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The EEG and rapid eye movements during REM sleep in normal and autistic children
Electroencephalography and Clinical Neurophysiology Elsevier Publishing Company, Amsterdam- Printed in The Netherlands
167
T H E E E G A N D R A P I D EYE M O V E M E N T S D U R I N G R E M SLEEP IN N O R M A L AND AUTISTIC CHILDREN 1 EDWARD M. ORNITZ, M.D., EDWARD R. RtTVO, M.D., MORTON B. BROWN, PH.D., STEVEN LA FRANCHI, TIMOTHY PARMELEE AND RICHARD D. WALTER, M . D . The Neuropsychiatric Institute, U.C.L.A. Center Jbr the Health Sciences, Los Angeles, Calif. 90024 (U.S.A.)
(Accepted for publication: May 28, 1968)
In previous investigations (Ornitz et al. 1967, 1968; Ritvo et al. 1967), we noted an unusual amount of large amplitude synchronous slow LEG activity during the REM sleep phase of two young autistic children. In three other young autistic children, we noted the presence of LEG activity in the spindling frequency range during REM sleep. Therefore we decided to follow up our observations with a quantitative study of the occurrence of these patterns in a series of agematched normal and autistic children. A second objective of this study was to quantify the occurrence of eye movement activity during REM sleep in these young autistic children to clarify a possible relationship between REM sleep and psychosis (see Discussion). METHODS
Subjects Six normal children (age range 19--45 months, mean 33 months) and eight autistic children (age range 22-47 months, mean 36 months) were studied for 14 first nights in the laboratory. Five of the autistic children were re-studied on a follow-up night. The diagnostic criteria for the autistic children have been described (Ornitz and Ritvo 1968; Ornitz et al. 1968). None of the autistic children had any history or signs of CNS disturbance. All were products of normal term deliveries. Two of the mothers of the autistic children had evidence of thyroid dysfunction during the pregnancy. Two pregnancies were complicated by minor viral infections, one 1 Supported by Grant No. USPHS-NB-02808 and by Grant No. USPHS-MH-13517.
by bronchitis, and one by elevated arterial pressure. None of the children had received any medication prior to the study. All subjects were brought to the laboratory at their regular bedtime. Recording Scalp electrodes were placed in standard positions according to the International 10-20 System. The LEG was recorded from bilateral frontal-temporal, temporal-occipital, temporalcentral, and central-occipital derivations on a Grass 16-channel electroencephalograph with filters set at 1-35 c/sec. Three channels recorded horizontal and vertical eye movements. Data analysis The number and duration of the following variables were tabulated for each second of each REM sleep period for every subject: Single eye movements; eye movement bursts; 10.5-15 c/see waves, synchronous slow waves, and irregular slow waves. The presence of the EEG patterns was judged according to the following criteria: (a) 10.5-15 c/see activity predominantly in frontal and central derivations; any individual epoch must last at least 0.5 sec; (grade 1 : meets above frequency criteria without regard to form; grade 2: meets above frequency criteria and has appearance of spindles; grade 3: unequivocal spindle, comparable to spindles found in Stage 2 of same night's record); (b) sinusoidal activity of less than 4 c/sec in any derivation; any individual epoch must last at least 3 full cycles with a constant frequency (graded according to amplitude); (c) irregular activity of less than 4 c/see in any derivation; may be 1 or 2 cycles, or 3 or more cycles of variable frequency in any Electroenceph. clin. NeurophysioL, 1969, 26:167-175
168
E.M.
ORNITZ et
epoch (graded according to amplitude). Eye movement bursts were measured from the first to the last rapid eye movement of a group of 3 or more eye movements in which the interval between any 2 eye movements did not exceed 3 sec. Single eye movements were defined as those eye movements not occurring as part of an eye movement burst. R E M sleep periods were defined as beginning with the first eye movement burst and ending with the last. The elapsed time between the first and last occurrence within each REM sleep period of each type of EEG pattern was calculated as a measure of dispersion of the pattern within the REM period. If eye movement bursts did not occur within 60 sec of 10.5-15 c/sec waves, the record was judged as a transition to Stage 2 sleep and was not included. All records were judged independently by two investigators. Final judgment was by concurrence.
al.
sleep time was 0.260/min and 0.053/min, respectively in the autistic and in the normal group. (See Table II for the statistical significance of these differences.) Two of the normal children had no occurrences of this pattern while all of the autistic children had occurrences. None of the normal children had grade 2 or grade 3 10.5-15 c/sec waves; three autistic children did have grade 2 waves and one autistic child had grade 3 waves. Because later R E M sleep periods occurred to a greater extent in the autistic group, the amount of accumulated sleep might have influenced the differences in this EEG pattern in the two diagnostic groups. Table II shows the duration and number of occurrences of 10.5-15 c/sec
GRADEI IO5 150 c/sec ACTIVITY DURING REM SLEEP IN 31MOOLD AUTISTICBOY Fpl
T3~j~,~.~.~,~J~'~,~/~.~
~.
RESULTS ¢
First nights in autistic and normal children The basic sleep cycle was equivalent in the normal and autistic children (Table I). 10.5-15 c/sec waves (see Fig. 1 and Fig. 2). The mean percent of total R E M sleep time during which this activity occurred was 0.34 and 0.04 respectively in the autistic and in the normal children; the mean number of individual occurrences of this pattern divided by total REM
,
/
EYE
Fig. 1 Underlined segments of EEG were judged as grade 1 10.5-15 c/sec waves. Note that this activity follows within several secondsof a burst of rapid eye movements.
TABLE I Sleep patterns of normal and autistic children Normal children (N = 6)
Autistic children (N = 8)
19 13.1
28 15.6
Time (min) from sleep onset to first REM sleep period (mean, S.D.)
142.0±51.2
151.5±58.9
Time (min) from sleep onset to second REM sleep period (mean, S.D.)
243.02k77.4
237.0+ 68.6
Time (min) from sleep onset to third REM sleep period (mean, S.D.) Total sleep time (mean, S.D.) recorded Percent time in REM sleep
281.0-1-54.4 371.0±59.0 11.1
301.04-60.6 388.0± 128.0 13.6
Number of REM sleep periods studied Mean duration of REM sleep periods (min)
Electroenceph. clin. Neurophysiol., 1969, 26:167-175
169
REM SLEEP IN AUTISTIC CHILDREN TABLE II Amount of 10.5-15 c/see, synchronous slow wave, and eye movement activity during REM sleep Normal children
Autistic children
P
t*
df
0.04 0.053 0.05
0.34 0.260 0.48
0.038
0.355
0.052 0.039 0.058 (0.028 0.048 (0.022
2.32 2.45 2.25 2.58 2.37 2.69
7.3 8.4 7.4 10.0)** 7.5 10.4)
Synchronous slow waves: Mean percent of total REM sleep time Mean number per rain of total REM sleep time
2.30 1.26
5.60 2.37
0.222 0.258
1.33 1.21
8.0 9.2
Single eye movements: Mean number per rain of first two REM periods
2.87
1.78
0.052 (0.046
2.19 2.23
10.9 11.8)
1.89 26.1
1.51 15.6
0.211 0.047 (0.036
1.35 2.34 2.46
9.3 8.3 9.5)
10.5-15 c/sec waves: Mean percent of total REM sleep time Mean number per rain of total REM sleep time Mean percent time for first two REM periods Mean number per rain of first two REM periods
Eye movement bursts: Mean number per min of first two REM periods Mean percent time for first two REM periods
* All values are based on separate variances and an approximate degrees of freedom solution. ** Values in parentheses were calculated after square root transformation of the data to obtain a more Gaussian distribution.
