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Pramipexole modulates fronto-subthalamic pathway in sequential working memory

Brain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of dopamine remains unclear. This pharmacological fMRI study examined whether and how the dopamine D2/3 receptor agonist pramipexole modulates fronto-subthalamic or fronto-stri...

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Autores principales: Heldmann, Marcus, Mönch, Eliana, Kesseböhmer, Antonia, Brüggemann, Norbert, Münte, Thomas F., Ye, Zheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066371/
https://www.ncbi.nlm.nih.gov/pubmed/36352204
http://dx.doi.org/10.1038/s41386-022-01494-z
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author Heldmann, Marcus
Mönch, Eliana
Kesseböhmer, Antonia
Brüggemann, Norbert
Münte, Thomas F.
Ye, Zheng
author_facet Heldmann, Marcus
Mönch, Eliana
Kesseböhmer, Antonia
Brüggemann, Norbert
Münte, Thomas F.
Ye, Zheng
author_sort Heldmann, Marcus
collection PubMed
description Brain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of dopamine remains unclear. This pharmacological fMRI study examined whether and how the dopamine D2/3 receptor agonist pramipexole modulates fronto-subthalamic or fronto-striatal pathways during sequential working memory. This study used a double-blind, randomized crossover design. Twenty-two healthy male volunteers completed a digit ordering task during fMRI scanning after receiving a single oral dose of 0.5-mg pramipexole or placebo. The pramipexole effects on task performance, regional activity, activity pattern similarity, and functional connectivity were analyzed. Pramipexole impaired task performance, leading to less accurate and slower responses in the digit ordering task. Also, it downregulated the maintenance-related subthalamic and dorsolateral prefrontal activity, increasing reaction times for maintaining sequences. In contrast, pramipexole upregulated the manipulation-related subthalamic and dorsolateral prefrontal activity, increasing reaction time costs for manipulating sequences. In addition, it altered the dorsolateral prefrontal activity pattern similarity and fronto-subthalamic functional connectivity. Finally, pramipexole reduced maintenance-related striatal activity, which did not affect the behavior. This study confirms the role of the fronto-subthalamic pathway in sequential working memory. Furthermore, it shows that D2 transmission can regulate sequential working memory by modulating the fronto-subthalamic pathway.
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spelling pubmed-100663712023-04-02 Pramipexole modulates fronto-subthalamic pathway in sequential working memory Heldmann, Marcus Mönch, Eliana Kesseböhmer, Antonia Brüggemann, Norbert Münte, Thomas F. Ye, Zheng Neuropsychopharmacology Article Brain dopamine may regulate the ability to maintain and manipulate sequential information online. However, the precise role of dopamine remains unclear. This pharmacological fMRI study examined whether and how the dopamine D2/3 receptor agonist pramipexole modulates fronto-subthalamic or fronto-striatal pathways during sequential working memory. This study used a double-blind, randomized crossover design. Twenty-two healthy male volunteers completed a digit ordering task during fMRI scanning after receiving a single oral dose of 0.5-mg pramipexole or placebo. The pramipexole effects on task performance, regional activity, activity pattern similarity, and functional connectivity were analyzed. Pramipexole impaired task performance, leading to less accurate and slower responses in the digit ordering task. Also, it downregulated the maintenance-related subthalamic and dorsolateral prefrontal activity, increasing reaction times for maintaining sequences. In contrast, pramipexole upregulated the manipulation-related subthalamic and dorsolateral prefrontal activity, increasing reaction time costs for manipulating sequences. In addition, it altered the dorsolateral prefrontal activity pattern similarity and fronto-subthalamic functional connectivity. Finally, pramipexole reduced maintenance-related striatal activity, which did not affect the behavior. This study confirms the role of the fronto-subthalamic pathway in sequential working memory. Furthermore, it shows that D2 transmission can regulate sequential working memory by modulating the fronto-subthalamic pathway. Springer International Publishing 2022-11-09 2023-04 /pmc/articles/PMC10066371/ /pubmed/36352204 http://dx.doi.org/10.1038/s41386-022-01494-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Heldmann, Marcus
Mönch, Eliana
Kesseböhmer, Antonia
Brüggemann, Norbert
Münte, Thomas F.
Ye, Zheng
Pramipexole modulates fronto-subthalamic pathway in sequential working memory
title Pramipexole modulates fronto-subthalamic pathway in sequential working memory
title_full Pramipexole modulates fronto-subthalamic pathway in sequential working memory
title_fullStr Pramipexole modulates fronto-subthalamic pathway in sequential working memory
title_full_unstemmed Pramipexole modulates fronto-subthalamic pathway in sequential working memory
title_short Pramipexole modulates fronto-subthalamic pathway in sequential working memory
title_sort pramipexole modulates fronto-subthalamic pathway in sequential working memory
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066371/
https://www.ncbi.nlm.nih.gov/pubmed/36352204
http://dx.doi.org/10.1038/s41386-022-01494-z
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