Activity-dependent competition drives development of the corticospinal (CS) system during early postnatal life. Animal studies have demonstrated that imbalance of activity between the motor cortex (Ml) in the two hemispheres causes aberrant CS circuit formation and motor impairments. Rebalancing Ml activity on the two sides later in development restores normal CS connections and motor function. In human hemiplegic CP, a neurological disorder characterized by poor motor control, motor areas become damaged during perinatal development. The damage tends to have a unilateral predominance. Decreased CS system activity on the affected side is thought to be crucial to development of hemiplegic CP. It is hypothesized that restoring balance between the activity of Ml on each side is essential for restitution of normal CS circuitry and motor skill. One treatment effective in improving motor function in children with hemiplegic CP is training of the affected side with concurrent restraint of the unaffected limb. During treatment, children engage in skilled, repetitive movements with the affective side, while the unaffected side is restrained with a sling. This behavioral treatment balances Ml activity by increasing activity of the affected side through training while decreasing activity of the unaffected side through restraint. The proposed work will also examine how different intensities of skill training influence recovery. The important issue of whether training of movements focusing on precise distal control and shaping of increasing skill difficulty is more effective than repetitive task performance without increasing skill difficulty has not been addressed. Understanding the mechanisms underlying behavioral improvements is an important step towards developing new therapies that can be applied to a broader population of children with hemiplegia, especially those with more debilitating impairments who have the greatest need for an effective treatment. This proposal takes a translational approach to the study of CP rehabilitation, built upon an understanding of the development of the cat motor system. The applicant will obtain training in TMS, human motor skill assessment and analysis, and translating hypotheses between the animal and the human. By understanding the mechanisms of recovery, particularly the interplay between training and CS system plasticity in recovery, the applicant will be in the unique position to translate these mechanisms to improve CP treatment.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Scientist Development Award - Research & Training (K01)
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NST-2 Subcommittee (NST)
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Chen, Daofen
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Smorenburg, Ana R P; Gordon, Andrew M; Kuo, Hsing-Ching et al. (2017) Does Corticospinal Tract Connectivity Influence the Response to Intensive Bimanual Therapy in Children With Unilateral Cerebral Palsy? Neurorehabil Neural Repair 31:250-260
Saussez, Geoffroy; Brandão, Marina B; Gordon, Andrew M et al. (2017) Including a Lower-Extremity Component during Hand-Arm Bimanual Intensive Training does not Attenuate Improvements of the Upper Extremities: A Retrospective Study of Randomized Trials. Front Neurol 8:495
Kuo, Hsing-Ching; Gordon, Andrew M; Henrionnet, Aline et al. (2016) The effects of intensive bimanual training with and without tactile training on tactile function in children with unilateral spastic cerebral palsy: A pilot study. Res Dev Disabil 49-50:129-39
Friel, Kathleen M; Kuo, Hsing-Ching; Fuller, Jason et al. (2016) Skilled Bimanual Training Drives Motor Cortex Plasticity in Children With Unilateral Cerebral Palsy. Neurorehabil Neural Repair 30:834-44
Bleyenheuft, Yannick; Dricot, Laurence; Gilis, Nathalie et al. (2015) Capturing neuroplastic changes after bimanual intensive rehabilitation in children with unilateral spastic cerebral palsy: A combined DTI, TMS and fMRI pilot study. Res Dev Disabil 43-44:136-49
Friel, Kathleen M; Kuo, Hsing-Ching; Carmel, Jason B et al. (2014) Improvements in hand function after intensive bimanual training are not associated with corticospinal tract dysgenesis in children with unilateral cerebral palsy. Exp Brain Res 232:2001-9
Friel, Kathleen M; Chakrabarty, Samit; Martin, John H (2013) Pathophysiological mechanisms of impaired limb use and repair strategies for motor systems after unilateral injury of the developing brain. Dev Med Child Neurol 55 Suppl 4:27-31
Friel, Kathleen; Chakrabarty, Samit; Kuo, Hsing-Ching et al. (2012) Using motor behavior during an early critical period to restore skilled limb movement after damage to the corticospinal system during development. J Neurosci 32:9265-76
Martin, John H; Chakrabarty, Samit; Friel, Kathleen M (2011) Harnessing activity-dependent plasticity to repair the damaged corticospinal tract in an animal model of cerebral palsy. Dev Med Child Neurol 53 Suppl 4:9-13