Earthquakes in Stable Continental Regions (SCR), where localized present-day tectonic loadingis negligible, remain difficult to explain. The New Madrid Seismic Zone (NMSZ) is a type-locale for such events, with four M>7 events in 1811-1812 and a regional seismicity that continues to this day. Here, we seek to determine the most favorable conditions for fault reactivation in such a context using 33 earthquakes in the 2.1-4.7 magnitude range with well-determined focal mechanisms while accounting for the vertical gradient of differential stress with depth. To do so, we developed a Mohr-Coulomb-based parametric analysis of fault reactivation that allows us to vary the orientation of the principal stresses, the shape ratio of the stress tensor, the fault friction coefficient, the pore fluid overpressure, and the gradient of differential stress with depth. Doing so, we are able to determine the lowest stress perturbation conditions required for fault reactivation. Our results show that the reactivation of the faults studied here requires pore fluid overpressure, unless their friction coefficient is 0.4 or less. We argue that such weak faults are unlikely and favor a triggering mechanism via deep fluids, possibly upwelling from the upper mantle where a low-velocity seismic anomaly could indicate their presence. This mechanism, documented in other intraplate areas, does not require local tectonic stress or strain accumulation to explain seismicity in active intraplate regions, where elastic strain is drawn from a prestressed crust.