University of Oulu

Järvelä, M., Kananen, J., Korhonen, V. et al. Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy. Commun Med 2, 122 (2022).

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

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Author: Järvelä, Matti1,2; Kananen, Janne1,2; Korhonen, Vesa1,2;
Organizations: 1Department of Diagnostic Radiology, Medical Research Center (MRC), Oulu University Hospital, Oulu, Finland
2Research unit of Medical Imaging, Physics and Technology, the Faculty of Medicine, University of Oulu, Oulu, Finland
3Research Unit of Neuroscience, Neurology, University of Oulu, Oulu, Finland
4Department of Neurology, Oulu University Hospital, Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.9 MB)
Persistent link:
Language: English
Published: Springer Nature, 2022
Publish Date: 2023-06-21


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 (MREGvlf) band are greater in NT1 compared to HC, while cardiac (MREGcard) and respiratory band variances are lower. Interestingly, these pulsations differences are prominent in the AAN region. We further find that fractional variance in MREGvlf shows promise as an effective bi-classification metric (AUC = 81.4%/78.5%), and that disease severity measured with narcolepsy severity score correlates with MREGcard 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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Series: Communications medicine
ISSN: 2730-664X
ISSN-E: 2730-664X
ISSN-L: 2730-664X
Volume: 2
Article number: 122
DOI: 10.1038/s43856-022-00187-4
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3126 Surgery, anesthesiology, intensive care, radiology
Funding: We offer our thanks to the funders of this study: Academy of Finland (275352, 314497, Profi 3) (V.Ki.), Jane and Aatos Erkko Foundation (V.Ki.), Instrumentarium Science Foundation (JK), North Ostrobothnia Regional Fund (JK), Finnish Brain Foundation sr (J.K.), Finnish Medical Foundation (J.K. and M.J.), Maire Taponen Foundation (J.K.), Orion Research Foundation (J.K. and M.J.), Suomalais-Norjalainen Lääketieteen Säätiö (M.J.), Tauno Tönning Foundation (J.K. and V.Ko.), The University of Oulu Scholarship Foundation (J.K.), Emil Aaltonen Foundation (M.J.), and Medical Research Center Oulu (J.K.).
Academy of Finland Grant Number: 275352
Detailed Information: 275352 (Academy of Finland Funding decision)
314497 (Academy of Finland Funding decision)
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