The goals of this project are first, to understand how spinal cord circuits help to coordinate movement in humans and, secondly, to understand how altered functioning of motor circuits contributes to abnormal movement. In FY2005 our clinical studies focused on primary lateral sclerosis, a disorder in which degeneration of the corticospinal tract produces progressive spasticity. This disorder preserves spinal cord neurons, but they do not receive input from the motor cortex. We found that the spinal motor neurons undergo changes in their excitability and firing behavior, such that individual motor neurons tend to fire more slowly, and greater numbers of motor neurons are activated to make stronger movements. These changes are likely to produce less efficient muscle contraction and greater fatigue. We hypothesize that these changes in firing behavior are intrinsic to the motor neuron, and may be caused by changes in behavior of classes of ion channels. A second line of investigation tested whether a subset of PLS patients whose disease progressed in an """"""""ascending"""""""" clinical pattern were likely to have degeneration of only the distal ends of the corticospinal axons, i.e. a dying-back degeneration. We hypothesized that movement related cortical potentials, which are generated by shorter axons between cortical motor and pre-motor areas, would be preserved if only the longest corticospinal axons were affected. If movement related cortical potentials were to be spared, these could be used to generate signals for prosthetic devices such as brain computer interfaces. The third study was a pilot investigation to test whether exercise alone can strengthen spinal circuits. Preliminary results in healthy volunteers indicate that circuits that help to produce alternating movements of antagonist muscles can be strengthened by practicing alternating movements.
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| Schanz, Olivia; Bageac, Devin; Braun, Laura et al. (2016) Cortical hyperexcitability in patients with C9ORF72 mutations: Relationship to phenotype. Muscle Nerve 54:264-9 |
| Meoded, Avner; Morrissette, Arthur E; Katipally, Rohan et al. (2015) Cerebro-cerebellar connectivity is increased in primary lateral sclerosis. Neuroimage Clin 7:288-96 |
| Statland, Jeffrey M; Barohn, Richard J; Dimachkie, Mazen M et al. (2015) Primary Lateral Sclerosis. Neurol Clin 33:749-60 |
| Floeter, Mary Kay; Katipally, Rohan; Kim, Meredith P et al. (2014) Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders. Neurology 83:620-7 |
| Su, Zhaoming; Zhang, Yongjie; Gendron, Tania F et al. (2014) Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS. Neuron 83:1043-50 |
| Flynn, Lauren; Stephen, Matthew; Floeter, Mary Kay (2014) Disease spread through contiguity and axonal tracts in primary lateral sclerosis. Muscle Nerve 49:439-41 |
| Peters, Tracy L; Floeter, Mary Kay (2009) Usage of support services in primary lateral sclerosis. Amyotroph Lateral Scler 10:187-91 |
| Floeter, Mary Kay; Mills, Reversa (2009) Progression in primary lateral sclerosis: a prospective analysis. Amyotroph Lateral Scler 10:339-46 |
| Lupu, Vitalie D; Danielian, Laura; Johnsen, Jacqueline A et al. (2008) Physiology of the motor cortex in polio survivors. Muscle Nerve 37:177-82 |
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