Electroencephalography Source Functional Connectivity Reveals Abnormal High-Frequency Communication Among Large-Scale Functional Networks in Depression.
- Authors
- Whitton, Alexis E; Deccy, Stephanie; Ironside, Manon L; Kumar, Poornima; Beltzer, Miranda; Pizzagalli, Diego A
- Year
- 2018
- Journal
- Biological psychiatry. Cognitive neuroscience and neuroimaging
- PMID
- 29397079
- DOI
- 10.1016/j.bpsc.2017.07.001
- PMCID
- PMC5801763
BACKGROUND: Functional magnetic resonance imaging studies of resting-state functional connectivity have shown that major depressive disorder (MDD) is characterized by increased connectivity within the default mode network (DMN) and between the DMN and the frontoparietal network (FPN). However, much remains unknown about abnormalities in higher frequency (>1 Hz) synchronization. Findings of abnormal synchronization in specific frequencies would contribute to a better understanding of the potential neurophysiological origins of disrupted functional connectivity in MDD. METHODS: We used the high temporal resolution of electroencephalography to compare the spectral properties of resting-state functional connectivity in individuals with MDD (n = 65) with healthy control subjects (n = 79) and examined the extent to which connectivity disturbances were evident in a third sample of individuals in remission from depression (n = 30). Exact low resolution electromagnetic tomography was used to compute intracortical activity from regions within the DMN and FPN, and functional connectivity was computed using lagged phase synchronization. RESULTS: Compared to control subjects, the MDD group showed greater within-DMN beta 2 band (18.5-21 Hz) connectivity and greater beta 1 band (12.5-18 Hz) connectivity between the DMN and FPN. This hyperconnectivity was not observed in the remitted MDD group. However, greater beta 1 band DMN-FPN connectivity was associated with more frequent depressive episodes since first depression onset, even after controlling for current symptom severity. CONCLUSIONS: These findings extend our understanding of the neurophysiological basis of abnormal resting-state functional connectivity in MDD and indicate that elevations in high-frequency DMN-FPN connectivity may be a neural marker linked to a more recurrent illness course.
Relative to the HC group, the MDD group showed significantly greater within-network lagged phase synchronization in the DMN at the beta 2 frequency band (p<0.05 FWE), specifically between the right parahippocampal gyrus (PHG) and right superior frontal gyrus (SFG) (A). The MDD group also showed significantly greater between-network lagged phase synchronization between the DMN and FPN at the beta 1 frequency band compared to HCs (p<0.001 uncorrected), specifically between the left SFG (a DMN region) and the right middle temporal gyrus (MTG; a FPN region) (B). Follow-up one-way ANOVAs showed that both indices of connectivity were lower in those with rMDD relative to the MDD group, and the rMDD and HC groups did not differ. For the purposes of visualization, ROIs shown here are displayed on a 2×2×2 MNI template brain (5 mm resolution is used in eLORETA for analyses).
LLM interpretation
This figure consists of two panels (A and B), each containing brain template images with highlighted regions of interest (ROIs) and a corresponding bar chart. Panel A shows greater lagged phase synchronization in the beta 2 band (18.5-21 Hz) between the right PHG and right SFG in the MDD group compared to HC and rMDD groups. Panel B shows greater lagged phase synchronization in the beta 1 band (12.5-18 Hz) between the left SFG (DMN) and right MTG (FPN) in the MDD group compared to HC and rMDD groups. In both charts, the MDD group exhibits the highest synchronization values, while the HC and rMDD groups show lower, comparable levels.
Scatterplot showing the Spearman’s rank order correlation between disease severity (operationalized as the mean number of major depressive episodes per year since first depression onset) and the strength of between-network DMN-FPN connectivity (12.5 – 18 Hz) in the MDD and rMDD groups.
LLM interpretation
This scatterplot illustrates the Spearman’s rank order correlation between DMN-FPN connectivity (x-axis, log10 scale) and the mean number of major depressive episodes (MDEs) per year (y-axis). Data points are categorized into two groups: MDD (black) and rMDD (grey), with a positive linear regression line indicating a trend where higher connectivity correlates with increased disease severity. The correlation is statistically significant, with a reported rho = 0.32 and p = .01.
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