The reticular formation plays a central role in the regulation of the state of consciousness and arousal. It consists of a complex network of interconnected circuits of neurons in the tegmentum of the brain stem, the lateral hypothalamic area, and the medial, intralaminar, and reticular nuclei of the thalamus (Fig 18–1). Many of these neurons are serotonergic (using serotonin as their neurotransmitter), or noradrenergic. Axons from these nonspecific thalamic nuclei project to most of the cerebral cortex, where they modulate the level of activity of large numbers of neurons.
FIGURE 18–1 Ascending reticular system.
The term reticular formation derives from the characteristic appearance of loosely packed cells of varying sizes and shapes, embedded in a dense meshwork of cell processes, including dendrites and axons. The reticular formation is not anatomically well defined because it includes neurons located in diverse parts of the brain. However, this does not imply that it lacks an important function. Indeed, the reticular formation plays a crucial role in maintaining behavioral arousal and consciousness. Some authorities refer to it as the reticular activating system.
In addition to sending ascending projections to the cortex, the reticular formation gives rise to descending axons, which pass to the spinal cord in the reticulospinal tract. Activity in reticulospinal axons modulates spinal reflex activity and may also modulate sensory input by regulating the gain at synapses within the spinal cord. The reticulospinal tract also carries axons that modulate autonomic activity in the spinal cord.
Regulation of arousal and level of consciousness is a generalized function of the reticular formation. The neurons of the reticular formation are excited by a variety of sensory stimuli that are conducted by way of collaterals from the somatosensory, auditory, visual, and visceral sensory systems. The reticular formation is, therefore, nonspecific in its response and performs a generalized regulatory function. When a novel stimulus is received, attention is focused on it while general alertness increases. This behavioral arousal is independent of the modality of stimulation and is accompanied by electroencephalographic changes from low-voltage to high-voltage activity over much of the cortex. The nonspecific thalamic regions project to the cortex, specifically to the distal dendritic fields of the large pyramidal cells. If the reticular formation is depressed by anesthesia or destroyed, sensory stimuli still produce activity in the specific thalamic and cortical sensory areas, but they do not produce generalized cortical arousal.
Many regions of the cerebral cortex produce generalized arousal when stimulated. Because different attributes of the external world (eg, color, shape, location, sound of various external stimuli) are represented in different parts of the cortex, it has been suggested that “binding” of neural activity in these different areas is involved in conscious actions and conscious recognition. Arousal, which is abolished by lesions in the mesencephalic reticular formation, does not require an intact corpus callosum, and many regions of the cortex can be injured without impairing consciousness. The cortex and the mesencephalic reticular activating system are mutually sustaining areas involved in maintaining consciousness. Lesions that destroy a large area of the cortex, a small area of the midbrain, or both produce coma (Fig 18–2).
FIGURE 18–2 Lesions that cause coma or loss of consciousness.
The loss of consciousness in syncope (fainting) is brief in duration and sudden in onset; more prolonged and profound loss of consciousness is described as coma. A patient in a coma is unresponsive and cannot be aroused. There may be no reaction, or only a primitive defense movement such as corneal reflex or limb withdrawal, to painful stimuli. Stupor and obtundation are still lesser grades of depressed consciousness and are characterized by variable degrees of impaired reactivity. Acute confusional states must be distinguished from coma or dementia (see Chapter 22). In the former case, the patient is disoriented and inattentive and may be sleepy but reacts appropriately to certain stimuli.
Coma may be of intracranial or extracranial origin. Intracranial causes include head injuries, cerebrovascular accidents, central nervous system infections, tumors, and increased intracranial pressure. Extracranial causes include vascular disorders (shock or hypotension caused by severe hemorrhage or myocardial infarction), metabolic disorders (diabetic acidosis, hypoglycemia, uremia, hepatic coma, addisonian crisis, electrolyte imbalance), intoxication (with alcohol, barbiturates, narcotics, bromides, analgesics, carbon monoxide, heavy metals), and miscellaneous disorders (hyperthermia, hypothermia, severe systemic infections). The Glasgow Coma Scale offers a practical bedside method of assessing the level of consciousness based on eye opening and verbal and motor responses (Table 18–1).
TABLE 18–1 Glasgow Coma Scale. A practical method of assessing changes in level of consciousness, based on eye opening and verbal and motor responses. The response can be expressed by the sum of the scores assigned to each response. The lowest score is 3, and the highest score is 15.
