Whole brain resting-state analysis reveals decreased functional connectivity in major depression

Abstract

Recently, both increases and decreases in resting-state functional connectivity have been found in major depression. However, these studies only assessed functional connectivity within a specific network or between a few regions of interest, while comorbidity and use of medication was not always controlled for. Therefore, the aim of the current study was to investigate whole-brain functional connectivity, unbiased by a priori definition of regions or networks of interest, in medication-free depressive patients without comorbidity. We analyzed resting-state fMRI data of 19 medication-free patients with a recent diagnosis of major depression (within 6 months before inclusion) and no comorbidity, and 19 age- and gender-matched controls. Independent component analysis was employed on the concatenated data sets of all participants. Thirteen functionally relevant networks were identified, describing the entire study sample. Next, individual representations of the networks were created using a dual regression method. Statistical inference was subsequently done on these spatial maps using voxel-wise permutation tests. Abnormal functional connectivity was found within three resting-state networks in depression: (1) decreased bilateral amygdala and left anterior insula connectivity in an affective network, (2) reduced connectivity of the left frontal pole in a network associated with attention and working memory, and (3) decreased bilateral lingual gyrus connectivity within ventromedial visual regions. None of these effects were associated with symptom severity or gray matter density. We found abnormal resting-state functional connectivity not previously associated with major depression, which might relate to abnormal affect regulation and mild cognitive deficits, both associated with the symptomatology of the disorder.

Keywords: amygdala; functional connectivity; independent component analysis; major depression; resting-state functional magnetic resonance imaging.

Figure 1

Group ICA functionally relevant resting-state networks. Depicted here are the 13 functionally relevant RSNs resulting from the group PICA step carried out on the concatenated data sets from both patients and controls. Most networks have previously been described (for example in: Beckmann et al., ; Damoiseaux et al., 2006) and show assemblies of regions associated with sensory processing, affective processing, and higher order cognitive processes. Images are z-statistics, ranging from 3 to 8, overlaid on the MNI-152 standard brain. The left hemisphere of the brain corresponds to the right side in this image.

Figure 2

Group main effects and between-group effects. Numbering corresponds to the networks depicted in Figure 1. (A) Depicted here are the group main and between-group effects for three RSNs. Group main effects are corrected for family-wise errors (p < 0.05) and between-group effects are corrected according to a local false discovery rate of 1%. RSN 12 shows an assembly of ventral affective regions, such as temporal poles, insula, medial prefrontal cortex, and amygdala, the latter two regions demonstrating decreased connectivity within the MDD group. RSN 11 shows brain regions linked to attention, of which the left frontal pole shows decreased connectivity in the MDD group. RSN 3 shows MDD-related decreased connectivity of the bilateral lingual gyrus with other medial visual areas. Images are z-statistics, ranging from 2 to 10, overlaid on the MNI-152 standard brain. The left hemisphere of the brain corresponds to the right side in this image. HC, healthy controls; MDD, major depressive disorder. (B) Distribution of the mean individual z-scores within the bilateral amygdala (12), left frontal pole (11), and bilateral lingual gyrus (3). Depicted in red are the controls, in black the MDD group, both sorted from smallest to highest z-value.