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Cortical midline late response during sleep in the cat
SHORT COMMUNICATIONS
311
Usually inspiratory and expiratory discharges in the pons were changed in the same manner as in the medulla by vagal stimt:lation, but in some cases the discharges lost their rhythmic activity and changed to a continuous pattern. In general the effect of stimulation on the discharges in the pons lasted longer than in the medulla. These results indicate that the alteration of inspiratory and expiratory unit discharges by stimulation of the vagal nerve is not always reciprocal in the medulla and the nature of the respiratory unit discharge in the pons is different from that in the medulla. Department of Pharmacology, Faculty of Medicine, University of Tokyo, Tokyo (Japan)
TAKEHIKO HUKUHARA NORIYUKI KUMADAKI HIROSHI KOJIMA HAJIME TAMAKI YOSHIAKI SAJI FUMINORI SAKAI
1 DmgEN, M. N. J., AND WOLDRING, S., Unit activity in buibar respiratory centre, J. NeurophysioL. 14 (1951) 211-225. 2 HUKUHARA,T., OKADA, H., AND NAKAYAMA,S., On the vagus-respiratory reflex, Jap. J. PhysioL, 6 (1956) 87-97. 3 NAKAVAMA,T., ASD Hog], T., Response of medullary respiratory neurones to stimulation of the vagus, Jap. J. Physiol., 14 (1964) 147-154. 4 WYss~ O. A. M., Reizphysiologische Analyse des afferenten Lungenvagus, Pfliigers Arch. ges. Physiol., 242 (1939) 215-233. 5 Wvss, O. A. M., Die nerv~se Steuerung der Atmung, Ergebn. Physiol., 54 (1964) 1-479.
Brain Research, 1 (1966) 310-31 !
Cortical midline late response during sleep in the cat During sleep in man, an evoked response to peripheral stimulation can be recorded with maximum amplitude focus in the vertex region. First repotted for auditory stimuli in 1938L the response was further described for auditory and somatic stimuli by Davis e t al. a and called the" K-complex. The waveform is initially vertex negative followed by a vertex positivity having a peak latency of about 750 msec. Abnormalities in the configuration of the K-complex have been useful in the diagnosis of cerebral pathology and in audiometric tests, but little is known about the cerebral structures and afferent pathways involved in this response. Recently, we have recorded from man very late somatosensory evoked responses during slow-wave sleep (stages 3 and 4) which we believe to be the summated form of the K-complex4. This stimulated an effort to find in cat long latency cerebral evoked responses to peripheral stimulation which might correspond to the summated Kcomplex. We have observed two kinds of late responses whose appearance is associated with EEG synchronization characteristic of 'slow-wave' sleep (SS). The first of these is modality specific and appears as a prolongation and enhancement of evoked activity recorded from the appropriate sensory projection area during waking (W), and rapid eye movement sleep (RS). The second type of response is modality Brain Research, 1 (1966) 311-314
312
SHORT COMMUNICATIONS
non-specific, appears only during SS, and has its maximum amplitude focus at midline lateral gyrus about half way between the bregma and the sagittal crest. This latter response, which we call the midline late response (MLR), appears to be the feline homolog of the K-complex. We have studied the MLR in both chronic and acute cat preparations. In chronic animals, cortical electrodes were screws in the skull penetrating to the dura; electrodes were also placed for recording EEG, neck muscle activity, and eye movements. Acute preparations were tracheotomized and venous cannulated under ether or halothane (Fluothane) anesthesia and maintained on gallamine triethiodide (Flaxedil), artificial respiration and local anesthesia. In these preparations electrodes were small solder balls resting on the dural or pial surface. In all animals evoked responses were recorded monopolarly against a screw electrode over frontal sinus. Somatic stimuli were 0.1 msec square wave shocks of low iatensity delivered to chronic animals via an electrode lo implanted around the ulnar nerve at the wrist and to acute animals via subcutaneous needles. Auditory stimuli were clicks from a speaker. Subcortical stimuli were delivered via bipolar electrodes implanted stereotaxically. For all stimuli the rate was 1 per 5 sec. Sleep stages in chronic animals were