The daily cycle of arousal, which includes periods of sleep and of waking, is regulated by reticular formation structures in the hypothalamus and brain stem. The sleep process of this 24-hour circadian rhythm does not merely represent a passive “turning off” of neuronal activity; rather, it is an active physiologic function. Nerve cells in the reticular formation of the pons begin to discharge just before the onset of sleep. Lesions of the pons just forward of the trigeminal nerve produce a state of hyperalertness and much less sleep than normal.
The sleep cycle consists of several stages that follow one another in an orderly fashion, each taking about 90 minutes. There are two distinct types of sleep: slow-wave sleep and rapid eye movement (REM) sleep.
Slow-wave sleep is further divided into stages. Stage 1 of slow-wave (spindle) sleep is characterized by easy arousal. Stages 2 to 4 are progressively deeper, and the electroencephalographic pattern becomes more synchronized. In stage 4, the deepest stage of slow-wave sleep, blood pressure, pulse rate, respiratory rate, and the amount of oxygen consumed by the brain are very low. The control mechanisms for slow-wave sleep are not known.
REM sleep is characterized by the sudden appearance of an asynchronous pattern on electroencephalograms. The sleepers show a striking loss of muscle tone in the limbs, and have vivid visual imagery and complex dreams. There is a specific need for REM sleep, which is triggered by neurons in the dorsal midbrain and pontine tegmentum.
The midline raphe system of the pons may be responsible for bringing on sleep; it may act through the secretion of serotonin, which modifies many of the effects of the reticular activating system. Paradoxic REM sleep follows when a second secretion (norepinephrine), produced by the locus ceruleus, supplants the raphe secretion. The effects resemble normal wakefulness.
Destruction of the rostral reticular nucleus of the pons abolishes REM sleep, usually without affecting slow-wave sleep or arousal. REM sleep is suppressed by dopa or monoamine oxidase inhibitors, which increase the norepinephrine concentration in the brain. Lesions of the raphe nuclei in the pons cause prolonged wakefulness.
C. Clinical Correlations
1. Hypersomnia and apnea—Hypersomnia (excessive daytime sleepiness) and recurrent apnea during sleep may occur. Affected patients are apt to be obese middle-aged men who snore loudly. Functional obstruction of the oropharyngeal airway during sleep has been implicated as a cause, and symptoms in severe cases may be relieved by tracheostomy.
2. Narcolepsy—Narcolepsy is a chronic clinical syndrome characterized by intermittent episodes of uncontrollable sleep. Sudden transient loss of muscle tone in the extremities or trunk (cataplexy) and pathologic muscle weakness during emotional reactions may also occur. There may be sleep paralysis, the inability to move in the interval between sleep and arousal, and hypnogogic hallucinations may occur at the onset of sleep. Sleep attacks can occur several times daily under appropriate or inappropriate circumstances with or without forewarning. The attacks last from minutes to hours.
Cases are discussed further in Chapter 25.
Borbely AA, Tobler I, Groos G: Sleep homeostasis and the circadian sleep–wake rhythm. In: Sleep Disorders: Basic and Clinical Research. MTP Press, 1983.
Crick FC, Koch C: Some reflections on visual awareness. Cold Spring Harb Symp Quant Biol 1990;55:953.
Haider B, McCormick DA: Rapid neocortical dynamics: Cellular and network mechanisms. Neuron 2009;62:171–189.
Jasper HH, Descarries L, Castelluci VF, Rossignol S (editors): Consciousness: At the Frontiers of Neuroscience. Lippincott-Raven, 1998.
Koch C, Braun J: On the functional anatomy of visual awareness. Cold Spring Harb Symp Quant Biol 1996;61:49.
Kryger MH, Roth T, Dement WC: Principles and Practice of Sleep Medicine. WB Saunders, 1990.
Llinas RR, Steriade M: Bursting of thalamic neurons and states of vigilance. J Neurophysiol 2006;95:3297–3308.
Posner JB, Saper CB, Schiff ND, Plum F (editors): Plum and Posner’s Diagnosis of Stupor and Coma. 4th ed. Oxford University Press, New York, 2007.
Steriade M, McCarley RW: Brainstem Control of Wakefulness and Sleep. Plenum, 1990.
Steriade M, McCormick DA, Sejnowski TJ: Thalamocortical oscillations in the sleeping and aroused brain. Science 1993;262:679.
BOX 18–1 Essentials for the Clinical Neuroanatomist
After reading and digesting this chapter, you should know and understand:
• The reticular formation
• Role in arousal and consciousness
• Glasgow Coma Scale (Table 18–1)