The neurophysiologic basis of the human sleep–wake cycle and the physiopathology of the circadian clock: a narrative review

Abstract The objectives of this review were to explain the neurologic processes that control the human sleep–wake cycle as well as the pathophysiology of the human circadian clock. Non-rapid eye movement and rapid eye movement sleep are the two main phases of sleep. When triggered by circadian input from the anterior hypothalamus and sleep–wake homeostatic information from endogenous chemical signals (example, adenosine), the ventrolateral preoptic nucleus initiates the onset of sleep. Arousal in which there is a conscious monitoring of the surroundings and the ability to respond to external stimuli is known as wakefulness. It contrasts the state of sleep, in which receptivity to external stimuli is reduced. The higher the synchronous firing rates of cerebral cortex neurons, the longer the brain has been awake. Sleep–wake disturbances induced by endogenous circadian system disruptions or desynchronization between internal and external sleep–wake cycles are known as circadian rhythm sleep–wake disorder (CRSWD). Patients with CRSWD usually report chronic daytime drowsiness and/or insomnia, which interferes with their activities. CRSWD is diagnosed based on the results of some functional evaluations, which include measuring the circadian phase using core body temperature, melatonin secretion timing, sleep diaries, actigraphy, and subjective experiences (example, using the Morningness–Eveningness Questionnaire). CRSWD is classified as a dyssomnia in the second edition of the International Classification of Sleep Disorders, with six subtypes: advanced sleep phase, delayed sleep phase, irregular sleep–wake, free running, jet lag, and shift work types. CRSWD can be temporary (due to jet lag, shift work, or illness) or chronic (due to delayed sleep–wake phase disorder, advanced sleep–wake phase disorder, non-24-h sleep–wake disorder, or irregular sleep–wake rhythm disorder). The inability to fall asleep and wake up at the desired time is a common symptom of all CRSWDs.