Neural mechanisms of grief regulation

Abstract

Background: The death of an attachment figure triggers intrusive thoughts of the deceased, sadness, and yearning for reunion. Recovery requires reduction of symptoms. We hypothesized that symptoms might correlate with a capacity to regulate attention toward reminders of the deceased, and activity in, and functional connectivity between, prefrontal regulatory regions and the amygdala.

Methods: Twenty recently bereaved subjects rated intrusive thoughts of the deceased versus a capacity to avoid thoughts (grief style). Reaction time was measured while subjects completed an Emotional Stroop (ES) task contrasting deceased-related with control words during functional magnetic resonance imaging (fMRI). Subjects subsequently visualized the death of the deceased and rated induced emotions.

Results: Subjects demonstrated attentional bias toward deceased-related words. Bias magnitude correlated with amygdala, insula, dorsolateral prefrontal cortex (DLPFC) activity. Amygdala activity predicted induced sadness intensity. A double dissociation between grief style and both prefrontal and amygdala subregion activity was found. Intrusiveness correlated with activation of ventral amygdala and rostral anterior cingulate (rACC); avoidance correlated with deactivation of dorsal amygdala and DLPFC. A double dissociation between regulatory region and task-dependent functional connectivity (FC) was found. High DLPFC-amygdala FC correlated with reduced attentional bias, while low rACC-amygdala FC predicted sadness intensity.

Conclusions: Results are consistent with a model in which activity in and functional connectivity between the amygdala and prefrontal regulatory regions indexes differences in mourners' regulation of attention and sadness during pangs of grief, and may be used to distinguish between clinically relevant differences in grief style.

Figure 1

Task design. In the Emotional Stroop (ES) task, subjects viewed four blocks of control words alternating with four blocks of deceased-related words. Each word was presented for 1500 msec. Deceased-related stimuli consisted of 16 randomly ordered nonemotional words that reminded subjects of their pet (e.g., “dog” not “friend”); 16 control words reminded subjects of their house (e.g., “bathroom” not “comfortable”). Subjects were told to ignore the semantic content of words and respond as quickly and accurately as possible regarding ink color. Following the ES task, subjects underwent 8 minutes 40 seconds of mood induction, as described in the text. ES, Emotional Stroop task.

Figure 2

Neural correlates of attentional bias in grief. On the y axis (left panel) the reaction time (RT) bias is plotted. It was calculated as the mean response time (RT) to deceased words minus mean response to control words, excluding error trials. The x axis represents each subject's relative rank by magnitude of bias. Response time bias was used to identify brain regions mediating attention toward the deceased (right panel). Implicated regions included the right insula, right amygdala, left angular gyrus, superior temporal gyrus, supramarginal gyrus, dorsolateral prefrontal cortex (DLPFC), and occipital cortex (voxel threshold p < .01; cluster threshold p < .01). Coordinates and Z scores are shown in Table 1. DLPFC, dorsolateral prefrontal cortex; RT, reaction time.

Figure 3

Neural correlates of cognitive grief style. Avoidance and intrusiveness were entered simultaneously as covariates into the GLM with differences in BOLD as the dependent variable. Regions of interest (ROI) were amygdala (left and right, separately), rostral anterior cingulate cortex (rACC), dorsal ACC (dACC), and dorsolateral prefrontal cortex (DLPFC). Within both the amygdala ROIs, intrusiveness correlated with activation (red) of ventral amygdala, while avoidance correlated with deactivation (blue) of dorsal amygdala. In the control regions, rACC activation correlated with intrusiveness, while DLPFC deactivation correlated with avoidance. Dorsal ACC was not correlated with either measure (p < .05, corrected). Coordinates and Z scores are shown in Table 1. ACC, anterior cingulate cortex; BOLD, blood oxygenation level-dependent; GLM, general linear model.

Figure 4

Task dependent functional connectivity (TDFC) in grief. (A) TDFC was determined by calculating the Pearson's correlation coefficient for attentional and emotional measures of interest with the z score of the change in functional connectivity between neutral and affect blocks. In the ROI pair of left DLPFC-left amygdala, attentional (RT) bias to deceased words, but not emotion, negatively correlated with the change in functional connectivity (FC) (r = −.504, p = .028). In the ROI pair rACC-left amygdala, sadness (and yearning, not shown), but not attention, correlated with the change in FC (r = −.696, p = .001). (B) To examine the basis for the results in (A), TDFC was examined for deceased-word and control-word blocks separately. Subjects with greater levels of attentional control (as indicated by decreased attentional bias) demonstrated greater FC between left DLPFC and left amygdala than those with lower control during the deceased word blocks (r = .571, p = .011) (top left), but not neutral blocks (bottom left). In the rACC-left amygdala pair, FC was lowest in those who subsequently reported high levels of sadness during deceased-word (top right) but not neutral (bottom right) blocks (r = −.589, p = .008). The x axes represent attentional bias as percent increase to deceased versus control words (left) and peak sadness (right). The y axes represent the correlation coefficient for FC between left DLPFC-left amygdala (left) and rACC-left amygdala (right). DLPFC, dorsolateral prefrontal cortex; FC, functional connectivity; rACC, rostral anterior cingulate cortex; ROI, regions of interest; RT, reaction time; TDFC, task dependent functional connectivity.