Resting-state theta band connectivity and graph analysis in generalized social anxiety disorder

Abstract

Background: Functional magnetic resonance imaging (fMRI) resting-state studies show generalized social anxiety disorder (gSAD) is associated with disturbances in networks involved in emotion regulation, emotion processing, and perceptual functions, suggesting a network framework is integral to elucidating the pathophysiology of gSAD. However, fMRI does not measure the fast dynamic interconnections of functional networks. Therefore, we examined whole-brain functional connectomics with electroencephalogram (EEG) during resting-state.

Methods: Resting-state EEG data was recorded for 32 patients with gSAD and 32 demographically-matched healthy controls (HC). Sensor-level connectivity analysis was applied on EEG data by using Weighted Phase Lag Index (WPLI) and graph analysis based on WPLI was used to determine clustering coefficient and characteristic path length to estimate local integration and global segregation of networks.

Results: WPLI results showed increased oscillatory midline coherence in the theta frequency band indicating higher connectivity in the gSAD relative to HC group during rest. Additionally, WPLI values positively correlated with state anxiety levels within the gSAD group but not the HC group. Our graph theory based connectomics analysis demonstrated increased clustering coefficient and decreased characteristic path length in theta-based whole brain functional organization in subjects with gSAD compared to HC.

Conclusions: Theta-dependent interconnectivity was associated with state anxiety in gSAD and an increase in information processing efficiency in gSAD (compared to controls). Results may represent enhanced baseline self-focused attention, which is consistent with cognitive models of gSAD and fMRI studies implicating emotion dysregulation and disturbances in task negative networks (e.g., default mode network) in gSAD.

Keywords: Connectomics; EEG; Graph theory; Major depressive disorder; Social anxiety disorders.

Fig. 1

WPLI connectivity during resting state in the healthy group (left column) and the gSAD group (middle column). WPLI mapping of three frequency waves: Alpha (first row), Beta (second row), Theta (third row) and Beta (forth row) were generated from the averaged 32 participants with gSAD and 32 controls. Paired t-tests were applied to every region across two groups; regions with 0.001 < p < 0.05 were marked in gray (third column), regions with p < 0.001 were marked in white. Channels 1 to 14 were located in the left hemisphere, 15–18 in the right hemisphere and 29–34 midline channels. Theta connectivity shows the midline frontal channel (Fz and FCz) is significantly higher in gSAD relative to healthy controls (marked with arrows.)

Fig. 2

Variation of averaged WPLI with the frequency in healthy and gSAD group. Additionally, group effects were observed in the theta frequency band where the gSAD group had significantly higher WPLI values compared to the HC group. (Fig. 2).

Fig. 3

(A) Power variation from 1 Hz–50 Hz; (B) averaged power of alpha, beta, theta and delta.

Fig. 4

(A) Characteristics path length of alpha, beta, theta and delta wave in the healthy control and gSAD groups. (B) Clustering coefficient of alpha, beta and theta in the two groups.

Fig. 5

Trait anxiety scores (A) and state anxiety scores (B) for gSAD subjects.