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Electrocortical desynchronization during functional blockade of the mesencephalic reticular formation
254
SHORT COMMUNICATIONS
Electrocortical desynchronization during functional blockade of the mesencephalic reticular formation The relationship between electrocortical synchronization and a form of behavioral coma which resembles natural sleep was reported by Bremer 5,6. In his work, sleep (i.e., the coma) was interpreted to be the result of the loss of sensory influx into the central nervous system after the complete transection of the afferent pathways in the mesencephalon. Later, Lindsley et al.12,13 showed that electrocortical synchronization and behavioral coma were the result of the lesion of the mesencephalic reticular formation and not of sensory loss. This reticular theory was supported in the early 1950's by other electrophysiological and behavioral findings, among them evidence from French et al. 1° that stimulation of the mesencephalic reticular formation will arouse a sleeping animal, and, as Moruzzi and Magoun 17 point out, produce electrocortical desynchronization of a previously synchronized EEG. This theory is still accepted, although it is now well established 1,4,7-9,21,z3 that neural compensation and/or recovery of function can occur in chronic preparations with massive reticular formation damage. Villablanca 23 showed the recovery of electrocortical desynchronization in healthy chronic preparations with complete mesencephalic transections. Moruzzi 15,16 has postulated an electrocortical synchronizing influence from brain stem structures posterior to the mesencephalic reticular formation. This hypothesis is based on the work of his colleagues, Batini et aL 2,3, who showed that complete brain stem transection at the pretrigeminal midpontine level would produce an almost continually desynchronized EEG, but a transection only a few millimeters anterior would result in the classical synchronous activity. Moruzzi and Batini have both suggested that perhaps a caudal system in the pons or the medulla or both is interrupted, which releases tonic inhibition of the reticular activating system and causes continuous desynchronization. A second explanation proposed by Moruzzi 1~,16 is that an upper pontine structure located between the pretrigeminal and mesencephalic levels maintains a tonic activating influence crucial for desynchronization and wakefulness. Moruzzi points out that either or both of these hypothetical mechanisms may produce a change in tone of the mesencephalic reticular activating system which leads to E E G desynchronization, but as yet there is no conclusive evidence in either case. These pontine and medullary structures may, for example, influence directly the central synchronizing structures such as the nonspecific thalamocortical system investigated by Skinner and Lindsley 19. The present results show that bilateral cryogenic blockade in the mesencephalic reticular formation will produce electrocortical synchronization during moderate blockade (Fig. 1A, B), but will result in electrocortical desynchronization if the size of the functional blockade is increased by lowering the temperature of the cryoprobe tips (Fig. 1C). The main conclusion to be drawn from these results is that a type of EEG desynchronization is produced which is not dependent upon an increase in excitation o f the mesencephalic reticular formation, since the latter structure is already blocked. Brain Research, 22 (1970) 254-258
SHORT COMMUNICATIONS
255
B
A NON-BLOCKED (39°C)
RF COOLED
(Z°C, Smin)
AS I
I
I
vc= ~ C RF COOLED
(-5°C,7mi~
Fig. 1. Moderate and intense cryogenic blockade in the mesencephalic reticular formation. A, Recordings from the anterior sigmoid gyrus (AS) and lateral gyrus of the primary visual cortex (VCx) during a non-cooled condition. Cable movement artifacts (indicated by vertical bars), recorded when the animal rubbed its head against the chamber window, are included as evidence that the animal was awake and mobile. B, Recordings from the same animal 5 min after onset of bilateral cooling in the mesencephalic reticular formation (RF). Cryoprobe-tip temperature was 2°C, and the animal was comatose. C, Recordings at 7 rain of cooling, with probe-tip temperature stabilized at --5°C. During this case of EEG desynchronization, the animal was comatose as indicated by the lack of cable movement artifacts. Calibrations: 100/~V and 1 sec.
