seen across six layers by seed-based functional connectivity analysis after removing depth-dependent physiological noise [42]. In addition, a recent study showed the existence of temporal correlation of resting state hemodynamic signals derived from optical imaging at sub-millimeter columnar scale in the visual cortex [43]. These studies suggest that functional connectivity could be a potentially useful method to investigate the laminar connectional architecture at the functional level. However, it is yet unclear whether resting state functional connectivity (FC) is in fact stronger along structural pathways that connect different layers of brain regions compared to say, other possible connections between layers that do not have a direct structural projection between them. While this question has been addressed at the meso-scale voxel level, it has not been investigated at the micro-scale layer level. To test these possibilities, many technical challenges need to be surmounted as we discuss below, to provide motivation for the methodological choices we have made.