Abnormal Global Functional Connectivity Patterns in Medication-Free Major Depressive Disorder

Abstract

Mounting studies have applied resting-state functional magnetic resonance imaging (rs-fMRI) to study major depressive disorder (MDD) and have identified abnormal functional activities. However, how the global functional connectivity patterns change in MDD is still unknown. Using rs-fMRI, we investigated the alterations of global resting-state functional connectivity (RSFC) patterns in MDD using weighted global brain connectivity (wGBC) method. First, a whole brain voxel-wise wGBC map was calculated for 23 MDD patients and 34 healthy controls. Two-sample t-tests were applied to compare the wGBC and RSFC maps and the significant level was set at p < 0.05, cluster-level correction with voxel-level p < 0.001. MDD patients showed significantly decreased wGBC in left temporal pole (TP) and increased wGBC in right parahippocampus (PHC). Subsequent RSFC analyses showed decreased functional interaction between TP and right posterior superior temporal cortex and increased functional interaction between PHC and right inferior frontal gyrus in MDD patients. These results revealed the abnormal global FC patterns and its corresponding disrupted functional connectivity in MDD. Our findings present new evidence for the functional interruption in MDD.

All roads lead to the default-mode network—global source of DMN abnormalities in major depressive disorder

“…This is further supported by studies showing relationship of GS to psychological features, e.g., trait personality [33,38], as well as abnormalities in schizophrenia [26,37,39], autism [40,41], and bipolar disorder [27]. While recent findings show changes in global rsFC in MDD [42][43][44][45], the impact of global rsFC on internetwork rsFC between DMN and non-DMN networks remains to be investigated-that is the focus of our study.…”

“…Global source of within-network DMN changes in MDD Previous findings in psychiatric disorders like schizophrenia [26,37,39,78], bipolar disorder [27], and MDD [42][43][44][45] demonstrated changes in global brain activity. Schizophrenia showed increased global activity [26,39] as well as its abnormal representation in sensory and higher order association cortical networks [37].…”

“…While bipolar disorder was featured by abnormal, i.e., increased or decreased representation of global brain activity in specific regions likes motor cortex (mania), hippocampus (depression), or medial prefrontal cortex (euthymia) [27]. Studies in MDD, analyzing only GSR data, showed changes in global FC in medial prefrontal cortex [79] and other regions [42][43][44][45]. These findings in MDD leave open though the source of especially GS changes in DMN, are they due to within-network rsFC changes of DMN or, alternatively, do they stem from abnormally increased inter-network rsFC of DMN with non-DMN networks; that was the main focus in our study.…”

“…However, the direction of changes remains inconsistent [10-17, 76, 79]. Focusing on specific networks, these and other more globally oriented [42][43][44][45] studies mostly neglected the investigation of the global brain activity and specifically how it impacts within-network rsFC in DMN. Following the findings in schizophrenia and bipolar disorder, we here instead investigated the topography of global activity in MDD.…”

Association between resting-state functional connectivity of amygdala subregions and peripheral pro-inflammation cytokines levels in bipolar disorder

“…Another fMRI study of BD also exhibited decreased FC from the amygdala to the TP, and this was consistent with our results [59]. Other several rs-fMRI studies have shown decreased FC of the TP in participants with psychiatric symptoms [60][61][62]. Other studies have shown TP abnormalities, including decreased gray matter density [63], reduced gray matter volume [64,65], lower mean diffusivity (re ects the microstructural integrity of white matter) [66], and decreased degree centrality (re ects the functional connections) [67] in BD patients.…”