Functioning of neural systems supporting emotion regulation in anxiety-prone individuals

Abstract

Previous neuroimaging studies suggest that prefrontal cortex (PFC) modulation of the amygdala and related limbic structures is an underlying neural substrate of effortful emotion regulation. Anxiety-prone individuals experience excessive negative emotions, signaling potential dysfunction of systems supporting down-regulation of negative emotions. We examined the hypothesis that anxious individuals require increased recruitment of lateral and medial PFC to decrease negative emotions. An emotion regulation task that involved viewing moderately negative images was presented during functional magnetic resonance imaging (fMRI). Participants with elevated trait anxiety scores (n=13) and normal trait anxiety scores (n=13) were trained to reduce negative emotions using cognitive reappraisal. Blood oxygenation level-dependent (BOLD) changes were contrasted for periods when participants were reducing emotions versus when they were maintaining emotions. Compared to healthy controls, anxious participants showed greater activation of brain regions implicated in effortful (lateral PFC) and automatic (subgenual anterior cingulate cortex) control of emotions during down-regulation of negative emotions. Left ventrolateral PFC activity was associated with greater self-reported reduction of distress in anxious participants, but not in healthy controls. These findings provide evidence of altered functioning of neural substrates of emotion regulation in anxiety-prone individuals. Anxious participants required greater engagement of lateral and medial PFC in order to successfully reduce negative emotions.

Figure 1

Depiction of a Reduce Trial and Corresponding Regressors of Interest. The figure shows what subjects saw and responded to over the course of the 24-second trial. Line graphs below the timeline show how Reduce and Baseline regressors were defined. Maintain trials were identical except that subjects were provided with the instruction “Keep Up Emotion” 6–8 seconds into the trial. The Maintain regressor was defined analogously to the Reduce regressor (i.e., it was time-locked to the 4–6 seconds when subjects were viewing the image but had not yet been prompted to “Rate Emotion”).

Figure 2

Subjective Distress During Baseline, Reduce, and Maintain periods for Anxious and Non-Anxious Participants. The response scale for subjective distress was 1–4 (1 = none; 2 = mild; 3 = moderate; 4 = severe). * p < .0125 (Bonferroni correction).

Figure 3

Effects of the emotion regulation task (Reduce-Maintain contrast) across all participants (N = 26). The cuts in the image were made at x = 18, y = −10, and z = 10. Periods of reducing emotion using cognitive reappraisal were associated with greater activation of right dorsolateral prefrontal cortex (BA 9), compared to periods of maintaining emotion (effect significant at p < .01). Bar graph shows % signal change during Reduce and Maintain trials (each relative to baseline activation); error bars represent the standard errors.

Figure 4

Between-group effects on the emotion regulation task. The cuts in both images were made at x = −5, y = 10, and z = −10. Activation shown results from comparing the anxious (n = 13) and control (n = 13) groups on the Reduce-Maintain contrast. Warm colors indicate regions that were more active in anxious subjects during periods of reducing emotions. 4A: Anxious subjects showed greater activation in dorsomedial prefrontal cortex/dorsal anterior cingulate cortex (BA 6/32; labeled “1” in figure), left dorsolateral prefrontal cortex (BA 8/9; labeled “2” in figure), left ventrolateral prefrontal cortex (BA 47; labeled “3” in figure), , subgenual anterior cingulate cortex (BA 25; labeled “4” in figure), and right ventrolateral prefrontal cortex (BA 44/45; labeled “5” in figure). 4B: Additional view of medial PFC activation. Bar graphs show % signal change during Reduce and Maintain trials (each relative to baseline activation) for the anxious and control groups (left DLPFC, sgACC, and right VLPFC are presented as examples). Error bars indicate standard errors.