Dysregulated Salience and Default Mode Network Interactions in Prolonged Grief Disorder
Poster No:
1485
Submission Type:
Late-Breaking Abstract Submission
Authors:
Nuttaon Blair1, Gyujoon Hwang1, B. Ward2, Stacy Claesges1, Abigail Webber1, Keri Hainsworth3, Yang Wang4, Elliot Stein5, Joseph Goveas1
Institutions:
1Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, 2Department of Psychiatry and Behavioral Medicine, Milwaukee, WI, 3Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, 4Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, 5National Institute on Drug Abuse, Intramural Research Program, Baltimore, MD
First Author:
Nuttaon Blair
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Co-Author(s):
Gyujoon Hwang, Ph.D.
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Stacy Claesges
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Abigail Webber
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Joseph Goveas
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin
Milwaukee, WI
Late Breaking Reviewer(s):
Rosanna Olsen
Rotman Research Institute, Baycrest Academy for Research and Education
Toronto, Ontario
Rotman Research Institute, Baycrest Academy for Research and Education
Toronto, Ontario
Introduction:
Prolonged Grief Disorder (PGD) is a psychiatric condition characterized by intense yearning for and/or intrusive thoughts of the deceased, accompanied by key associated symptoms such as avoidance of reminders of the deceased and emotion dysregulation (e.g., loneliness), resulting in significant functional impairment. Building on prior findings highlighting dysfunction in key large-scale brain network nodes in PGD (Hwang et al (2024), Kakarala et al (2020)), we hypothesized that disruptions between and/or within these networks –specifically the salience, default mode, and executive control networks – will differentiate PGD from integrated (adaptive) grief, with network aberrations correlating with clinical severity.
Methods:
Participants who had experienced the loss of a loved one for 365 days or longer were recruited and assigned to one of two groups: 1) probable PGD (Prolonged Grief-13 item Revised scale (PG-13-R) score ≥ 25; n = 42, mean age 62.6 ± 8.8 years), and 2) integrated grief (IG), (PG-13-R < 20; n = 45). To compare older adults with probable PGD to those with IG, we performed group independent component analysis on resting-state BOLD data from the entire cohort (n=87) (Beckmann and Smith (2004)). Using visual selection to identify components with the highest correlations with Yeo's seven-network parcellation (Yeo et al (2011)), we a priori selected the following large-scale networks: left and right executive control (ECN), salience (SN), default mode (DMN), visual (VN), ventral attention (vAttn), dorsal attention (dAttn), and sensorimotor (SMN) networks. Resting state functional connectivity (rsFC) strength between all network pairs was computed, and group differences between PGD and IG were computed. Abnormalities within brain networks exhibiting disrupted interactions were assessed using fractional amplitude of low-frequency fluctuations (fALFF) (Taylor and Saad (2013)). The relationship between those network interactions showing significant group differences and clinical symptoms were examined. All models were adjusted for covariates, including demographics, time since loss, and depression severity, unless specified otherwise (see below).
Results:
Higher rsFC between the SN and DMN was observed in PGD compared with IG (pcorr = 0.014) (Figure 1A), which positively correlated with overall grief symptom severity (p = 0.01) and grief-related avoidance (p = 0.01) (Figure 1B: left and middle). SN-DMN rsFC strength negatively correlated with depressive symptom severity, adjusting for covariates as above (except depression measure was replaced with grief measure in this model) (p<0.001) (Figure 1B: right). In PGD, higher fALFF in the DMN, but not the SN, was found relative to the IG group (p=0.04) (Figure 2).
Conclusions:
In a cross sectional design, late-life PGD (vs. those with IG) is characterized both by greater DMN-SN connectivity strength and higher within DMN local connectivity. This heightened between network connectivity corresponds to maladaptive avoidance strategies and more severe grief symptoms, which may contribute to the restoration of purpose and meaning in life without the deceased, thus delaying the transition to adaptive, integrated grief. Additionally, the higher within-DMN local connectivity may support persistent self-referential and intrusive thoughts about the deceased and the prioritization of emotionally salient stimuli. The directional strength dissociation in the relationship of SN-DMN functional connectivity with grief and depressive symptoms suggests distinct neurobiological mechanisms underlying PGD and depression, conditions highly comorbid in chronic grief. Future longitudinal research should explore whether these observed neurobiological correlates of PGD are plastic and might thus serve as potential therapeutic targets.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 1
Keywords:
Aging
FUNCTIONAL MRI
Other - Prolonged Grief Disorder, Functional connectivity, Salience, Default Mode Network, Large-scale network
1|2Indicates the priority used for review
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2. Hwang, G., Blair, N. P., Ward, B. D., McAuliffe, T. L., Claesges, S. A., Webber, A. R., Hainsworth, K. R., Wang, Y., Reynolds, C. F., Stein, E. A., & Goveas, J. S. (2024). Amygdala-centered emotional processing in Prolonged Grief Disorder: Relationship with clinical symptomatology. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, S2451.
3. Kakarala, S. E., Roberts, K. E., Rogers, M., Coats, T., Falzarano, F., Gang, J., Chilov, M., Avery, J., Maciejewski, P. K., Lichtenthal, W. G., & Prigerson, H. G. (2020). The neurobiological reward system in Prolonged Grief Disorder (PGD): A systematic review. Psychiatry Research: Neuroimaging, 303, 111132.
4. Taylor, P. A., & Saad, Z. S. (2013). FATCAT: (An efficient) functional and tractographic connectivity analysis toolbox. Brain Connectivity, 3(5), 523-535.
5. Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, Roffman JL, Smoller JW, Zöllei L, Polimeni JR, Fischl B, Liu H, Buckner RL. (2011). The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. Sep;106(3):1125-65.