OBJECTIVE: A non-invasive measure of cerebral motor system dysfunction would be valuable as a biomarker in amyotrophic lateral sclerosis (ALS). Task-based magnetoencephalography (tMEG) measures the magnetic fields generated by cortical neuronal oscillatory activity during task performance. Gamma activations are periods of high-power and high-frequency cortical oscillations integral to motor control. METHODS: tMEG was undertaken during 60 bilateral isometric hand grip exercises in ALS (n = 42) and compared with healthy controls (HC, n = 33). Gamma activation spread (GAS) was estimated by calculating the number of activated regions during each 100 ms time-bin and compared statistically between groups. Gamma activation patterns were visualised by plotting each participant's brain activity separately as a 2-dimensional video. RESULTS: There was no difference in grip strength between groups. GAS was greatly increased in the ALS group compared to HC (p < 0.001) and correlated positively with rate of ALSFRS-R progression (t = 1.35, p = 0.023) and a fine motor sub-score (t = -1.18, p = 0.047). CONCLUSIONS: ALS was associated with a marked increase in regional spread of gamma frequency activation, greater in those with higher disease progression rates. SIGNIFICANCE: The regional spread of gamma activity may reflect disease activity in ALS, with potential application as an experimental medicine readout.