Cytoarchitectonically defined cortical layers can be considerably thinner than the resolutions of any of the data reviewed here. Individual cortical layers can have thicknesses between 100 μm and 800 μm. Until now, it is not fully understood what the ultimate limit of the localization specificity in blood-volume-based layer-fMRI will be. While animal studies have shown that layer-dependent CBV responses can be locally precise to an accuracy level of 200 μm in the rat olfactory bulb (Poplawsky et al. 2019), the best current spatial resolution of human layer-fMRI with VASO is ≈ 500 μm (Fig. 2). Thus, it is important to note that the layer-specific connectivity tools discussed here, do not represent activity of individual neuron clusters in isolated layers with Nyquist sampling across cortical depth. Instead, the findings on directional connectivity reviewed here are based on depth-specific signals variations that represent variable super-positions of neural activity from multiple cytoarchitectonically-defined cortical layers.