Visual evoked potentials of infants

395

SOCII~TI~ d'E.E.G, et de NEUROPHYSIOLOGIE CLINIQUE DE L A N G U E FRANI~AISE . Sdance du 3 octobre 1972

Communications

Visual Evoked Potentials of Infants *. R. J.

ELLINGSON,G. H. LATHROP,B. NELSON and T. DANAHY.

Nebraska Psychiatric Institute University of Nebraska Medical Center Omaha, Nebraska 68105 U.S.A.

The human visual evoked potential (V.E.P.) recorded from derivation OZ-A1 consists of 8 components. We have chosen to label them as shown in Fig. 1. The early components (P0, NO, and P1) are of low voltage (usually less than 1 b~V), and are often not seen. We have shown that components P0-P2 are of relatively constant latency both in infants and adults, and that they show no variation related to the wakefulness-sleep cycle (ELJ.~NGSON, 1970, ELHNGSONet al., 1973). Components N2, P3, and N3, on the other hand, do vary in relation to the wakefulness-sleep cycle in adults. Specifically, their latencies are longer during slow wave sleep than during wakefulness, and the voltage of the N3 component increases during slow wave sleep, or is commonly absent during wakefulness, being replaced by a sequence of rhythmic waves called the <> (BARLOW, 1960). In the newborn, components N2, P3, and N3 also vary in latency and amplitude with time, but not in relation to the sleep cycle, nor in relation to any other variables we have been able to identify. Since the recordings of sleep-wakefulness behavior, E.E.G., and V.E.P.s in newborns in our earlier studies (ELLINGSON, 1970, Er.LTN~SON et al., 1973) were less than 90 minutes long, the question arose as to whether there might be longer-term cycling of V.E.P. configuration in newborns, whether or not such cycling could be related to other variables. It seemed possible that the V.E.P. of the immature brain might have a period of its own, which becomes connected to the wakefulnesssleep cycle only after the postnatal development of neuronal circuitry and/or after exposure for a time to the extrauterine environment. We have therefore repeated our observations in part on 7 additional normal full-term newborns, using recording periods up to three-and-a-half hours.

* Supported by Grant No. HD-00370 from the National Institute of Child Health and Human Development, NIH, DHEW, U.S.A. Tir~s f part : R. J. ELL~NGSON (/t l'adresse ci-dessus).

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Fio. l. - - Average visual evoked p o t e n t i a l (V.E.P.) d u r i n g quiet sleep in a n o r m a l full-term n e w b o r n 2 days after birth. The labeling o f the 8 c o m p o n e n t s is ours and is relevant only to V.E.P.s f r o m OZ-A1 or very similar derivations. N o t e the p r o l o n g e d N3 c o m p o n e n t (outlasting the period of analysis) a n d its irregular configuration. This feature is c o m m o n in infancy, is occasionally seen as late as 6 years o f age, but is n o t seen in the a d u l t V.E.P. S = stimulus, which is preceded by a 10 b V square-wave c a l i b r a t i o n signal. In this a n d Fig. 3 a n u p w a r d deflection indicates increasing n e g a t i v i t y at OZ.

We have also shown that the V.E.P. shows some maturational changes by 3 months of age, but save for a striking decrease in latency, these changes are relatively slight (ELLIN6SON etal., 1973). The question remains : At what age is V.E.P. maturity attained in terms of configurational stability and of variation in relationship to the wakefulness-sleep cycle ? To attempt to find an approximate answer, we have made extended recordings of V.E.P.s on 2 separate days on 4 infants at 12 months of age and 2 at 20 months. Stage

W (wakefulness)

D(drowsiness)

A(active sleep)

Q(quiet sleep)

EEG pattern

low-voltage irregular/mixed/ rarely highvoltage slow

low-voltage irregular/mixed/ rarely highvoltage slow

low-voltage irregular/mixed/ rarely highvoltage slow

mixed/highvoltage slow/ trac~ alternant

Respiration

irregular

irregular

irregular

regular

Submental D~G pattern

usually phasic

usually phasic

phasic

tonic

Eye movements

usually present, variable/eyes open, "bright"

few or none/ eyes open or half closed, "glassy"

R~Ms present/ eyes closed

none/eyes closed

Body movements

usually present/ vocalization, crying

occasional

pr~se~t

Table I. - Criteria of the stages of the wakeful~ess-sleep indeterminate stage of sleep is omitted.

rare or absent

cycle, after Anders et al. (1970).

