The purpose of this research career development proposal is to extend Dr. Sanger's training beyond his current theoretical background into clinicallyoriented research on children with movement disorders. Dr. Sanger's past research has focused on computational models of movement and motor learning. This research plan proposes to apply this background in a clinical research setting by performing a quantitative investigation of increased upperextremity movement in children with hyperkinetic cerebral palsy (CP). It is not known whether abnormal movements result from random noise, decreased ability to modulate the amplitude of movements, or inappropriate planning of motor sequences. This proposal suggests two related hypotheses: (1) Hyperkinetic CP is a result of a restriction in the variability of motor commands such that desired smooth movements are not available, and (2) Progression of abnormal movements over time is reflected by an increasing restriction in the variability of motor commands and worsening energetic efficiency. To test these hypotheses, position sensors and surface electomyographic (EMG) recordings of reaching movements will be made at 6 month intervals in children of different ages with hyperkinetic CP. Kinematic and EMG data will be analyzed to determine energy expenditure, variability of the set of kinematic patterns, and total information content of movement. If the hypotheses are correct, then we expect progression of symptoms in dyskinetic CP to be reflected in decreasing dimensionality, information content, and energy efficiency of the patterns of movements. The results of this study may allow early identification of children at risk for hyperkinetic CP as well as prediction of the progression and ultimate severity of symptoms. Dr. Andriacchi, Dr. Mobley, and Dr. Hlatky will serve as mentors for Dr. Sanger's work on this project. Dr. Andriacchi will provide instruction on the measurement of kinematics and energetics in children, Dr. Mobley will provide instruction on the clinical evaluation of children with movement disorders, and Dr. Hlatky will guide the design and implementation of clinical trials and outcome measure validation. The proposal includes coursework in cellular and molecular neurobiology and in the design of clinical research studies.
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