determined from EEG, EMG, and eye movement polygraph recordings and from observation of the animal through a one-way vision window in a sound attenuating, shielded recording chaniber. Evoked responses were averaged on a four-channel analog system11. Fig. 1 shows the cortical distribution of the MLR for somatosensory and auditory stimuli. The MLR appears when the chronic animal goes into SS and when the EEG becomes synchronized in the acute. It consists of a negativity at 60-80 msec and a positivity at 110-150 msec. It can be seen that the response is largest at middle midline and that the amplitude decreases more rapidly anteriorly than posteriorly. Anteriorly the MLR is narrowly restricted to the lateral gyrus; posteriorly the distribution widens to include posterior suprasylvian gyrus. Fig. 1 shows also that the MLR may be differentiated easily from late responses seen only in specific sensory cortex. These latter responses consist of a negativity at 50-70 msec and a positivity at 75-125 msec. The MLR has other characteristics which clearly dissociate it from the modality specific late responses. Among these are: (a) High-frequency stimulation of the mesencephalic reticular formation adequate to desynchronize the EEG abolishes the MLR but produces little or no suppression of the specific late responses; (b) low-frequency stimulation of the basal forebrain region adequate to increase cortical synchronization12 markedly enhances the MLR while producing little or no enhancement of the specific late responses. Our direct comparisons show that the properties of the MLR are different from those of 'association area' responses recorded in the chloralosed and unanesthetized cat (Albe-Fessard and Fessard 1 and references cited therein; Albe-Fessard et al.2; Hirsch and HirschT; Hirsch et al.5.~; Thompson etal. la and references cited therein). Most reports of association area responses attribute to them a shorter latency than that of the MLR. Association area responses are recorded maximally from anterior marginal, and anterior and posterior suprasylvian gyri. The MLR is restricted to the Brain Research, 1 (1966) 311-314
SHORT COMMUNICATIONS
313
lateral gyrazs and is small or absent anteriorly. It is, however, recorded from the posterior suprasylvian gyrus and could be confused with association area responses if latencies are not carefully observed. Most important, the MLR is abolished by chloralose anesthesia while earlier responses which we concurrently record from traditional association areas are sharply potentiated. Of the long latency sensory evoked responses in cat associated with cortical synchronizationS, s, those most similar to the MLR are reported by Hughes s who believes the responses he records from mesial and lateral cortex to be K-complexes. Hughes finds his response to be largest in mesial cortex anterior to the genu of the corpus cal!osum. Although we have not mapped the mesiai cortex extensively, we find that the MLR may be recorded readily from middle mesial cortex (suprasolenial and parasplenial gyri). On the lateral surface the MLR decreases sharply in amplitude anteriorly and has a definite posterior focus. The long latency responses recorded by Hirsch e t al. 5 from curarized cats were seen most readily in suprasylvian gyrus and are thus probably related to association area responses. We have recorded the MLR routinely in 15 out of 16 chronically implanted cats, but we have found it very difficult to record in acute, paralyzed animals since in this preparation it is difficult to obtain good EEG synchronization.
SOMATOSENSORY
AUDITORY
msec
Fig. 1. Cortical distribution of the midline late response (MLR) evoked by shock to the right ulnar nerve and by clicks during waking (W), rapid eye movement sleep (RS), and slow wave sleep (SS) in the cat. At the middle midline location, several average responses during SS are shown to indicate MLR v~,riability. At other locations, each response shown represents the median of at least three average responses. Each average is based on 10 single responses. In contrast to the common distribution of the MLR, note the responses occurring in specific sensory areas contralaterally for somatosensory and bilaterally for auditogy stimulation. Positivity upwards; reference: frontal sinus; stimulation occurred at beginning of trace.
