The goals of this project are to first, to understand the role of spinal cord circuits in coordinating simple movements in humans and, secondly, to evaluate whether changes in the functioning of motor circuits contribute to abnormalities of movement. In FY2004 our clinical studies have focused on two neurological disorders, primary lateral sclerosis and spastic paraplegia, in which degeneration of the corticospinal tract produces progressive spasticity. In these disorders, spinal neurons remain intact, but do not receive input from the motor cortex. Two questions are being explored. First, to investigate the functioning of spinal circuits, we are assessing the excitability and firing behavior of motor neurons innervating spastic muscles in patients with PLS. A goal of this study is to determine whether abnormalities of firing can be modified by peripheral sensory inputs. Work to date indicates that there are functional abnormalities of motor neurons in PLS patients that alter their responsiveness to peripheral and descending inputs. We also are examining whether spinal interneuron circuits can be modified, since peripheral sensory inputs to motor neurons are relayed through spinal interneurons. These studies have initially focused on healthy controls. In one study, we found that repetitive stimulation was able to transiently strengthen one of the spinal interneuron circuits, disynaptic reciprocal inhibition. This circuit is known to function abnormally in spasticity. Current studies are assessing whether a longer lasting plasticity can be achieved through repetitive performance of an alternating motor movement. A second line of investigation is directed at understanding the likely underlying pathophysiologic processes in PLS and spastic paraplegia. We have hypothesized that , in a subset of PLS patients, corticospinal axons selectively undergo a dying-back degeneration that produces a characteristic """"""""ascending"""""""" clinical pattern. A similar hypothesis has been proposed for uncomplicated hereditary spastic paraparesis, in which long sensory as well motor tracts degenerate. To test this hypothesis we are prospectively assessing the serial functioning of the long tracts in a cohort of patients. We are also testing whether movement related cortical potentials, which are generated by shorter intracortical axons, are preserved at a time when corticospinally generated motor evoked potentials are lost.
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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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