Amygdala and ventromedial prefrontal cortex are inversely coupled during regulation of negative affect and predict the diurnal pattern of cortisol secretion among older adults

Abstract

Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62- to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing negative affect resulted in ventral lateral, dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast to previous work, decreasing negative affect did not produce the predicted robust pattern of higher PFC and lower amygdala activation. Individuals demonstrating the predicted effect (decrease < attend in the amygdala), however, exhibited higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast. Furthermore, participants displaying higher VMPFC and lower amygdala signal when decreasing compared with the attention control condition evidenced steeper, more normative declines in cortisol over the course of the day. Individual differences yielded the predicted link between brain function while reducing negative affect in the laboratory and diurnal regulation of endocrine activity in the home environment.

Figures

Figure 1.

Depicted here is the response of the left and right amygdala. On the ordinate, we plot the AUC for percentage signal change estimates from 5 to 12 s after the instruction. Each regulation condition is represented on the abscissa. A main effect of condition indicates that increasing negative affect (black bar) produces larger signal change across the left and right amygdalae (n = 16 because of removal of one outlier in the right amygdala for the attend condition) compared to the other two conditions (attending, gray bars; decreasing, white bars). Error bars represent a 95% confidence interval (CI), which was computed on a within-subjects basis in accordance with Loftus and Masson (1994).

Figure 2.

a–d depict the four prefrontal cortex regions (centered under the green crosshairs) that were responsive to the regulation instructions. a, Left inferior frontal gyrus (BA 44). b, Left superior frontal gyrus (BA 9). c, Left anterior dorsal medial frontal gyrus (BA 10). d, Left superior dorsal medial frontal gyrus (BA 6). For each region, there are three cardinal views of the statistically defined cluster of interest (coronal, axial, and sagittal) as well as the estimated impulse response function for the increase (black line), attend (gray line), and decrease (dotted line) instructions in response to negative pictures. Responses were quantified as the AUC of percentage signal change estimates from 5 to 12 s after the instruction, a period indicated by the gray shading in each graph. Confidence intervals (CI; 95%), computed on a within-subjects basis in accordance with Loftus and Masson (1994) and scaled to represent each time point, are depicted at the top right of each line graph. The Talairach coordinates of the maximum F statistic for each region are presented in Table 1.

Figure 3.

a, Two regions in left (L) and right (R) VMPFC (maximum, t(16) = −4.79 at Talairach coordinates x = −23, y = 43, z = −10; and maximum, t(16) = −5.28 at x = 5, y = 37, z = −12, respectively) demonstrate an inverse across-subjects correlation with the left amygdala. For illustrative purposes, we extracted mean signal across all voxels for the decrease and attend conditions separately for the two VMPFC regions and also for the left amygdala. We then computed zero-order correlations between the amygdala and VMPFC across subjects and depicted those associations in the accompanying scatter plots. Subjects with lower activation in the amygdala (top middle and right) (abscissa) exhibit higher activation in the right and left VMPFC (ordinate). Represented on all axes is the difference in AUC for percentage signal change between the decrease and attend conditions (decrease–attend). b, We next computed zero-order, across-subjects correlations between diurnal cortisol slope (abscissa) and the difference in AUC for percentage signal change between the decrease and attend conditions (decrease–attend) across all voxels in the left and right VMPFC (bottom left and middle) and the amygdala (bottom right) (ordinate) clusters. Subjects with higher activation in VMPFC and lower activation in the amygdala exhibit the steepest declines in salivary cortisol over the course of the day.

Figure 4.

Depicted here is proportional change in pupil diameter, reported separately for the increase (black line), attend (gray line), and decrease (dotted line) instructions in response to negative pictures. The shaded panel delineates the middle regulation period (2.5–3.5 s), with early (0.5–2 s) and late (4–5 s) periods appearing as unshaded before and after, respectively. Confidence intervals (CI; 95%), computed separately for the early, middle, and late regulation periods on a within-subjects basis in accordance with Loftus and Masson (1994), are depicted beneath the line graph.