Constructing the resting state structural connectome

Abstract

Background: Many recent studies have separately investigated functional and white matter (WM) based structural connectivity, yet their relationship remains less understood. In this paper, we proposed the functional-by-structural hierarchical (FSH) mapping to integrate multimodal connectome data from resting state fMRI (rsfMRI) and the whole brain tractography-derived connectome.

Methods: FSH first observes that the level of resting-state functional correlation between any two regions in general decreases as the graph distance of the corresponding structural connectivity matrix between them increases. As not all white matter tracts are actively in use (i.e., "utilized") during resting state, FSH thus models the rsfMRI correlation as an exponential decay function of the graph distance of the rsfMRI-informed structural connectivity or rsSC. rsSC is mathematically computed by multiplying entry-by-entry the tractography-derived structural connectivity matrix with a binary white matter "utilization matrix" U. U thus encodes whether any specific WM tract is being utilized during rsFMRI, and is estimated using simulated annealing. We applied this technique and investigated the hierarchical modular structure of rsSC from 7 depressed subjects and 7 age/gender matched controls.

Results: No significant group differences were detected in the modular structures of either the resting state functional connectome or the whole brain tractography-derived connectome. By contrast, FSH results revealed significantly different patterns of association in the bilateral posterior cingulate cortex and right precuneus, with the depressed group exhibiting stronger associations among regions instrumental in self-referential operations.

Discussion: The results of this study support that enhanced sensitivity can be obtained by integrating multimodal imaging data using FSH, a novel computational technique that may increase power to detect group differences in brain connectomes.

Keywords: connectivity; fMRI; major depression; multimodal; neuroimaging.

Figure 1

(A–D) This shows the FSH mapping results for all node pairs, collected from all subjects in the HC group for region pairs with direct structural connections (A and B) versus those without direct structural connections (C and D). Left panels display the model fitting without the utilization matrix U and the right panels show fitting with the utilization matrix in the proposed exponential decay model. The y axis indicates observed resting state fMRI correlation values and the x axis the predicted resting state fMRI correlation values.

Figure 2

(A) The following three regions (in gray) exhibit significant group differences after FDR correction:. 1. Left posterior cingulate. 2. Right posterior cingulate. 3. Right precuneus. The frequency of shared community membership for these regionsin HC and LLD. 100% indicates all seven subjects from the same diagnostic group have this region assigned to the same community as the gray region. 2B:. The mean consistency values (V) for each region.

Figure 3

Communities and connectivities for the resting-state structural connectome (rsSC), structural connectome, and functional connectome in healthy control (HC) and late-life depressed subjects (LLD), for nodes exhibiting significant group differences in the modular structure of rsSC shown in Figure 2. The left posterior cingulate (circled in panels indicated “L”), right posterior cingulate (circled in panels indicated “R”) and the right precuneus (caudal and posterior to the right posterior cingulate in panels indicated “R”, also circled). For each diagnostic group, nodes that are coded the same color (either red or blue) form a community or module in the average tree for that group (computed by applying PLACE to the edge-wise average of all subjects' connectivity matrices in the same group, see methods section). Edges linked to the bilateral posterior cingulate are indicated in red, while edges linked to the right precuneus are in blue. For the functional connectome, edges were thresholded for the level of correlation >0.25. Of note, only the rsSC demonstrated significant differences in community structure. Visually, the pattern of associations in the rsSC are similar to those in Figure 2A for the left and right posterior cingulate (in that for HC there is a stronger association with ipsilateral precuneus), and for the right precuneus (in LLD there is a stronger association with occipital and posterior parietal cortices, consistent with a pattern of dorsal and anterior precuneus functional connectivity; also see discussion section).