Specialization of amygdala subregions in emotion processing

Abstract

The amygdala is important for human fear processing. However, recent research has failed to reveal specificity, with evidence that the amygdala also responds to other emotions. A more nuanced understanding of the amygdala's role in emotion processing, particularly relating to fear, is needed given the importance of effective emotional functioning for everyday function and mental health. We studied 86 healthy participants (44 females), aged 18-49 (mean 26.12 ± 6.6) years, who underwent multiband functional magnetic resonance imaging. We specifically examined the reactivity of four amygdala subregions (using regions of interest analysis) and related brain connectivity networks (using generalized psycho-physiological interaction) to fear, angry, and happy facial stimuli using an emotional face-matching task. All amygdala subregions responded to all stimuli (p-FDR < .05), with this reactivity strongly driven by the superficial and centromedial amygdala (p-FDR < .001). Yet amygdala subregions selectively showed strong functional connectivity with other occipitotemporal and inferior frontal brain regions with particular sensitivity to fear recognition and strongly driven by the basolateral amygdala (p-FDR < .05). These findings suggest that amygdala specialization to fear may not be reflected in its local activity but in its connectivity with other brain regions within a specific face-processing network.

Keywords: centromedial; fMRI; facial expressions; fear; superficial.

FIGURE 1

Amygdala and subregions responses during the (Fear), (Anger), and (Happy) conditions (as indicated by the relevant emojis) relative to Shapes. The Emotional Face Matching Task (EFMT) involved pictures of real faces from the Radboud Faces Database. (a) Four anatomically‐defined amygdala subregions were generated for each hemisphere using Anatomy Toolbox (Version 2.1); these were considered together when reporting on whole amygdala activation. (b) Amygdala and all subregions were significantly activated by all emotions (relative to Shapes; p‐FDR < .05). However, there were no differences between emotions. The superficial amygdala exhibited significantly higher response to all emotions, compared to all other subregions, and the centromedial amygdala was significantly more highly activated than amygdalostriatal and basolateral subregions ( BOLD, blood oxygen level dependent). (c) Greater activation in males (♂, n = 42) versus females (♀, n = 44) in amygdala and subregions responses during the EFMT across emotions. Statistically significant differences between conditions are indicated (). (d) Greater activation in right (R) versus left (L) in amygdala and subregions responses during EFMT across emotions. Statistically significant differences between conditions are indicated (). Error bars represent the 95% confidence interval of the mean. Results are significant at ***p‐FDR < .001; *p‐FDR < .05; ⁺ p‐FDR < .06.

FIGURE 2

Whole amygdala connectivity during emotional face recognition (vs. Shapes) as revealed by generalized psycho‐physiological interaction (gPPI) analyses. (a) Whole‐brain voxelwise analysis: amygdala connectivity network in response to emotional faces (cluster forming threshold, p < .001; cluster‐corrected threshold, p‐FEW < .05). The color bar represents the T‐score. (b) Region of interest (ROI) analysis: Bar graphs depict level of connectivity of the amygdala with a selected ROI by Emotion (statistically significant at p‐FDR < .05, unless the error bar is the same color as the bar graph). Emotion‐related connectivity differences in amygdala connectivity with selected ROIs are indicated by * and — over the relevant emotions. FFA, fusiform face area; IFC, inferior frontal cortex; OTC, occipitotemporal cortex; R, right; , Fear; , Anger; , Happy; *, statistically significant differences between emotions at p‐FDR < .05.

FIGURE 3

Amygdala subregions connectivity during emotional face recognition (vs. shapes) as revealed by generalized psycho‐physiological interaction (gPPI) analysis. Bar graphs depict level of connectivity of each subregion with a selected region of interest (ROI) by Emotion (statistically significant at p‐FDR < .05, unless the error bar is the same color as the bar graph). Connectivity differences between amygdala subregions is indicated by * and — over the relevant regions. FFA, fusiform face area; IFC, inferior frontal cortex; R, right; , Fear; , Anger; , Happy; ***p‐FDR < .001, **p‐FDR < .01, *p‐FDR < .05.