These results are supported by the previous observation that cortical hyperexcitability precedes the development of clinical symptoms in pre-symptomatic carriers of a SOD1 mutation [32], thereby suggesting that the early abnormalities in ALS occur within the corticomotorneurons, with anterograde excitotoxicity (often referred to as ‘dying forward’). The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.