Our current understanding of the anatomy and physiology of alertness comes largely from the elegant experiments of Bremer and of Moruzzi and Magoun in the 1930s and 1940s. Observing cats in which the brainstem had sectioned between the pons and midbrain and at the level of the lower medulla, Bremer found that the rostral section caused a sleep-like state and “synchronized” EEG rhythms that were characteristic of sleep; animals with the lower section remained awake with appropriate “desynchronized” EEG rhythms. He interpreted this to mean, in large part correctly, that a constant stream of sensory stimuli, provided by trigeminal and spinal sources, funneled through the upper brainstem was required to maintain the awake state. Subsequently, a system of “nonspecific” projections from the thalamus to all cortical regions, independent of any specific sensory nucleus, has been demonstrated. A critical refinement of this concept resulted from the observation by Moruzzi and Magoun that electrical stimulation of the medial midbrain tegmentum and adjacent areas just above this level caused a lightly anesthetized animal to become suddenly alert and its EEG to change correspondingly, that is, to become “desynchronized,” in a manner identical to normal arousal by sensory stimuli. The sites at which stimulation led to arousal consisted of a series of points extending from the nonspecific medial thalamic nuclei down through the caudal midbrain. These loci were situated along a loosely organized core of neurons that anatomists refer to as the reticular system, or reticular formation.
The anatomic studies of the Scheibels have described widespread innervation of the reticular formation by multiple bifurcating and collateral axons of the ascending sensory systems, implying that this area is maintained in a tonically active state by ascending sensory stimulation. Because this region, especially the medial thalamus, projects widely to the cerebral hemispheres, the concept arose of a reticular activating system (RAS, or ARAS, ascending reticular activating system) that maintains the alert state and the inactivation or destruction of which led to an unarousable state. In this way, despite a number of experimental inconsistencies (see Steriade), the paramedian upper brainstem tegmentum and lower diencephalon have come to be conceived as the locus of the arousal system of the brain. The anatomic boundaries of the RAS are somewhat indistinct. The neurons of this system are interspersed throughout the paramedian regions of the upper (rostral) pontine and midbrain tegmentum; at the thalamic level, the RAS includes the functionally related posterior paramedian, parafascicular, and medial portions of the centromedian and adjacent intralaminar nuclei.
What is more salient for clinical work is that the nuclei of the reticular formation receive collaterals from the spinothalamic and trigeminal–thalamic pathways and project not just to the sensory cortex of the parietal lobe, as do the thalamic relay nuclei for somatic sensation, but to the whole of the cerebral cortex. Thus, it would seem that sensory stimulation has a double effect—it conveys information to the brain from somatic structures and the environment and also activates those parts of the nervous system on which the maintenance of consciousness depends. The cerebral cortex not only receives impulses from the RAS but reciprocally modulates this incoming information via corticofugal projections to the reticular formation. Although the physiology of the RAS is far more complicated than this simple formulation would suggest, it nevertheless, as a working idea, retains a great deal of clinical credibility, and makes comprehensible some of the neuropathologic observations noted further on, as well as the effects of deep brain stimulation to improve function in minimally conscious patients (see further on).