Connectome analysis of functional and structural hemispheric brain networks in major depressive disorder

Abstract

Neuroimaging studies have shown topological disruptions of both functional and structural whole-brain networks in major depressive disorder (MDD). This study examined common and specific alterations between these two types of networks and whether the alterations were differentially involved in the two hemispheres. Multimodal MRI data were collected from 35 MDD patients and 35 healthy controls, whose functional and structural hemispheric networks were constructed, characterized, and compared. We found that functional brain networks were profoundly altered at multiple levels, while structural brain networks were largely intact in patients with MDD. Specifically, the functional alterations included decreases in intra-hemispheric (left and right) and inter-hemispheric (heterotopic) functional connectivity; decreases in local, global and normalized global efficiency for both hemispheric networks; increases in normalized local efficiency for the left hemispheric networks; and decreases in intra-hemispheric integration and inter-hemispheric communication in the dorsolateral superior frontal gyrus, anterior cingulate gyrus and hippocampus. Regarding hemispheric asymmetry, largely similar patterns were observed between the functional and structural networks: the right hemisphere was over-connected and more efficient than the left hemisphere globally; the occipital and partial regions exhibited leftward asymmetry, and the frontal and temporal sites showed rightward lateralization with regard to regional connectivity profiles locally. Finally, the functional-structural coupling of intra-hemispheric connections was significantly decreased and correlated with the disease severity in the patients. Overall, this study demonstrates modality- and hemisphere-dependent and invariant network alterations in MDD, which are helpful for understanding elaborate and characteristic patterns of integrative dysfunction in this disease.

Fig. 1. Intra- and inter-hemispheric connectivity.

Alterations of intra- and inter-hemispheric connectivity for functional (a) and structural (b) brain networks. MDD major depressive disorder, HCs healthy controls, LH left hemisphere, RH right hemisphere, n.s. non-significant; **P < 0.01; ***P < 0.001

Fig. 2. Hemispheric brain network efficiency.

Alterations of hemispheric network efficiency for functional (a) and structural (b) brain networks. MDD major depressive disorder, HCs healthy controls, LH left hemisphere, RH right hemisphere, n.s. non-significant, *P < 0.05; **P < 0.01; ***P < 0.001

Fig. 3. Intra- and inter-hemispheric nodal degree.

Alterations of intra-hemispheric (a, c) and inter-hemispheric (b, d) nodal degree for functional (a, b) and structural (c, d) brain networks. Regions showing significant effects were mapped onto the brain surface with the BrainNet Viewer (Xia et al., 2013). See Supplementary Table 2 for abbreviations of these regions. MDD major depressive disorder, HCs healthy controls. ^aRegions with significant effects after correcting for regional size. ^bRegions with significant effects after correcting for different network densities

Fig. 4. Functional-structural connectivity overlapping.

Decreased numbers of functional–structural overlapping for intra- hemispheric connections in MDD (a) and their relationships with disease severity of patients (b). LH left hemisphere, RH right hemisphere, HAMD Hamilton Depression Scale