10.5-15.0 c/sec WAVE,SYNCHRONOUSSLOW WAVE, AND EYE MOVEMENTACTIVITY DURING REM SLEEP IN CHILDREN 2.8
0.60-
80,t
0.500.40-
0.30 0.20-
0.00
2,I
2.01.6-
6.0
1.2
4.0
0.8
2,0
0.4
0.0
0.0
10.5-15.0 c/see WAVES
N
A
SYNCHRONOUS SLOWWAVES
EYE MOVEMENT BURSTS
44.0 40.0
0.9 F
36.0
0.8
32.0
20£
0.7
28.0
0.6
24.0
16£
0.5
20.0 12.0
0.4
16,0
0.5
12.0
8.0
0.2
8.O
4.0 ~ [ 0.1
waves calculated for the first two REM sleep periods only, in the two groups. For all REM sleep periods in which more than one of these waves occurred, the mean time interval between the first and the last of these waves was 65.3% of the REM sleep period in the autistic children. Only two normals had more than one occurrence of this pattern in at least one REM period. Synchronous slow waves (see Fig. 3 and 4). Although all sinusoidal waves less than 4 c/see were recorded, most of this activity was between 2.5 and 3.5 c/see. The mean percent of total REM sleep time during which this activity occurred in the two groups, as well as the mean number of individual occurrences of this pattern divided by total R E M sleep time are shown in Table II (no significant differences were found). All of the children in both groups had occurrences of synchronous slow waves. The higher means in
0.0 N
N : NORMAL A =AUTISTIC
Fig. 2
4.0
FI~ 0.0
N
-
0.0
N
Group means and individual subject values for six normal and eight autistic children. EEG data are from all REM sleep periods; eye movement data are from first and second REM sleep periods. Electroenceph. clin. NeurophysioL, 1969~ 26:167-175
E.M. ORNITZ et al.
170
GR,~DEt SYNCHRONOUSSLOWWAVESDURINGREM SLEEPIN 22M0OLD AUTrSTICGIRL Fpl -
T
3
~
ioo~v l
Fig. 3 Underlined segment of EEG was judged as a grade 1 synchronous slow wave. Note that this activity occurs immediately after a burst of rapid eye movements. An episode of 10.5-15 c/sec activity can be seen in Fpa-T3. GRADE3 SYNCHRONOUSSLOWWAVESDURINGREM SLEEP IN 47M0 OLD AUTISTIC GIRL
rpl-Ts .',j%\/~/'wV"N'X",v' "J'~,w"v ~./'fw ~ , ~ / X X F ' v ~ ' ~ / "
.
/ ~ "~
', .
V
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~
'
V U
f ~ ~.Jk/'~"~/~/
~
d
' t
IOOIV J
Isec
Fig. 4 Underlined segments of EEG were judged as grade 3 synchronous slow waves. Extremely large amplitude activity caused blocking of pens. GRAOE I IRREGULAR SLOW WAVES DURING REM SLEEP IN 2 4 M 0 OLD NORMAL BOY
i sec
Fig. 5 Underlined segments of EEG were judged as irregular slow
waves.
the autistic group were due to exceptionally high values in two autistic children (Fig. 2). All but one R E M sleep period contained more than one synchronous slow wave. These waves were distributed over 84.7 ~o of the R E M sleep time in the autistic children and 73.5 ~o in the normals.
Irregular slow waves (see Fig. 5). Unlike the 10.5-15 c/sec and synchronous slow wave activity, it was difficult to obtain concurrence among those judging this activity. Whereas irregular slow waves seemed to occur during R E M sleep in both diagnostic groups with about the same frequency as synchronous slow waves, this E E G pattern could not be reliably quantified. Rapid eye movement activity. The mean number of single eye movements occurring during the first two R E M sleep periods was 1.78/min and 2.87/min, respectively in the autistic and in the normal group. (For the difference between these means see Table II.) The difference between the two groups in the mean number of eye movement bursts occurring during the first two R E M sleep periods was not significant. On the other hand, the difference in the mean percent of time during which eye movement bursts occurred during the first two R E M sleep periods was significant (see Table II). Therefore, the duration but not the initiation of rapid eye movement bursts was reduced in the autistic children. Relationships between EEG patterns and rapid eye movement activity 1. Quantitative relationships (see Table III): Correlation coefficients were computed for the amount of 10.5-15 c/sec and synchronous slow wave activity and the several measures of rapid eye movement activity recorded during the first two R E M sleep periods of each night. N o relationship between either E E G pattern and the number of single eye movements could be established in either diagnostic group. No relationship between 10.5-15 c/sec activity and rapid eye movement burst activity could be demonstrated. However, in the six normal children, there were strong positive linear correlations between the amount of synchronous slow wave activity and the amount of eye movement burst activity (significant at P < 0.05). In contrast, there was no relationship between the quantity of synchronous slow wave activity and the quantity of rapid eye movement burst activity in the group of eight autistic children. Because two autistic children had exceptionally high values for synchronous slow waves, correlations Electroenceph. clin. Neurophysiol., 1969, 26:167-175
171
REM SLEEP IN AUTISTIC CHILDREN TABLE III
Quantitative relationship between synchronous slow waves and eye movement bursts during the first two REM sleep periods of each subject night Correlations between:
Normal children N~6
Autistic children N=8
N~6
Number of synchronous slow waves (/min) and number of eye movement bursts (/rain)
r = --0.8647
r
+0.2589
r -- +0.5117"
Percent of REM sleep time during which synchronous slow waves and during which eye movement bursts occurred
r = +0.8813
r
--0.0485
r =: +0.6414"
* These values for r were obtained after removal of two children with exceptionally high values for synchronous slow waves from the autistic group. TABLE IV Temporal relationship between synchronous slow waves and eye movement bursts during the first two REM sleep periods of each subject night Normal children
Autistic children
Mean percent of synchronous slow waves occurring during eye movement bursts
29.7
26.7
Mean percent of REM sleep time during which eye movement bursts occur
26.1
15.6
Increase in mean percent of synchronous slow waves occurring during eye movement bursts above expected value Mean percent of synchronous slow waves occurring during 3 sec intervals preceding eye movement bursts
3.58 •0.6
11.1 11.5
Mean percent of REM sleep time during which 3 sec intervals preceding eye movement bursts occur
9.46
7.43
Increase in mean percent of synchronous slow waves occurring during 3 sec intervals preceding eye movement bursts above expected value
1.13
4.07
between this activity and eye m o v e m e n t burst activity were c o m p u t e d separately for the six other autistic children. While the correlation coefficients were increased they did n o t achieve significance (P > 0.05) 1.
1 Using a z transformation of r, the difference between the correlation coefficients (for percent of REM sleep time during which synchronous slow waves and eye movement bursts occurred) for the entire normal and entire autistic groups is significant at P=0.05. However, when the normal group is compared to the autistic group after removal of the two autistic children with high values for synchronous slow waves, the difference is no longer significant.