In 3 chronic cats, cryoprobes described by Skinner 18 and Skinner and Lindsley z° were implanted bilaterally in the mesencephalic reticular formation. Monopolar recording electrodes were placed on the surface of the frontal and posterior regions of the cortex, and the indifferent electrode was placed in the frontal sinus bone. Histological verification confirmed that the 6-mm cooling portion of each cryoprobe was implanted in the mesencephalic reticular formation just posterior to the level of the red nucleus (Horsley-Clarke stereotaxic coordinates: anterior, 2.0; lateral, 2.5; depth, 0.0 to --6.0). Fig. 1B shows that after 5 min of cooling, the temperature of each probe tip was at + 2 ° C , and electrocortical spindle bursts were present. The spindles present in the frontal regions of the cortex (upper trace) were larger in amplitude than those in the more posterior regions (lower trace), showing a cortical distribution similar to that for recruiting responsesl4, 22 and barbiturate spindles 14. After 7 min of cooling, the probe-tip temperature stabilized at --5°C, and the previously synchronized electrocortical activity was completely abolished in the frontal region, although a lower frequency type of synchronization persisted in the visual cortex (Fig. 1C). Only the frontally projecting 8-12 c/sec spindle bursts were affected during this period Brain Research, 22 (1970) 254-258
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SHORT COMMUNICATIONS
of enlarged blockade in the mesencephalon, and the desynchronization persisted continuously. When the probe-tip temperatures were stabilized at +2°C by circulating the cryoprobe coolant at a lower flow rate, the spindle burst pattern of EEG synchronization remained continuously. Throughout both the +2°C and --5°C cooling, the animals remained comatose, but they regained normal awake activities quickly and spontaneously after the cessation of cooling. Even in a quiet and darkened chamber, the animals arose spontaneously and appeared normally active after the cooled tissue rewarmed and the functional blockade was reversed. Movement artifacts are shown in the normal awake records to emphasize the absence of motor activity during the cryogenically induced desynchronization records in which no movement artifacts are evident. Cooling to 0°C has been reported by Skinner and Lindsley2° to produce an anatomically limited functional blockade whose boundary extends approximately 3 mm from the surface of the implanted cryoprobe. Based on this finding and on the dimensions of the cryoprobe tip, the bilateral cooling to --5°C in the mesencephalic reticular formation would produce a functional blockade 3-4 mm anterior and posterior, 9-10 mm in depth, and 3-4 mm medial and lateral to the position of each cryoprobe. In this region of the brain stem a complete transectional blockade would result, except for intact ascending and descending pathways in the subcollicular tegmental region. The anterior boundary of the blockade would extend into the prerubric region at the anterior border of the red nucleus, and the posterior boundary would extend to the anterior portion of the superior olivary nucleus and the posterior border of the inferior colliculus. Jasper 11 has suggested that very mild cooling has an excitatory effect on neural tissue. If this were the case, one would not expect to be able to produce any electrocortical synchronization by cooling in the mesencephalon because the milder part of the cooling gradient would always stimulate tissue at the more central distal boundary and produce desynchronization. Since mild cooling in the mesencephalon does produce electrocortical synchronization, it does not seem possible that cryogenic blockade could have any excitatory effect. There are at least two possible alternative interpretations that account for the desynchronized electrocortical activity produced by the more intense cryogenic blockade in the mesencephalic reticular formation. First, the posterior part of the functional blockade disrupted the lower pontine and medullary inhibitory mechanisms, suggested by Batini et al.2, 3 and Moruzzi 15,16. Disruption of a tonic inhibitory influence would lead to excitation by means of disinhibition. Disruption of an upper pontine excitatory system would lead to greater synchronization, which is not the case, so the second hypothesis of Moruzzi's15,16 is ruled out as an explanation of the present results. A second interpretation is that the anterior extent of the cooling blocked a synchronizing mechanism in the prerubric region that is similar in its action to the one in the caudal brain stem region postulated by Batini and Moruzzi. If the first interpretation is correct, then the present results show: (1) this synchronizing mechanism in the brain stem extends anteriorly to the midpontine Brain Research, 22 (1970) 254-258
