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  • Print publication year: 2008
  • Online publication date: August 2009

Introduction: the basic neurology of sleep




Sleep is not an inactive state.

Dating back to early modern classifications of sleep based on electrophysiological measurements, the inherent activities of various neural substrates in sleep have been readily recognized.

Normal sleep has been classified as having two characteristic divisions: non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. These sleep states are defined by neurophysiological parameters of electroencephalogram (EEG), electrooculogram (EOG), and surface electromyogram (EMG), as detailed by Dr. Billiard in the following chapter. These characteristics clearly distinguish the NREM and REM sleep states from the wakefulness state.

Behaviorally, sleep is a reversible state characterized by perceptual disengagement and apparent unresponsiveness to the environment with closed eyes, reduced movements, and recumbency. Early behaviorally based studies revealed that even in those with unequivocal electrophysiologic correlates of being asleep, arousal to one's own name and responsiveness to other auditory stimuli persist.

Additionally, the understanding that continues to evolve of the neurophysiology and neurochemistry of normal sleep suggests that many of the neurologic substrates involved are by no means passive, but rather very active in sleep. An example is the increase in cerebral blood flow that occurs in normal sleep. Both animal and human studies have shown that cerebral blood flow in NREM sleep may increase up to 25% greater than in wakefulness, and up to 80% greater in REM sleep. These changes in cerebral blood flow, at least in part, correlate with concomitant increased brain oxygen metabolism in sleep.

