Amygdala Functional Connectivity Features in Grief: A Pilot Longitudinal Study

Abstract

Objective: Acute grief, in an important minority of older adults, can become protracted, intense, and debilitating, leading to the development of complicated grief (CG). However, the neurobiologic mechanisms underlying a maladaptive grief response after an attachment loss are unknown. The current study aimed to examine the amygdala brain network features that cross-sectionally explain the symptom variance and longitudinally relate to grief symptom trajectories after an attachment loss.

Methods: Baseline amygdala functional connectivity (Fc) was assessed using a seed-based resting-state functional magnetic resonance imaging method in 35 adults who were within 1-year after death of a loved one and 21 healthy comparison (HC) participants. Magnetic resonance imaging scans were obtained at baseline, and clinical assessments, including the inventory of complicated grief (ICG) were completed at weeks 0, 8, 16, and 26 (endpoint).

Results: Relative to HC participants, grief participants showed increased amygdala Fc in the posterior default mode (bilateral medial temporal lobes and left precuneus) and thalamus. Amygdala Fc in the default mode and ventral affective regions positively correlated with ICG scores at baseline. Furthermore, increased baseline amygdala functional connections with the dorsal frontal executive control and salience network regions correlated with worsening ICG scores over time. These longitudinal findings persisted after controlling for covariates, including baseline depressive and anxiety symptoms.

Conclusion: These results provide novel preliminary evidence suggesting amygdala-based brain network measures to cross-sectionally explain symptom variance and longitudinally correlate with grief symptom trajectories in grievers. Amygdala brain network function measures may have the potential to serve as biomarkers of CG.

Keywords: Amygdala; bereavement; brain network; complicated grief; emotion processing; emotion regulation; functional connectivity; grief; resting-state functional MRI.

Figure 1.

Amygdala functional connectivity group differences. (A) illustrates brain regions showing significant differences in grief participants relative to the healthy comparison group. Bright color indicates increased functional connectivity. (B) and (C) are histograms indicating individual data distribution for grief (green) and control (yellow) groups, respectively. In the histograms, the whiskers indicate one standard error for the data. The height of the bar indicates the average adjusted m value of the significant cluster. Abbreviations. R: right; L: left; Thal: thalamus; Precu: precuneus; Amyg: amygdala; Hipp: hippocampus; PHG: parahippocampal gyrus; Fc: functional connectivity; HC: healthy comparison; adj: adjusted for covariates.

Figure 2.

Cross-sectional association between amygdala functional connectivity and inventory of complicated grief scores in grief. (A) illustrates brain regions showing significant results. Relationships between adjusted mean amygdala Fc in the (B) left PHG and (C) left SFG clusters and adjusted ICG scores in grief participants at baseline. The color bar indicates the value of the partial F statistic; a greater partial F value indicates a more significant relationship. R: right; L: left; SFG: superior frontal gyrus; Amyg: amygdala; Hipp: hippocampus; PHG: parahippocampal gyrus; ICG: inventory of complicated grief; Fc: functional connectivity; adj: adjusted for covariates.

Figure 3.

Conjunction analysis between the cross-sectional t-test differences (Figure 2A) and linear regression (Figure 3A) data. Overlapped left parahippocampal gyrus/amygdala cluster.

Figure 4.

Linear relationship between baseline amygdala functional connectivity and the inventory of complicated grief score rate-of-change in grief participants. (A) illustrates brain regions showing significant results. Relationships between adjusted mean baseline amygdala Fc in the (B) left IFG/MFG/SFG; (C) right SFG; and (D) left MFG clusters and adjusted ICG rate- of-change in grief participants. The color bar indicates the value of the partial F statistic; a greater partial F value indicates a more significant relationship. R: right; L: left; SFG: superior frontal gyrus; MFG: middle frontal gyrus; IFG: inferior frontal gyrus; ICG: inventory of complicated grief; Fc: functional connectivity; adj: adjusted for covariates.