 Our project has first an interest for the fundamental research aiming at increasing basic knowledge of pathophysiology of ALS, and specifically on the functional effects of the underlying neurodegenerative mechanisms. By testing the excitability of spinal interneurons in patients recently diagnosed, and by doing so for clinically uninvolved muscles, we will be able to evaluate whether an interneuron pathology could be involved in ALS. Our results will help to understand better the chain reactions in the neurodegenerative processes that dramatically evolve until the death of all motor neurons. Our project has also an interest for the development of therapeutic approaches for ALS. Indeed, our methods will help to determine specific electrophysiological biomarkers that will help to evaluate quantitatively spinal and corticospinal neural processes: their changes during the course of the disease follow-up study, the effect of therapeutic agents andor rehabilitation methods on their excitability, and their repercussions on motor neuron activity evaluation of therapeutics. Lastly, our methods could be tested in other neuromuscular diseases to determine possible differences in spinal neural activity. Indeed, the motor dysfunction common to several neuromuscular diseases can make it difficult to make a definitive diagnosis. The development of specific biomarkers is crucial for an early diagnosis, and to evaluate the best treatment for the patients as rapidly as possible. 