2. Temporal relationships (see Table IV): Th e distribution o f synchronous slow waves in respect to b o t h the eye m o v e m e n t burst an d pre-eye m o v e m e n t burst periods was almost identical in the n o r m a l an d autistic children. H o w e v e r , as the percent d u r a t i o n o f eye m o v e m e n t burst time was less in the autistic than in the n o r m a l children (see above), the concentration o f sync h r o n o u s slow waves during the eye m o v e m e n t bursts increased in the autistic children (significant at P = 0.042). Th e n o r m a l children showed no tendency t o w a r d increased c o n c e n t r a t i o n o f synchronous slow waves during eye m o v e m e n t bursts. Th e increased c o n c e n t r a t i o n o f syn-
Electroenceph. clin. NeurophysioL, 1969, 26:167-175
172
E.M. ORNITZ et al.
chronous slow waves during the eye movement bursts in the autistic children did not, however, distinguish them fiom the normal group ( P = 0.161, t=1.52 with 9.84 ° of freedom). Finally, neither the autistic nor the normal children showed a significant concentration of synchronous slow waves preceding the eye movement bursts. In summary, within the group of normal children, there was a tendency for a greater amount of eye movement burst activity to be associated with a greater amount of synchronous slow wave activity, whereas in the group of autistic children this quantitative relationship was minimal. In both diagnostic groups, the temporal distribution of synchronous slow waves was similar in respect to eye movement burst activity, and the increased concentration of this EEG pattern during the shorter eye movement bursts in the autistic children did not discriminate between the two diagnostic groups. Follow-up nights in autistic children Five autistic children were studied on a second night. One 22-month- and one 25-monthold were re-studied at 23 and 26 months respectively. One 39-month-old was re-studied at 48 months. Two 47-month-olds were re-studied, one at 58 months and the other at 68 months. In four of these five children, the number of occurrences and duration of 10.5-15 c/sec activity during REM sleep decreased on re-study, the decrement tending to be proportional to the increasing age of the child. In one child there was an increase in this activity. For the autistic group, the mean number of these waves per minute of REM sleep time (for the first two REM sleep periods) was 0.125/min. Whereas this represented a group decrement from the initial recordings in the autistic children, their group values remained higher than the normal mean of 0.038/min (difference significant at P = 0.043). In all five autistic children the percent of REM sleep time during which eye movement bursts occurred increased on re-study, the increase tending to reflect the increasing age of the individual child. The mean percent time of eye movement burst activity on re-study was 20 ~ which approached the normal mean value of 26.1 ~o (difference not significant).
DISCUSSION
The major findings of this investigation are that in a group of young autistic children there is an unusually large amount of 10.5-15 c/sec activity in the EEG, a decrease in the amount of rapid eye movement activity, and an absence of the normal quantitative association of synchronous slow wave activity and rapid eye movement burst activity during REM sleep. It was also shown that in normal 2- and 3-year-old children the EEG of REM sleep, which has been characterized as a low voltage fast record (Dement and Kleitman 1957; Roffwarg et al. 1964; Roffwarg et al. 1966), contains over 270 of synchronous slow wave activity. The mean percent sleep time spent in REM sleep and the mean accumulated sleep times prior to the onset of each REM sleep period were equivalent in the normal and autistic groups. This finding confirms previous studies (Ornitz et al. 1965a,b) indicating no gross abnormality in the patterning of the n o n - R E M REM sleep cycle in autistic children. The smaller values in both groups for percent time spent in REM sleep (13.670 for the autistic and 11.1 for the normals) in this study as compared to the earlier studies (22.270 and 20.270, respectively) reflect the narrower definition of REM sleep used; i.e., from the first to the last eye movement burst, and the fact that all night recording was not done. Therefore, in the context of a normal n o n - R E M - R E M sleep cycle in autistic children, the present study is concerned with several abnormal findings within REM sleep. The presence of an abnormal amount of 10.5-15 c/sec activity during REM sleep suggests a possible defect of maturation in the EEG of young autistic children. Parmelee et al. (1968, in press) have demonstrated 12-15 c/sec activity during active (REM) sleep in premature, term, 3- and 8-month-old infants, the amount of this activity becoming progressively less with increasing age. Quantitative comparisons with our data are not possible because in the infant studies this activity was quantified as part of specific EEG patterns containing other frequency bands. However, the almost complete absence of 10.5-15 c/sec activity in our normal children (0.04~) Electroenceph. clin. NeurophysioL, 1969, 26:167-175
173
REM SLEEP IN AUTISTIC CHILDREN
indicates that the autistic subjects have retained a considerable amount (0.34~o) of a frequency band found in REM sleep during earlier developmental stages. The fact that a few of the autistic but none of the normal children had activity which not only shaled the frequency characteristics of sleep spindles (Gibbs and Gibbs 1950) but also had the wave form (grade 2 and grade 3) of spindles found in stage 2 sleep also suggests a deficient differentiation of sleep stages in the autistic children. Our finding that 26.1 ~ of REM sleep time in young normal children is taken up by rapid eye movement bursts is almost identical to the 2 5 ~ reported for normal adults (Aserinsky 1967). The significant reduction of both single eye movements and eye movement burst time in the autistic children is consistent with the reduced eye movement activity found in actively ill adult schizophrenics (Feinberg et al. 1965; Feinberg 1967). This finding in both patient groups is consistent with the developmental relationship between childhood autism and later schizophrenia (Ornitz and Ritvo 1968). We have further found that the number of rapid eye movement bursts is not reduced in the autistic children while their duration is reduced. This suggests that CNS influences initiating eye movement activity are intact while those factors sustaining the activity are either deficient or inhibited. The rapid eye movements of REM sleep and the phasic depression of afferent transmission during the eye movement bursts are dependent on the integrity of vestibular nuclei (Pompeiano and Morrison 1965; Carli et al. 1967). There is an absence of the phasic depression of sensory input during the rapid eye movements of REM sleep in autistic children (Ornitz et al. 1968). The present finding of reduced oculomotor activity during REM sleep provides further evidence of impaired central vestibular function in the sleeping autistic child and is consistent with the reduced nystagmoid response to vestibular stimulation in the waking autistic child (Colbert et al. 1959; Ritvo et al. in preparation). Reding and Fernandez (1968) have demonstrated a relationship between spontaneous rapid eye movements and induced nystagmus during REM sleep. In this study, we have measured the 2.5-3.5
c/sec sinusoidal EEG activity in REM sleep and demonstrated its quantitative association with the rapid eye movement bursts in the normal children. This activity is distinct from that which has been described in adults as "sawtooth" or "sharp" waves (Berger et al. 1962; Dement 1964) as it is not concentrated in the pre-burst intervals. Most interesting was the finding of a reduction, in the autistic children, of the quantitative association between this EEG pattern and the oculomotor activity. Therefore, we postulate that a neurophysiologic influence underlying the organization of cortical activity (as manifested by this EEG pattern) and the rapid eye movements may be impaired in the autistic children. This organizing influence as well as its postulated impairment is probably of subcortical origin and may be mediated through central vestibular mechanisms. The unusual presence of the 10.5-15 c/sec activity during REM sleep in the autistic children suggests that the impaired organization of EEG and oculomotor activity may be on a maturational basis. The tendency in the autistic children for both the 10.5-15 c/sec EEG and the eye movement activity to approach more normal values with increasing age also suggests a maturational factor and emphasizes the importance of studying these children at a young age. SUMMARY
1. 10.5-15 c/sec EEG activity, synchronous slow wave EEG activity and eye movement activity during REM sleep were quantified in eight young autistic and six age-matched normal children. 2. A significantly greater amount of 10.5-15 c/sec activity was found in the autistic children than in the normals. 3. A significantly reduced number of single eye movements and percent time of eye movement burst activity was found in the autistic children as compared with the normals. 4. Considerable synchronous slow wave activity was found in both groups of children. However, there was a strong quantitative association between the synchronous slow waves and the eye movement bursts in the normals, while this association was reduced in the autistic children. Electroenceph. clin. NeurophysioL, 1969, 26:167-175
E.M. 0RNITZ et al.