Brain Research, 1 (1966)311-314
314
SHORT COMMUNICATIONS
This may explain why Hirsch et al. 5 did not record the M L R in their paralyzed preparations. The correspondence in midline focus, waveform, modality non-specificity, and relation to spontaneous cortical activity between the cat midline late response and the K-ccmplex type of late activity recorded in man suggests that these are homologous responses. There r~mains, however, the very large latency differences ~o be explained. If further research verifies the homology, we may have a guide to the magnitude o f latency differences in late evoked responses between species, and an elucidation o f cerebral evoked activity reflected by the long observed but little understood K-complex. This work was supported by grant M-05286 from the National Institute of Mental Health and by the Veterans Administration.
V. A. Hospitals, West Haven, Conn. and Sepulveda, Calif. ; Yale University School of Medicine, New Haven, Conn. ; Department of Anatomy, University of California, Los Angeles, Calif. (U.S.A.)
WILLIAM R. GOFF MAURICE B. STERMAN TRUETT ALLISON
ALBE-FESSARD, D., AND FESSARD, A., Thalamic integrations and their consequences at the telencephalic level. In G. MoRuzzl, A. FESSARDAND H. H. JASPER (Eds.), Brain Mechanisms, Progress in Brain Research, Vol. 1, Elsevier, Amsterdam, 1963, pp. 115-148. 2 ALBE-FESSARD,D., MASSION,J., HALL, R., ET RO~ENBLITH,W., Modifications au cours de la veille et du sommeil des valeurs moyenne~ de r~ponses nerveuses centrales induites par des stimulations somatiques chez le chat iibre, C. R. Acad. Sci. (Paris), 258 (1964) 353-356. 3 DAVIS,H., DAVIS, P. A., LOOMIS,A. L., HARVEY,E. N., AND HOBART,G., Electrical reactions of the humar~ brain to auditory stimulation during sleep, J. Neurophysiol., 2 (1939) 500-514. 4 GOFF,W. R., ALLISON,T., SHAPIRO, A., AND ROSNER,B. S., Cerebral somatosensory responses evoked during sleep in man, Electroenceph. clin. Neurophysiol., in press. 5 HIRSCH,J. F., ANDERSON,R. E., CALVET,J., AND SCHERRER,J., Short and long latency cortical resp¢.nses to somesthetic stimulation in the cat, Exp. Neurol., 4 (1961) 562-583. 6 HIRSCH,J. F., BENOIT,O., EXHUNGERFt.,ItD,D., Reponses corticales ~ iongue iatence chez l'animal chronique, J. PhysioL, 54 (1962) 353. 7 I-hRscx, J. F., ETHIRSCH,J. C., Syst6matisation des r~pons~'.sdites associatives des cyrus marginal et su~rasylvien du chat, J. Physiol., 57 (19~5) 250-251. 8 HUGHES,J. R., Studies on the supracallosai mesial cortex of unanesthetized, conscious mammals. i. Cat. B. Electrical aetivity~ E!ectroenceph. ella. Neurophysioi., 11 (1959) 459-469. 9 LocMIs, A. L., HARVEY,E. N., ANDHOBART,G., Disturbance-patterns in sleep, J. Neurophysiol., 1 (1~38) 413-430. 10 POM~EIANO,O., AND SWETT,J. E., EEG and behavioral manifestations of sleep induced by cutaneous nerve stimulation in normal cats, Arch. ital. Biol., 100 (1962) 311-342. I i Ros,~rR, B. S., ALLISON,T., SWANSON,E., AND GOFF, W. R., A new ~nstrument for the summation of evoked responses from the nervous system, Electroenceph. clin. Neurophysiol., 12 (1960) 745747. 12 STE'~MAN,M. B., ANDCLEMENTE,C. D., Forebrain irihibitory mechanisms: Sleep patterns induced by basal forebrain stimulation in the behaving cat, Exp. Neurol., 6 (1962) 103-117. ! 3 THOMPSON,R. F., JOHNSON,R. H., At~DHOOVES,J. J., Or.~.anization of auditory, somatic sensory ano visual proj~ilun to association fields of cerebra! cortex in the cat, J. NeurophysioL, 26 (19o3) 343-364.
