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Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

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Science  01 Nov 2019:
Vol. 366, Issue 6465, pp. 628-631
DOI: 10.1126/science.aax5440
  • Fig. 1 Large oscillations in CSF signals appear in the fourth ventricle during sleep.

    (A) Example scan positioning. Thick yellow line: position of the functional image relative to the anatomy. The bottom edge intersects with the fourth ventricle (red arrow), allowing CSF inflow to be measured. A subset of the 40 acquired slices are displayed. (B) Example functional image from the bottom slice. Inflow through the ventricle is detected as a bright signal (red arrow). (C) EEG spectrogram from this individual shows long periods of NREM sleep and wake (~10 Hz occipital alpha). (D) Behavioral responses from this individual. (E) Time series of a single CSF voxel (smoothed with 10-TR kernel) shows large, slow dynamics in sleep that subside during wakefulness. (F) Mean power spectral density (PSD) of occipital EEG confirms slow-delta power in sleep, as opposed to high alpha power in wake (n = 13 participants sleep; 11 participants wake). (G) PSD of CSF signal shows increased 0.05 Hz power during sleep (n = 13 participants sleep; 11 participants wake). Shaded regions denote 95% CIs; red lines and asterisks mark nonoverlapping CIs. (H) Low-frequency (LF, 0 to 0.1 Hz) CSF power increased during sleep (n = 11 participants for pairwise comparison). a.u., arbitrary units. (I) This sleep-selective power increase was specific to the ventricle ROI and not observed in a neighboring size-matched control ROI (n = 11 participants).

  • Fig. 2 Ventricle signals correspond to a ~0.05-Hz pulsatile inflow of CSF.

    (A) Schematic of acquisition. New CSF flowing into the imaging volume will generate bright signals. (B) Inflow signals will be largest in the bottom slice and decrease in amplitude inwards. If flow exceeds the critical velocity, then CSF in the bottom slice is completely replaced, and signal amplitudes are large in inner slices as well. (C) Mean amplitude across slices decays in ascending slices. Error bars are standard error across all sleep segments, with the ROI present in four contiguous slices (n = 129 segments, 11 participants). (D) Example time series from the bottom slices of the imaging volume in the fourth ventricle demonstrates the largest signal in the lower slices (e.g., second) and smaller signals in higher slices (e.g., fourth). Orange arrows schematically illustrate flow velocity (larger arrows denote higher velocity), and black arrows point out individual events.

  • Fig. 3 CSF flow oscillations are anticorrelated to a hemodynamic oscillation in the cortical gray matter that appears during sleep, with CSF flow increasing when blood volume decreases.

    (A) Example time series of the cortical gray-matter BOLD signal and the mean CSF signal from one participant. During wake, signals are low-amplitude and synchronized to respiration (0.25 Hz). (B) During sleep, a large-amplitude BOLD oscillation appears, and its time course is coupled to the ventricle CSF signal (~0.05 Hz). (C) Mean cortical gray-matter BOLD signal power increases during sleep (n = 11 participants for pairwise test). (D) Mean cross-correlation between the zero-thresholded negative derivative of BOLD and CSF signals shows strong correlation (n = 176 segments, 13 participants). The shaded blue region indicates the standard error across segments; the black dashed line denotes the 95% interval of shuffled distribution. (E) Example time series showing the correlation, suggesting that CSF flows up the fourth ventricle when cerebral blood volume decreases.

  • Fig. 4 EEG slow-delta waves are coupled to and precede BOLD and CSF oscillations.

    (A) Mean amplitude envelope of slow-delta EEG, (B) mean derivative of BOLD signals, and (C) mean CSF signal, all locked to the peaks of CSF waves during sleep. The shaded region represents the standard error across peak-locked trials (n = 123 peaks). (D) Calculated impulse response of the CSF signal to the EEG envelope shows a time course similar to that of previously established hemodynamic models. Shading indicates standard deviation across model folds. (E) Diagram of model linking the time course of neural activity to CSF flow. Variables include CBF and cerebral blood volume (CBV).

Supplementary Materials

  • Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep

    Nina E. Fultz, Giorgio Bonmassar, Kawin Setsompop, Robert A. Stickgold, Bruce R. Rosen, Jonathan R. Polimeni, Laura D. Lewis

    Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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    • Materials and Methods 
    • Supplementary Text
    • Figs. S1 to S10
    • References 

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