Altered effective connectivity of emotion perception and regulation networks during an emotional face perception task in adults with alcohol use disorder

Abstract

Impairments in emotional regulation and mood symptoms are interrelated and associated with alcohol use disorder (AUD) risk, but the underlying aberrant neural circuitry involved is poorly understood. In the present study, we examined alterations in effective (directional) connectivity (EC) during emotional face processing in individuals with and without AUD. We utilized functional MRI data from the Human Connectome Project obtained during an emotional face processing task in 70 participants with AUD and 70 controls (CON). Focusing on ventromedial prefrontal cortex (VMPFC), bilateral ventrolateral prefrontal cortex (VLPFC), amygdala (AMY), and fusiform gyrus (FG), and right (R) hypothalamus (HTN) nodes, we performed dynamic causal modeling analysis to test group-level differences in EC. Linear regressions characterized EC relationships with measures of cumulative alcohol exposure and depression and anxiety. Compared to CON participants, AUD participants had lower ECs from VMPFC → bilateral VLPFC, left (L)-VLPFC → L-VLPFC and VMPFC, R-VLPFC → L-FG, R-FG → HTN, and R-AMY → L-VLPFC; and greater ECs from VMPFC → VMPFC, L-VLPFC → R-VLPFC and bilateral FG, L-FG → R-AMY and HTN, R-AMY → VMPFC and L-FG, and L-AMY → HTN connectivities. In regression analyses, these cortical-to-cortical and cortical-to-subcortical ECs were associated with cumulative alcohol exposure. EC from R-VLPFC to L-FG was negatively associated with depression. Individuals with AUD have disrupted EC in cortical-to-cortical and cortical-to-subcortical circuits during emotional face processing in brain regions purported to govern emotion control, which may explain linkages between cumulative alcohol exposure and depression.

Keywords: Alcohol use disorder; Cumulative alcohol exposure; Depression; Dynamic causal modeling; Effective connectivity; Emotional face perception.

Fig. 1

Participant selection procedure. See Table 1 and the materials and methods section for more detailed information about the matching between the alcohol use disorder (AUD) participants (n = 70) and the control participants (n = 70)

Fig. 2

The brain activation clusters detected by SPM12 second-level random effects 1-sample t test analysis for the contrast of emotional-face minus neutral-shape when the two groups were combined (n = 140), with cluster-defining threshold p =.001 and cluster level p <.05 (FWE corrected, two-tail). The clusters are overlaid in color on axial slices of the Montreal Neurological Institute brain template image in gray. The number near the top/upper-left corner of each slice indicates slice location (mm) of the MNI z coordinate. The reader’s left side of each slice is the subjects’ left brain hemisphere

Fig. 3

The main results of the analyses of group comparison in effective connectivities (ECs) and the analyses of the linear regression between ECs and cumulative alcohol usage and depression, visualized with the BrainNet Viewer (http://www.nitrc.org/projects/bnv/) (Xia et al. 2013). For the group comparisons, lines with arrows representing if ECs were different from zero in the Control group (n = 70, posterior probability [PP] > 0.95, left panel) or the group difference (AUD [n = 70] minus CON [n = 70]), PP > 0.95, the second panel from left) in ECs. A red line denotes that an EC was greater than zero in the Control group (left panel) or greater in the AUD group than the CON group (the second panel from left); and a blue line denotes that an EC was smaller than zero in the Control group (left panel) or smaller in the Alcohol group than the Control group (the second panel from left). Line width is proportional to the EC strength. For the linear regression analyses (across all participants, n = 140), lines with arrows representing if ECs showed linear relationship with the cumulative alcohol usage (PP > 0.95, the third panel from left) or the depression (PP = 0.89, the right panel). A red line denotes that an EC showed positive linear relationship with the cumulative alcohol usage (the third panel from left); and a blue line denotes that an EC showed negative linear relationship with the cumulative alcohol usage (third panels from left) or the depression (the right panels). Line width is proportional to the linear regression coefficient. AUD alcohol use disorder, CON control, VMPFC ventrolateral prefrontal cortex, VLPFC ventrolateral prefrontal cortex, AMY amygdala, FG fusiform gyrus, HTH hypothalamus

Fig. 4

Schematic Circuit Diagram of Emotional Face Processing Network Showing DCM Analysis Findings. A: Circuit Diagram Showing DCM Analysis Results of EC for emotional faces minus shapes contrast in CON participants (n = 70, beta: ≥0.3 Hz, posterior probability [PP] > 0.95). This diagram represents EC during emotional face processing in healthy adults. B: Circuit Diagram Showing DCM Analysis Results of EC Group Differences for AUD minus CON participants (N = 140, n = 70 per group, beta: ≥0.3 Hz, PP > 0.95) for emotional face minus shape contrast. This diagram represents EC modulation as a function of AUD diagnostic status reflecting how EC differs between AUD and CON groups. C: Circuit diagram showing DCM analysis results of linear regression between EC outcomes (emotional faces minus shapes) and cumulative alcohol use in the full sample collapsed across AUD and CON participants (N = 140, beta: ≥0.1 Hz, PP > 0.95). D: Circuit diagram showing DCM analysis results of linear regression between EC outcomes (emotional faces minus shapes) and AASR depression scores in the full sample collapsed across AUD and CON participants (N = 140, PP = 0.89). In the figure, red lines represent EC between nodes that is greater in response to emotional faces compared to shapes in A, greater in AUD compared to CON participants in B, and positively association with cumulative alcohol use in C. Blue lines represent EC between nodes that is lower (more negative) in response to emotional faces compared to shapes in A, lower in AUD compared to CON participants in B, and negatively associated with cumulative alcohol use and depression scores in C and D, respectively. Strength of EC in Hz is presented next to each line. AUD alcohol use disorder; CON control; VMPFC ventromedial prefrontal cortex; VLPFC ventrolateral prefrontal cortex; AMY amygdala; FG Fusiform Gyrus; HTN Hypothalamus; L Left; R Right