Dear Dr. Virtanen,

we read with interest your recent paper entitled “Spontaneous Hemodynamic Oscillations during Human Sleep and Sleep Stage Transitions Characterized with Near-Infrared Spectroscopy” (PLOS One 2011; 6:e25415). One of the conclusions of your paper was that slow-wave sleep entails a lower level of slow spontaneous hemodynamic activity than other wake-sleep states. You attributed this result to differences in neuronal activation patterns between sleep stages as well as a reduction in autonomic nervous system activity. A few years ago, we measured variability in cerebral perfusion pressure (CPP, i.e., the difference between arterial and intracranial pressure) and cerebral blood flow (CBF) in newborn lambs during different wake-sleep states. The results of our experiments (Sleep 2004;27:36-41) showed that variability in CBF at low frequencies below the breathing rate, which broadly correspond to low-frequency oscillations in your analysis, was significantly lower in non-rapid-eye-movement (NREM) sleep than either in quiet wakefulness or in rapid-eye-movement (REM) sleep. Analysis of spectral coherence revealed that a significant fraction of CBF variability was linearly related to CPP variability in each wake-sleep state. However, this fraction differed among wake-sleep states, being significantly higher in REM sleep (65%) than either in quiet wakefulness (49%) or NREM sleep (41%). These findings are in agreement with your observations on human subjects, suggesting that in NREM sleep (and to a minor extent also in quiet wakefulness), the low-frequency variability in CBF is mainly driven by variability in cerebrovascular tone, whereas during REM sleep, CBF variability is strongly dependent on CPP variability.

Yours sincerely

Dr. Alessandro Silvani, MD PhD
Prof. Giovanna Zoccoli, MD PhD
Department of Human and General Physiology
University of Bologna