Chapter 40 - The Neurobiology of Sleep and Dreaming

Abstract

Sleep contains two distinct sub-states—rapid eye movement (REM) and non-REM (NREM) sleep that alternate with a cycle of about 90 min and are measured using electroencephalography (EEG), electrooculography (EOG) and electromyography (EMG), collectively termed polysomnography (PSG). Following sleep onset, NREM first passes through three stages (N1-N3) of increasing depth, as indexed by progressive slowing of EEG frequencies after which the EEG returns to a wake-like, fast frequency in REM, the sleep stage associated with the greatest likelihood and intensity of dreams. This brain-activated REM state is accompanied by saccadic (rapid) eye movements, suppressed skeletal muscle tone (atonia) and distinct, phasic central potentials–ponto-geniculo-occipital (PGO) waves. Sympathetic outflow diminishes in the transition from waking to NREM and, during N3, parasympathetic outflow is predominant. With the onset of REM, sympathetic influence increases, although not to the level of waking. Transitions from wake to sleep and between sleep stages are actively controlled by brainstem and diencephalic neuronal groups with distinct neurochemical signatures. Groups promoting waking include the locus coeruleus (norepinephrine), dorsal raphe (serotonin), tuberomammillary hypothalamus (histamine), lateral hypothalamus (orexin) and mesopontine and basal forebrain nuclei (acetylcholine). Groups promoting NREM sleep include GABAergic neurons of the anterior hypothalamus while the brain activated REM-sleep state relies on cholinergic activation in the absence of the other wake-promoting neurochemicals. According to the two-process model of sleep propensity, homeostatic mechanisms (Process S) interact with circadian factors (Process C) to regulate behaviorally expressed sleep and waking. Process C is controlled by an endogenous molecular circadian clock in cells of the suprachiasmatic nucleus (SCN) of the anterior hypothalamus that can be entrained to the ambient photoperiod. Process S, is a mechanism that increases sleep pressure as a function of the amount of time since the last sleep episode and is believed to result from “endogenous somnogens,” that accumulate during waking such as adenosine. By acting in concert, processes C and S promote a single, daily consolidated nocturnal sleep bout in healthy adult humans. As waking neuromodulatory influences are withdraw following sleep onset, intrinsic oscillations in reciprocally interconnected thalamic and cortical circuits that appear in the human EEG as the characteristic wave forms of N2 and N3 sleep–spindles, k-complexes, delta waves and the (<1 Hz) slow oscillation. However, during REM, these oscillations are abolished by cholinergic activation of the thalamus from the brainstem. The Reciprocal Interaction suggests that regular alternation of REM and NREM sleep results from the interaction of aminergic REM-off and cholinergic REM-on neuronal populations in the pontine brainstem whereas other models of REM-NREM alternation emphasize mutually inhibitory interactions between brainstem GABAergic cell populations. Functional neuroimaging studies show decreasing activation throughout the brain with sleep onset that continues to decline as NREM deepens. However, with the transition to REM, there is selective re-activation of the limbic cortex and subcortex as well as visual association areas while frontolateral associative cortices remain deactivated. This activation pattern allows speculation as to the neural basis of REM dream features including heightened perception, emotion, instinctual programs and social cognition in the absence of critical awareness and accurate reality monitoring. Across the lifespan, human sleep undergoes distinct developmental changes including transition from multiple sleep bouts across the 24 hour day in infancy to consolidated nocturnal sleep by approximately age 6. The high percentage of REM seen in neonates decreases to adult levels of about 25% by age 4. Adolescence and aging are associated with shifts in circadian sleep propensity later and earlier into the night respectively while, by middle age, the deepest stage of NREM, N3, becomes greatly reduced. All mammals and some birds display both REM and NREM sleep whereas poikilotherms and invertebrates show regular periods of quiescence with circadian rhythmicity. Sleep disorders can arise from excess or deficiency in arousal mechanisms, from mechanical or central disruption of respiration, from impaired gating of sensory input or motor output or from misalignment of sleep with circadian rhythms. Sleep appears to have multiple functions that include energy conservation, defense from predation, metabolic restoration, and consolidation of memory and promoting brain plasticity.