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Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy

BACKGROUND: Narcolepsy is a chronic neurological disease characterized by daytime sleep attacks, cataplexy, and fragmented sleep. The disease is hypothesized to arise from destruction or dysfunction of hypothalamic hypocretin-producing cells that innervate wake-promoting systems including the ascend...

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Autores principales: Järvelä, Matti, Kananen, Janne, Korhonen, Vesa, Huotari, Niko, Ansakorpi, Hanna, Kiviniemi, Vesa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525269/
https://www.ncbi.nlm.nih.gov/pubmed/36193214
http://dx.doi.org/10.1038/s43856-022-00187-4
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author Järvelä, Matti
Kananen, Janne
Korhonen, Vesa
Huotari, Niko
Ansakorpi, Hanna
Kiviniemi, Vesa
author_facet Järvelä, Matti
Kananen, Janne
Korhonen, Vesa
Huotari, Niko
Ansakorpi, Hanna
Kiviniemi, Vesa
author_sort Järvelä, Matti
collection PubMed
description BACKGROUND: Narcolepsy is a chronic neurological disease characterized by daytime sleep attacks, cataplexy, and fragmented sleep. The disease is hypothesized to arise from destruction or dysfunction of hypothalamic hypocretin-producing cells that innervate wake-promoting systems including the ascending arousal network (AAN), which regulates arousal via release of neurotransmitters like noradrenalin. Brain pulsations are thought to drive intracranial cerebrospinal fluid flow linked to brain metabolite transfer that sustains homeostasis. This flow increases in sleep and is suppressed by noradrenalin in the awake state. Here we tested the hypothesis that narcolepsy is associated with altered brain pulsations, and if these pulsations can differentiate narcolepsy type 1 from healthy controls. METHODS: In this case-control study, 23 patients with narcolepsy type 1 (NT1) were imaged with ultrafast fMRI (MREG) along with 23 age- and sex-matched healthy controls (HC). The physiological brain pulsations were quantified as the frequency-wise signal variance. Clinical relevance of the pulsations was investigated with correlation and receiving operating characteristic analysis. RESULTS: We find that variance and fractional variance in the very low frequency (MREG(vlf)) band are greater in NT1 compared to HC, while cardiac (MREG(card)) and respiratory band variances are lower. Interestingly, these pulsations differences are prominent in the AAN region. We further find that fractional variance in MREG(vlf) shows promise as an effective bi-classification metric (AUC = 81.4%/78.5%), and that disease severity measured with narcolepsy severity score correlates with MREG(card) variance (R = −0.48, p = 0.0249). CONCLUSIONS: We suggest that our novel results reflect impaired CSF dynamics that may be linked to altered glymphatic circulation in narcolepsy type 1.
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spelling pubmed-95252692022-10-02 Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy Järvelä, Matti Kananen, Janne Korhonen, Vesa Huotari, Niko Ansakorpi, Hanna Kiviniemi, Vesa Commun Med (Lond) Article BACKGROUND: Narcolepsy is a chronic neurological disease characterized by daytime sleep attacks, cataplexy, and fragmented sleep. The disease is hypothesized to arise from destruction or dysfunction of hypothalamic hypocretin-producing cells that innervate wake-promoting systems including the ascending arousal network (AAN), which regulates arousal via release of neurotransmitters like noradrenalin. Brain pulsations are thought to drive intracranial cerebrospinal fluid flow linked to brain metabolite transfer that sustains homeostasis. This flow increases in sleep and is suppressed by noradrenalin in the awake state. Here we tested the hypothesis that narcolepsy is associated with altered brain pulsations, and if these pulsations can differentiate narcolepsy type 1 from healthy controls. METHODS: In this case-control study, 23 patients with narcolepsy type 1 (NT1) were imaged with ultrafast fMRI (MREG) along with 23 age- and sex-matched healthy controls (HC). The physiological brain pulsations were quantified as the frequency-wise signal variance. Clinical relevance of the pulsations was investigated with correlation and receiving operating characteristic analysis. RESULTS: We find that variance and fractional variance in the very low frequency (MREG(vlf)) band are greater in NT1 compared to HC, while cardiac (MREG(card)) and respiratory band variances are lower. Interestingly, these pulsations differences are prominent in the AAN region. We further find that fractional variance in MREG(vlf) shows promise as an effective bi-classification metric (AUC = 81.4%/78.5%), and that disease severity measured with narcolepsy severity score correlates with MREG(card) variance (R = −0.48, p = 0.0249). CONCLUSIONS: We suggest that our novel results reflect impaired CSF dynamics that may be linked to altered glymphatic circulation in narcolepsy type 1. Nature Publishing Group UK 2022-09-30 /pmc/articles/PMC9525269/ /pubmed/36193214 http://dx.doi.org/10.1038/s43856-022-00187-4 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
Järvelä, Matti
Kananen, Janne
Korhonen, Vesa
Huotari, Niko
Ansakorpi, Hanna
Kiviniemi, Vesa
Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy
title Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy
title_full Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy
title_fullStr Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy
title_full_unstemmed Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy
title_short Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy
title_sort increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9525269/
https://www.ncbi.nlm.nih.gov/pubmed/36193214
http://dx.doi.org/10.1038/s43856-022-00187-4
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