The goals of this project are to understand how the brain uses spinal cord circuits to coordinate movement and how neurological disorders alter the functioning of motor circuits. In previous years, we have examined changes in cortical and spinal motor circuits in disorders that selectively affect specific neuron classes. In FY2006 we studied functional changes in cortical motor circuits in long-term survivors of polio who have lower motor neuron loss and in patients with primary lateral sclerosis (PLS), a neurodegenerative disorder affecting upper motor neurons. In polio survivors, we found changes in the activation of the corticospinal system that maximize the motor output to muscles that had been affected by polio. These adaptations were not correlated with symptoms of post-polio syndrome. In patients with PLS we reported that the slow cortical EEG potentials associated with voluntary movement from pre-motor and motor areas of the cortex were diminished, but that changes in the beta-frequency oscillatory signals associated with movement were preserved. ? ? In FY2007, we expanded on these observations in PLS patients in three areas. The first was a collaboration with Dr. Ou Bai to use single-trial changes in oscillatory signals for an EEG-based brain-computer interface. The preliminary findings are promising that these signals may be useful for development of a neural-driven prosthesis in patients with motor neuron disorders. Further description of this project can be found in the Human Motor Control section report. The second line of study was aimed at assessing the extent of (non-motor) frontal cortical dysfunction in PLS patients, and to compare them to patients with amyotrophic lateral sclerosis (ALS). It has been proposed that ALS and fronto-temporal dementia have a common pathology, and that many ALS patients have frontal cognitive dysfunction. In this study, we have worked extensively with the Cognitive Neuroscience section to use the same testing battery that they have used in their studies of patients with fronto-temporal dementia. This protocol, which is planned to run for 3 years, includes neuropsychological tests, psychiatric assessment, and anatomical MRI with diffusion tensor imaging. The imaging studies will be examined in an exploratory fashion to determine whether any quantitative measures correlate to motor function or cognitive deficits. Lastly, recognizing that PLS is likely to be complex disorder, we are collecting samples from PLS patients for the NINDS DNA repository for motor neuron diseases at Coriell, so that this rare population will be accessible to the general scientific community for further studies.
| 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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