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Dopamine D1-signaling modulates maintenance of functional network segregation in aging

Past research has shown that as individuals age, there are decreases in within-network connectivity and increases in between-network connectivity, a pattern known as functional dedifferentiation. While the mechanisms behind reduced network segregation are not fully understood, evidence suggests that...

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Autores principales: Pedersen, Robin, Johansson, Jarkko, Salami, Alireza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318303/
https://www.ncbi.nlm.nih.gov/pubmed/37408790
http://dx.doi.org/10.1016/j.nbas.2023.100079
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author Pedersen, Robin
Johansson, Jarkko
Salami, Alireza
author_facet Pedersen, Robin
Johansson, Jarkko
Salami, Alireza
author_sort Pedersen, Robin
collection PubMed
description Past research has shown that as individuals age, there are decreases in within-network connectivity and increases in between-network connectivity, a pattern known as functional dedifferentiation. While the mechanisms behind reduced network segregation are not fully understood, evidence suggests that age-related differences in the dopamine (DA) system may play a key role. The DA D1-receptor (D1DR) is the most abundant and age-sensitive receptor subtype in the dopaminergic system, known to modulate synaptic activity and enhance the specificity of the neuronal signals. In this study from the DyNAMiC project (N = 180, 20-79y), we set out to investigate the interplay among age, functional connectivity, and dopamine D1DR availability. Using a novel application of multivariate Partial Least squares (PLS), we found that older age, and lower D1DR availability, were simultaneously associated with a pattern of decreased within-network and increased between-network connectivity. Individuals who expressed greater distinctiveness of large-scale networks exhibited more efficient working memory. In line with the maintenance hypotheses, we found that older individuals with greater D1DR in caudate exhibited less dedifferentiation of the connectome, and greater working memory, compared to their age-matched counterparts with less D1DR. These findings suggest that dopaminergic neurotransmission plays an important role in functional dedifferentiation in aging with consequences for working memory function at older age.
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spelling pubmed-103183032023-07-05 Dopamine D1-signaling modulates maintenance of functional network segregation in aging Pedersen, Robin Johansson, Jarkko Salami, Alireza Aging Brain Article Past research has shown that as individuals age, there are decreases in within-network connectivity and increases in between-network connectivity, a pattern known as functional dedifferentiation. While the mechanisms behind reduced network segregation are not fully understood, evidence suggests that age-related differences in the dopamine (DA) system may play a key role. The DA D1-receptor (D1DR) is the most abundant and age-sensitive receptor subtype in the dopaminergic system, known to modulate synaptic activity and enhance the specificity of the neuronal signals. In this study from the DyNAMiC project (N = 180, 20-79y), we set out to investigate the interplay among age, functional connectivity, and dopamine D1DR availability. Using a novel application of multivariate Partial Least squares (PLS), we found that older age, and lower D1DR availability, were simultaneously associated with a pattern of decreased within-network and increased between-network connectivity. Individuals who expressed greater distinctiveness of large-scale networks exhibited more efficient working memory. In line with the maintenance hypotheses, we found that older individuals with greater D1DR in caudate exhibited less dedifferentiation of the connectome, and greater working memory, compared to their age-matched counterparts with less D1DR. These findings suggest that dopaminergic neurotransmission plays an important role in functional dedifferentiation in aging with consequences for working memory function at older age. Elsevier 2023-06-15 /pmc/articles/PMC10318303/ /pubmed/37408790 http://dx.doi.org/10.1016/j.nbas.2023.100079 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pedersen, Robin
Johansson, Jarkko
Salami, Alireza
Dopamine D1-signaling modulates maintenance of functional network segregation in aging
title Dopamine D1-signaling modulates maintenance of functional network segregation in aging
title_full Dopamine D1-signaling modulates maintenance of functional network segregation in aging
title_fullStr Dopamine D1-signaling modulates maintenance of functional network segregation in aging
title_full_unstemmed Dopamine D1-signaling modulates maintenance of functional network segregation in aging
title_short Dopamine D1-signaling modulates maintenance of functional network segregation in aging
title_sort dopamine d1-signaling modulates maintenance of functional network segregation in aging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318303/
https://www.ncbi.nlm.nih.gov/pubmed/37408790
http://dx.doi.org/10.1016/j.nbas.2023.100079
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