Interhemispheric functional connectivity and its relationships with clinical characteristics in major depressive disorder: a resting state fMRI study

Abstract

Background: Abnormalities in large-scale, structural and functional brain connectivity have been increasingly reported in patients with major depressive disorder (MDD). However, MDD-related alterations in functional interaction between the cerebral hemispheres are still not well understood. Resting state fMRI, which reveals spontaneous neural fluctuations in blood oxygen level dependent signals, provides a means to detect interhemispheric functional coherence. We examined the resting state functional connectivity (RSFC) between the two hemispheres and its relationships with clinical characteristics in MDD patients using a recently proposed measurement named "voxel-mirrored homotopic connectivity (VMHC)".

Methodology/principal findings: We compared the interhemispheric RSFC, computed using the VMHC approach, of seventeen first-episode drug-naive patients with MDD and seventeen healthy controls. Compared to the controls, MDD patients showed significant VMHC decreases in the medial orbitofrontal gyrus, parahippocampal gyrus, fusiform gyrus, and occipital regions including the middle occipital gyrus and cuneus. In MDD patients, a negative correlation was found between VMHC of the fusiform gyrus and illness duration. Moreover, there were several regions whose VMHC showed significant negative correlations with the severity of cognitive disturbance, including the prefrontal regions, such as middle and inferior frontal gyri, and two regions in the cereballar crus.

Conclusions/significance: These findings suggest that the functional coordination between homotopic brain regions is impaired in MDD patients, thereby providing new evidence supporting the interhemispheric connectivity deficits of MDD. The significant correlations between the VMHC and clinical characteristics in MDD patients suggest potential clinical implication of VMHC measures for MDD. Interhemispheric RSFC may serve as a useful screening method for evaluating MDD where neural connectivity is implicated in the pathophysiology.

Figure 1. Regions showing significant differences in VMHC between MDD patients and healthy controls.

Blue colors indicate reduced VMHC in patients compared to the controls. A: medial orbitofrontal gyrus; B: parahippocampal gyrus/fusiform gyrus; and C: middle occipital gyrus/cuneus. The threshold was set at a corrected p<0.05. Slices are 2 mm apart. The numbers at the top left of the map refer to the x-coordinates in the MNI space. The Z-score bar is shown at the lower right of the figure.

Figure 2. Regions showing significant correlations between VMHC and clinical variables in MDD patients.

(1): the region showing significant correlation between the VMHC and illness duration; (2): the regions showing significant correlations between the VMHC and severity of cognitive disturbance. Blue colors indicate negative correlations. A: fusiform gyrus; B: middle frontal gyrus; C: inferior frontal gyrus; D: cerebellum crus_2; and E: cerebellum_6. The threshold was set at a corrected p<0.05. Slices are 3 mm apart. The numbers at the top left of the map refer to the x-coordinates in the MNI space. The Z-score bars are shown at right of the figure.