Introduction We sought a combination of abnormalities to define a more sensitive measure of cortical excitability in amyotrophic lateral sclerosis (ALS). Methods The automatic threshold tracking method was employed to assess the resting motor threshold, intracortical facilitation (ICF), short-interval intracortical inhibition (SICI), and short-interval intracortical faciilitation (SICF) in patients and controls. Results SICF at interstimulus intervals (ISI) between 1 and 1.8 ms and 2 and 3 ms as well as average SICI and SICI at ISIs of 1 and 2.5 ms were significantly reduced in ALS. The SICI curve was altered, displaying a solitary peak. Discriminant analysis revealed that the combination of SICI 2.5 ms and the mean SICF between 1 and 1.8 ms ISIs was the most sensitive parameter to distinguish patients with ALS from healthy participants. Discussion Along with the reduced SICI and its altered shape, connectivity between motor cortical circuits is changed in ALS. Combination with SICF increases the diagnostic utility of SICI in ALS.