Unilateral spastic cerebral palsy (USCP) is characterized by movement deficits, particularly upper extremity (UE) impairments on one side of the body. Although strides have been made to improve UE rehabilitation approaches, even the best available therapies fail to fully ameliorate UE impairments, are costly, and require large amounts of time. Thus, there is an urgent need to optimize the effectiveness and cost of UE therapies. Our long-term goal is to develop evidence-based strategies to improve movement in children with USCP. Early damage to the developing brain can result in a re-wiring of the direct corticospinal tract (CST) projections innervating UE function. In many children with USCP, there are no CST connections from the damaged hemisphere, and instead ipsilateral (same-sided) CST pathways control movement of the affected UE. Previously, this type of reorganization was believed to be maladaptive and unresponsive to treatment. However, during the first funding period of this R01, we determined that UE therapy efficacy is independent of CST laterality. Importantly, we found that the hemisphere containing CST connectivity to the affected hand showed neuroplastic changes in response to intensive therapy. Nonetheless, this heterogeneity in the brain connectivity means it is unlikely that a one-size-fits-all rehabilitation approach will be suitable. Therefore, our next goal is to leverage these findings using an individualized approach to obtain the same or greater changes using a fraction of the dosage by enhancing the neuroplastic changes with transcranial direct current stimulation (tDCS). Our preliminary results show that tDCS enhances the efficacy of UE training only if it is targeted to an individual?s CST laterality determined with single-pulse transcranial magnetic stimulation (TMS). The overall objective for this renewal is to vertically extend what has been learned under our prior R01 by determining how to optimally target tDCS to enhance the efficacy of UE training in children with USCP. Our central hypothesis is that bimanual training (BT) combined with a tDCS montage targeting the hemisphere with CST connectivity to the impaired UE muscles will improve UE function more than BT plus sham stimulation. We will test this by conducting a randomized clinical trial (RCT) to determine the efficacy of targeted tDCS/BT for improving UE function and interactions between tDCS/BT and motor cortex physiology in children with USCP. Our working hypotheses are that children who receive targeted anodal tDCS will show the most robust changes in hand function and motor cortex physiology. Determination of the synergistic effects of tDCS and BT may substantially reduce the required rehabilitation time and cost necessary to improve UE function. The proposed work is innovative because it may increase accessibility of treatment, particularly for centers that serve families of lower socio-economic status, due to the reduced cost of therapy.

Public Health Relevance

Unilateral spastic cerebral palsy is an extremely common pediatric neurological disorder of movement, and existing efficacious therapies are time intensive and costly. Non-invasive brain stimulation, aiming to influence the excitability of the brain in the area that controls movement, may enhance physical rehabilitation approaches. This study will examine the combined effects of non-invasive brain stimulation and hand movement therapy in children with unilateral spastic cerebral palsy, and will inform future precision- interventions aiming to increase availability and decrease cost of treatment.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Motor Function, Speech and Rehabilitation Study Section (MFSR)
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Nitkin, Ralph M
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Winifred Masterson Burke Med Research Institute
White Plains
United States
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Gillick, Bernadette T; Gordon, Andrew M; Feyma, Tim et al. (2018) Non-Invasive Brain Stimulation in Children With Unilateral Cerebral Palsy: A Protocol and Risk Mitigation Guide. Front Pediatr 6:56
Marneweck, Michelle; Kuo, Hsing-Ching; Smorenburg, Ana R P et al. (2018) The Relationship Between Hand Function and Overlapping Motor Representations of the Hands in the Contralesional Hemisphere in Unilateral Spastic Cerebral Palsy. Neurorehabil Neural Repair 32:62-72
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
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