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Cited by 104Cerebrospinal fluid and hydrocephalusSleep and Wakefulness ResearchTraumatic Brain Injury and Neurovascular Disturbances

The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.

Autonomic arousals contribute to brain fluid pulsations during sleep

Open access
Picchioni, Dante, Özbay, Pinar S., Mandelkow, Hendrik, de Zwart, Jacco A., Wang, Yicun, van Gelderen, Peter, Duyn, Jeff H.·2022·NeuroImage
DOI 10.1016/j.neuroimage.2022.118888PMC PMC11395500

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Abstract

During sleep, slow waves of neuro-electrical activity engulf the human brain and aid in the consolidation of memories. Recent research suggests that these slow waves may also promote brain health by facilitating the removal of metabolic waste, possibly by orchestrating the pulsatile flow of cerebrospinal fluid (CSF) through local neural control over vascular tone. To investigate the role of slow waves in the generation of CSF pulsations, we analyzed functional MRI data obtained across the full sleep-wake cycle and during a waking respiratory task. This revealed a novel generating mechanism that relies on the autonomic regulation of cerebral vascular tone without requiring slow electrocortical activity or even sleep. Therefore, the role of CSF pulsations in brain waste clearance may, in part, depend on proper autoregulatory control of cerebral blood flow.

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  • The anti-correlated nature of blood and CSF is not likely to be the result of hemoglobin absorption.

    “Likewise, the anti-correlated nature of blood and CSF is not likely to be the result of hemoglobin absorption”

    From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [42]

    The Results section reports a negative correlation between the fMRI global-signal derivative and the CSF signal, interpreting it as consistent with decreased cerebral blood volume causing CSF inflow. Materials and Methods explains the CSF signal through MRI inflow sensitivity. Neither passage evaluates or explicitly rules out hemoglobin absorption as the cause of the anti-correlation. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • A slightly faster 0.05 Hz oscillation in CSF flow was observed in the 4th ventricle of human subjects while sleeping in an MR scanner and was temporally directly correlated with autonomic arousals.

    “a slightly faster 0.05 Hz oscillation in CSF flow was observed in the 4th ventricle of human subjects while sleeping in an MR scanner17 and was temporally directly correlated with autonomic arousals42.”

    From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [42]

  • The anti-correlated nature of blood and CSF has been established with MR imaging.

    “this relationship has been established with MR imaging17,42.”

    From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [42]

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Research works printed but not linked: 45