(Received Janaary 21st, i 966) Brain Research, 1 (1966)31 i-314
311
Usually inspiratory and expiratory discharges in the pons were changed in the same manner as in the medulla by vagal stimt:lation, but in some cases the discharges lost their rhythmic activity and changed to a continuous pattern. In general the effect of stimulation on the discharges in the pons lasted longer than in the medulla. These results indicate that the alteration of inspiratory and expiratory unit discharges by stimulation of the vagal nerve is not always reciprocal in the medulla and the nature of the respiratory unit discharge in the pons is different from that in the medulla. Department of Pharmacology, Faculty of Medicine, University of Tokyo, Tokyo (Japan)
TAKEHIKO HUKUHARA NORIYUKI KUMADAKI HIROSHI KOJIMA HAJIME TAMAKI YOSHIAKI SAJI FUMINORI SAKAI
1 DmgEN, M. N. J., AND WOLDRING, S., Unit activity in buibar respiratory centre, J. NeurophysioL. 14 (1951) 211-225. 2 HUKUHARA,T., OKADA, H., AND NAKAYAMA,S., On the vagus-respiratory reflex, Jap. J. PhysioL, 6 (1956) 87-97. 3 NAKAVAMA,T., ASD Hog], T., Response of medullary respiratory neurones to stimulation of the vagus, Jap. J. Physiol., 14 (1964) 147-154. 4 WYss~ O. A. M., Reizphysiologische Analyse des afferenten Lungenvagus, Pfliigers Arch. ges. Physiol., 242 (1939) 215-233. 5 Wvss, O. A. M., Die nerv~se Steuerung der Atmung, Ergebn. Physiol., 54 (1964) 1-479.
Brain Research, 1 (1966) 310-31 !
Cortical midline late response during sleep in the cat During sleep in man, an evoked response to peripheral stimulation can be recorded with maximum amplitude focus in the vertex region. First repotted for auditory stimuli in 1938L the response was further described for auditory and somatic stimuli by Davis e t al. a and called the" K-complex. The waveform is initially vertex negative followed by a vertex positivity having a peak latency of about 750 msec. Abnormalities in the configuration of the K-complex have been useful in the diagnosis of cerebral pathology and in audiometric tests, but little is known about the cerebral structures and afferent pathways involved in this response. Recently, we have recorded from man very late somatosensory evoked responses during slow-wave sleep (stages 3 and 4) which we believe to be the summated form of the K-complex4. This stimulated an effort to find in cat long latency cerebral evoked responses to peripheral stimulation which might correspond to the summated Kcomplex. We have observed two kinds of late responses whose appearance is associated with EEG synchronization characteristic of 'slow-wave' sleep (SS). The first of these is modality specific and appears as a prolongation and enhancement of evoked activity recorded from the appropriate sensory projection area during waking (W), and rapid eye movement sleep (RS). The second type of response is modality Brain Research, 1 (1966) 311-314
312
SHORT COMMUNICATIONS
non-specific, appears only during SS, and has its maximum amplitude focus at midline lateral gyrus about half way between the bregma and the sagittal crest. This latter response, which we call the midline late response (MLR), appears to be the feline homolog of the K-complex. We have studied the MLR in both chronic and acute cat preparations. In chronic animals, cortical electrodes were screws in the skull penetrating to the dura; electrodes were also placed for recording EEG, neck muscle activity, and eye movements. Acute preparations were tracheotomized and venous cannulated under ether or halothane (Fluothane) anesthesia and maintained on gallamine triethiodide (Flaxedil), artificial respiration and local anesthesia. In these preparations electrodes were small solder balls resting on the dural or pial surface. In all animals evoked responses were recorded monopolarly against a screw electrode over frontal sinus. Somatic stimuli were 0.1 msec square wave shocks of low iatensity delivered to chronic animals via an electrode lo implanted around the ulnar nerve at the wrist and to acute animals via subcutaneous needles. Auditory stimuli were clicks from a speaker. Subcortical stimuli were delivered via bipolar electrodes implanted stereotaxically. For all stimuli the rate was 1 per 5 sec. Sleep stages in chronic animals were determined from EEG, EMG, and eye