Age-Related Increase in Locus Coeruleus Activity and Connectivity to PFC during Ambiguity Processing
Presented During:
Saturday, June 28, 2025: 11:30 AM - 12:45 PM
Brisbane Convention & Exhibition Centre
Room:
M3 (Mezzanine Level)
Poster No:
606
Submission Type:
Abstract Submission
Authors:
Arjun Dave1, Shuer Ye1, Leona Bätz1, Xiaqing Lan1, Heidi Jacobs2, Maryam Ziaei1
Institutions:
1Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway, 2Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, USA
First Author:
Arjun Dave
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Co-Author(s):
Shuer Ye
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Leona Bätz
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Xiaqing Lan
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Heidi Jacobs
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
Boston, USA
Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital
Boston, USA
Maryam Ziaei
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Kavli Institute for Systems Neuroscience, Norwegian University of Science and Technology
Trondheim, Norway
Introduction:
Interpreting facial expressions can be complex, especially when signals are ambiguous, such as a smile paired with furrowed brows. For older adults, age-related cognitive decline amplifies these difficulties, affecting emotional processing and mental well-being (Dexter & Ossmy, 2023). The locus coeruleus (LC), a vital brainstem structure, regulates attention, arousal, memory, and stress (Poe et al., 2020). Its connections to the prefrontal cortex, particularly the dorsolateral prefrontal cortex (dlPFC), help resolve ambiguity (Grueschow et al., 2020) and support mental well-being (Morris et al., 2020). Despite these insights, the role of LC activity and LC-prefrontal connectivity in processing emotional ambiguity remains unclear. This study investigates age-related differences in LC activity and LC-prefrontal connectivity during emotional ambiguity processing, along with its link to mental well-being in healthy aging.
Methods:
Using ultra-high field 7T MRI, we examined emotional ambiguity processing in 75 younger adults (mean age: 25.8±4.02 years; 35 females) and 69 older adults (mean age: 71.3±4.1 years; 35 females) during an emotion recognition task. Participants identified facial expressions ranging from unambiguous (100% fearful/happy) to intermediate (30% fearful/70% happy to 70% fearful/30% happy) with an increment of 10%, and absolute ambiguity (50% fearful/50% happy). They also completed behavioral assessments of executive function, empathy, theory of mind, and mental well-being. A Principal Component Analysis derived an 'emotional resilience index' from mental well-being questionnaire data.
The LC mask was delineated using the Van Egroo et al. (2021, 2023) method, normalizing the LC images with a 10x10 voxel ROI in the pontine tegmentum and constructing a study-specific template. The LC was then manually segmented on a study-specific template based on voxel intensities and known anatomical location, with segmentation repeated after four weeks for consistency. LC activity was analyzed with a general linear model to evaluate task-specific responses to absolute ambiguity, while functional connectivity between the LC and prefrontal cortical regions was explored using generalized psychophysiological interaction analysis to study age-related differences in LC activity and LC-prefrontal coupling, respectively.
The LC mask was delineated using the Van Egroo et al. (2021, 2023) method, normalizing the LC images with a 10x10 voxel ROI in the pontine tegmentum and constructing a study-specific template. The LC was then manually segmented on a study-specific template based on voxel intensities and known anatomical location, with segmentation repeated after four weeks for consistency. LC activity was analyzed with a general linear model to evaluate task-specific responses to absolute ambiguity, while functional connectivity between the LC and prefrontal cortical regions was explored using generalized psychophysiological interaction analysis to study age-related differences in LC activity and LC-prefrontal coupling, respectively.
Results:
Behaviorally, participants showed longer response times and lower confidence levels during absolute ambiguity conditions. Also, older adults recognized ambiguous faces as happy more frequent than younger adults. Neuroimaging revealed significant age-related differences in LC activity and LC-prefrontal connectivity during emotional ambiguity processing. Older adults exhibited higher LC activity during the absolute ambiguity condition compared to younger adults. When examining LC-prefrontal connectivity, older adults demonstrated stronger functional connectivity between the LC and dorsolateral prefrontal cortex (dlPFC) during the absolute ambiguity condition compared to younger adults. This enhanced LC-dlPFC connectivity was associated with better emotional well-being in older adults, including lower anxiety, stress, and higher emotional resilience. Notably, these associations were absent in younger adults, suggesting an age-specific role of LC-dlPFC connectivity in supporting emotional well-being.
Conclusions:
Our findings highlight age-related differences in LC activity and its connectivity with prefrontal regions, specifically the dlPFC, during emotional ambiguity processing. The observed age-related higher LC activity and LC-dlPFC connectivity suggest these neural mechanisms may serve as adaptive mechanisms to counteract age-related cognitive declines, thereby supporting emotional resilience and mental well-being in late adulthood. These insights advance our understanding of the neural substrates underlying emotional ambiguity processing in older adults and underscore the importance of this neural pathway in promoting healthy aging.
Emotion, Motivation and Social Neuroscience:
Emotional Perception 1
Social Cognition
Higher Cognitive Functions:
Decision Making
Lifespan Development:
Aging 2
Keywords:
Aging
Anxiety
Norpinephrine
Other - Locus Coeruleus; Prefrontal Cortex; Functional Connectivity
1|2Indicates the priority used for review
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1. Dexter, M., & Ossmy, O. (2023). The effects of typical ageing on cognitive control: recent advances and future directions. Frontiers in Aging Neuroscience, 15. https://doi.org/10.3389/fnagi.2023.1231410
2. Grueschow, M., Kleim, B., & Ruff, C. C. (2020). Role of the locus coeruleus arousal system in cognitive control. Journal of Neuroendocrinology, 32(12). https://doi.org/10.1111/jne.12890
3. Morris, L. S., McCall, J. G., Charney, D. S., & Murrough, J. W. (2020). The role of the locus coeruleus in the generation of pathological anxiety. Brain and Neuroscience Advances, 4, https://doi.org/10.1177/2398212820930321
4. Poe, G. R., Foote, S., Eschenko, O., Johansen, J. P., Bouret, S., Aston-Jones, G., Harley, C. W., Manahan-Vaughan, D., Weinshenker, D., Valentino, R., Berridge, C., Chandler, D. J., Waterhouse, B., & Sara, S. J. (2020). Locus coeruleus: a new look at the blue spot. Nature Reviews. Neuroscience, 21(11), 644–659. https://doi.org/10.1038/s41583-020-0360-9
5. Van Egroo, M., Riphagen, J. M., Ashton, N. J., Janelidze, S., Sperling, R. A., Johnson, K. A., Yang, H., Bennett, D. A., Blennow, K., Hansson, O., Zetterberg, H., & Jacobs, H. I. L. (2023). Ultra-high field imaging, plasma markers and autopsy data uncover a specific rostral locus coeruleus vulnerability to hyperphosphorylated tau. Molecular Psychiatry, 28(6), 2412–2422. https://doi.org/10.1038/s41380-023-02041-y
6. Van Egroo, M., Van Hooren, R. W. E., & Jacobs, H. I. L. (2021). Associations between locus coeruleus integrity and nocturnal awakenings in the context of Alzheimer’s disease plasma biomarkers: a 7T MRI study. Alzheimer S Research & Therapy, 13(1). https://doi.org/10.1186/s13195-021-00902-8