174
5. It is postulated that the depressed eye movement burst activity in the autistic children is a manifestation of deficient or inhibited central vestibular function. The reduced quantitative association between the synchronous slow waves and the eye movement bursts further suggests impairment of an organizing influence underlying integration of cortical and oculomotor activity. 6. These neurophysiologic abnormalities in the autistic children may be related to maturational factors as suggested by the persistence of 10.5-15 c/sec frequencies in the REM sleep EEG and the tendency to approach more normal values with increasing age. RI~SUMI~ EEG ET MOUVEMENTSOCULAIRESRAPIDES PENDANT LES PHASES DE MOUVEMENTS OCULAIRES DU SOMMEIL CHEZ LES ENFANTSNORMAUXET AUTISTIQUES
1. L'activit6 EEG, de 10,5-15 c/sec, l'activit6 EEG d'ondes lentes synchrones et l'activit6 de mouvements oculaires ont 6t6 quantifi6es pendant les phases de mouvements oculaires chez huit jeunes enfants autistiques et six enfants normaux appareill6s quant/t l'~ge. 2. On observe une proportion d'activit6 de 10,5-15 c/sec nettement plus grande chez les enfants autistiques que chez les normaux. 3. On note chez les enfants autistiquesune r6duction significative des mouvements oculaires isol6s et du pourcentage de temps des bouff6es de mouvements oculaires par comparaison aux normaux. 4. Une activit6 d'ondes lentes synchrones consid6rable est observ6e dans les deux groupes d'enfants. Cependant, on observe une association quantitative nette entre les ondes lentes synchrones et les bouff6es de mouvements oculaires chez les normaux, alors que cette association est r6duite chez les enfants autistiques. 5. Les auteurs sugg~rent que la r6duction des mouvements oculaires chez les enfants autistiques est une manifestation de la d6ficience ou de l'inhibition des fonctions vestibulaires centrales. La r6duction de l'association quantitative entre ondes lentes synchrones et bouff6es de mouvements oculaires sugg6re en outre une atteinte de l'influence organisatrice qui soustend l'int6gration des activit6s corticale et oculo-motrice.
6. Les anomalies neurophysiologiques observ6es chez les enfants autistiques peuvent ~tre corr616es h des facteurs maturationnels, ce qui est sugg6r6 par la persistance des fr6quences de 10,5-15 c/sec au cours de I'EEG pendant les phases de mouvements oculaires du sommeil et par la tendance ~t la normalisation avec l'fige. The authors are grateful for the helpful technical assistance of Mrs. L. Dietrich and Miss A.. Mason. Statistical analysis was facilitated by the Health Sciences Computing Facility supported by N.I.H. Grant FR 3.
REFERENCES ASERINSKY, E. Physiological activity associated with segments of the rapid eye movement period. Res. Publ. Ass. Res. nerv. Dis., 1967, 45: 338-350. BERGER,R. J., OLLEY,P. and OSWALD,I. The EEG, eyemovements and dreams of the blind. Quart. J. exp. Psychol., 1962, 14: 183-186. CARLI,G., DIETE-SPIFF,K. and POMPEIANO,O. Vestibular influences during sleep. V. Vestibular control on somatic afferent transmission in the cuneate nucleus during desynchronized sleep. Arch. ital. Biol., 1967, 105: 83-103. COLBERT, E. G., KOEGLER,R. R. and MARKHAM,C. H. Vestibular dysfunction in childhood schizophrenia. Arch. gen. Psyehiat., 1959, 1: 600-617. DEMENT,W. and KLEITMAN,N. Cyclic variations in EEG during sleep and their relation to eye movements, body motility, and dreaming. Electroenceph. clin. Neurophysiol., 1957, 9: 673-690. DEMENT,W. C. Eye movements during sleep. In M. BENDER fled.), The oculomotor system. Harper (Hoeber), New York, 1964: 3662,16. FEINBERG, I. Sleep electroencephalographic and eyemovement patterns in patients with schizophrenia and with chronic brain syndrome. Res. Publ. Ass. Res. nerv. Dis., 1967, 45: 211-240. FEINBERG,I., KORESKO,R. L. and GOTTLIEB,F. Further observations on electrophysiological sleep patterns in schizophrenia. Comprehens. Psychiat., 1965, 6: 21-24. GIBBS, F. A. and GIBBS,E. L. Atlas ofelectroencephalography, Vol. 1. Addison-Wesley, Cambridge, 1950, 324 p. ORNITZ, E. M. and RITVO, E. R. Perceptual inconstancy in early infantile autism. Arch. gen. Psychiat., 1968, 18: 76-98. ORNITZ, E. M., RITVO, E. R., CARR, E. M., PANMAN, L. M. and WALTER, R. n . The variability of the auditory averaged evoked response during sleep and dreaming in children and adults. Electroenceph. clin. Neurophysiol., 1967, 22: 514-524. ORNITZ,E. M., RITVO,E. R., PANMAN,L. M., LEE, Y. H., CARR,E. M. and WALTER,R. D. The auditory evoked response in normal and autistic children during sleep. Electroenceph. clin. Neurophysiol., 1968, 25: 221-230. Electroenceph. clin. Neurophysiol., 1969, 26:167-175
REM SLEEP IN AUTISTICCHILDREN ORNITZ,E. M., RITVO,E. R. and WALTER,R. D. Dreaming sleep in autistic twins. Arch. gen. Psychiat., 1965a, 12: 77-79. ORNITZ,E. M., RITVO,E. R. and WALTER,R. D. Dreaming sleep in autistic and schizophrenic children. Amer. J. Psychiat., 1965b, 122: 419-424. PARMELEE JR., A. H., AKIYAMA,Y., SCHULTZ, i . A., WENNER, W. H., SCHULTE,F. J. and STERN,E. The electroencephalogram in active and quiet sleep in infants. In P. KELLAWAYand I. PETERS~N (Eds.), Clinical electroencGvhalography of children. Almqvist and Wiksell, Uppsala, Stockholm, 1968: 77-88. PARMELEE JR., A. H., SCHULTE, F. J., AKIYAMA,Y., WENNER, W. H., SCHULTZ, M. A. and STERN, E. Maturation of EEG activity during sleep in premature infants. Electroenceph. din. Neurophysiol., 1968, 24: 319-329.
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POMPEIANO,O. and MORRISON,A. R. Vestibular influences during sleep. I. Abolition of the rapid eye movements of desynchronized sleep following vestibular lesions. Arch. ital. Biol., 1965, 103: 569-595. REDING, G. R. and FERNANDEZ,C. Effects of vestibular stimulation during sleep. Electroenceph. clin. Neurophysiol., 1968, 24: 75-79. R.ITVO,E. ex..,ORNITZ,E. M. and WALTER,R. D. Clinical application of the auditory averaged evoked response at sleep onset in the diagnosis of deafness. Pediatrics, 1967, 40: 1003-1008. ROFFWARG,H. P., DEMENT, W. C. and FISHER,C. Preliminary observations of sleep-dream pattern in neonates, infants, children, and adults. In E. HARMS(Ed.), International series of monographs on ehiM psychiatry. Pergamon, New York, 1964, 2: 60-72. R.OFFWARG, H. P., Muzto, J. N. and DEMENT, W. C. Ontogenetic development of the human sleep-dream cycle. Science, 1966, 152: 604-619.
