Amygdala-centric circuit aberrations during fear processing correlate with loneliness in acute grief
Poster No:
573
Submission Type:
Late-Breaking Abstract Submission
Authors:
Gyujoon Hwang1, Nuttaon Blair1, B. Ward1, Timothy McAuliffe1, Stacy Claesges1, Abigail Webber1, Yang Wang1, Elliot Stein2, Joseph Goveas1
Institutions:
1Medical College of Wisconsin, Milwaukee, WI, 2National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD
First Author:
Co-Author(s):
Introduction:
Each year, over 60 million people die globally, leaving an average of five to nine bereaved individuals per death to experience acute grief (AG), which typically lasts one year. Symptoms of AG–such as those specific to grief, depression, anxiety, and trauma–vary widely across individuals. The neurobiological mechanisms underlying AG's progression into adaptive or pathological grieving remain unclear. Disruptions in negative emotional processing are hypothesized in late-life AG but have yet to be systematic studied. As such, we investigated the neural circuitry of emotional processing in the acutely grieving brain using a generalizable negative affect task during functional MRI.
Methods:
In a cross-sectional design, acutely grieving older adults (AG; n = 97, 64.5 ± 8.9 years old) were compared to demographically matched non-bereaved comparison participants (NB; n = 35). Participants completed clinical assessments and an emotional face-matching task during functional MRI scanning (Hariri, Tessitore, Mattay, Fera, & Weinberger, 2002). Contrast maps (fearful face minus shape and angry faces minus shapes) were generated to examine group differences in brain activity within hypothesized affective processing and regulatory regions (i.e. amygdala, anterior insula, dorsal anterior cingulate, dorsolateral prefrontal cortex [dlPFC]) (Hwang et al., 2024).
ROIs showing significant activation differences were used as seeds to perform two seed-based, whole-brain functional connectivity (FC) analyses: 1) generalized psychophysiological interaction (gPPI) (McLaren, Ries, Xu, & Johnson, 2012) to assess task-dependent FC, and 2) resting-state functional connectivity (rsFC) (resting data collected before faces task) for task-independent FC. Significant brain measures were correlated with principal components (PCs) derived from ten clinical symptom measures in the AG group. Demographics and Hamilton Depression Rating Scale scores were included as covariates in all models; time since loss was additionally controlled for in correlation analyses within the AG group.
ROIs showing significant activation differences were used as seeds to perform two seed-based, whole-brain functional connectivity (FC) analyses: 1) generalized psychophysiological interaction (gPPI) (McLaren, Ries, Xu, & Johnson, 2012) to assess task-dependent FC, and 2) resting-state functional connectivity (rsFC) (resting data collected before faces task) for task-independent FC. Significant brain measures were correlated with principal components (PCs) derived from ten clinical symptom measures in the AG group. Demographics and Hamilton Depression Rating Scale scores were included as covariates in all models; time since loss was additionally controlled for in correlation analyses within the AG group.
Results:
Top four PCs explained more than 75% of the total variance in the clinical symptom scores: "Depression" (PC1), "Loneliness" (PC2), "Avoidance" (PC3), and "Anxious Arousal" (PC4). The left amygdala activation was greater in the AG group during fear processing, compared to the NB group (pcorr < 0.05), which positively correlated with the loneliness PC (Figure 1A-B). Activity in the left dlPFC was also higher in the AG group (r = 0.215, praw = 0.035), with task-dependent FC between these two ROIs negatively associated with the loneliness PC (r = -0.216, praw = 0.034) (Figure 1C-E).
Whole brain, task-dependent FC during fear processing between the left amygdala seed and left inferior parietal lobule/lateral occipital cortex was higher in AG (pcorr < 0.05) (Figure 2A). rsFC between the left amygdala seed and bilateral posterior cingulate cortex/precuneus cluster was also higher in the AG, compared to the NB group (pcorr < 0.05) (Figure 2B).
No group activation differences were found for the anterior insula or dorsal anterior cingulate ROIs. Angry face minus shape contrast maps did not show significant group differences in activation.
Whole brain, task-dependent FC during fear processing between the left amygdala seed and left inferior parietal lobule/lateral occipital cortex was higher in AG (pcorr < 0.05) (Figure 2A). rsFC between the left amygdala seed and bilateral posterior cingulate cortex/precuneus cluster was also higher in the AG, compared to the NB group (pcorr < 0.05) (Figure 2B).
No group activation differences were found for the anterior insula or dorsal anterior cingulate ROIs. Angry face minus shape contrast maps did not show significant group differences in activation.
·Figure 1
·Figure 2
Conclusions:
Lower fronto-limbic FC during fear processing suggests suboptimal functioning of the emotional regulatory system, despite heightened amygdala and dlPFC activity in AG. These disruptions, particularly in processing fear (but not anger), correlate with heightened loneliness. Further research is needed to determine whether these disruptions hinder social bonding, amplify loneliness, and exacerbate poor grief outcomes. Additionally, the heightened amygdala connectivity with posterior default mode network nodes may signal loss-related rumination, which requires further exploration. Future studies should explore whether interventions targeting amygdala-centric circuit abnormalities can alleviate loneliness during acute grief.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
fMRI Connectivity and Network Modeling
Keywords:
ADULTS
Aging
Emotions
FUNCTIONAL MRI
Psychiatric
Other - Acute Grief
1|2Indicates the priority used for review
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Provide references using APA citation style.
Hwang, G., Blair, N. P., Ward, B. D., McAuliffe, T. L., Claesges, S. A., Webber, A. R., . . . Goveas, J. S. (2024). Amygdala-centered emotional processing in Prolonged Grief Disorder: Relationship with clinical symptomatology. Biol Psychiatry Cogn Neurosci Neuroimaging. doi:10.1016/j.bpsc.2024.12.008
McLaren, D. G., Ries, M. L., Xu, G., & Johnson, S. C. (2012). A generalized form of context-dependent psychophysiological interactions (gPPI): a comparison to standard approaches. Neuroimage, 61(4), 1277-1286. doi:10.1016/j.neuroimage.2012.03.068