Cortical depth-dependent human fMRI of resting-state networks using EPIK

Recent laminar-fMRI studies have substantially improved understanding of the evoked cortical responses in multiple sub-systems; in contrast, the laminar component of resting-state networks spread over the whole brain has been less studied due to technical limitations. Animal research strongly suggests that the supragranular layers of the cortex play a critical role in maintaining communication within the default mode network (DMN); however, whether this is true in this and other human cortical networks remains unclear. Here, we used EPIK, which offers unprecedented coverage at sub-millimeter resolution, to investigate cortical broad resting-state dynamics with depth specificity in healthy volunteers. Our results suggest that human DMN connectivity is primarily supported by intermediate and superficial layers of the cortex, and furthermore, the preferred cortical depth used for communication can vary from one network to another. This has major implications for the characterization of network-related diseases and should occupy future high-resolution studies. In addition, the laminar connectivity profile of some networks showed a tendency to change upon engagement in a motor task. In line with these connectivity changes, we observed that the amplitude of the low-frequency-fluctuations (ALFF), as well as the regional homogeneity (ReHo), exhibited a different laminar slope when subjects were either performing a task or were in a resting state (less variation among laminae, i.e., lower slope, during task performance compared to rest). The varied laminar profiles concerning network connectivity, ALFF, and ReHo, observed across two brain states (task vs. rest) suggest the potential diagnostic value of laminar fMRI in psychiatric diseases, e.g., to differentiate the cortical dynamics associated with disease stages linked, or not linked, to behavioral changes. The evaluation of laminar-fMRI across the brain encompasses computational challenges; nonetheless, it enables the investigation of a new dimension of the human neocortex, which may be key to understanding neurological disorders from a novel perspective.