The

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Methods. Brief flashes of light from a Grass P.S.-2 photostimulator were presented to the subjects at irregular intervals of 3-8 seconds throughout recording periods of up to 3 1/2 hours while the infants lay in a sound- and electrically-shielded room. Eight channels of E.E.G., 2 channels of electro-oculogram, submental E.M.G., and respiration were recorded simultaneously on a Grass Model 78 E.E.G. polygraph and a PI-6208 magnetic tape recorder. Body movements were recorded by an observer. Single recordings were made on the newborns: Recordings were made on 2 days a week apart in the case of the 12 and 20 month olds. Stages of the wakefulness-sleep cycle were classified for each recording according to the criteria of ANDERS et aL (1971) (newborns ; Table I) or according to the criteria of RECHTSCHAFFENand KALES (1968) (12 and 20 month olds). V.E.P.s from derivation OZ-A1 were averaged off-line in blocks of 32 responses, using a P.D,P.-12 computer. Each average V.E.P. was then classified according to the stage of the wakefulnesssleep cycle predominating while the 32 individual V.E.P.s of which it was the average had been recorded. The latencies and some amplitudes of V.E.P. components were measured and the latencies were graphed. Pearson product-moment coefficients of correlation were calculated (1) between blindly selected V.E.P.s rnm the first and second recording sessions for typical stages of wakefulness, slow-wave sleep, and R.E.M. sleep for each of the 12 month old subjects, and (2) between V.E.P.s derived simultaneously from O1-A1, O2-A2, and OZ-A1 derivations for each stage for each subject. RESULTS

Newborns. Fig. 2 shows a typical plot. There is no relationship between latencies of the V.E.P. c o m p o n e n t s and the wakefulness-sleep cycle, n o r is there any evident cycling of V.E.P. latencies independent of the wakefulness-sleep cycle. Inspection of the average V.E,P.s themselves also failed to reveal any cyclic changes. Five of 7 subjects showed such considerable V.E.P. variability. The other two showed relatively simple and stable V.E.P.s which varied little with the wakefulness-sleep cycle or otherwise. The averiige V.E.P.s of one of these subjects are s h o w n in Fig. 3. NOUVEAU'NE~ P,GE DIUN JOUR

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FIG. 2. - - Parallel plots of stages of the wakefulness-sleep cycle (STADE) and components of 4l successive V.E.P.s and their latencies during a single recording session in a newborn. N3 is not plotted because the great variability of its time course and waveform in the newborn make it impossible in general to determine the peak of the wave (see Fig. 1). W = wakefulness ; D = drowsiness ; A = active sleep ; Q = quiet sleep. Cross-hatched bars indicate periods of transition from one state to another.

12 and 20 month old infants. At 12 m o n t h s of age the V.E.P. has matured beyond that of the 13 week old (ELLINGSONet al., 1973), but less than one might expect. Its variability within recording sessions (Fig. 4) is s o m e w h a t less t h a n at birth and 3 months, and relationships with the wakefulnesssleep cycle seem to the be emerging, but considerable diurnal variability remains. Even at 20 m o n t h s

