We report on a novel technique for localized interface passivation in High-Resistivity (HR) silicon-based substrates. Called Field Effect Depletion Regions (FEDR), it relies on alternating dielectrics with fixed charge densities of different signs Qox,pos and Qox,neg near the substrate interface to passivate the Parasitic Surface Conduction (PSC). TCAD simulations based on a Coplanar Waveguide (CPW) structure on FEDR-passivated HR substrates describe the substrate response against fixed charge density, pattern pitch and DC bias variations. It is shown that in the best cases, FEDR enables maintaining roughly one order of magnitude improvement on the substrate effective resistivity versus unpassivated HR up to 100 GHz (eff ~1 kΩ.cm). Moreover, this work provides some guidelines on finding the best pattern periodicity while respecting technology constraints.