Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions
(2023) In eLife 12.- Abstract
The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that... (More)
The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project [HCP] 7T dataset, n=184). Although the main rostrocaudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.
(Less)
- author
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- in
- eLife
- volume
- 12
- article number
- RP87188
- publisher
- eLife Sciences Publications
- external identifiers
-
- pmid:37650882
- scopus:85169502663
- ISSN
- 2050-084X
- DOI
- 10.7554/eLife.87188
- language
- English
- LU publication?
- yes
- id
- b5e85159-56ec-4b25-87e8-af650a69dde6
- date added to LUP
- 2023-12-08 10:03:24
- date last changed
- 2024-04-21 04:02:29
@article{b5e85159-56ec-4b25-87e8-af650a69dde6,
abstract = {{<p>The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging, and whether it is associated with cognition and mood. Here, we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years of age (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project [HCP] 7T dataset, n=184). Although the main rostrocaudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory, and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography, and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale (HADS) ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.</p>}},
author = {{Veréb, Dániel and Mijalkov, Mite and Canal-Garcia, Anna and Chang, Yu Wei and Gomez-Ruiz, Emiliano and Gerboles, Blanca Zufiria and Kivipelto, Miia and Svenningsson, Per and Zetterberg, Henrik and Volpe, Giovanni and Betts, Matthew and Jacobs, Heidi I.L. and Pereira, Joana B.}},
issn = {{2050-084X}},
language = {{eng}},
publisher = {{eLife Sciences Publications}},
series = {{eLife}},
title = {{Age-related differences in the functional topography of the locus coeruleus and their implications for cognitive and affective functions}},
url = {{http://dx.doi.org/10.7554/eLife.87188}},
doi = {{10.7554/eLife.87188}},
volume = {{12}},
year = {{2023}},
}