398

SOCII~TI~ D'E.E.G. ET DE NEUROPHYSIOLOGIE CLINIQUE DE LANGUE FRANt~AISE the variability o f t h e V. E . P . within sessions a n d its diurnal variabilitywas greater t h a n in the adult in b o t h of the subjects tested. T h e m e a n coefficient o f correlation betwen the V.E.P.s of the 2 recording sessions (averaged across all states a n d all 4 subjects u s i n g the z-transformation) for the 12 m o n t h old g r o u p was .84. This is to be c o m p a r e d with .58 for newborns, .70 for 3 m o n t h old infants a n d .82 for adults (ELLINCSON et aL, 1973). By this m e a s u r e t h e 12 m o n t h olds do n o t differ f r o m the adults. T h e m e a n coefficient a m o n g the 3 occipital-area derivations (averaged across all states a n d all subjects) for the 12 m o n t h old g r o u p was .78, c o m p a r e d with .68 for newborns, .67 for 3 m o n t h olds, a n d .90 for adults. By this m e a s u r e the 12 m o n t h olds are m o r e m a t u r e t h a n the y o u n g e r infant groups, b u t h a v e n o t yet attained the a d u l t level of h o m o g e n e i t y of V.E.P. [configuration within the occipital area,

OZ-AI

DISCUSSION.

W e remain u n a b l e to d e m o n s t r a t e cyclic variations in V.E.P. c o n f i g u r a t i o n in the n e w b o r n over periods o f time u p to three-and-a-half hours. T h e early c o m p o n e n t s o f the V.E.P. (P0-P2) are o f relatively stable • latency, b u t are variable in expression, except for c o m p o n e n t P2, which is the m o s t stable a n d is a l m o s t always indentifiable. T h e late c o m p o n e n t s (N2-N3) are irregularly variable in all respects. It is concluded that the overall c o n f i g u r a t i o n o f the V.E.P. o f t h e imm a t u r e cerebral cortex o f the n e w b o r n at birth varies r a n d o m l y in time, b u t the possibility r e m a i n s that very long-term cyclic variations (circadian .9) m i g h t occur.

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FIG. 3 - - Successive average V,E.P.s of a normal full-term newborn one day after birth, during a recording period of 2 hours 40 minutes. Note the stability in the latency of the P2 (major downward) component. The only variability in this relatively stable V.E,P. is some fluctuation in the amplitudes of the late components (P2-N3). It should be noted, however, that such fluctuations are not linked to the stages of the sleep cycle, that is, there are no systematic changes which occur as the stage of sleep shifts from Q to A and back again. S ~ stimulus ; Q = quiet sleep ; A = active sleep.

t

Even at 12 a n d 20 m o n t h s t h e latency o f c o m p o n e n t P2 r e m a i n s the only variable stable e n o u g h to be used to characterize the individual subject. D a t a o f DUSTMAN a n d BECI,: (1969) suggest t h a t stability a p p r o x i m a t i n g that of the adult is attained at least by 3-4 years o f age. O u r present correla-

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399

tional data suggest that such a stage is approached by the end of the first year of life, although other analyses of our data do not converge on such a conclusion. It appears that full maturation of the human V.E.P. requires an extended period of time. The most important maturational change, however, is probably decrease in latency. At birth V.E.P. latency is approximately 2 1/2 tim~s the adult level (ELLINGSDN, 1960, 1967). B~tween 6 and 12 weeks after birth it decreases rapidly to about 1 1/2 tim~s the adult level, and th~n approaches th~ azlult level more gradually over the next 2 to 3 years. Subtler maturational changes, such as increasingly close associatioa of V.E.P. configuration with the wakefulness-sleep cycle, decrease in diflrnal variability, and the ENFANT ~.G~ DE 12 MOIS 3 ~0 ~

