Our current mechanistic understanding of potential sources of altered cortical network excitability in ALS-FTD is derived largely from mutant murine models (SOD1 and TDP-43 mutations) of ALS and ALS-FTD [17, 30, 45, 48, 65], but does not extend to provide a physiological basis for altered network excitability. This evidence concerns the gene SOD1 and frontotemporal dementia.