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

Illustration of our functional hypotheses that were motivated by previous invasive anatomical tract tracing studies. The width of the lines represent the strength of the connections. a Thamalocortical hypotheses: we hypothesized that FC between the entire thalamus and cortical layers I and VI will be significantly stronger than between the thalamus and other layers (blue, left panel). Furthermore, FC between somatosensory thalamus (ventral posterolateral nucleus, VPL) and layers IV, VI of the primary somatosensory cortex (S1) will be stronger than with other layers (yellow, right panel). b Cortico-cortical hypothesis: inter-hemispheric cortico-cortical FC between homologous regions in superficial layers (layers I–III) will be stronger compared to that in deeper layers (layers V–VI). c 6 surfaces plus white matter and pial surface overlayed on anatomical MRI (white matter surface: yellow, layer VI surface: brown, layer V: green, layer IV: lime, layer III: blue, layer II:, cyan, layer I: purple, and pial surface: red; the white dots are the vertices on these surfaces). d Illustration of the relative distance of 6 intermediate surfaces to white matter surface

Schematic illustrating the laminar analysis pipeline for extracting mean time series from the six cortical layers for all 68 brain regions in the Desikan–Killiany atlas [9]

Top: an illustration of the method for calculating FC between all layers across all cortical regions to investigate global trends (i, j represents layer number; m, n represents regions, and Cij represents the mean Pearson’s correlation between two given layers calculated across all cortical regions). Bottom: the mean Pearson’s correlation values between a given layer and all layers across all cortical regions in the Desikan–Killiany [9] atlas. No significant differences were found. 21 pairs are included. The error bar indicates the calculated standard deviation

a Mean thalamo-cortical FC values between the entire thalamus and all cortical layers estimated from BOLD data before blind deconvolution; b mean FC between the somatosensory thalamus (VPL) and six different layers of primary somatosensory cortex before blind deconvolution; c mean inter-hemispheric cortico-cortical laminar FC values estimated before blind deconvolution. *Significant difference with p (corrected) < 0.05, the error bar indicates the estimated standard deviation

Region-specific HRF plot and multiple comparisons across the layers for left orbitofrontal cortex (OFC) (a–d) and left primary somatosensory cortex (S1) (e, f). The mean left OFC (a) and left S1 (e) HRF plot for six layers separately. Layer VI (red), layer V (yellow), layer IV (green), layer III (cyan), layer II (blue), and layer I (purple); multiple comparisons across the layers for left OFC (b) and left S1 (f) for response height; time to peak multiple comparisons across layers for left OFC (c) and left S1 (g); FWHM multiple comparisons across the layers for left OFC (d) and left S1 (h). *Significant difference with p (corrected) < 0.05. The error bar indicates the estimated standard deviation

Summary of one-way ANOVA analysis performed on HRF parameters (response height, time to peak, and FWHM) for 68 regions. 66 out of 68 region had significant difference across the layers for the response height, 62 out of 68 regions for time to peak, and 36 regions for FWHM at p (corrected) < 0.05

Comparison of the individual-level average FC values before and after deconvolution for all paths. Blue represents FC values with non-deconvolved data, and red for FC values after deconvolution

a Mean thalamo-cortical FC values between the entire thalamus and six cortical layers after blind deconvolution, i.e., using latent neural time series; b mean FC between the sensory core thalamus (VPL) and six different layers of primary somatosensory cortex after blind deconvolution; c mean inter-hemispheric cortico-cortical laminar FC values after blind deconvolution. *Significant difference with p (corrected) < 0.05. The error bar indicates the estimated standard deviation