Reference: ORNITZ,E. M., RITVO,E. R., BROWN,M. B., LA FRANCHI,S., PARMELEE,T. and WALTER,R.. D. The EEG and rapid eye movements during REM sleep in normal and autistic children. Electroenceph. clin. Neurophysiol., 1969, 26: 167-175.
167
T H E E E G A N D R A P I D EYE M O V E M E N T S D U R I N G R E M SLEEP IN N O R M A L AND AUTISTIC CHILDREN 1 EDWARD M. ORNITZ, M.D., EDWARD R. RtTVO, M.D., MORTON B. BROWN, PH.D., STEVEN LA FRANCHI, TIMOTHY PARMELEE AND RICHARD D. WALTER, M . D . The Neuropsychiatric Institute, U.C.L.A. Center Jbr the Health Sciences, Los Angeles, Calif. 90024 (U.S.A.)
(Accepted for publication: May 28, 1968)
In previous investigations (Ornitz et al. 1967, 1968; Ritvo et al. 1967), we noted an unusual amount of large amplitude synchronous slow LEG activity during the REM sleep phase of two young autistic children. In three other young autistic children, we noted the presence of LEG activity in the spindling frequency range during REM sleep. Therefore we decided to follow up our observations with a quantitative study of the occurrence of these patterns in a series of agematched normal and autistic children. A second objective of this study was to quantify the occurrence of eye movement activity during REM sleep in these young autistic children to clarify a possible relationship between REM sleep and psychosis (see Discussion). METHODS
Subjects Six normal children (age range 19--45 months, mean 33 months) and eight autistic children (age range 22-47 months, mean 36 months) were studied for 14 first nights in the laboratory. Five of the autistic children were re-studied on a follow-up night. The diagnostic criteria for the autistic children have been described (Ornitz and Ritvo 1968; Ornitz et al. 1968). None of the autistic children had any history or signs of CNS disturbance. All were products of normal term deliveries. Two of the mothers of the autistic children had evidence of thyroid dysfunction during the pregnancy. Two pregnancies were complicated by minor viral infections, one 1 Supported by Grant No. USPHS-NB-02808 and by Grant No. USPHS-MH-13517.
by bronchitis, and one by elevated arterial pressure. None of the children had received any medication prior to the study. All subjects were brought to the laboratory at their regular bedtime. Recording Scalp electrodes were placed in standard positions according to the International 10-20 System. The LEG was recorded from bilateral frontal-temporal, temporal-occipital, temporalcentral, and central-occipital derivations on a Grass 16-channel electroencephalograph with filters set at 1-35 c/sec. Three channels recorded horizontal and vertical eye movements. Data analysis The number and duration of the following variables were tabulated for each second of each REM sleep period for every subject: Single eye movements; eye movement bursts; 10.5-15 c/see waves, synchronous slow waves, and irregular slow waves. The presence of the EEG patterns was judged according to the following criteria: (a) 10.5-15 c/see activity predominantly in frontal and central derivations; any individual epoch must last at least 0.5 sec; (grade 1 : meets above frequency criteria without regard to form; grade 2: meets above frequency criteria and has appearance of spindles; grade 3: unequivocal spindle, comparable to spindles found in Stage 2 of same night's record); (b) sinusoidal activity of less than 4 c/sec in any derivation; any individual epoch must last at least 3 full cycles with a constant frequency (graded according to amplitude); (c) irregular activity of less than 4 c/see in any derivation; may be 1 or 2 cycles, or 3 or more cycles of variable frequency in any Electroenceph. clin. NeurophysioL, 1969, 26:167-175
168
E.M.
ORNITZ et
epoch (graded according to amplitude). Eye movement bursts were measured from the first to the last rapid eye movement of a group of 3 or more eye movements in which the interval between any 2 eye movements did not exceed 3 sec. Single eye movements were defined as those eye movements not occurring as part of an eye movement burst. R E M sleep periods were defined as beginning with the first eye movement burst and ending with the last. The elapsed time between the first and last occurrence within each REM sleep period of each type of EEG pattern was calculated as a measure of dispersion of the pattern within the REM period. If eye movement bursts did not occur within 60 sec of 10.5-15 c/sec waves, the record was judged as a transition to Stage 2 sleep and was not included. All records were judged independently by two investigators. Final judgment was by concurrence.
al.
sleep time was 0.260/min and 0.053/min, respectively in the autistic and in the normal group. (See Table II for the statistical significance of these differences.) Two of the normal children had no occurrences of this pattern while all of the autistic children had occurrences. None of the normal children had grade 2 or grade 3 10.5-15 c/sec waves; three autistic children did have grade 2 waves and one autistic child had grade 3 waves. Because later R E M sleep periods occurred to a greater extent in the autistic group, the amount of accumulated sleep might have influenced the differences in this EEG pattern in the two diagnostic groups. Table II shows the duration and number of occurrences of 10.5-15 c/sec
GRADEI IO5 150 c/sec ACTIVITY DURING REM SLEEP IN 31MOOLD AUTISTICBOY Fpl
T3~j~,~.~.~,~J~'~,~/~.~
~.
RESULTS ¢
First nights in autistic and normal children The basic sleep cycle was equivalent in the normal and autistic children (Table I). 10.5-15 c/sec waves (see Fig. 1 and Fig. 2). The mean percent of total R E M sleep time during which this activity occurred was 0.34 and 0.04 respectively in the autistic and in the normal children; the mean number of individual occurrences of this pattern divided by total REM
,
/
EYE
Fig. 1 Underlined segments of EEG were judged as grade 1 10.5-15 c/sec waves. Note that this activity follows within several secondsof a burst of rapid eye movements.
TABLE I Sleep patterns of normal and autistic children Normal children (N = 6)
Autistic children (N = 8)
19 13.1
28 15.6
Time (min) from sleep onset to first REM sleep period (mean, S.D.)
142.0±51.2
151.5±58.9
Time (min) from sleep onset to second REM sleep period (mean, S.D.)
243.02k77.4
237.0+ 68.6
Time (min) from sleep onset to third REM sleep period (mean, S.D.) Total sleep time (mean, S.D.) recorded Percent time in REM sleep
281.0-1-54.4 371.0±59.0 11.1
301.04-60.6 388.0± 128.0 13.6
Number of REM sleep periods studied Mean duration of REM sleep periods (min)
Electroenceph. clin. Neurophysiol., 1969, 26:167-175
169
REM SLEEP IN AUTISTIC CHILDREN TABLE II Amount of 10.5-15 c/see, synchronous slow wave, and eye movement activity during REM sleep Normal children
Autistic children
P
t*
df
0.04 0.053 0.05
0.34 0.260 0.48
0.038
0.355
0.052 0.039 0.058 (0.028 0.048 (0.022
2.32 2.45 2.25 2.58 2.37 2.69
7.3 8.4 7.4 10.0)** 7.5 10.4)
Synchronous slow waves: Mean percent of total REM sleep time Mean number per rain of total REM sleep time
2.30 1.26
5.60 2.37
0.222 0.258
1.33 1.21
8.0 9.2
Single eye movements: Mean number per rain of first two REM periods
2.87
1.78
0.052 (0.046
2.19 2.23
10.9 11.8)
1.89 26.1
1.51 15.6
0.211 0.047 (0.036
1.35 2.34 2.46
9.3 8.3 9.5)
10.5-15 c/sec waves: Mean percent of total REM sleep time Mean number per rain of total REM sleep time Mean percent time for first two REM periods Mean number per rain of first two REM periods
Eye movement bursts: Mean number per min of first two REM periods Mean percent time for first two REM periods
* All values are based on separate variances and an approximate degrees of freedom solution. ** Values in parentheses were calculated after square root transformation of the data to obtain a more Gaussian distribution.
