Regulation of emotional responses elicited by threat-related stimuli

Abstract

The capacity to voluntarily regulate emotions is critical for mental health, especially when coping with aversive events. Several neuroimaging studies of emotion regulation found the amygdala to be a target for downregulation and prefrontal regions to be associated with downregulation. To characterize the role of prefrontal regions in bidirectional emotion regulation and to investigate regulatory influences on amygdala activity and peripheral physiological measures, a functional magnetic resonance imaging (fMRI) study with simultaneous recording of self-report, startle eyeblink, and skin conductance responses was carried out. Subjects viewed threat-related pictures and were asked to up- and downregulate their emotional responses using reappraisal strategies. While startle eyeblink responses (in successful regulators) and skin conductance responses were amplified during upregulation, but showed no consistent effect during downregulation, amygdala activity was increased and decreased according to the regulation instructions. Trial-by-trial ratings of regulation success correlated positively with activity in amygdala during upregulation and orbitofrontal cortex during downregulation. Downregulation was characterized by left-hemispheric activation peaks in anterior cingulate cortex, dorsolateral prefrontal cortex, and orbitofrontal cortex and upregulation was characterized by a pattern of prefrontal activation not restricted to the left hemisphere. Further analyses showed significant overlap of prefrontal activation across both regulation conditions, possibly reflecting cognitive processes underlying both up- and downregulation, but also showed distinct activations in each condition. The present study demonstrates that amygdala responses to threat-related stimuli can be controlled through the use of cognitive strategies depending on recruitment of prefrontal areas, thereby changing the subject's affective state.

Figure 1

Experimental paradigm. Pictures were presented for 2.5 s, after which the regulation instruction (increase, decrease, or view) appeared in the center of the picture for 0.5 s. From this point on subjects were to regulate their emotions for 6 s; at 2 s into the regulation phase an acoustic startle probe was delivered. After the regulation phase subjects had to rate their success in regulation on a scale from 1–5 by button presses. Before the next trial began a gray square appeared, indicating the subjects to relax. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 2

Subjects' threat and disgust ratings. Directly after scanning, subjects viewed all previously seen pictures again and indicated for each picture whether it was perceived as frightening/threatening, disgusting, or not eliciting an emotion; 64% of the negative pictures were rated as frightening/threatening by more than 50% of the subjects, while only 14% of the negative pictures were rated as disgusting by more than 50% of the subjects.

Figure 3

Startle eyeblink and SCR amplitudes in the regulation phase. Upregulation (increase) significantly enhanced startle eyeblink and SCR amplitudes in comparison to the condition of viewing the pictures. Downregulation (decrease) showed a nonsignificant attenuation of startle eyeblink responses and a trend toward a significant enhancement of SCR amplitudes. Startle amplitudes are depicted separately for increase‐view and decrease‐view because each graph depicts only successful regulators in that condition as determined by success ratings. Error bars denote standard error of the mean. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 4

Amygdala activation in the view‐minus‐decrease (top) and increase‐minus‐view (bottom) contrasts and corresponding time‐courses. In comparison to simply viewing the pictures, left amygdala activity was significantly downregulated when decreasing and right amygdala activity was significantly upregulated when increasing (left amygdala activity was also upregulated, but this cannot be seen on this coronal section). Activations are overlaid on subjects' mean anatomy at a level of P < 0.001 uncorrected (for visualization, images were masked by the amygdala region of interest mask); color scales denote t‐values. To depict temporal characteristics of amygdala activation, time‐courses were extracted from a 6‐mm sphere around the highest activated voxel; error bars in time‐courses denote standard error of the mean. The gray background represents the time range in which effects of regulation were expected. Assuming that the hemodynamic response exhibits a lag of about 4–6 s [Rosen et al., 1998] and regarding that a 3‐s interval (2.5 s picture presentation plus 0.5 s instruction) preceded the regulation phase regulatory effects are expected to start between 7–9 s after picture onset (zero on the time‐axis represents trial‐start). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 5

Prefrontal activation peaks and respective parameter estimates. Parameter estimates on the right side stem from the highest activated voxel in the cluster surrounded by the circle. The top panel shows that the OFC exhibits significant overlap of activation across downregulation and upregulation (as revealed by conjunction analysis: conjunction [(increase‐minus‐view) (decrease‐minus‐view)]). The middle panel shows a region in left DLPFC that was significantly stronger activated for downregulation than for upregulation (as revealed by inclusive masking of the decrease‐minus‐increase contrast with the decrease‐minus‐view contrast). The bottom panel shows a region in right DLPFC that was significantly stronger activated for upregulation than for downregulation (as revealed by inclusive masking of the increase‐minus‐decrease contrast with the increase‐minus‐view contrast). Activations are overlaid on subjects' mean anatomy at a level of P < 0.001 uncorrected; the color scale denotes t‐values. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]

Figure 6

Correlation between left amygdala activation and trial‐by‐trial success ratings in the increase condition. On the left side, a horizontal section displays left amygdala activity that correlated positively with subjects' ratings of regulation success during scanning. Activations are overlaid on subjects' mean anatomy at a level of P < 0.001 uncorrected; the color scale denotes t‐values. For the regression plot on the right side data were extracted from a 6‐mm sphere around the highest activated voxel in the amygdala (denoted by the circle). Each data point represents one subject's mean hemodynamic response over trials with the same success rating. Note that not all categories were used by all subjects (i.e., some subjects did not use the rating “2,” others never rated their success above “4,” etc.). [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]