SHORT COMMUNICATIONS
257
pretrigeminal region (Horsley-Clarke coordinate, posterior 1.0); (2) its ascending pathways must travel via the subcollicular region; and (3) most importantly, its desynchronizing effect does not result from a release of inhibition of the mesencephalic reticular formation, because this latter structure is already functionally blocked. I f the second interpretation is correct, then the mesencephalic reticular formation is bounded anteriorly as well as posteriorly by a synchronizing structure which, when blocked, produces E E G desynchronization by means of the reduction of a tonic synchronizing influence. In neither of the above interpretations could the synchronizing influence occur by disinhibition of the mesencephalic reticular formation, since the latter structure is functionally blocked in either case. It thus appears that there is a mechanism underlying electrocortical desynchronization which is independent of the ascending reticular activating system. Furthermore, the animal remains comatose during this type of E E G desynchronization, just as it does in paradoxical or desynchronized sleep. This comatose behavior is in contrast to the arousal behavior elicited by activation of the mesencephalic reticular formation, and again suggests an independent mechanism. This work was supported by Grant No. HE 05435 from the Heart Institute, National Institutes of Health, U. S. Public Health Service, and Grant No. GRS P69-23. The author acknowledges the assistance of T. J. Skinner and W. King. The results were demonstrated in live animals at the 7th International Congress of Electroencephalography and Clinical Neurophysiology, San Diego, September, 1969. Department of Physiology, Section of Neurophysiology, Baylor College of Medicine and The Methodist Hospital, Houston, Texas 77025 (U.S.A.)
JAMES E. SKINNER
I ADAMETZ,J. H., Rate of recoveryof functioning in cats with rostral reticular lesions, J. Neurosurg., 16 (1959) 85-98. 2 BATINI,C., MAGNI, E., PALESTINI,M., ROSSI, G. E., AND ZANCHETTI,A., Neural mechanisms underlying the enduring EEG and behavioral activation in the midpontine pretrigeminal cat, Arch. ital. BioL, 97 (1959) 13-25. 3 BATINI,C., MORUZZI,G., PALESTINI,M., Rossi, G. F., AND ZANCHETTI,m., Persistent patterns of wakefulness in the pretrigeminal midpontine preparation, Science, 127 (1958) 30-32. 4 BATSEL,H. L., Electroencephalographic synchronization and desynchronization in the chronic 'cerveau isol6' of the dog, Electroenceph. clin. Neurophysiol., 12 (1960) 421-430. 5 BREMER,F., Cerveau isol6 et physiologic du sommeil, C. R. Soc. BioL (Paris), 118 (1935) 12351241. 6 BREMER,F., L'activit6 c6r6brale au cours du sommeil et de la narcose. Contribution ~t l'6tude du m6canisme du sommeil, Bull. Acad. roy. Mdd. Belg., 4 (1937) 68-86. 7 CHow, K. L., DEMENT,W. C., AND MITCHELL,S. A., JR., Effects of lesions of the rostral thalamus on brain waves and behavior in cats, Electroenceph. clin. Neurophysiol., 11 (1959) 107-120. 8 CHOW,K. L., AND RANDELL,W., Learning and EEG studies of cats with lesions in the reticular formation, Paper read at the first annual meeting of the Psychonomics Society, Chicago, 1960. 9 Dory, R. W., BECK,E. C., AND KOOI, R. A., Effect of brain stem lesions on conditioned responses in cats, Exp. Neurol., 1 (1959) 360-385. Brain Research, 22 (1970) 254-258
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SHORT COMMUNICATIONS