  1. Acharya, 2016, American clinical neurophysiology society guideline 2: guidelines for standard electrode position nomenclature, J. Clin. Neurophysiol., 33, 308, 10.1097/WNP.0000000000000316 · DOI
  2. Aldea, 2019, Cerebrovascular smooth muscle cells as the drivers of intramural periarterial drainage of the brain, Front. Aging Neurosci., 11, 1, 10.3389/fnagi.2019.00001 · DOI
  3. Allen, 2007, Photoplethysmography and its application in clinical physiological measurement, Physiol. Meas., 28, R1, 10.1088/0967-3334/28/3/R01 · DOI · Paper page
  4. Amzica, 1997, The K-complex: its slow (<1-Hz) rhythmicity and relation to delta waves, Neurology, 49, 952, 10.1212/WNL.49.4.952 · DOI
  5. Benarroch, 2018, Brainstem integration of arousal, sleep, cardiovascular, and respiratory control, Neurology, 91, 958, 10.1212/WNL.0000000000006537 · DOI
  6. Benveniste, 2017, The glymphatic pathway: waste removal from the CNS via cerebrospinal fluid transport, Neuroscientist, 23, 454, 10.1177/1073858417691030 · DOI
  7. Birn, 2008, The respiration response function: the temporal dynamics of fMRI signal fluctuations related to changes in respiration, Neuroimage, 40, 644, 10.1016/j.neuroimage.2007.11.059 · DOI
  8. Bright, 2009, Characterization of regional heterogeneity in cerebrovascular reactivity dynamics using novel hypocapnia task and BOLD fMRI, Neuroimage, 48, 166, 10.1016/j.neuroimage.2009.05.026 · DOI
  9. Carley, 1996, Respiratory and electrocortical responses to acoustic stimulation, Sleep, 19, S189, 10.1093/sleep/19.suppl_10.189 · DOI
  10. Cash, 2009, The human K-complex represents an isolated cortical down-state, Science, 324, 1084, 10.1126/science.1169626 · DOI · Paper page
  11. Catcheside, 2002, Noninvasive cardiovascular markers of acoustically induced arousal from non-rapid-eye-movement sleep, Sleep, 25, 797, 10.1093/sleep/25.7.797 · DOI
  12. Chang, 2009, Relationship between respiration, end-tidal CO2, and BOLD signals in resting-state fMRI, Neuroimage, 47, 1381, 10.1016/j.neuroimage.2009.04.048 · DOI
  13. Colrain, 2005, The K-complex: a 7-decade history, Sleep, 28, 255, 10.1093/sleep/28.2.255 · DOI
  14. Cox, 1996, AFNI: software for analysis and visualization of functional magnetic resonance neuroimages, Comput. Biomed. Res., 29, 162, 10.1006/cbmr.1996.0014 · DOI · Paper page
  15. de Zambotti, 2018, Dynamic coupling between the central and autonomic nervous systems during sleep: a review, Neurosci. Biobehav. Rev., 90, 84, 10.1016/j.neubiorev.2018.03.027 · DOI · Paper page
  16. de Zwart, 2005, Temporal dynamics of the BOLD fMRI impulse response, Neuroimage, 24, 667, 10.1016/j.neuroimage.2004.09.013 · DOI
  17. Diekelmann, 2010, The memory function of sleep, Nat. Rev. Neurosci., 11, 114, 10.1038/nrn2762 · DOI · Paper page
  18. Dumas, 2012, Functional magnetic resonance imaging detection of vascular reactivity in cerebral amyloid angiopathy, Ann. Neurol., 72, 76, 10.1002/ana.23566 · DOI
  19. Duyn, 2020, Physiological changes in sleep that affect fMRI inference, Curr. Opin. Behav. Sci., 33, 42, 10.1016/j.cobeha.2019.12.007 · DOI
  20. Glover, 2000, Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR, Magn. Reson. Med., 44, 162, 10.1002/1522-2594(200007)44:1<162::AID-MRM23>3.0.CO;2-E · DOI
  21. Greitz, 1993, On the pulsatile nature of intracranial and spinal CSF-circulation demonstrated by MR imaging, Acta Radiol., 34, 321, 10.1177/028418519303400403 · DOI
  22. Hablitz, 2019, Increased glymphatic influx is correlated with high EEG delta power and low heart rate in mice under anesthesia, Sci. Adv., 5, eaav5447, 10.1126/sciadv.aav5447 · DOI · Paper page
  23. Halasz, 2004, The nature of arousal in sleep, J. Sleep Res., 13, 1, 10.1111/j.1365-2869.2004.00388.x · DOI
  24. Halasz, 2016, The K-complex as a special reactive sleep slow wave - a theoretical update, Sleep Med. Rev., 29, 34, 10.1016/j.smrv.2015.09.004 · DOI
  25. Hamel, 2006, Perivascular nerves and the regulation of cerebrovascular tone, J. Appl. Physiol., 100, 1059, 10.1152/japplphysiol.00954.2005 · DOI
  26. Holter, 2017, Interstitial solute transport in 3D reconstructed neuropil occurs by diffusion rather than bulk flow, Proc. Natl. Acad. Sci. U. S. A., 114, 9894, 10.1073/pnas.1706942114 · DOI · Paper page
  27. Iadecola, 2017, The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease, Neuron, 96, 17, 10.1016/j.neuron.2017.07.030 · DOI · Paper page
  28. Ingvar, 1963, Respiratory regulation in sleep, Ann. N. Y. Acad. Sci., 109, 870, 10.1111/j.1749-6632.1963.tb13512.x · DOI
  29. Liu, 2000, Comparison of the temporal response in perfusion and BOLD-based event-related functional MRI, Magn. Reson. Med., 43, 768, 10.1002/(SICI)1522-2594(200005)43:5<768::AID-MRM22>3.0.CO;2-8 · DOI
  30. Liu, 2017, The global signal in fMRI: nuisance or information?, Neuroimage, 150, 213, 10.1016/j.neuroimage.2017.02.036 · DOI
  31. Mandeville, 1998, Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation, Magn. Reson. Med., 39, 615, 10.1002/mrm.1910390415 · DOI
  32. Mestre, 2018, Flow of cerebrospinal fluid is driven by arterial pulsations and is reduced in hypertension, Nat. Commun., 9, 4878, 10.1038/s41467-018-07318-3 · DOI · Paper page
  33. Moehlman, 2019, All-night functional magnetic resonance imaging sleep studies, J. Neurosci. Methods, 316, 83, 10.1016/j.jneumeth.2018.09.019 · DOI
  34. Mokri, 2001, The Monro-Kellie hypothesis: applications in CSF volume depletion, Neurology, 56, 1746, 10.1212/WNL.56.12.1746 · DOI
  35. Moruzzi, 1949, Brain stem reticular formation and activation of the EEG. 1949, Electroencephalogr. Clin. Neurophysiol., 1, 455, 10.1016/0013-4694(49)90219-9 · DOI · Paper page
  36. Nedergaard, 2013, Neuroscience. Garbage truck of the brain, Science, 340, 1529, 10.1126/science.1240514 · DOI · Paper page
  37. Ozbay, 2018, Contribution of systemic vascular effects to fMRI activity in white matter, Neuroimage, 176, 541, 10.1016/j.neuroimage.2018.04.045 · DOI
  38. Ozbay, 2019, Sympathetic activity contributes to the fMRI signal, Commun. Biol., 2, 421, 10.1038/s42003-019-0659-0 · DOI
  39. Peca, 2013, Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy, Neurology, 81, 1659, 10.1212/01.wnl.0000435291.49598.54 · DOI
  40. Raitama, 2021, Spectral analysis of physiological brain pulsations affecting the BOLD signal, Hum. Brain Mapp., 42, 4298, 10.1002/hbm.25547 · DOI
  41. Rooney, 2007, Magnetic field and tissue dependencies of human brain longitudinal 1H2O relaxation in vivo, Magn. Reson. Med., 57, 308, 10.1002/mrm.21122 · DOI
  42. van Opstal, 2017, Cerebrovascular function in presymptomatic and symptomatic individuals with hereditary cerebral amyloid angiopathy: a case-control study, Lancet Neurol., 16, 115, 10.1016/S1474-4422(16)30346-5 · DOI
  43. van Veluw, 2020, Vasomotion as a driving force for paravascular clearance in the awake mouse brain, Neuron, 105, 549, 10.1016/j.neuron.2019.10.033 · DOI · Paper page
  44. Vinje, 2019, Respiratory influence on cerebrospinal fluid flow - a computational study based on long-term intracranial pressure measurements, Sci. Rep., 9, 9732, 10.1038/s41598-019-46055-5 · DOI
  45. Wang, 2020, Bidirectional relationship between sleep and Alzheimer's disease: role of amyloid, tau, and other factors, Neuropsychopharmacology, 45, 104, 10.1038/s41386-019-0478-5 · DOI · Paper page