10.5-15.0 c/sec WAVE,SYNCHRONOUSSLOW WAVE, AND EYE MOVEMENTACTIVITY DURING REM SLEEP IN CHILDREN 2.8
0.60-
80,t
0.500.40-
0.30 0.20-
0.00
2,I
2.01.6-
6.0
1.2
4.0
0.8
2,0
0.4
0.0
0.0
10.5-15.0 c/see WAVES
N
A
SYNCHRONOUS SLOWWAVES
EYE MOVEMENT BURSTS
44.0 40.0
0.9 F
36.0
0.8
32.0
20£
0.7
28.0
0.6
24.0
16£
0.5
20.0 12.0
0.4
16,0
0.5
12.0
8.0
0.2
8.O
4.0 ~ [ 0.1
waves calculated for the first two REM sleep periods only, in the two groups. For all REM sleep periods in which more than one of these waves occurred, the mean time interval between the first and the last of these waves was 65.3% of the REM sleep period in the autistic children. Only two normals had more than one occurrence of this pattern in at least one REM period. Synchronous slow waves (see Fig. 3 and 4). Although all sinusoidal waves less than 4 c/see were recorded, most of this activity was between 2.5 and 3.5 c/see. The mean percent of total REM sleep time during which this activity occurred in the two groups, as well as the mean number of individual occurrences of this pattern divided by total R E M sleep time are shown in Table II (no significant differences were found). All of the children in both groups had occurrences of synchronous slow waves. The higher means in
0.0 N
N : NORMAL A =AUTISTIC
Fig. 2
4.0
FI~ 0.0
N
-
0.0
N
Group means and individual subject values for six normal and eight autistic children. EEG data are from all REM sleep periods; eye movement data are from first and second REM sleep periods. Electroenceph. clin. NeurophysioL, 1969~ 26:167-175
E.M. ORNITZ et al.
170
GR,~DEt SYNCHRONOUSSLOWWAVESDURINGREM SLEEPIN 22M0OLD AUTrSTICGIRL Fpl -
T
3
~
ioo~v l
Fig. 3 Underlined segment of EEG was judged as a grade 1 synchronous slow wave. Note that this activity occurs immediately after a burst of rapid eye movements. An episode of 10.5-15 c/sec activity can be seen in Fpa-T3. GRADE3 SYNCHRONOUSSLOWWAVESDURINGREM SLEEP IN 47M0 OLD AUTISTIC GIRL
rpl-Ts .',j%\/~/'wV"N'X",v' "J'~,w"v ~./'fw ~ , ~ / X X F ' v ~ ' ~ / "
.
/ ~ "~
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'
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Fig. 4 Underlined segments of EEG were judged as grade 3 synchronous slow waves. Extremely large amplitude activity caused blocking of pens. GRAOE I IRREGULAR SLOW WAVES DURING REM SLEEP IN 2 4 M 0 OLD NORMAL BOY
i sec
Fig. 5 Underlined segments of EEG were judged as irregular slow
waves.
the autistic group were due to exceptionally high values in two autistic children (Fig. 2). All but one R E M sleep period contained more than one synchronous slow wave. These waves were distributed over 84.7 ~o of the R E M sleep time in the autistic children and 73.5 ~o in the normals.
Irregular slow waves (see Fig. 5). Unlike the 10.5-15 c/sec and synchronous slow wave activity, it was difficult to obtain concurrence among those judging this activity. Whereas irregular slow waves seemed to occur during R E M sleep in both diagnostic groups with about the same frequency as synchronous slow waves, this E E G pattern could not be reliably quantified. Rapid eye movement activity. The mean number of single eye movements occurring during the first two R E M sleep periods was 1.78/min and 2.87/min, respectively in the autistic and in the normal group. (For the difference between these means see Table II.) The difference between the two groups in the mean number of eye movement bursts occurring during the first two R E M sleep periods was not significant. On the other hand, the difference in the mean percent of time during which eye movement bursts occurred during the first two R E M sleep periods was significant (see Table II). Therefore, the duration but not the initiation of rapid eye movement bursts was reduced in the autistic children. Relationships between EEG patterns and rapid eye movement activity 1. Quantitative relationships (see Table III): Correlation coefficients were computed for the amount of 10.5-15 c/sec and synchronous slow wave activity and the several measures of rapid eye movement activity recorded during the first two R E M sleep periods of each night. N o relationship between either E E G pattern and the number of single eye movements could be established in either diagnostic group. No relationship between 10.5-15 c/sec activity and rapid eye movement burst activity could be demonstrated. However, in the six normal children, there were strong positive linear correlations between the amount of synchronous slow wave activity and the amount of eye movement burst activity (significant at P < 0.05). In contrast, there was no relationship between the quantity of synchronous slow wave activity and the quantity of rapid eye movement burst activity in the group of eight autistic children. Because two autistic children had exceptionally high values for synchronous slow waves, correlations Electroenceph. clin. Neurophysiol., 1969, 26:167-175
171
REM SLEEP IN AUTISTIC CHILDREN TABLE III
Quantitative relationship between synchronous slow waves and eye movement bursts during the first two REM sleep periods of each subject night Correlations between:
Normal children N~6
Autistic children N=8
N~6
Number of synchronous slow waves (/min) and number of eye movement bursts (/rain)
r = --0.8647
r
+0.2589
r -- +0.5117"
Percent of REM sleep time during which synchronous slow waves and during which eye movement bursts occurred
r = +0.8813
r
--0.0485
r =: +0.6414"
* These values for r were obtained after removal of two children with exceptionally high values for synchronous slow waves from the autistic group. TABLE IV Temporal relationship between synchronous slow waves and eye movement bursts during the first two REM sleep periods of each subject night Normal children
Autistic children
Mean percent of synchronous slow waves occurring during eye movement bursts
29.7
26.7
Mean percent of REM sleep time during which eye movement bursts occur
26.1
15.6
Increase in mean percent of synchronous slow waves occurring during eye movement bursts above expected value Mean percent of synchronous slow waves occurring during 3 sec intervals preceding eye movement bursts
3.58 •0.6
11.1 11.5
Mean percent of REM sleep time during which 3 sec intervals preceding eye movement bursts occur
9.46
7.43
Increase in mean percent of synchronous slow waves occurring during 3 sec intervals preceding eye movement bursts above expected value
1.13
4.07
between this activity and eye m o v e m e n t burst activity were c o m p u t e d separately for the six other autistic children. While the correlation coefficients were increased they did n o t achieve significance (P > 0.05) 1.
1 Using a z transformation of r, the difference between the correlation coefficients (for percent of REM sleep time during which synchronous slow waves and eye movement bursts occurred) for the entire normal and entire autistic groups is significant at P=0.05. However, when the normal group is compared to the autistic group after removal of the two autistic children with high values for synchronous slow waves, the difference is no longer significant.