10 FRENCH, J. D., VON AMERONGEN,F. K., AND MAGOUN, H. W., An activating system in brain stem of monkeys, Arch. Neurol. Psychiat. (Chic.), 68 (1952) 591-604. 11 JASPER, H. H., Personal communication. 12 LINDSLEY,D. B., BOWDEN, J. W., AND MAGOUN, H. W., Effect upon the EEG of acute injury to the brain stem activating system, Electroenceph. clin. Neurophysiol., 1 (1949) 475-486. 13 LINDSLEY,D. B., SCHREINER,L. H., KNOWLES,W. B., AND MAGOUN,H. W., Behavioral and EEG changes following chronic brain stem lesions in the cat, Electroenceph. clin. NeurophysioL, 2 (1950) 483-498. 14 MORISON, R. S., AND DEMPSEY, E. W., A study of thalamo-cortical relations, Amer. J. Physiol., 135 (1942) 281-292. 15 MORUZZr, G., Synchronizing influences of the brain stem and the inhibitory mechanisms underlying the production of sleep by sensory stimulation, Electroenceph. clin. Neurophysiol., Suppl. 13 (1960) 231-256. 16 MOROZZI, G., Reticular influences on the EEG, Electroenceph. clin. NeurophysioL, 16 (1964) 2-17. 17 MoRtrZZI, G., ANO MAGOUN, H. W., Brain stem reticular formation and activation of the EEG, Electroenceph. clin. Neurophysiol., 1 (1949)455-473. 18 SKINNER, J. E., A cryoprobe and cryoplate for reversible functional blockade in the brains of chronic animal preparations, Electroenceph. clin. Neurophysiol., 29 (1970) 204-205. 19 SKINNER, J. E., AND LINDSLEY, D. B., Electrophysiological and behavioral effects of blockade of the nonspecific thalamocortical system, Brain Research, 6 (1967) 95-118. 20 SKINNER, J. E., AND LINDSLEY, D. B., Reversible cryogenic blockade of neural function in the brain of unrestrained animals, Science, 161 (1968) 595-597. 21 SPRAGUE,J. M., CHAMBERS,W. W., AND STELLAR,E., Attentive, affective and adaptive behavior in the cat, Science, 133 (1961) 165-173. 22 STARZL, T. E., AND MAGOUN, H. W., Organization of the diffuse thalamic projection system, J. NeurophysioL, 14 (1951) 133-146. 23 VILLABLANCA,J., The electrocorticogram in the chronic cerveau isol6 cat, Electroenceph. clin. NeurophysioL, 19 (1965) 576-586. (Accepted June 3rd, 1970)
Brain Research, 22 (1970) 254-258
SHORT COMMUNICATIONS
Electrocortical desynchronization during functional blockade of the mesencephalic reticular formation The relationship between electrocortical synchronization and a form of behavioral coma which resembles natural sleep was reported by Bremer 5,6. In his work, sleep (i.e., the coma) was interpreted to be the result of the loss of sensory influx into the central nervous system after the complete transection of the afferent pathways in the mesencephalon. Later, Lindsley et al.12,13 showed that electrocortical synchronization and behavioral coma were the result of the lesion of the mesencephalic reticular formation and not of sensory loss. This reticular theory was supported in the early 1950's by other electrophysiological and behavioral findings, among them evidence from French et al. 1° that stimulation of the mesencephalic reticular formation will arouse a sleeping animal, and, as Moruzzi and Magoun 17 point out, produce electrocortical desynchronization of a previously synchronized EEG. This theory is still accepted, although it is now well established 1,4,7-9,21,z3 that neural compensation and/or recovery of function can occur in chronic preparations with massive reticular formation damage. Villablanca 23 showed the recovery of electrocortical desynchronization in healthy chronic preparations with complete mesencephalic transections. Moruzzi 15,16 has postulated an electrocortical synchronizing influence from brain stem structures posterior to the mesencephalic reticular formation. This hypothesis is based on the work of his colleagues, Batini et aL 2,3, who showed that complete brain stem transection at the pretrigeminal midpontine level would produce an almost continually desynchronized EEG, but a transection only a few millimeters anterior would result in the classical synchronous activity. Moruzzi and Batini have both suggested that perhaps a caudal system in the pons or the medulla or both is interrupted, which releases tonic inhibition of the reticular activating system and causes continuous desynchronization. A second explanation proposed by Moruzzi 1~,16 is that an upper pontine structure located between the pretrigeminal and mesencephalic levels maintains a tonic activating influence crucial for desynchronization and wakefulness. Moruzzi points out that either or both of these hypothetical mechanisms may produce a change in tone of the mesencephalic