Just to expand a little, Chris said this:
"L. Tim Long had a hypothesis that the New Madrid zone is the result of fluids at the base of the crust that work their way up, set off a few earthquakes, and then eventually the area shuts itself back off."

So there may be a puddle of fluid, probably mostly water, that seeps out of the mantle or lower crust for an unknown reason, and percolates up through the rock where earthquakes are possible. When it seeps in, the rocks are lubricated and the fluid pressure may increase, making it easier for the faults to have earthquakes. The stress to drive the earthquakes is present all the time.

For all I know, this hypothesis is still viable, maybe Chris knows if it is still bandied around.

John