review of Cerebral Palsy Registries/Surveillance Groups: Relationships between Registry Characteristics and Knowledge Dissemination. Int J Phys Med Rehabil 3:
Hawe, Rachel L; Dewald, Jules P A (2014) Assessment of the contralesional corticospinal tract in early-onset pediatric hemiplegia: Preliminary findings. Conf Proc IEEE Eng Med Biol Soc 2014:5336-9
Sukal-Moulton, Theresa; Krosschell, Kristin J; Gaebler-Spira, Deborah J et al. (2014) Motor impairment factors related to brain injury timing in early hemiparesis. Part I: expression of upper-extremity weakness. Neurorehabil Neural Repair 28:13-23
Sukal-Moulton, Theresa; Krosschell, Kristin J; Gaebler-Spira, Deborah J et al. (2014) Motor impairments related to brain injury timing in early hemiparesis. Part II: abnormal upper extremity joint torque synergies. Neurorehabil Neural Repair 28:24-35
Sukal-Moulton, Theresa; Murray, Theresa M; Dewald, Julius P A (2013) Loss of independent limb control in childhood hemiparesis is related to time of brain injury onset. Exp Brain Res 225:455-63
Hawe, Rachel L; Sukal-Moulton, Theresa; Dewald, Julius P A (2013) The effect of injury timing on white matter changes in the corpus callosum following unilateral brain injury. Neuroimage Clin 3:115-22
Stienen, Arno H A; Moulton, Theresa Sukal; Miller, Laura C et al. (2011) Wrist and Finger Torque Sensor for the quantification of upper limb motor impairments following brain injury. IEEE Int Conf Rehabil Robot 2011:5975464
Hurley, Donna S; Sukal-Moulton, Theresa; Msall, Michael E et al. (2011) The cerebral palsy research registry: development and progress toward national collaboration in the United States. J Child Neurol 26:1534-41