reticular activating system which leads to E E G desynchronization, but as yet there is no conclusive evidence in either case. These pontine and medullary structures may, for example, influence directly the central synchronizing structures such as the nonspecific thalamocortical system investigated by Skinner and Lindsley 19. The present results show that bilateral cryogenic blockade in the mesencephalic reticular formation will produce electrocortical synchronization during moderate blockade (Fig. 1A, B), but will result in electrocortical desynchronization if the size of the functional blockade is increased by lowering the temperature of the cryoprobe tips (Fig. 1C). The main conclusion to be drawn from these results is that a type of EEG desynchronization is produced which is not dependent upon an increase in excitation o f the mesencephalic reticular formation, since the latter structure is already blocked. Brain Research, 22 (1970) 254-258
SHORT COMMUNICATIONS
255
B
A NON-BLOCKED (39°C)
RF COOLED
(Z°C, Smin)
AS I
I
I
vc= ~ C RF COOLED
(-5°C,7mi~
Fig. 1. Moderate and intense cryogenic blockade in the mesencephalic reticular formation. A, Recordings from the anterior sigmoid gyrus (AS) and lateral gyrus of the primary visual cortex (VCx) during a non-cooled condition. Cable movement artifacts (indicated by vertical bars), recorded when the animal rubbed its head against the chamber window, are included as evidence that the animal was awake and mobile. B, Recordings from the same animal 5 min after onset of bilateral cooling in the mesencephalic reticular formation (RF). Cryoprobe-tip temperature was 2°C, and the animal was comatose. C, Recordings at 7 rain of cooling, with probe-tip temperature stabilized at --5°C. During this case of EEG desynchronization, the animal was comatose as indicated by the lack of cable movement artifacts. Calibrations: 100/~V and 1 sec.
In 3 chronic cats, cryoprobes described by Skinner 18 and Skinner and Lindsley z° were implanted bilaterally in the mesencephalic reticular formation. Monopolar recording electrodes were placed on the surface of the frontal and posterior regions of the cortex, and the indifferent electrode was placed in the frontal sinus bone. Histological verification confirmed that the 6-mm cooling portion of each cryoprobe was implanted in the mesencephalic reticular formation just posterior to the level of the red nucleus (Horsley-Clarke stereotaxic coordinates: anterior, 2.0; lateral, 2.5; depth, 0.0 to --6.0). Fig. 1B shows that after 5 min of cooling, the temperature of each probe tip was at + 2 ° C , and electrocortical spindle bursts were present. The spindles present in the frontal regions of the cortex (upper trace) were larger in amplitude than those in the more posterior regions (lower trace), showing a cortical distribution similar to that for recruiting responsesl4, 22 and barbiturate spindles 14. After 7 min of cooling, the probe-tip temperature stabilized at --5°C, and the previously synchronized electrocortical activity was completely abolished in the frontal region, although a lower frequency type of synchronization persisted in the visual cortex (Fig. 1C). Only the frontally projecting 8-12 c/sec spindle bursts were affected during this period Brain Research, 22 (1970) 254-258
256
SHORT COMMUNICATIONS
of enlarged blockade in the mesencephalon, and the desynchronization persisted continuously. When the probe-tip temperatures were stabilized at +2°C by circulating the cryoprobe coolant at a lower flow rate, the spindle burst pattern of EEG synchronization remained continuously. Throughout both the +2°C and --5°C cooling, the animals remained comatose, but they regained normal awake activities quickly and spontaneously after the cessation of cooling. Even in a quiet and darkened chamber, the animals arose spontaneously and appeared normally active after the cooled tissue rewarmed and the functional blockade was reversed. Movement artifacts are shown in the normal awake records to emphasize the absence of motor activity during the cryogenically induced desynchronization records in which no movement artifacts are evident. Cooling to 0°C has been reported by Skinner and Lindsley2° to produce an anatomically limited functional blockade whose boundary