Resting-state functional connectivity in late-life depression: higher global connectivity and more long distance connections

Abstract

Functional magnetic resonance imaging recordings in the resting-state (RS) from the human brain are characterized by spontaneous low-frequency fluctuations in the blood oxygenation level dependent signal that reveal functional connectivity (FC) via their spatial synchronicity. This RS study applied network analysis to compare FC between late-life depression (LLD) patients and control subjects. Raw cross-correlation matrices (CM) for LLD were characterized by higher FC. We analyzed the small-world (SW) and modular organization of these networks consisting of 110 nodes each as well as the connectivity patterns of individual nodes of the basal ganglia. Topological network measures showed no significant differences between groups. The composition of top hubs was similar between LLD and control subjects, however in the LLD group posterior medial-parietal regions were more highly connected compared to controls. In LLD, a number of brain regions showed connections with more distant neighbors leading to an increase of the average Euclidean distance between connected regions compared to controls. In addition, right caudate nucleus connectivity was more diffuse in LLD. In summary, LLD was associated with overall increased FC strength and changes in the average distance between connected nodes, but did not lead to global changes in SW or modular organization.

Keywords: aging; default mode network; functional connectivity; functional magnetic resonance; graph theory; late-life depression; network analysis; resting-state.

Figure 1

Major steps of functional connectivity analysis. Parcellation of the brain into areas based on the anatomical atlas and extraction of demeaned time series BOLD signal from each area (A), construction of correlation matrices (B) thresholding and binarization of correlation matrices; generation of binary adjacency matrices (C) visualized in (D), analysis of topology and microcircuit patterns (E). In the blue boxes are the names of main software tools used at relevant stages. Section “Materials and Methods” for further details.

Figure 2

Areas with significantly different average Euclidean distances to its neighbors (inter-group differences), superimposed on the whole brain connectivity projected onto one axial plane, averaged for all subjects in each group (pale gray lines), FDR: 5% corrected. LLD-related increases in black, decreases in red. R\L, right\left hemisphere; front, frontal; G, gyrus; inf, inferior; occ, occipital; temp, temporal.

Figure 3

Connections specific for the right caudate in LLD group. These connections are superimposed on the whole brain connectivity (projected onto one axial plane), averaged for all subjects in each group (pale gray lines). The thickness of black lines is proportional to the frequency of occurrence of a particular caudate connection in relation to the total number of connections in each group. Depicted in red are core elements of the default mode network (DMN). R\L, right\left hemisphere; front, frontal; G, gyrus; inf, inferior; occ, occipital; blue oval depicts a cluster of closely located structures of the primary visual cortex, consisting of bilateral cuneal, and supracalcarine cortices as well as left lingual and intracalcarine cortices.

Figure 4

Areas with significantly different frequencies of right caudate connections between the groups (z-score > 2) superimposed on the whole brain connectivity (projected onto one axial plane), averaged for all subjects in each group (pale gray lines). LLD-related increases in black, decreases in red (note: only connections shared in the two groups were taken into account), R\L, right\left hemisphere; G, gyrus; front, frontal; occ, occipital.