Disrupted hemispheric connectivity specialization in patients with major depressive disorder: Evidence from the REST-meta-MDD Project

Abstract

Background: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied.

Methods: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes).

Results: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities.

Limitations: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results.

Conclusions: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

Keywords: DLPFC, Dorsolateral prefrontal cortex; DMN, Default mode network; DPARSF, Data Processing Assistant for Resting-State fMRI; DSM, Diagnosic and Statistical Manual of Mental Disorders; EEG, Electroencephalographic; FC, Functional connectivity; FDR, False discovery rate; FEDN, First-episode, drug-naive; FEF, Frontal eye fields; HAMD, Hamilton Depression Rating Scale; HC, Healthy control; IFG, Inferior frontal gyrus; IPL, Inferior parietal lobule; IPS/SPL, Intraparietal sulcus/superior parietal lobule; LMM, Linear mixed model; MDD, Major depressive disorder; MFG, Middle frontal gyrus; MTG, Middle temporal gyrus; Major depressive disorder; PAS, Parameter of asymmetry; PCC, Posterior cingulate cortex; PET, Positron emission tomography; ROIs, Regions of interest; STS, Superior temporal sulcus; VMHC, Voxel-mirrored homotopic connectivity; fMRI Abbreviations ACC, Anterior cingulate gyrus; fMRI, Functional magnetic resonance imaging; hemispheric asymmetry; parameter of asymmetry; rTMS, repetitive transcranial magnetic stimulation; rs-fMRI, Resting-state fMRI.