extends approximately 3 mm from the surface of the implanted cryoprobe. Based on this finding and on the dimensions of the cryoprobe tip, the bilateral cooling to --5°C in the mesencephalic reticular formation would produce a functional blockade 3-4 mm anterior and posterior, 9-10 mm in depth, and 3-4 mm medial and lateral to the position of each cryoprobe. In this region of the brain stem a complete transectional blockade would result, except for intact ascending and descending pathways in the subcollicular tegmental region. The anterior boundary of the blockade would extend into the prerubric region at the anterior border of the red nucleus, and the posterior boundary would extend to the anterior portion of the superior olivary nucleus and the posterior border of the inferior colliculus. Jasper 11 has suggested that very mild cooling has an excitatory effect on neural tissue. If this were the case, one would not expect to be able to produce any electrocortical synchronization by cooling in the mesencephalon because the milder part of the cooling gradient would always stimulate tissue at the more central distal boundary and produce desynchronization. Since mild cooling in the mesencephalon does produce electrocortical synchronization, it does not seem possible that cryogenic blockade could have any excitatory effect. There are at least two possible alternative interpretations that account for the desynchronized electrocortical activity produced by the more intense cryogenic blockade in the mesencephalic reticular formation. First, the posterior part of the functional blockade disrupted the lower pontine and medullary inhibitory mechanisms, suggested by Batini et al.2, 3 and Moruzzi 15,16. Disruption of a tonic inhibitory influence would lead to excitation by means of disinhibition. Disruption of an upper pontine excitatory system would lead to greater synchronization, which is not the case, so the second hypothesis of Moruzzi's15,16 is ruled out as an explanation of the present results. A second interpretation is that the anterior extent of the cooling blocked a synchronizing mechanism in the prerubric region that is similar in its action to the one in the caudal brain stem region postulated by Batini and Moruzzi. If the first interpretation is correct, then the present results show: (1) this synchronizing mechanism in the brain stem extends anteriorly to the midpontine Brain Research, 22 (1970) 254-258
SHORT COMMUNICATIONS
257
pretrigeminal region (Horsley-Clarke coordinate, posterior 1.0); (2) its ascending pathways must travel via the subcollicular region; and (3) most importantly, its desynchronizing effect does not result from a release of inhibition of the mesencephalic reticular formation, because this latter structure is already functionally blocked. I f the second interpretation is correct, then the mesencephalic reticular formation is bounded anteriorly as well as posteriorly by a synchronizing structure which, when blocked, produces E E G desynchronization by means of the reduction of a tonic synchronizing influence. In neither of the above interpretations could the synchronizing influence occur by disinhibition of the mesencephalic reticular formation, since the latter structure is functionally blocked in either case. It thus appears that there is a mechanism underlying electrocortical desynchronization which is independent of the ascending reticular activating system. Furthermore, the animal remains comatose during this type of E E G desynchronization, just as it does in paradoxical or desynchronized sleep. This comatose behavior is in contrast to the arousal behavior elicited by activation of the mesencephalic reticular formation, and again suggests an independent mechanism. This work was supported by Grant No. HE 05435 from the Heart Institute, National Institutes of Health, U. S. Public Health Service, and Grant No. GRS P69-23. The author acknowledges the assistance of T. J. Skinner and W. King. The results were demonstrated in live animals at the 7th International Congress of Electroencephalography and Clinical Neurophysiology, San Diego, September, 1969. Department of Physiology, Section of Neurophysiology, Baylor College of Medicine and The Methodist Hospital, Houston, Texas 77025 (U.S.A.)
