Resting-state functional connectivity reflects structural connectivity in the default mode network

Abstract

Resting-state functional connectivity magnetic resonance imaging (fcMRI) studies constitute a growing proportion of functional brain imaging publications. This approach detects temporal correlations in spontaneous blood oxygen level-dependent (BOLD) signal oscillations while subjects rest quietly in the scanner. Although distinct resting-state networks related to vision, language, executive processing, and other sensory and cognitive domains have been identified, considerable skepticism remains as to whether resting-state functional connectivity maps reflect neural connectivity or simply track BOLD signal correlations driven by nonneural artifact. Here we combine diffusion tensor imaging (DTI) tractography with resting-state fcMRI to test the hypothesis that resting-state functional connectivity reflects structural connectivity. These 2 modalities were used to investigate connectivity within the default mode network, a set of brain regions--including medial prefrontal cortex (MPFC), medial temporal lobes (MTLs), and posterior cingulate cortex (PCC)/retropslenial cortex (RSC)--implicated in episodic memory processing. Using seed regions from the functional connectivity maps, the DTI analysis revealed robust structural connections between the MTLs and the retrosplenial cortex whereas tracts from the MPFC contacted the PCC (just rostral to the RSC). The results demonstrate that resting-state functional connectivity reflects structural connectivity and that combining modalities can enrich our understanding of these canonical brain networks.

Figure 1.

Functional connectivity reflects structural connectivity in the DMN. (a) Task-free, functional connectivity in the DMN is shown in a group of 6 subjects. The PCC/RSC and MPFC clusters are best appreciated on the sagittal view. Prominent bilateral MTL clusters are seen on the coronal image (left side of image corresponds to left side of brain). (b) DTI fiber tractography in a single subject demonstrates the cingulum bundle (blue tracts) connecting the PCC/RSC to the MPFC. The yellow tracts connect the bilateral MTL to the PCC/RSC. Note that generally the tracts from the MPFC enter the more rostral aspect of the PCC/RSC ROI corresponding to the PCC proper, whereas the tracts from MTL enter the more caudal aspect of the PCC/RSC ROI corresponding to the RSC proper. Left and right columns show slightly different views of the same tracts to highlight the distinct entry points into the PCC/RSC. There were no tracts connecting the MPFC to the MTL.

Figure 2.

DTI fiber tractography in 3 additional subjects. In all cases, the MPFC fibers (blue tracts) enter the rostral (PCC proper) aspect of the PCC/RSC ROI, whereas the MTL fibers (yellow tracts) enter the more caudal aspect (RSC proper) of the PCC/RSC ROI. Left and right columns show slightly different views of the same tracts to highlight the distinct entry points into the PCC/RSC. There were no tracts connecting the MPFC to the MTL.

Figure 3.

Tracts are consistent across subjects. (a) Sagittal views of the MPFC–PCC/RSC tracts (blue–green) and MTL–PCC/RSC tracts (red–yellow) where the color scales indicate the number of subjects that had a tract in a given voxel. The more medial sagittal views at x = 10 and x = 15 demonstrate the distinct entry points of the 2 tracts into the PCC/RSC with the MPFC fibers entering rostrally and the MTL fibers entering caudally. (b) Coronal views show the red–yellow MTL fibers coursing between the hippocampus and parahippocampal gyrus (whose anterior extent at y = −10 includes entorhinal cortex). There were no tracts connecting the MPFC to the MTL.