movement polygraph recordings and from observation of the animal through a one-way vision window in a sound attenuating, shielded recording chaniber. Evoked responses were averaged on a four-channel analog system11. Fig. 1 shows the cortical distribution of the MLR for somatosensory and auditory stimuli. The MLR appears when the chronic animal goes into SS and when the EEG becomes synchronized in the acute. It consists of a negativity at 60-80 msec and a positivity at 110-150 msec. It can be seen that the response is largest at middle midline and that the amplitude decreases more rapidly anteriorly than posteriorly. Anteriorly the MLR is narrowly restricted to the lateral gyrus; posteriorly the distribution widens to include posterior suprasylvian gyrus. Fig. 1 shows also that the MLR may be differentiated easily from late responses seen only in specific sensory cortex. These latter responses consist of a negativity at 50-70 msec and a positivity at 75-125 msec. The MLR has other characteristics which clearly dissociate it from the modality specific late responses. Among these are: (a) High-frequency stimulation of the mesencephalic reticular formation adequate to desynchronize the EEG abolishes the MLR but produces little or no suppression of the specific late responses; (b) low-frequency stimulation of the basal forebrain region adequate to increase cortical synchronization12 markedly enhances the MLR while producing little or no enhancement of the specific late responses. Our direct comparisons show that the properties of the MLR are different from those of 'association area' responses recorded in the chloralosed and unanesthetized cat (Albe-Fessard and Fessard 1 and references cited therein; Albe-Fessard et al.2; Hirsch and HirschT; Hirsch et al.5.~; Thompson etal. la and references cited therein). Most reports of association area responses attribute to them a shorter latency than that of the MLR. Association area responses are recorded maximally from anterior marginal, and anterior and posterior suprasylvian gyri. The MLR is restricted to the Brain Research, 1 (1966) 311-314
SHORT COMMUNICATIONS
313
lateral gyrazs and is small or absent anteriorly. It is, however, recorded from the posterior suprasylvian gyrus and could be confused with association area responses if latencies are not carefully observed. Most important, the MLR is abolished by chloralose anesthesia while earlier responses which we concurrently record from traditional association areas are sharply potentiated. Of the long latency sensory evoked responses in cat associated with cortical synchronizationS, s, those most similar to the MLR are reported by Hughes s who believes the responses he records from mesial and lateral cortex to be K-complexes. Hughes finds his response to be largest in mesial cortex anterior to the genu of the corpus cal!osum. Although we have not mapped the mesiai cortex extensively, we find that the MLR may be recorded readily from middle mesial cortex (suprasolenial and parasplenial gyri). On the lateral surface the MLR decreases sharply in amplitude anteriorly and has a definite posterior focus. The long latency responses recorded by Hirsch e t al. 5 from curarized cats were seen most readily in suprasylvian gyrus and are thus probably related to association area responses. We have recorded the MLR routinely in 15 out of 16 chronically implanted cats, but we have found it very difficult to record in acute, paralyzed animals since in this preparation it is difficult to obtain good EEG synchronization.
SOMATOSENSORY
AUDITORY
msec
Fig. 1. Cortical distribution of the midline late response (MLR) evoked by shock to the right ulnar nerve and by clicks during waking (W), rapid eye movement sleep (RS), and slow wave sleep (SS) in the cat. At the middle midline location, several average responses during SS are shown to indicate MLR v~,riability. At other locations, each response shown represents the median of at least three average responses. Each average is based on 10 single responses. In contrast to the common distribution of the MLR, note the responses occurring in specific sensory areas contralaterally for somatosensory and bilaterally for auditogy stimulation. Positivity upwards; reference: frontal sinus; stimulation occurred at beginning of trace.
