Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans

Abstract

In the present study, we investigated changes in regional cerebral blood flow (rCBF) in humans during the progression from relaxed wakefulness through slow wave sleep (SWS). These changes were examined as a function of spindle (12-15 Hz) and delta (1.5-4.0 Hz) electroencephalographic (EEG) activity of SWS. rCBF was studied with positron emission tomography (PET) using the H215O bolus method. A maximum of six 60 sec scans were performed per subject during periods of wakefulness and stages 1-4 of SWS, as determined by on-line EEG monitoring. Spectral analysis was performed off-line on the EEG epochs corresponding to the scans for computation of activity in specific frequency bands. The relationship between EEG frequency band activity and normalized rCBF was determined by means of a voxel-by-voxel analysis of covariance. delta activity covaried negatively with rCBF most markedly in the thalamus and also in the brainstem reticular formation, cerebellum, anterior cingulate, and orbitofrontal cortex. After the effect of delta was removed, a significant negative covariation between spindle activity and the residual rCBF was evident in the medial thalamus. These negative covariations may reflect the disfacilitation and active inhibition of thalamocortical relay neurons in association with delta and spindles, as well as the neural substrates underlying the progressive attenuation of sensory awareness, motor responsiveness, and arousal that occur during SWS. delta activity covaried positively with rCBF in the visual and auditory cortex, possibly reflecting processes of dream-like mentation purported to occur during SWS.

Fig. 1.

EEG during wake and sleep stages when scans were performed after H₂¹⁵O injections.A, EEG samples taken from actual scan periods showing typical patterns for each state or stage (wake, stage 2, and stages 3–4 SWS), according to which injections were performed.B, Hypnogram of a typical study, showing scans in one subject during different state–stages of sleep and wake.C, Spectra of EEG epochs (from A) showing typical peaks in α, ς, and δ bands (marked bybars) during each stage, respectively. D, Average frequency band activity ( $\overline{x}$ ± SEM) for α, ς, and δ, respectively, across wake, drowsy, and sleep stages 1 through 4 SWS for all subjects (n = 6) and scans (n = 32). C, D, Values taken from P₃ electrode and EEG activity expressed in arbitrary amplitude units; SEM. 22:00, 10 P.M.; 23:00, 11 P.M.; 24:00, midnight; 1:00, 1 A.M.

Fig. 2.

Normalized rCBF decreases as a function of δ and ς (spindle) EEG activity. The merged rCBF/MRIs indicate the location of maximal significant negative covariation between normalized rCBF and δ or ς activity, with the range of t values for the PET data coded by color scale. Top, rCBF versus δ. Maximal significant negative covariation of rCBF as a function of δ activity, centered over the thalamus and shown in the sagittal, coronal, and horizontal planes; also evident, anterior cingulate and cerebellum. Image sections are centered at the following coordinates (Talairach and Tournoux, 1988): x = 0 mm,y = −16 mm, z = 6 mm.Bottom, rCBF versus ς (−δ). Maximal significant negative covariation of rCBF as a function of ς after removing the effect of δ, centered over midline-medial thalamus. Image sections are centered at the following coordinates (Talairach and Tournoux, 1988):x = −1 mm, y = −16 mm,z = 9 mm. The scatterplots shown beside the PET/MRIs illustrate the nature of the covariations by plotting the residuals of normalized rCBF, obtained in the thalamus, against the residuals of absolute δ activity after the effect of subject (top) was removed, or the residuals of absolute ς activity after the effect of subject and δ (bottom) were removed. For this purpose, the rCBF values were extracted from an 8-mm-radius spherical volume-of-interest centered over the medial thalamus. Each point represents one scan/subject, and the line is the linear regression. Dotsin the plot are color-coded: blue = wake,cyan = drowsy, green = stage 1,yellow = stage 2, red = stage 3, white = stage 4. rCBF, Regional cerebral blood flow.

Fig. 3.

Normalized rCBF increases as a function of δ activity. The merged rCBF/MRIs indicate the location of maximal positive significance for normalized rCBF and δ covariation, centered in the primary visual cortex bilaterally, showing also the left secondary auditory cortex (Table 1). Image sections are centered at the following coordinates (Talairach and Tournoux, 1988): x= 11 mm, y = −80 mm, z = 14 mm. Thescatterplot shown beside the images illustrates the nature of the covariation by plotting the residuals of normalized rCBF, obtained in the visual cortex (volume-of-interest,r = 8 mm) against the residuals of absolute δ activity after the effect of subject was removed. See Figure 2 for details. rCBF, Regional cerebral blood flow.