CoChat
Sign Up
Cited by 110Cerebrospinal fluid and hydrocephalusSleep and Wakefulness ResearchAdvanced Neuroimaging Techniques and Applications

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

Apparent diffusion coefficient changes in human brain during sleep – Does it inform on the existence of a glymphatic system?

Open access
Demiral, Şükrü Barış, Tomasi, Dardo, Sarlls, Joelle, Lee, Hedok, Wiers, Corinde E., Zehra, Amna, Srivastava, Tansha, Ke, Kenneth, Shokri-Kojori, Ehsan, Freeman, Clara R., Lindgren, Elsa, Ramirez, Veronica, Miller, Gregg, Bandettini, Peter, Horovitz, Silvina, Wang, Gene-Jack, Benveniste, Helene, Volkow, Nora D.·2019·NeuroImage
DOI 10.1016/j.neuroimage.2018.10.043PMC PMC6289767
Open this paper in CoChat — free account

Abstract

The role of sleep in brain physiology is poorly understood. Recently rodent studies have shown that the glymphatic system clears waste products from brain more efficiently during sleep compared to wakefulness due to the expansion of the interstitial fluid space facilitating entry of cerebrospinal fluid (CSF) into the brain. Here, we studied water diffusivity in the brain during sleep and awake conditions, hypothesizing that an increase in water diffusivity during sleep would occur concomitantly with an expansion of CSF volume - an effect that we predicted based on preclinical findings would be most prominent in cerebellum. We used MRI to measure slow and fast components of the apparent diffusion coefficient (ADC) of water in the brain in 50 healthy participants, in 30 of whom we compared awake versus sleep conditions and in 20 of whom we compared rested-wakefulness versus wakefulness following one night of sleep-deprivation. Sleep compared to wakefulness was associated with increases in slow-ADC in cerebellum and left temporal pole and with decreases in fast-ADC in thalamus, insula, parahippocampus and striatal regions, and the density of sleep arousals was inversely associated with ADC changes. The CSF volume was also increased during sleep and was associated with sleep-induced changes in ADCs in cerebellum. There were no differences in ADCs with wakefulness following sleep deprivation compared to rested-wakefulness. Although we hypothesized increases in ADC with sleep, our findings uncovered both increases in slow ADC (mostly in cerebellum) as well as decreases in fast ADC, which could reflect the distinct biological significance of fast- and slow-ADC values in relation to sleep. While preliminary, our findings suggest a more complex sleep-related glymphatic function in the human brain compared to rodents. On the other hand, our findings of sleep-induced changes in CSF volume provide preliminary evidence that is consistent with a glymphatic transport process in the human brain.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.neuroimage.2018.10.043

Cites

12 of 12 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Multiple studies have proven the existence of a glymphatic system in humans.

    “Multiple studies have proven the existence of a glymphatic system in humans10,16,105–107.”

    From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [106]

    The Introduction says it is currently unknown whether a glymphatic system as described in rodents exists in the human brain. The Discussion describes the human findings as preliminary and not conclusive, and other clinical studies as providing indirect evidence—not proof. (LLM, conf=0.89)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 53