Adey, WR, Bors, E, Porter, RW. EEG sleep patterns after high cervical lesions in man. Arch Neurol 1968; 19:377–83.
Basheer, R, Strecker, RF, Thakkar, MM, McCarley, RW. Adenosine and sleep–wake regulation. Prog Neurobiol 2004; 73:379–96.
Batini, C, Moruzzi, G, Palestini, M, Rossi, GF, Zanchetti, A. Effects of complete pontine transections of the sleep–wakefulness rhythm: the midpontine pretrigeminal preparation. Arch Ital Biol 1959; 97:1–12.
Belsky, G, Henriksen, S, McGarr, K. Effects of anticholinesterase (DFP) on the sleep–wakefulness cycle of the cat. Psychophysiology 1968; 5:243.
Blanco-Centurion, C, Xu, M, Murillo-Rodriguez, E, et al. Adenosine and sleep homeostasis in the basal forebrain. J Neurosci 2006; 26:8092–100.
Bremer, F. Cerveau “isolé” et physiologie du sommeil. C R Soc Biol (Paris) 1935; 118:1235–41.
Carlsson, A, Lindqvist, M, Magnusson, T. 3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists. Nature 1957; 180:1200.
Carskadon MA, Dement WC. Normal human sleep: an overview. In: Kryger, MH, Roth, T, Dement, WC, eds. Principles and Practice of Sleep Medicine, 2nd edn. Philadelphia, PA: Saunders, 1994: 16–25.
Celesia, GG, Jasper, HH. Acetylcholine released from the cerebral cortex in relation to state of activation. Neurology 1966; 16:1053–63.
Datta, S, Mavanji, V, Patterson, EH, Ulloor, J. Regulation of rapid eye movement sleep in the freely moving rat: local microinjection of serotonin, norepinephrine, and adenosine into the brainstem. Sleep 2003; 26:513–20.
Dement, W, Kleitman, N. Cyclic variations in EEG during sleep and their relation to eye movements, body motility, and dreaming. Electroencephalogr Clin Neurophysiol 1957; 9:673–90.
Dinner DS. Physiology of sleep. In: Levin, KH, Lüders, HO, eds. Comprehensive Clinical Neurophysiology. Philadelphia, PA: Saunders, 2000: 589–96.
Domino, EF, Yamamoto, K, Dren, AT. Role of cholinergic mechanisms in states of wakefulness and sleep. Prog Brain Res 1968; 28:113–33.
Drucker-Colin, R, Pedraza, JGB. Kainic acid lesions of gigantocellular tegmental field (FTG) neurons do not abolish REM sleep. Brain Res 1983; 272:387–91.
Fischer-Perroudon, C, Mouret, J, Jouvet, M. Sur un cas d'agrypnie (4 mois sans sommeil) au cours d'une maladie de Morvan: effet favorable du 5-hydroxytryptophane. Electroencephalogr Clin Neurophysiol 1974; 36:1–18.
Freemon, FR, Salinas-Garcia, RF, Ward, JW. Sleep patterns in a patient with a brain stem infarction involving the raphe nucleus. Electroencephalogr Clin Neurophysiol 1974; 36:657–60.
Friedman, L, Jones, BE. Computer graphics analysis of sleep–wakefulness state changes after pontine lesions. Brain Res Bull 1984; 13:53–68.
Heller, HC. A global rather than local role for adenosine in sleep homeostasis. Sleep 2006; 29:1382–3.
Hobson, JA, Alexander, J, Frederickson, CJ. The effect of lateral geniculate lesions on phasic electrical activity of the cortex during desynchronized sleep in the cat. Brain Res 1969; 14:607–21.
Jones, BE. The respective involvement of noradrenaline and its delaminated metabolites in waking and paradoxical sleep: a neuropharmacological model. Brain Res 1972; 39:121–36.
Jones, BE. Basic mechanisms of sleep–wake states. In: Kryger, MH, Roth, T, Dement, WC, eds. Principles and Practice of Sleep Medicine, 2nd edn. Philadelphia, PA: Saunders, 1994: 145–62.
Jones, BE, Beaudet, A. Distribution of acetylcholine and catecholamine neurons in the cat brainstem: a choline acetyltransferase and tylosine hydroxylase immunohistochemical study. J Comp Neurol 1987; 261:15–32.
Jones, BE, Cuello, AC. Afferents to the basal forebrain cholinergic cell area from pontomesencephalic catecholamine, serotonin, and acetylcholine neurons. Neuroscience 1989; 31:37–61.
Jones, BE, Yang, TZ. The efferent projections from the reticular formation and the locus coeruleus studied by anterograde and retrograde axonal transport in the rat. J Comp Neurol 1985; 242:56–92.
Jouvet, M. The role of monoamines and acetylcholine-containing neurons in the regulation of the sleep–waking cycle. Ergeb Physiol 1972; 64:166–307.
Jouvet, M, Renault, J. Insomnie persistante après lesions des moyaux du raphe chez le chat. C R Soc Biol (Paris) 1966; 160:1461–5.
Lindsley, D, Bourden, J, Bagoun, H. Effects upon the EEG of acute injury to the brain stem activating system. Electroencephalogr Clin Neurophysiol 1949; 1:475–86.
Madsen, PL, Schmidt, JF, Wildschiodtz, G, et al. Cerebral O2 metabolism and cerebral blood flow in humans during sleep and rapid-eye movement sleep. J Appl Physiol 1991; 70:2597–601.
Magnes, J, Moruzzi, G, Pompeiano, O. Synchronization of the EEG produced by low frequency electrical stimulation of the region of the solitary tract. Arch Ital Biol 1961; 99:33–67.
Mangold, R, Sokoloff, K, Conner, E, et al. The effects of sleep and lack of sleep on the cerebral circulation and metabolism of normal young men. J Clinical Invest 1955; 34:1092–100.
Markand, ON, Dyken, ML. Sleep abnormalities in patients with brain stem lesions. Neurology 1976; 26:769–76.
Mauthner, L. Zur pathologie und physiologie des schlafes nebst bermerkungen ueber die “Nona.”Wein Klin Wochenschr 1890; 40: 961.
