PROJECT SUMMARY/ABSTRACT Cerebral palsy (CP) results from a perinatal brain injury and is one of the most prevalent and costly pediatric neurologic conditions in the United States. Individuals with CP frequently experience lifelong mobility challenges. The modern treatment approaches being used to overcome these challenges place greater emphasis on the neurological basis for how youth with CP plan their leg movements, execute motor actions, and integrate sensory information. Despite this neuroscience-informed approach, these new therapies are still limited by substantial knowledge gaps regarding how the aberrant sensorimotor cortical activity and/or spinal cord specifically affects the gait of youth with CP. Our ultramodern magnetoencephalographic (MEG) brain imaging results have revealed that cortical aberrations play a substantial role in the uncharacteristic leg motor actions and sensory processes seen in youth with CP. Furthermore, our high-resolution MRI pipelines have shown that the structural integrity of spinal cord tissue is compromised in individuals with CP. From these experiments, we have inferred that the altered cortical dynamics and spinal cord integrity likely impacts the ability of youth with CP to make feed-forward predictions and/or online corrections to their leg kinematics during gait. However, this conjecture has yet to be fully established due to physical limitations of the MEG/MRI recording environments. To move forward, we will use our extensive MEG foundational work to develop new electroencephalographic (EEG) methods that have the scientific rigor and flexibility to precisely quantify the sensorimotor cortical activity during real-time gait. Furthermore, we will utilize cutting-edge neurophysiological tests to concurrently quantify how the spinal cord interneuronal dynamics are modulated during gait. The Aims of this study will: (1) establish multimodal MEG-EEG neuroimaging proxies of the aberrant sensorimotor cortical oscillations seen in youth with CP that are known to impact the extent of the mobility deficits, (2) quantify the sensorimotor EEG cortical oscillations and spinal cord interneuronal dynamics of youth with CP during gait, and (3) decipher if alterations in the sensorimotor cortical oscillations and spinal cord interneuronal dynamics are better predictors of the mobility deficits seen in youth with CP relative to the most commonly used clinical metrics. To achieve these Aims, youth with CP and neurotypical controls will undergo a series of experiments that will use simultaneous MEG-EEG neuroimaging, EEG neuroimaging during gait, and assessments of the spinal cord interneuronal dynamics during gait. Furthermore, the participants will undergo a battery of clinical assessments (e.g., balance, spasticity, selective control, strength and sensation). We foresee that the body of new knowledge gained through this project will set-the-stage for the design and testing of innovative therapeutic protocols that target the specific neurophysiological deficits that are limiting the mobility of youth with CP.

PROJECT NARRATIVE Cerebral palsy (CP) results from a perinatal brain injury that instigates lifelong challenges in mobility. The current project will use brain imaging, spinal cord assessments and clinical tests to accelerate the development of new biomarkers that capture the connection between nervous system dysfunction and the altered mobility seen in youth with CP. The new indices developed through this important project will provide unprecedented neurophysiological specificity for developing therapeutic targets for individuals with CP.