  1. Abe, 2017, Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia, PLoS Biol., 15, 10.1371/journal.pbio.2001494 · DOI
  2. Abe, 2017, Modulation of water diffusion by activation-induced neural cell swelling in Aplysia Californica, Sci. Rep., 7, 6178, 10.1038/s41598-017-05586-5 · DOI
  3. Benveniste, 1992, Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted magnetic resonance microscopy, Stroke, 23, 746, 10.1161/01.STR.23.5.746 · DOI
  4. Bernardi, 2016, Sleep reverts changes in human gray and white matter caused by wake-dependent training, Neuroimage, 129, 367, 10.1016/j.neuroimage.2016.01.020 · DOI
  5. Buysse, 1989, The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research, Psychiatr. Res., 28, 193, 10.1016/0165-1781(89)90047-4 · DOI · Paper page
  6. Caccamo, 2005, Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders, Neurobiol. Aging, 26, 645, 10.1016/j.neurobiolaging.2004.06.013 · DOI · Paper page
  7. Calderon-Garciduenas, 2017, Alzheimer disease, Handb. Clin. Neurol., 145, 325, 10.1016/B978-0-12-802395-2.00023-7 · DOI
  8. Calderon-Garcidueñas, 2018, Chapter 23 - Alzheimer disease, 325, 10.1016/B978-0-12-802395-2.00023-7 · DOI
  9. Canto, 2017, The sleeping cerebellum, Trends Neurosci., 40, 309, 10.1016/j.tins.2017.03.001 · DOI
  10. Cedernaes, 2017, Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease, Sleep Med. Rev., 31, 102, 10.1016/j.smrv.2016.02.002 · DOI
  11. Dang-Vu, 2008, Spontaneous neural activity during human slow wave sleep, Proc. Natl. Acad. Sci. U. S. A., 105, 15160, 10.1073/pnas.0801819105 · DOI · Paper page
  12. Davis, 1994, Rapid monitoring of changes in water diffusion coefficients during reversible ischemia in cat and rat brain, Magn. Reson. Med., 31, 454, 10.1002/mrm.1910310416 · DOI
  13. de Crespigny, 1999, Rapid monitoring of diffusion, DC potential, and blood oxygenation changes during global ischemia. Effects of hypoglycemia, hyperglycemia, and TTX, Stroke, 30, 2212, 10.1161/01.STR.30.10.2212 · DOI
  14. Decanniere, 1995, Correlation of rapid changes in the average water diffusion constant and the concentrations of lactate and ATP breakdown products during global ischemia in cat brain, Magn. Reson. Med., 34, 343, 10.1002/mrm.1910340311 · DOI
  15. Eide, 2018, Delayed clearance of cerebrospinal fluid tracer from entorhinal cortex in idiopathic normal pressure hydrocephalus: a glymphatic magnetic resonance imaging study, J. Cerebr. Blood Flow Metab., 10.1177/0271678X18760974 · DOI
  16. Elvsashagen, 2015, Widespread changes in white matter microstructure after a day of waking and sleep deprivation, PLoS One, 10, 10.1371/journal.pone.0127351 · DOI
  17. Elvsashagen, 2017, Evidence for cortical structural plasticity in humans after a day of waking and sleep deprivation, Neuroimage, 156, 214, 10.1016/j.neuroimage.2017.05.027 · DOI
  18. Gakuba, 2018, General anesthesia inhibits the activity of the "glymphatic system", Theranostics, 8, 710, 10.7150/thno.19154 · DOI · Paper page
  19. Glasser, 2013, The minimal preprocessing pipelines for the Human Connectome Project, Neuroimage, 80, 105, 10.1016/j.neuroimage.2013.04.127 · DOI · Paper page
  20. Griswold, 2002, Generalized autocalibrating partially parallel acquisitions (GRAPPA), Magn. Reson. Med., 47, 1202, 10.1002/mrm.10171 · DOI
  21. Harris, 2000, The relationship between the apparent diffusion coefficient measured by magnetic resonance imaging, anoxic depolarization, and glutamate efflux during experimental cerebral ischemia, J. Cerebr. Blood Flow Metab., 20, 28, 10.1097/00004647-200001000-00006 · DOI
  22. Hoddevik, 2017, Factors determining the density of AQP4 water channel molecules at the brain-blood interface, Brain Struct. Funct., 222, 1753, 10.1007/s00429-016-1305-y · DOI
  23. Jonelis, 2012, Age-related influences of prior sleep on brain activation during verbal encoding, Front. Neurol., 3, 49, 10.3389/fneur.2012.00049 · DOI
  24. Ju, 2017, Slow wave sleep disruption increases cerebrospinal fluid amyloid-beta levels, Brain, 140, 2104, 10.1093/brain/awx148 · DOI · Paper page
  25. Kim, 2015, Ppcor: an R package for a fast calculation to semi-partial correlation coefficients, Commun. Stat. Appl. Meth., 22, 665
  26. Le Bihan, 1988, Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging, Radiology, 168, 497, 10.1148/radiology.168.2.3393671 · DOI
  27. Lee, 2015, The effect of body posture on brain glymphatic transport, J. Neurosci., 35, 11034, 10.1523/JNEUROSCI.1625-15.2015 · DOI · Paper page
  28. Macey, 2018, Obstructive sleep apnea and cortical thickness in females and males, PLoS One, 13, 10.1371/journal.pone.0193854 · DOI
  29. MacFall, 1991, Diffusion/microcirculation MRI in the rat brain, Magn. Reson. Med., 19, 305, 10.1002/mrm.1910190219 · DOI
  30. Moeller, 2010, Multiband multislice GE-EPI at 7 tesla, with 16-fold acceleration using partial parallel imaging with application to high spatial and temporal whole-brain fMRI, Magn. Reson. Med., 63, 1144, 10.1002/mrm.22361 · DOI · Paper page
  31. Mugler, 1990, Three-dimensional magnetization-prepared rapid gradient-echo imaging (3D MP RAGE), Magn. Reson. Med., 15, 152, 10.1002/mrm.1910150117 · DOI
  32. Mulkern, 1999, Multi-component apparent diffusion coefficients in human brain, NMR Biomed., 12, 51, 10.1002/(SICI)1099-1492(199902)12:1<51::AID-NBM546>3.0.CO;2-E · DOI
  33. Nedergaard, 2016, Brain drain, Sci. Am., 314, 44, 10.1038/scientificamerican0316-44 · DOI
  34. Nicholson, 1998, Extracellular space structure revealed by diffusion analysis, Trends Neurosci., 21, 207, 10.1016/S0166-2236(98)01261-2 · DOI · Paper page
  35. Osorio, 2014, Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals, Neurobiol. Aging, 35, 1318, 10.1016/j.neurobiolaging.2013.12.030 · DOI
  36. Popovic, 2014, Automatic scoring of sleep stages and cortical arousals using two electrodes on the forehead: validation in healthy adults, J. Sleep Res., 23, 211, 10.1111/jsr.12105 · DOI
  37. Pullens, 2017, Technical Note: a safe, cheap, and easy-to-use isotropic diffusion MRI phantom for clinical and multicenter studies, Med. Phys., 44, 1063, 10.1002/mp.12101 · DOI
  38. Ratner, 2017, Cerebrospinal and interstitial fluid transport via the glymphatic pathway modeled by optimal mass transport, Neuroimage, 152, 530, 10.1016/j.neuroimage.2017.03.021 · DOI
  39. Ringstad, 2017, Glymphatic MRI in idiopathic normal pressure hydrocephalus, Brain, 140, 2691, 10.1093/brain/awx191 · DOI · Paper page
  40. Sehy, 2002, Evidence that both fast and slow water ADC components arise from intracellular space, Magn. Reson. Med., 48, 765, 10.1002/mrm.10301 · DOI
  41. Sevick, 1992, Cytotoxic brain edema: assessment with diffusion-weighted MR imaging, Radiology, 185, 687, 10.1148/radiology.185.3.1438745 · DOI
  42. Sharma, 2018, Obstructive sleep apnea severity affects amyloid burden in cognitively normal elderly. A longitudinal study, Am. J. Respir. Crit. Care Med., 197, 933, 10.1164/rccm.201704-0704OC · DOI
  43. Shokri-Kojori, 2018, β-Amyloid accumulation in the human brain after one night of sleep deprivation, Proc. Natl. Acad. Sci. Unit. States Am., 115, 4483, 10.1073/pnas.1721694115 · DOI · Paper page
  44. Silva, 1997, Evidence for the exchange of arterial spin-labeled water with tissue water in rat brain from diffusion-sensitized measurements of perfusion, Magn. Reson. Med., 38, 232, 10.1002/mrm.1910380211 · DOI
  45. Sizonenko, 2007, Developmental changes and injury induced disruption of the radial organization of the cortex in the immature rat brain revealed by in vivo diffusion tensor MRI, Cerebr. Cortex, 17, 2609, 10.1093/cercor/bhl168 · DOI
  46. Sotak, 2004, Nuclear magnetic resonance (NMR) measurement of the apparent diffusion coefficient (ADC) of tissue water and its relationship to cell volume changes in pathological states, Neurochem. Int., 45, 569, 10.1016/j.neuint.2003.11.010 · DOI
  47. Spira, 2013, Self-reported sleep and beta-amyloid deposition in community-dwelling older adults, JAMA Neurol., 70, 1537
  48. Spira, 2016, Sleep duration and subsequent cortical thinning in cognitively normal older adults, Sleep, 39, 1121, 10.5665/sleep.5768 · DOI
  49. Stejskal, 1965, Spin diffusion measurements: spin echoes in the presence of a time-dependent field gradient, J. Chem. Phys., 42
  50. Sykova, 2004, Extrasynaptic volume transmission and diffusion parameters of the extracellular space, Neuroscience, 129, 861, 10.1016/j.neuroscience.2004.06.077 · DOI
  51. van Gelderen, 1994, Water diffusion and acute stroke, Magn. Reson. Med., 31, 154, 10.1002/mrm.1910310209 · DOI
  52. Verheul, 1994, Comparison of diffusion-weighted MRI with changes in cell volume in a rat model of brain injury, NMR Biomed., 7, 96, 10.1002/nbm.1940070115 · DOI
  53. Vorisek, 1997, Evolution of anisotropic diffusion in the developing rat corpus callosum, J. Neurophysiol., 78, 912, 10.1152/jn.1997.78.2.912 · DOI · Paper page