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l~'m. 4. - - Parallel plots of stages of the wakefulness-sleep cycle (STADE) after Rechtschaffen and Kales (1968) and the components of 41 successive V.E.P.s and their latencies during a single recording session in a 12 month old. Note the flatness of the latency curves for components N1 and P2. establishment of stable topographical relationships occur more gradually. Thus, maturation of the V.E.P. might be compared with that of the E.E.G. itself, which requires 12 to 20 years to mature fully, although the most striking postnatal maturational changes occur between birth and 3 to 4 months o f age. R~stsM~. Les auteurs ont montr6 dans un travail ant6rieur que la co~afiguration du P.E.V. chez le nouveaun6 et chez l'enfant de 3 mois montre une grande var iabilit6 diurne ; par ailleurs et contrairement au P.E.V. de l'adulte la configuration de ce P.E.V. n'est pas li6e au cycle de veille-sommeil. Les auteurs apportent g ce propos des donn~es compldmentaires : 1° Ils ont enregistr6 les P.E.V. de 7 nouveau-n6s pendant des p6riodes allant jusqu'/t 3 h. et demie, afin de rechercher des variations cycliques 6ventuelles de ce potentiel ind~pendantes du cycle veillesommeil. Ces recherches n ' o n t pas permis de mettre en 6vidence de telles variations cycliques. 2 ° Des enregistrements identiques ont 6t6 effectu6s/1 une huitaine d'intervalle chez 6 enfants dont 4 de 12 mois et 2 de 20 mois afin de d6terminer si ~ ces figes le P.E.V. a, ou non, atteint une configuration stable et s'il pr6sente ou non un rapport avec le cycle veille-sommeil. Bien que le P.E.V. ait quelquepeu <>~t l'~ge de 12 mois, et un peu davantage b. 20 mois, sa variabilit6 pendant le m~me enregistrement, ainsi que sa variabilit6 diurne, restent toujours plus grande que celle de l'adulte. M~me ~ 20 mois la Iatence du composant P2 reste la seule variable suffisamment stable pour pouvoir caract6riser le sujet individuel. Pour atteindre la maturation compl6te, le P.E.V. chez l'hommeexige une p6riode de temps prolong6, et ceci bien que la diminution de la latence du P.E.V. s'ach6ve en grande partie/~ l'fige .de 3 mois.

Rev. d'E.E.G. Neurophysiol.,

1972, t. 2, n ° 4.

27

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SOCIETE D'E.E.G. ET DE NEUROPHYSIOLOGIE CLINIQUE DE LANGUE FRAN~AISE

BIBLIO GRAPHY ANDERS (T.), EMDE (R.) and PARMELEE (A.). Eds. A manual of standardized terminology, techniques and criteria for scoring of states of sleep and wakefulness in newborn infants. U.C.L.A. Brain Information Service, N.LN.D.S. Neurological Information Network, edit., Los Angeles, 1971, 40 p. BARLOW (J. S.). Rhythmic activity induced by photic stimulation in relation to intrinsic alpha activity in the brain of man. Electroenceph. Clin. Neurophysiol., 1960, 12, 317-326. DUSTMAN(R. E.) and BECK (E. C.). The effects of maturation and aging on the wave form of visually evoked potentials. Electroenceph. Clin. Neurophysiol., 1969, 26, 2-11. ELLINGSON(R. J.). Cortical electrical responses to visual stimulation in the human infant. Electroenceph. Clin. Neurophysiol., 1960, 12, 663-677. ELLtN~SON (R. J.). Methods of recording cortical evoked responses in human infants. Regional development of the brain in early life. Editor A. Minkowski, Blaekwell, edit., London, 1967, 413-435. ELL1NGSON (R. J.). Variability of visual evoked responses in the human newborn. Electroenceph. Clin. NeurophysioL, 1970, 29, 10-19. ELLINGSON(R. J.), LATHROP (G. H.), DANAHY(T.) and NELSON(B.). Variability of visual evoked potentials in human infants and adults. Electroenceph. Clin. Neurophysiol., 1973, 34, 113-124. RECHTSCHAFFEN(A.) and KALES(A.), Eds. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. National Institutes of Health Publication No. 204, U.S. Government Printing Office, edit., Washington, I968, 52 p.