Abnormal modulation of amygdala activity in schizophrenia in response to direct- and averted-gaze threat-related facial expressions

Abstract

Objective: Reduced amygdala activation in individuals with schizophrenia is thought to contribute to impairments in emotion recognition and social functioning. Recent work, however, suggests that amygdala abnormalities in schizophrenia are more nuanced than generalized hypoactivation and that modulation of amygdala responses across different stimulus types may be more closely related to social functioning than to overall levels of amygdala activation during a task. The authors investigated amygdala modulation during emotion recognition in patients by manipulating the gaze direction of threat-related expressions.

Method: Blood-oxygen-level-dependent functional MRI was used to measure neural activation in 37 healthy volunteers and 35 schizophrenia patients while participants identified the emotion (anger or fear) displayed on facial stimuli that appeared with either direct or averted gaze.

Results: Analysis of percent signal change in the amygdala bilaterally revealed a three-way interaction of emotion, gaze, and group, demonstrating significantly reduced amygdala responses to direct-gaze anger expressions in the patient group but comparable levels of activation across groups in all other conditions. Within the patient group, amygdala responses to direct-gaze anger expressions were positively correlated with level of functioning.

Conclusions: These findings extend previous reports of amygdala hypoactivation in schizophrenia by identifying abnormal amygdala modulation in response to varying emotional stimuli. Additionally, the strong relationship between amygdala activation and social and occupational functioning underscores the need for investigations of amygdala modulation in schizophrenia that further specify the nature of these impairments and that examine a potential causal link between amygdala activation and functioning.

FIGURE 1.. Performance by Schizophrenia Patients and Healthy Comparison Subjects on an Emotion Recognition Task Using Direct- and Averted-Gaze Threat-Related Facial Expressions^a

^a The right-hand panel shows a significant emotion-by-gaze-by-group interaction in anatomically defined amygdala. Mean percent signal change estimates are collapsed across both right and left amygdala.

FIGURE 2.. Regions Show ing Stimulus Characteristic-by-Group Interactions in Schizophrenia Patients and Healthy Comparison Subjects on an Emotion Recognition Task Using Direct- and Averted-Gaze Threat-Related Facial Expressions^a

^a In panel A, mean percent signal change is extracted from the peak voxel in the left inferior frontal gyrus cluster to demonstrate the direction of the interaction. Images are cluster-level-corrected at p<0.01. In panel B, mean percent signal change is extracted from the peak voxel in the left caudate cluster to demonstrate the direction of the interaction. Image is cluster-level-corrected at p<0.05.

FIGURE 3.. Association Betw een Clinical Measures and Amygdala Activity in Schizophrenia Patients on an Emotion Recognition Task Using Direct- and Averted-Gaze Threat-Related Facial Expressions^a

^a On the left, a scatterplot of the association between percent signal change in the amygdala bilaterally in response to direct-gaze anger expressions and Scale for the Assessment of Negative Symptoms anhedonia ratings. On the right, a scatterplot of the association between percent signal change in the amygdala bilaterally in response to direct-gaze anger expressions and level of social and occupational functioning. Both correlations are significant at a Bonferroni-corrected level of p<0.006