Anti-correlated cortical networks of intrinsic connectivity in the rat brain

Abstract

In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.

FIG. 1.

Schematic location of seeds (see also Table 1).

FIG. 2.

Seed correlation map for seed ℓ01 (anterior motor cortex), showing the anti-correlation relationship between the lateral secondary cortical network (red) and more midline structures, including the cingulate and medial prefrontal cortices (blue). (a) Sagittal and coronal slices of networks overlaid on T₂-weighted anatomical template image. Vertical gray dashes below the images indicate the location of the orthogonal slices shown. The green dot denotes the location of the seed (ℓ01) of this map; the purple dots indicate the location of the other seeds studied in this paper. (b) Medial and lateral views of the anti-correlated networks (ℓ01 seed) projected onto surface reconstruction of rat brain.

FIG. 3.

ROI-ROI correlation relationships within and between networks. The addition of global signal correction (black bars) reduces the correlations between the midline ROIs but does not substantially alter most correlations within the lateral network nor the anti-correlations between networks. Circles denote correlations that are significantly different from zero at the group level (^op<0.05; ^oop<0.01; ^ooop<0.001; only those surviving false discovery rate correction at q=0.05 are shown). Asterisks denote significant differences between results with and without global signal removal (*p<0.05; **p<0.01; ***p<0.001; only those surviving false discovery rate correction at q=0.05 are shown). ROI, regions of interest.

FIG. 4.

Seed correlation maps showing positive (red) and negative (blue) correlations (|T|>2.9, p_cluster<0.05) for individual seeds within (a) the midline cingulate/PFC network and (b) lateral secondary cortical network. The white and yellow outlines delineate the overlap in positive correlations across all three seeds in the midline and lateral networks, respectively. Green dots denote seed location for each map. Slice positions denoted A-P relative to bregma.

FIG. 5.

Seed correlation maps showing positive (red) and negative (blue) correlations (|T|>2.9, p_cluster<0.05) after global signal removal for individual seeds within (a) the midline cingulate/PFC network and (b) lateral secondary cortical network. The white and yellow outlines delineate the overlap in positive correlations across all three seeds in the midline and lateral networks, respectively. Green dots denote seed location for each map. Slice positions denoted A-P relative to bregma.