ALS is frequently regarded as a disease just of the motor cortex, but degeneration is also seen presymptomatically in other cortical areas with functional connectivity to the motor cortex. It seems that the areas of highest functional connectivity overlapped with areas of highest damage. This is theorized by researchers to be due to a loss of certain neurons which serve to modulate the activity of other neurons ("inhibitory neurons") in a process called "cortical hyperexcitability". In a recent study, researchers measured levels of GABA to support the evidence of this process in PALS. In a similar study published 04-18-2012, GABA was also found decreased in the motor cortex of PALS vs healthy control subjects.
Emerging evidence in another neurodegenerative disease, Alzheimer's Disease (AD), indicates a similar functional connectivity method of progression. In another more recent study this was also linked to a similar-sounding process called "network hypersynchrony".