McGinty, D. Somnolence, recovery and hyposomnia following ventro-medial diencephalic lesions in the rat. Electroencephalogr Clin Neurophysiol 1969; 26:70–9.
McGinty, D, Harper, RM. Dorsal raphe neurons: depression of firing during sleep in cats. Brain Res 1976; 101:569–75.
Mendelson WB. GABA-benzodiazepine receptor-chloride ionophore complex: implications for the pharmacology of sleep. In: Wauquier, A, Monti, JM, Gaillard, JM, Radulovacki, M, eds. Sleep: Neurotransmitters and Neuromodulators. New York, NY: Raven Press, 1985: 229 ff.
Mignot, E. A year in review: basic science, narcolepsy, and sleep in neurologic diseases. Sleep 2004; 27:1209–12.
Monnier, M, Sauer, R, Hatt, AM. The activating effect of histamine on the central nervous system. Int Rev Neurobiol 1970; 12:265–305.
Moruzzi, G. The sleep–waking cycle. Ergeb Physiol 1972; 64:1–165.
Moruzzi, G, Mogoun, H. Brainstem reticular formation and activation in the EEG. Electroencephalogr Clin Neurophysiol 1949; 1: 455–73.
Nauta, W. Hypothalamic regulation of sleep in rats: experimental study. J Neurophysiol 1946; 9:285–316.
Noor, Alam MD, Szymusiak, R, McGinty, D. Adenosinergic regulation of sleep: multiple sites of action in the brain. Sleep 2006; 29:1384–5.
Oswald, I, Taylor, AM, Treisman, M. Discriminative responses to stimulation during human sleep. Brain 1960; 83:440–53.
Porkka-Heiskanen, T, Strecker, RE, Thakkar, M, et al. Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science 1997; 276:1265–8.
Radulovacki M, Virus RM. Purine, 1-methylisoguanosine and pyrimidine compounds and sleep in rats. In: Wauquier, A, Monti, JM, Gaillard, JM, Radulovacki, M, eds. Sleep: Neurotransmitters and Neuromodulators. New York, NY: Raven Press, 1985: 221 ff.
Rechtschaffen, A, Kales, A. A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. Los Angeles, CA: UCLA Brain Information Service/Brain Research Institute, 1968.
Reivich, M, Issacs, G, Evarts, E, Kety, S. The effect of slow wave sleep and REM sleep on regional cerebral blood flow in cats. J Neurochem 1968; 15:301–6.
Riou, F, Cespuglio, R, Jouvet, M. Endogenous peptides and sleep in the rat. I: Peptides decreasing paradoxical sleep. Neuropeptides 1982; 2:243–54.
Sakai K. Some anatomical and physiological properties of pontomesencephalic tegmental neurons with special reference to the PGO waves and postural atonia during paradoxical sleep in the cat. In: Hobson, JA, Brazier, MA, eds. The Reticular Formation Revisited. New York, NY: Raven Press, 1980: 427–47.
Santiago, TV, Guerra, E, Neubauer, JA, Edelman, NH. Correlation between ventilation and brain blood flow during sleep. J Clin Invest 1984; 73:497–506.
Sastre, J, Sakai, K, Jouvet, M. Persistence of paradoxical sleep after destruction of the pontine gigantocellular tegmental field with kainic acid in the cat. C R Acad Sci (Paris) 1979; 289:959–64.
Siegel JM. Brainstem mechanisms generating REM sleep. In: Kryger, MH, Roth, T, Dement, WC, eds. Principles and Practice of Sleep Medicine, 2nd edn. Philadelphia, PA: Saunders, 1994: 125–44.
Siegel, JM, Tomaszewski, KS, Nienhuis, R. Behavioral organization of reticular formation: studies in the unrestrained cat, II. Cells related to facial movements. J Neurophysiol 1983; 50:717–23.
Siegel, JM, Nienhuis, R, Tomaszewski, KS. REM sleep signs rostral to chronic transections at the pontomedullary junction. Neurosci Lett 1984; 45:241–6.
Simon-Arceo, K, Ramirez-Salado, I, Calvo, JM. Long-lasting enhancement of rapid eye movement sleep and pontogeniculooccipital waves by vasoactive intestinal peptide microinjection into the amygdala temporal lobe. Sleep 2003; 26:259–64.
Smith HR. Stimulant-dependent sleep disorder. In: Gilman S, ed. MedLink Neurology [online]. Accessed December, 2007.
Steriade M. Brain electrical activity and sensory processing during waking and sleep states. In: Kryger, MH, Roth, T, Dement, WC, eds. Principles and Practice of Sleep Medicine, 2nd edn. Philadelphia, PA: Saunders, 1994: 105–24.
Steriade, M, Hobson, JA. Neuronal activity during the sleep–waking cycle. Prog Neurobiol 1976; 6:155–376.
Sterman, MB, Clemente, CD. Forebrain inhibitory mechanisms: cortical synchronization induced by basal forebrain stimulation. Exp Neurol 1962; 6:91–102.
Sterman, MB, Clemente, CD. Forebrain inhibitory mechanisms: sleep patterns induced by basal forebrain stimulation in the behaving cat. Exp Neurol 1962; 6:103–17.
Townsend, RE, Prinz, PN, Obrist, WD. Human cerebral blood flow during sleep and waking. J Appl Physiol 1973; 35:620–5.
Villablanca, J. The electrocorticogram in the chronic cerveau isolé cat. Electroencephalogr Clin Neurophysiol 1965; 19: 576–86.
Economo, C. Encephalitis Lethargica: Its Sequelae and Treatment. London: Oxford University Press, 1931.
Williams, HL, Hammack, JT, Daly, RL, Dement, WC, Lubin, A. Responses to auditory stimulation, sleep loss and the EEG stages of sleep. Electroencephalogr Clin Neurophysiol 1964; 16:269–79.
Zepelin, H, Rechtschaffen, A. Mammalian sleep, longevity and energy metabolism. Brain Behav Evol 1974; 10:425–70.