On-line detection of sleep-wake states and application to produce intermittent hypoxia only in sleep in rats

Abstract

Sleep-disordered breathing is associated with adverse clinical consequences such as daytime sleepiness and hypertension. The mechanisms behind these associations have been studied in animal models, especially rats, but intermittent stimuli such as hypoxia have been applied without reference to sleep-wake states. To determine mechanisms underlying the adverse physiological consequences of stimuli associated with sleep-disordered breathing requires criteria for detection of sleep-wake states on-line to trigger stimuli only in sleep. This study aimed to develop such a system for freely behaving rats. Twelve rats with implanted electroencephalogram and neck electromyogram electrodes were studied in the light and dark phases. Electroencephalogram frequencies in the high (20–30 Hz) and low (2–4 Hz) frequency bands distinguished non-rapid eye movement (REM) sleep, whereas neck electromyogram distinguished REM. Using these parameters in a simple algorithm led to detection accuracies of 94.5 ± 1.0 (SE) % for wakefulness, 96.2 ± 0.8% for non-REM sleep, and 92.3 ± 1.6% for REM compared with blinded human judgment. The algorithm was then used to trigger hypoxic stimuli only in sleep. Because frequency and amplitude analysis is readily performed using a variety of commercial systems, incorporation of these parameters into such an algorithm will facilitate studies investigating mechanisms underlying the physiological consequences of sleep-related respiratory stimuli in a fashion that more effectively models clinical disorders.