JAMES E. SKINNER
I ADAMETZ,J. H., Rate of recoveryof functioning in cats with rostral reticular lesions, J. Neurosurg., 16 (1959) 85-98. 2 BATINI,C., MAGNI, E., PALESTINI,M., ROSSI, G. E., AND ZANCHETTI,A., Neural mechanisms underlying the enduring EEG and behavioral activation in the midpontine pretrigeminal cat, Arch. ital. BioL, 97 (1959) 13-25. 3 BATINI,C., MORUZZI,G., PALESTINI,M., Rossi, G. F., AND ZANCHETTI,m., Persistent patterns of wakefulness in the pretrigeminal midpontine preparation, Science, 127 (1958) 30-32. 4 BATSEL,H. L., Electroencephalographic synchronization and desynchronization in the chronic 'cerveau isol6' of the dog, Electroenceph. clin. Neurophysiol., 12 (1960) 421-430. 5 BREMER,F., Cerveau isol6 et physiologic du sommeil, C. R. Soc. BioL (Paris), 118 (1935) 12351241. 6 BREMER,F., L'activit6 c6r6brale au cours du sommeil et de la narcose. Contribution ~t l'6tude du m6canisme du sommeil, Bull. Acad. roy. Mdd. Belg., 4 (1937) 68-86. 7 CHow, K. L., DEMENT,W. C., AND MITCHELL,S. A., JR., Effects of lesions of the rostral thalamus on brain waves and behavior in cats, Electroenceph. clin. Neurophysiol., 11 (1959) 107-120. 8 CHOW,K. L., AND RANDELL,W., Learning and EEG studies of cats with lesions in the reticular formation, Paper read at the first annual meeting of the Psychonomics Society, Chicago, 1960. 9 Dory, R. W., BECK,E. C., AND KOOI, R. A., Effect of brain stem lesions on conditioned responses in cats, Exp. Neurol., 1 (1959) 360-385. Brain Research, 22 (1970) 254-258
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SHORT COMMUNICATIONS
10 FRENCH, J. D., VON AMERONGEN,F. K., AND MAGOUN, H. W., An activating system in brain stem of monkeys, Arch. Neurol. Psychiat. (Chic.), 68 (1952) 591-604. 11 JASPER, H. H., Personal communication. 12 LINDSLEY,D. B., BOWDEN, J. W., AND MAGOUN, H. W., Effect upon the EEG of acute injury to the brain stem activating system, Electroenceph. clin. Neurophysiol., 1 (1949) 475-486. 13 LINDSLEY,D. B., SCHREINER,L. H., KNOWLES,W. B., AND MAGOUN,H. W., Behavioral and EEG changes following chronic brain stem lesions in the cat, Electroenceph. clin. NeurophysioL, 2 (1950) 483-498. 14 MORISON, R. S., AND DEMPSEY, E. W., A study of thalamo-cortical relations, Amer. J. Physiol., 135 (1942) 281-292. 15 MORUZZr, G., Synchronizing influences of the brain stem and the inhibitory mechanisms underlying the production of sleep by sensory stimulation, Electroenceph. clin. Neurophysiol., Suppl. 13 (1960) 231-256. 16 MOROZZI, G., Reticular influences on the EEG, Electroenceph. clin. NeurophysioL, 16 (1964) 2-17. 17 MoRtrZZI, G., ANO MAGOUN, H. W., Brain stem reticular formation and activation of the EEG, Electroenceph. clin. Neurophysiol., 1 (1949)455-473. 18 SKINNER, J. E., A cryoprobe and cryoplate for reversible functional blockade in the brains of chronic animal preparations, Electroenceph. clin. Neurophysiol., 29 (1970) 204-205. 19 SKINNER, J. E., AND LINDSLEY, D. B., Electrophysiological and behavioral effects of blockade of the nonspecific thalamocortical system, Brain Research, 6 (1967) 95-118. 20 SKINNER, J. E., AND LINDSLEY, D. B., Reversible cryogenic blockade of neural function in the brain of unrestrained animals, Science, 161 (1968) 595-597. 21 SPRAGUE,J. M., CHAMBERS,W. W., AND STELLAR,E., Attentive, affective and adaptive behavior in the cat, Science, 133 (1961) 165-173. 22 STARZL, T. E., AND MAGOUN, H. W., Organization of the diffuse thalamic projection system, J. NeurophysioL, 14 (1951) 133-146. 23 VILLABLANCA,J., The electrocorticogram in the chronic cerveau isol6 cat, Electroenceph. clin. NeurophysioL, 19 (1965) 576-586. (Accepted June 3rd, 1970)
Brain Research, 22 (1970) 254-258