2. Temporal relationships (see Table IV): Th e distribution o f synchronous slow waves in respect to b o t h the eye m o v e m e n t burst an d pre-eye m o v e m e n t burst periods was almost identical in the n o r m a l an d autistic children. H o w e v e r , as the percent d u r a t i o n o f eye m o v e m e n t burst time was less in the autistic than in the n o r m a l children (see above), the concentration o f sync h r o n o u s slow waves during the eye m o v e m e n t bursts increased in the autistic children (significant at P = 0.042). Th e n o r m a l children showed no tendency t o w a r d increased c o n c e n t r a t i o n o f synchronous slow waves during eye m o v e m e n t bursts. Th e increased c o n c e n t r a t i o n o f syn-
Electroenceph. clin. NeurophysioL, 1969, 26:167-175
172
E.M. ORNITZ et al.
chronous slow waves during the eye movement bursts in the autistic children did not, however, distinguish them fiom the normal group ( P = 0.161, t=1.52 with 9.84 ° of freedom). Finally, neither the autistic nor the normal children showed a significant concentration of synchronous slow waves preceding the eye movement bursts. In summary, within the group of normal children, there was a tendency for a greater amount of eye movement burst activity to be associated with a greater amount of synchronous slow wave activity, whereas in the group of autistic children this quantitative relationship was minimal. In both diagnostic groups, the temporal distribution of synchronous slow waves was similar in respect to eye movement burst activity, and the increased concentration of this EEG pattern during the shorter eye movement bursts in the autistic children did not discriminate between the two diagnostic groups. Follow-up nights in autistic children Five autistic children were studied on a second night. One 22-month- and one 25-monthold were re-studied at 23 and 26 months respectively. One 39-month-old was re-studied at 48 months. Two 47-month-olds were re-studied, one at 58 months and the other at 68 months. In four of these five children, the number of occurrences and duration of 10.5-15 c/sec activity during REM sleep decreased on re-study, the decrement tending to be proportional to the increasing age of the child. In one child there was an increase in this activity. For the autistic group, the mean number of these waves per minute of REM sleep time (for the first two REM sleep periods) was 0.125/min. Whereas this represented a group decrement from the initial recordings in the autistic children, their group values remained higher than the normal mean of 0.038/min (difference significant at P = 0.043). In all five autistic children the percent of REM sleep time during which eye movement bursts occurred increased on re-study, the increase tending to reflect the increasing age of the individual child. The mean percent time of eye movement burst activity on re-study was 20 ~ which approached the normal mean value of 26.1 ~o (difference not significant).
DISCUSSION
The major findings of this investigation are that in a group of young autistic children there is an unusually large amount of 10.5-15 c/sec activity in the EEG, a decrease in the amount of rapid eye movement activity, and an absence of the normal quantitative association of synchronous slow wave activity and rapid eye movement burst activity during REM sleep. It was also shown that in normal 2- and 3-year-old children the EEG of REM sleep, which has been characterized as a low voltage fast record (Dement and Kleitman 1957; Roffwarg et al. 1964; Roffwarg et al. 1966), contains over 270 of synchronous slow wave activity. The mean percent sleep time spent in REM sleep and the mean accumulated sleep times prior to the onset of each REM sleep period were equivalent in the normal and autistic groups. This finding confirms previous studies (Ornitz et al. 1965a,b) indicating no gross abnormality in the patterning of the n o n - R E M REM sleep cycle in autistic children. The smaller values in both groups for percent time spent in REM sleep (13.670 for the autistic and 11.1 for the normals) in this study as compared to the earlier studies (22.270 and 20.270, respectively) reflect the narrower definition of REM sleep used; i.e., from the first to the last eye movement burst, and the fact that all night recording was not done. Therefore, in the context of a normal n o n - R E M - R E M sleep cycle in autistic children, the present study is concerned with several abnormal findings within REM sleep. The presence of an abnormal amount of 10.5-15 c/sec activity during REM sleep suggests a possible defect of maturation in the EEG of young autistic children. Parmelee et al. (1968, in press) have demonstrated 12-15 c/sec activity during active (REM) sleep in premature, term, 3- and 8-month-old infants, the amount of this activity becoming progressively less with increasing age. Quantitative comparisons with our data are not possible because in the infant studies this activity was quantified as part of specific EEG patterns containing other frequency bands. However, the almost complete absence of 10.5-15 c/sec activity in our normal children (0.04~) Electroenceph. clin. NeurophysioL, 1969, 26:167-175
173
REM SLEEP IN AUTISTIC CHILDREN
indicates that the autistic subjects have retained a considerable amount (0.34~o) of a frequency band found in REM sleep during earlier developmental stages. The fact that a few of the autistic but none of the normal children had activity which not only shaled the frequency characteristics of sleep spindles (Gibbs and Gibbs 1950) but also had the wave form (grade 2 and grade 3) of spindles found in stage 2 sleep also suggests a deficient differentiation of sleep stages in the autistic children. Our finding that 26.1 ~ of REM sleep time in young normal children is taken up by rapid eye movement bursts is almost identical to the 2 5 ~ reported for normal adults (Aserinsky 1967). The significant reduction of both single eye movements and eye movement burst time in the autistic children is consistent with the reduced eye movement activity found in actively ill adult schizophrenics (Feinberg et al. 1965; Feinberg 1967). This finding in both patient groups is consistent with the developmental relationship between childhood autism and later schizophrenia (Ornitz and Ritvo 1968). We have further found that the number of rapid eye movement bursts is not reduced in the autistic children while their duration is reduced. This suggests that CNS influences initiating eye movement activity are intact while those factors sustaining the activity are either deficient or inhibited. The rapid eye movements of REM sleep and the phasic depression of afferent transmission during the eye movement bursts are dependent on the integrity of vestibular nuclei (Pompeiano and Morrison 1965; Carli et al. 1967). There is an absence of the phasic depression of sensory input during the rapid eye movements of REM sleep in autistic children (Ornitz et al. 1968). The present finding of reduced oculomotor activity during REM sleep provides further evidence of impaired central vestibular function in the sleeping autistic child and is consistent with the reduced nystagmoid response to vestibular stimulation in the waking autistic child (Colbert et al. 1959; Ritvo et al. in preparation). Reding and Fernandez (1968) have demonstrated a relationship between spontaneous rapid eye movements and induced nystagmus during REM sleep. In this study, we have measured the 2.5-3.5
c/sec sinusoidal EEG activity in REM sleep and demonstrated its quantitative association with the rapid eye movement bursts in the normal children. This activity is distinct from that which has been described in adults as "sawtooth" or "sharp" waves (Berger et al. 1962; Dement 1964) as it is not concentrated in the pre-burst intervals. Most interesting was the finding of a reduction, in the autistic children, of the quantitative association between this EEG pattern and the oculomotor activity. Therefore, we postulate that a neurophysiologic influence underlying the organization of cortical activity (as manifested by this EEG pattern) and the rapid eye movements may be impaired in the autistic children. This organizing influence as well as its postulated impairment is probably of subcortical origin and may be mediated through central vestibular mechanisms. The unusual presence of the 10.5-15 c/sec activity during REM sleep in the autistic children suggests that the impaired organization of EEG and oculomotor activity may be on a maturational basis. The tendency in the autistic children for both the 10.5-15 c/sec EEG and the eye movement activity to approach more normal values with increasing age also suggests a maturational factor and emphasizes the importance of studying these children at a young age. SUMMARY
1. 10.5-15 c/sec EEG activity, synchronous slow wave EEG activity and eye movement activity during REM sleep were quantified in eight young autistic and six age-matched normal children. 2. A significantly greater amount of 10.5-15 c/sec activity was found in the autistic children than in the normals. 3. A significantly reduced number of single eye movements and percent time of eye movement burst activity was found in the autistic children as compared with the normals. 4. Considerable synchronous slow wave activity was found in both groups of children. However, there was a strong quantitative association between the synchronous slow waves and the eye movement bursts in the normals, while this association was reduced in the autistic children. Electroenceph. clin. NeurophysioL, 1969, 26:167-175
E.M. 0RNITZ et al.
