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HANDBOOK OF PHYSIOLOCi' 



NEUROPHYSIOLOGY 11 



tion of active cortical loci (39, 79, 245), fastigial 

 nuclei (198) and caudate nucleus (247). 



Behavior arousal can be assessed in acute experi- 

 ments when the animal is capable of moving or in 

 chronic preparations in which electrodes have been 

 implanted in appropriate structures. Employing the 

 latter procedure, Segundo li al. {244) were able to 

 induce immediate arousal in sleeping animals upon 

 applying short low-voltage bursts to active cortical 

 loci and to the reticular system. Awakening occurred 

 without any suggestion that it was secondary to pain 

 or movement. Concurrent EEG recording showed 

 appropriate transition from the synchrony of sleep to 

 the desynchrony of wakefulness. By contrast, stimula- 

 tion of other regions failed to evoke wakefulness even 

 though much stronger excitation was employed. 



The sleep-inducing responses reported by Hess 

 (115) presuinably are elicited by driving the thalamic 

 portion of the reticular system at a rate comparable 

 to slow the EEG frequencies observed during sleep. 

 That such is the case is suggested by the findings of 

 Akimoto et al. (6) who were able to induce sleep in 

 dogs by stimulating the diflfuse thalamic projection 

 system with 5 cps pulses, while 30 to 90 cps bursts to 

 the same region awakened the animals. This evidence, 

 together with that demonstrating that thalamically- 

 induced recruiting is obliterated during EEG arousal 

 (198), supports the suggestion that rhythms subserving 

 both wakefulness and sleep are mediated by common 

 neural pathways. 



There is no doubt that the entire central brain stem 

 from the medulla to the diencephalon participates in 

 the arousal reaction since the response can be elicited 

 from the reticular formation (85, 244), thalamus (85, 

 244) and septal region (105). In addition, transient 

 arousal is possible even in animals decerebrated at the 

 intercoUicular level upon the application of olfactory 

 stimulation (13, 34, 37). The activating function of 

 the more cephalic portions of the system, however, 

 appears to require the energizing influence of its 

 caudal .segment (37) since medullary transection does 

 not induce coma (158, 159) while mesencephalic de- 

 cerebration does (33, 158, 159). Moreover, increasing 

 the size of chronic lesions in the RAS induces pro- 

 gressively deepening stupor (81, 159), and compara- 

 ble interference with these mechanisms in man elicits 

 prolonged or permanent coma (48, 78, 128). By con- 

 trast, experimental lesions in the lateral sensory tracts 

 do not induce apparent alternation in the wakeful 

 state (158). 



The RAS is capable, probably, of some spontane- 

 ous or autochthonous discharge (37, 59, 196) al- 



though, certainly, the bulk of its tonic potency is de- 

 rived from its several inputs. However, some receptor 

 systems exert a more powerful excitatory influence 

 upon the RAS than do others. Stimulation of the 

 visual nerves has been found to be least effective (13) 

 and somatic sensory excitation most potent in this 

 regard (85). In the encep/iale isole where sensation is 

 retained only from the head, relatively normal wake- 

 fulness is exhibited (33). In such preparations de- 

 struction of olfactory, visual, acoustic, vestibular or 

 vagal afferent inputs does not interfere with arousal 

 while bilateral destruction of the gasserian ganglia 

 abolishes wakefulness (227, 231). Moreover, in trun- 

 cation experiments, the capacity to arouse is retained 

 until the transection is made rostral to the trigeminal 

 nucleus at which time the sleep-state of the cerveau 

 isole is induced. Clearly, therefore, somatic sensibility 

 from the head is a more powerful contributor to tonic 

 reticular excitation than are all other inpiU systems. 



PROLONGED WAKEFULNESS. While the brain-stem re- 

 ticular system is a critical structure in the mechanism 

 of arousal, it has no intrinsic capacity to induce or 

 sustain wakefulness when separated from higher struc- 

 tures (78). The activity generated within the reticular 

 system must be exerted upon thalamodiencephalic 

 centers, and through them upon the cortex, in order 

 for the alert state to be displayed. Destruction of any 

 portion of this system, the RAS, its thalamic transport 

 or its cortical terminus, render wakefulness impossible 

 or seriously distorted (78). 



Reference is made repeatedly in this review to 

 active cortical loci which, when stimulated, elicit 

 arousal (38, 39, 79). It has been proposed that such 

 loci contribute to this process of arousal by function- 

 ing in the maintenance of prolongation of sensory- 

 induced awakening (78). It is true that decorticate 

 animals and man exhibit transient brief periods of 

 apparent wakefulness but during such temporary 

 arousal, alertness or appropriate reaction to en- 

 vironment is impossible. It appears, therefore, that 

 crude arousal is possible without cortical contribu- 

 tion but, certainly, the intact cortex is essential for 

 prolonged sustained alert wakefulness characteristic 

 of the normal adult subject. 



Xeurohiimoral Riticular Mechanisms 



The influences of metabolic substances, humoral 

 agents, drugs and circulating homones upon arousal 

 mechanisms mediated by the reticular system have 

 attracted much attention recently (24, 26, 28, 30, 



