Disorders of Consciousness
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| RETICULAR FORMATION: NUCLEI AND AREAS IN THE BRAINSTEM AND DIENCEPHALON |
Consciousness is a state of wakefulness and awareness of self and surroundings. In describing the state between normal consciousness and coma (unarousable unresponsiveness), many clinicians refer to a spectrum or gradation of states of diminished consciousness leading to coma. Lethargy has been used to describe a state of reduced wakefulness with deficits in attention; obtundation, a reduction in alertness and interaction with the environment; and stupor, state of unresponsiveness with little or no spontaneous movement, from which the patient can be aroused temporarily with vigorous stimulation. These descriptions are imprecise and have, in general, been applied to diffuse metabolic pathologies causing brain dysfunction. Other terminology may be more specific. For example, the vegetative state, which may follow coma, describes a state in which the individual is unaware but has sleep-wake cycles without detectable cerebral cortical dysfunction. The minimally conscious state describes severely altered consciousness in association with minimal awareness of self or environment. Akinetic mutism is a condition of extreme slowing or absence of bodily movement, with loss of speech. Wakefulness and awareness are preserved, but cognition is slowed because of bilateral lesions to the inferior frontal lobes, cerebral hemispheres, paramedian mesencephalic reticular formation (RF), or posterior diencephalon. The locked-in syndrome is a state of preserved consciousness and cognition with complete paralysis of the voluntary motor system because of complete destruction of corticospinal and corticobulbar pathways at or below the pons, or severe peripheral nervous system disease. Eye movements may be preserved, allowing for some communication, and cortical function is intact.
The anatomic
substrate for a disorder in consciousness is dysfunction in the reticular
formation and the ascending reticular activating system (ARAS)
because activation of the cerebral cortex during arousal and wake-fulness
depends on the influence of these structures. In the absence of the ARAS,
stimulation of any of the sensory pathways (e.g., somatosensory, auditory, and
visual) cannot arouse the cerebral cortex. Three groups of nuclei in the brainstem
(locus ceruleus, raphe, and ventral tegmental) contribute to the modulating
effect of the ARAS. An additional group of nuclei in the basal forebrain (basal
nucleus of Meynert) also contributes to the diffuse modulating system.
The main nuclei of the reticular formation are present in the medulla, pons, and midbrain. The locus ceruleus is located beneath the lateral part of the floor of the rostral pontine fourth ventricle. Its axons are distributed to the cerebral cortex, thalamus, hypothalamus, cerebellar cortex, brainstem, and spinal cord. These norepinephrine-containing neurons are involved in the regulation of attention, cortical arousal, and the sleep-wake cycle. The raphe nuclei are clustered in the midline of the medulla, pons, and midbrain and constitute the serotonergic projections involved in the sleep-wake cycle. The nuclei near the pontomedullary junction constitute the nucleus raphe magnus, which projects to the spinal cord for the modulation of slow pain. The nuclei in the rostral pons and midbrain project to the thalamus, the limbic system, and cerebral cortex. The ventral tegmental area is located posteromedial to the compact nigra, and its dopaminergic neurons project chiefly to the accumbens, amygdala, and prefrontal cortex. Last, cholinergic neurons in the pons and midbrain project to the thalamus and regulate the excitability of the thalamic nuclei. Taken together, the outputs from all of these nuclei funnel through the paramedian midbrain reticular formation and divide into posterior and lateral anterior roots in the diencephalon. The posterior root projects to relay nuclei and to intralaminar and other nuclei that have widespread cortical connections. The anterior root enters the lateral hypothalamic zone and is joined by projections from other neurons in the hypothalamus and basal forebrain. Lesions in the medulla or pons do not affect arousal and wakefulness. However, paramedian tegmental lesions in the rostral midbrain interrupt the ARAS and result in coma.
