Resting state fMRI connectivity is sensitive to laminar connectional architecture in the human brain

Previous invasive studies indicate that human neocortical graymatter contains cytoarchitectonically distinct layers, with notable differences in their structural connectivity with the rest of the brain. Given recent improvements in the spatial resolution of anatomical and functional magnetic resonance imaging (fMRI), we hypothesize that resting state functional connectivity (FC) derived from fMRI is sensitive to layer-specific thalamo-cortical and cortico-cortical microcircuits. Using sub-millimeter resting state fMRI data obtained at 7 T, we found that: (1) FC between the entire thalamus and cortical layers I and VI was significantly stronger than between the thalamus and other layers. Furthermore, FC between somatosensory thalamus (ventral posterolateral nucleus, VPL) and layers IV, VI of the primary somatosensory cortex were stronger than with other layers; (2) Inter-hemispheric cortico-cortical FC between homologous regions in superficial layers (layers I-III) was stronger compared to deep layers (layers V-VI). These findings are in agreement with structural connections inferred from previous invasive studies that showed that: (i) M-type neurons in the entire thalamus project to layer-I; (ii) Pyramidal neurons in layer-VI target all thalamic nuclei, (iii) C-type neurons in the VPL project to layer-IV and receive inputs from layer-VI of the primary somatosensory cortex, and (iv) 80% of collosal projecting neurons between homologous cortical regions connect superficial layers. Our results demonstrate for the first time that resting state fMRI is sensitive to structural connections between cortical layers (previously inferred through invasive studies), specifically in thalamo-cortical and cortico-cortical networks.