174
5. It is postulated that the depressed eye movement burst activity in the autistic children is a manifestation of deficient or inhibited central vestibular function. The reduced quantitative association between the synchronous slow waves and the eye movement bursts further suggests impairment of an organizing influence underlying integration of cortical and oculomotor activity. 6. These neurophysiologic abnormalities in the autistic children may be related to maturational factors as suggested by the persistence of 10.5-15 c/sec frequencies in the REM sleep EEG and the tendency to approach more normal values with increasing age. RI~SUMI~ EEG ET MOUVEMENTSOCULAIRESRAPIDES PENDANT LES PHASES DE MOUVEMENTS OCULAIRES DU SOMMEIL CHEZ LES ENFANTSNORMAUXET AUTISTIQUES
1. L'activit6 EEG, de 10,5-15 c/sec, l'activit6 EEG d'ondes lentes synchrones et l'activit6 de mouvements oculaires ont 6t6 quantifi6es pendant les phases de mouvements oculaires chez huit jeunes enfants autistiques et six enfants normaux appareill6s quant/t l'~ge. 2. On observe une proportion d'activit6 de 10,5-15 c/sec nettement plus grande chez les enfants autistiques que chez les normaux. 3. On note chez les enfants autistiquesune r6duction significative des mouvements oculaires isol6s et du pourcentage de temps des bouff6es de mouvements oculaires par comparaison aux normaux. 4. Une activit6 d'ondes lentes synchrones consid6rable est observ6e dans les deux groupes d'enfants. Cependant, on observe une association quantitative nette entre les ondes lentes synchrones et les bouff6es de mouvements oculaires chez les normaux, alors que cette association est r6duite chez les enfants autistiques. 5. Les auteurs sugg~rent que la r6duction des mouvements oculaires chez les enfants autistiques est une manifestation de la d6ficience ou de l'inhibition des fonctions vestibulaires centrales. La r6duction de l'association quantitative entre ondes lentes synchrones et bouff6es de mouvements oculaires sugg6re en outre une atteinte de l'influence organisatrice qui soustend l'int6gration des activit6s corticale et oculo-motrice.
6. Les anomalies neurophysiologiques observ6es chez les enfants autistiques peuvent ~tre corr616es h des facteurs maturationnels, ce qui est sugg6r6 par la persistance des fr6quences de 10,5-15 c/sec au cours de I'EEG pendant les phases de mouvements oculaires du sommeil et par la tendance ~t la normalisation avec l'fige. The authors are grateful for the helpful technical assistance of Mrs. L. Dietrich and Miss A.. Mason. Statistical analysis was facilitated by the Health Sciences Computing Facility supported by N.I.H. Grant FR 3.
REFERENCES ASERINSKY, E. Physiological activity associated with segments of the rapid eye movement period. Res. Publ. Ass. Res. nerv. Dis., 1967, 45: 338-350. BERGER,R. J., OLLEY,P. and OSWALD,I. The EEG, eyemovements and dreams of the blind. Quart. J. exp. Psychol., 1962, 14: 183-186. CARLI,G., DIETE-SPIFF,K. and POMPEIANO,O. Vestibular influences during sleep. V. Vestibular control on somatic afferent transmission in the cuneate nucleus during desynchronized sleep. Arch. ital. Biol., 1967, 105: 83-103. COLBERT, E. G., KOEGLER,R. R. and MARKHAM,C. H. Vestibular dysfunction in childhood schizophrenia. Arch. gen. Psyehiat., 1959, 1: 600-617. DEMENT,W. and KLEITMAN,N. Cyclic variations in EEG during sleep and their relation to eye movements, body motility, and dreaming. Electroenceph. clin. Neurophysiol., 1957, 9: 673-690. DEMENT,W. C. Eye movements during sleep. In M. BENDER fled.), The oculomotor system. Harper (Hoeber), New York, 1964: 3662,16. FEINBERG, I. Sleep electroencephalographic and eyemovement patterns in patients with schizophrenia and with chronic brain syndrome. Res. Publ. Ass. Res. nerv. Dis., 1967, 45: 211-240. FEINBERG,I., KORESKO,R. L. and GOTTLIEB,F. Further observations on electrophysiological sleep patterns in schizophrenia. Comprehens. Psychiat., 1965, 6: 21-24. GIBBS, F. A. and GIBBS,E. L. Atlas ofelectroencephalography, Vol. 1. Addison-Wesley, Cambridge, 1950, 324 p. ORNITZ, E. M. and RITVO, E. R. Perceptual inconstancy in early infantile autism. Arch. gen. Psychiat., 1968, 18: 76-98. ORNITZ, E. M., RITVO, E. R., CARR, E. M., PANMAN, L. M. and WALTER, R. n . The variability of the auditory averaged evoked response during sleep and dreaming in children and adults. Electroenceph. clin. Neurophysiol., 1967, 22: 514-524. ORNITZ,E. M., RITVO,E. R., PANMAN,L. M., LEE, Y. H., CARR,E. M. and WALTER,R. D. The auditory evoked response in normal and autistic children during sleep. Electroenceph. clin. Neurophysiol., 1968, 25: 221-230. Electroenceph. clin. Neurophysiol., 1969, 26:167-175
REM SLEEP IN AUTISTICCHILDREN ORNITZ,E. M., RITVO,E. R. and WALTER,R. D. Dreaming sleep in autistic twins. Arch. gen. Psychiat., 1965a, 12: 77-79. ORNITZ,E. M., RITVO,E. R. and WALTER,R. D. Dreaming sleep in autistic and schizophrenic children. Amer. J. Psychiat., 1965b, 122: 419-424. PARMELEE JR., A. H., AKIYAMA,Y., SCHULTZ, i . A., WENNER, W. H., SCHULTE,F. J. and STERN,E. The electroencephalogram in active and quiet sleep in infants. In P. KELLAWAYand I. PETERS~N (Eds.), Clinical electroencGvhalography of children. Almqvist and Wiksell, Uppsala, Stockholm, 1968: 77-88. PARMELEE JR., A. H., SCHULTE, F. J., AKIYAMA,Y., WENNER, W. H., SCHULTZ, M. A. and STERN, E. Maturation of EEG activity during sleep in premature infants. Electroenceph. din. Neurophysiol., 1968, 24: 319-329.
175
POMPEIANO,O. and MORRISON,A. R. Vestibular influences during sleep. I. Abolition of the rapid eye movements of desynchronized sleep following vestibular lesions. Arch. ital. Biol., 1965, 103: 569-595. REDING, G. R. and FERNANDEZ,C. Effects of vestibular stimulation during sleep. Electroenceph. clin. Neurophysiol., 1968, 24: 75-79. R.ITVO,E. ex..,ORNITZ,E. M. and WALTER,R. D. Clinical application of the auditory averaged evoked response at sleep onset in the diagnosis of deafness. Pediatrics, 1967, 40: 1003-1008. ROFFWARG,H. P., DEMENT, W. C. and FISHER,C. Preliminary observations of sleep-dream pattern in neonates, infants, children, and adults. In E. HARMS(Ed.), International series of monographs on ehiM psychiatry. Pergamon, New York, 1964, 2: 60-72. R.OFFWARG, H. P., Muzto, J. N. and DEMENT, W. C. Ontogenetic development of the human sleep-dream cycle. Science, 1966, 152: 604-619.
Reference: ORNITZ,E. M., RITVO,E. R., BROWN,M. B., LA FRANCHI,S., PARMELEE,T. and WALTER,R.. D. The EEG and rapid eye movements during REM sleep in normal and autistic children. Electroenceph. clin. Neurophysiol., 1969, 26: 167-175.