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Metadata

Authors
Picchioni, D., Özbay, P. S., Mandelkow, H., de Zwart, J. A., Wang, Y., van Gelderen, P., & Duyn, J. H.
Affiliations
National Institutes of Health (US)
Corresponding author
Duyn, Jeff H.
ORCID
Venue
NeuroImage
Publisher
Elsevier BV
Published
2022-04
Volume
249
Pages
118888
ISSN
1053-8119 (ISSN-L)
DOI
10.1016/j.neuroimage.2022.118888
PMC
PMC11395500
OpenAlex
W4221070906
Cited by
104
References
12
Citations by year
2026: 26 · 2025: 36 · 2024: 18 · 2023: 17 · 2022: 6
FWCI
10.68
Type
journal article
Language
en
Open access
Licence
Locations
  • NeuroImage (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, public-domain)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of Neurological Disorders and Stroke
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
cerebrospinal fluid pulsation, autonomic arousal, slow waves, sleep, cerebrovascular tone, autoregulation, cerebral blood flow, brain waste clearance, sleep-wake cycle, respiratory arousals
MeSH terms
Adult, Arousal, Autonomic Nervous System, Cerebrospinal Fluid, Humans, Magnetic Resonance Imaging, Pulsatile Flow, Sleep Stages, Brain Waves

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