Brain Research, 1 (1966)311-314
314
SHORT COMMUNICATIONS
This may explain why Hirsch et al. 5 did not record the M L R in their paralyzed preparations. The correspondence in midline focus, waveform, modality non-specificity, and relation to spontaneous cortical activity between the cat midline late response and the K-ccmplex type of late activity recorded in man suggests that these are homologous responses. There r~mains, however, the very large latency differences ~o be explained. If further research verifies the homology, we may have a guide to the magnitude o f latency differences in late evoked responses between species, and an elucidation o f cerebral evoked activity reflected by the long observed but little understood K-complex. This work was supported by grant M-05286 from the National Institute of Mental Health and by the Veterans Administration.
V. A. Hospitals, West Haven, Conn. and Sepulveda, Calif. ; Yale University School of Medicine, New Haven, Conn. ; Department of Anatomy, University of California, Los Angeles, Calif. (U.S.A.)
WILLIAM R. GOFF MAURICE B. STERMAN TRUETT ALLISON
ALBE-FESSARD, D., AND FESSARD, A., Thalamic integrations and their consequences at the telencephalic level. In G. MoRuzzl, A. FESSARDAND H. H. JASPER (Eds.), Brain Mechanisms, Progress in Brain Research, Vol. 1, Elsevier, Amsterdam, 1963, pp. 115-148. 2 ALBE-FESSARD,D., MASSION,J., HALL, R., ET RO~ENBLITH,W., Modifications au cours de la veille et du sommeil des valeurs moyenne~ de r~ponses nerveuses centrales induites par des stimulations somatiques chez le chat iibre, C. R. Acad. Sci. (Paris), 258 (1964) 353-356. 3 DAVIS,H., DAVIS, P. A., LOOMIS,A. L., HARVEY,E. N., AND HOBART,G., Electrical reactions of the humar~ brain to auditory stimulation during sleep, J. Neurophysiol., 2 (1939) 500-514. 4 GOFF,W. R., ALLISON,T., SHAPIRO, A., AND ROSNER,B. S., Cerebral somatosensory responses evoked during sleep in man, Electroenceph. clin. Neurophysiol., in press. 5 HIRSCH,J. F., ANDERSON,R. E., CALVET,J., AND SCHERRER,J., Short and long latency cortical resp¢.nses to somesthetic stimulation in the cat, Exp. Neurol., 4 (1961) 562-583. 6 HIRSCH,J. F., BENOIT,O., EXHUNGERFt.,ItD,D., Reponses corticales ~ iongue iatence chez l'animal chronique, J. PhysioL, 54 (1962) 353. 7 I-hRscx, J. F., ETHIRSCH,J. C., Syst6matisation des r~pons~'.sdites associatives des cyrus marginal et su~rasylvien du chat, J. Physiol., 57 (19~5) 250-251. 8 HUGHES,J. R., Studies on the supracallosai mesial cortex of unanesthetized, conscious mammals. i. Cat. B. Electrical aetivity~ E!ectroenceph. ella. Neurophysioi., 11 (1959) 459-469. 9 LocMIs, A. L., HARVEY,E. N., ANDHOBART,G., Disturbance-patterns in sleep, J. Neurophysiol., 1 (1~38) 413-430. 10 POM~EIANO,O., AND SWETT,J. E., EEG and behavioral manifestations of sleep induced by cutaneous nerve stimulation in normal cats, Arch. ital. Biol., 100 (1962) 311-342. I i Ros,~rR, B. S., ALLISON,T., SWANSON,E., AND GOFF, W. R., A new ~nstrument for the summation of evoked responses from the nervous system, Electroenceph. clin. Neurophysiol., 12 (1960) 745747. 12 STE'~MAN,M. B., ANDCLEMENTE,C. D., Forebrain irihibitory mechanisms: Sleep patterns induced by basal forebrain stimulation in the behaving cat, Exp. Neurol., 6 (1962) 103-117. ! 3 THOMPSON,R. F., JOHNSON,R. H., At~DHOOVES,J. J., Or.~.anization of auditory, somatic sensory ano visual proj~ilun to association fields of cerebra! cortex in the cat, J. NeurophysioL, 26 (19o3) 343-364.
(Received Janaary 21st, i 966) Brain Research, 1 (1966)31 i-314