Cited by

Sorted by citations

Metadata

Authors
Demiral, Ş. B., Tomasi, D., Sarlls, J., Lee, H., Wiers, C. E., Zehra, A., Srivastava, T., Ke, K., Shokri-Kojori, E., Freeman, C. R., Lindgren, E., Ramirez, V., Miller, G., Bandettini, P., Horovitz, S., Wang, G.-J., Benveniste, H., & Volkow, N. D.
Affiliations
  • National Institutes of Health (US)
  • Yale University (US)
Corresponding author
  • Demiral, Şükrü Barış
  • Volkow, Nora D.
ORCID
Venue
NeuroImage
Publisher
Elsevier BV
Published
2019-01
Volume
185
Pages
263-273
ISSN
1053-8119 (ISSN-L)
DOI
10.1016/j.neuroimage.2018.10.043
PMC
PMC6289767
OpenAlex
W2896768947
Cited by
110
References
12
Citations by year
2026: 14 · 2025: 17 · 2024: 22 · 2023: 16 · 2022: 10 · 2021: 18 · 2020: 9 · 2019: 4
FWCI
5.09
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • NeuroImage (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute on Alcohol Abuse and Alcoholism (Y1AA-3009)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
Keywords
glymphatic system, sleep, apparent diffusion coefficient, water diffusion coefficient, cerebrospinal fluid volume, interstitial fluid, sleep deprivation, sleep arousal, cerebellum, brain waste clearance, human brain
MeSH terms
Glymphatic System, Adult, Brain, Cerebrospinal Fluid, Female, Humans, Male, Sleep, Diffusion Magnetic Resonance Imaging

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review