Neurophysiology of Sleep and Wakefulness: Basic Science and Clinical Implications

Abstract

Increased attention to the prevalence of excessive sleepiness has led to a clear need to treat this symptom, thus reinforcing the need for a greater understanding of the neurobiology of sleep and wakefulness. Although the physiological mechanisms of sleep and wakefulness are highly interrelated, recent research reveals that there are distinct differences in the active brain processing and the specific neurochemical systems involved in the two states. In this review, we will examine the specific neuronal pathways, transmitters, and receptors composing the ascending arousal system that flow from the brainstem through the thalamus, hypothalamus, and basal forebrain to the cerebral cortex. We will also discuss the mutually inhibitory interaction between the core neuronal components of this arousal system and the sleep-active neurons in the ventrolateral preoptic nucleus, which serves as a brainstem-switch, regulating the stability of the sleep-wake states. In addition, we will review the role of homeostatic and circadian processes in the sleep-wake cycle, including the influence of the suprachiasmatic nucleus on coordination of sleep-wake systems. Finally, we will summarize how the above processes are reflected in disorders of sleep and wakefulness, including insomnia, narcolepsy, disorders associated with fragmented sleep, circadian rhythm sleep disorders, and primary neurological disorders such as Parkinson’s and Alzheimer’s diseases.

Sleep stability and transitions in patients with idiopathic REM sleep behavior disorder and patients with Parkinson’s disease

“…These ''sleep-wake switches'' are mutually dependent and have been referred to as the wake-sleep and REM-NREM sleep switches, respectively. Despite the mutually inhibitory loops involved in the two switching mechanisms, if either side of the two loops is weakened or injured, unwanted instability can occur in either of the states, irrespective of which side is damaged (Schwartz and Roth, 2008). As neurons of the brain stem and basal brain structures are affected in synucleinopathies (Braak et al, 2003), we propose that the neurodegeneration will have a progressive impact on the wake-sleep and REM-NREM transitions and stability.…”

Sleep stability and transitions in patients with idiopathic REM sleep behavior disorder and patients with Parkinson's disease

“…Sleep is strongly regulated by groups of neurons located in the brainstem and midbrain areas, which form reciprocal connections (Luppi et al, 2011;Saper et al, 2010Saper et al, , 2001Schwartz and Roth, 2008). These ''sleep-wake switches'' are mutually dependent and have been referred to as the wake-sleep and REM-NREM sleep switches, respectively.…”

Diurnal variations in arousal: a naturalistic heart rate study in children with ADHD

“…Several theoretical models have explained the behavioral symptoms in this developmental disorder in terms of arousal regulation deficits [51,52,68]. As arousal is closely related to sleep-wake regulation [50], it is not surprising that arousal is characterized by a circadian rhythm [54]. To date, several research domains have pointed to differential circadian arousal patterns in ADHD.…”