Default-mode network connectivity and white matter burden in late-life depression

Abstract

The brain's default-mode network has been the focus of intense research. This study characterizes the default-mode network activity in late-life depression and the correlation of the default-mode network activity changes with the white-matter hyperintensities burden. We hypothesized that elderly depressed subjects would have altered default-mode network activity, which would correlate with the increased white-matter hyperintensities burden. Twelve depressed subjects (mean Hamilton Depression Rating Scale 19.8±4.1, mean age 70.5±4.9) and 12 non-depressed, comparison subjects (mean age 69±6.5) were included. Functional magnetic resonance imaging (fMRI) data were collected while subjects performed a low cognitive load, event-related task. We compared the default-mode network activity in these groups (including depressed subjects pre- and post-antidepressant treatment). We analyzed the resting connectivity patterns of the posterior cingulate cortex. Deconvolution was used to evaluate the correlation of resting-state connectivity scores with the white-matter hyperintensities burden. Compared with non-depressed elderly, depressed subjects pretreatment had decreased connectivity in the subgenual anterior cingulate cortex and increased connectivity in the dorsomedial prefrontal cortex and the orbito-frontal cortex. The abnormal connectivity was significantly correlated with the white-matter hyperintensities burden. Remitted elderly depressed subjects had improved functional connectivity compared to pretreatment, although alterations persisted in the anterior cingulate and the prefrontal cortex when remitted elderly depressed subjects were compared with non-depressed elderly. Our study provides evidence for altered default-mode network connectivity in late-life depression. The correlation between white-matter hyperintensities burden and default-mode network connectivity emphasizes the role of vascular changes in late-life depression etiopathogenesis.

Figure 1

Automated white-matter hyperintensities segmentation on the flair image of one subject is shown here, (A) A single slice from a subject's FLAIR image (B) white-matter hyperintensities segmentation result with underlying flair image for anatomical reference. The automated white-matter hyperintensities segmentation correlates with semi-quantitative, visual rating methods, such as those used for the Cardiovascular Health Study. In the current study, 37% of the depressed subjects had a moderate-severe burden of white-matter hyperintensities, as quantified by the Cardiovascular Health Study.

Figure 2

t-maps of the resting-state connectivity for (A) elderly comparison group, late-life depression group before treatment (B) and after treatment (C). The maps were thresholded at a corrected p < 0.001. Compared with the elderly comparison group (A), the pretreatment late-life depression group (B) had lower default-mode activation in the subgenual anterior cingulate cortex and higher default-mode network activation in the dorso-medial prefrontal cortex and the orbitofrontal cortex.

Fig 3

Resting State connectivity scores (Posterior Cingulate Cortex — Anterior Cingulate Cortex) comparison between nondepressed elderly, late-life depression group before treatment and late-life depression group after treatment.

Figure 4

The group comparisons of the functional connectivity activities with two-sample t-test (a corrected p < 0.05) between (A) the comparison group and late-life depression group before treatment; (B) late-life depression group after treatment and late-life depression group before treatment; (C) the comparison group and the late-life depression group after treatment. In Blue: increased connectivity. In orange/yellow: decreased connectivity. A: When compared with the elderly comparison group, the late-life depression group before treatment had decreased connectivity in the sACC (1) and increased connectivity in the dmPFC (2) and OFC (3). B: Compared to pre-treatment late-life depression group, the post-treatment late-life depression group has improved connectivity in vmPFC/ACC and decreased connectivity in dmPFC. C: Compared with the non-depressed group, the post-treatment late-life depression group has decreased connectivity in sACC (1) and increased connectivity in rostral ACC (4) and dorsal ACC (5).

Figure 5

The white-matter hyperintensities burden and resting state score for the pretreatment late-life depression group shows a significant negative correlation (averaged r =−0.72, corrected p < 0.05) in the medial frontal region: (A) t map, (B) signed r map.

Fig 6

Correlation plot of resting state connectivity scores and normalized white matter hyperintensities burden (nWMH) in the medial frontal region (r=−0.72) (see also Fig 5).