The goals of this project are to first, 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 FY2003 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. Sensory inputs to motor neurons are relayed through spinal interneuron circuits. In the last year, in healthy control subjects, we showed that repetitive sensory stimulation was able to transiently strengthen one of the spinal interneuron circuits, disynaptic reciprocal inhibition, that is known to function abnormally in spasticity. 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 documenting the serial functioning of the long tracts in a cohort of patients, and are planning studies to assess the physiological function short-axon intrinsic connections of the motor cortex.
| Cardenas, Agustin M; Sarlls, Joelle E; Kwan, Justin Y et al. (2017) Pathology of callosal damage in ALS: An ex-vivo, 7 T diffusion tensor MRI study. Neuroimage Clin 15:200-208 |
| 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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