Electroencephalography and Clinical Neuroph ysiology , 1978, 44:411--423

411

Elsevier]North-Holland Scientific Publishers Ltd.

AUDITORY EVOKED POTENTIAL DEVELOPMENT IN EARLY CHILDHOOD: A L O N G I T U D I N A L STUDY* ELIZABETH S. OHLRICH, ANN B. BARNET, IRA P. WEISS and BETTY L. SHANKS Children's Hospital National Medical Center, 111 Michigan Ave., N.W., Washington, D.C. 20010 (U.S.A.)

(Accepted for publication: August 10, 1977)

Sensory averaged evoked potentials (EPs) afford a m e t h o d of studying the neural development of the maturing child. Most research on EP development has utilized groups of children at different ages. For the few studies in which longitudinal data were collected, little analysis of the responses of individual subjects were reported. Considerable variability in EP characteristics has been found both among and within subjects, b u t within-subject variability is less (Dustman and Beck 1963; Ellingson 1974). Most measurements of intra-subject variability, however, have been based on short term experiments. Although some relevant reports are available (Dustman and Beck 1963, 1965; Ellingson et al. 1974; Rust 1975), there has been little systematic attention to questions concerning the extent to which individual normal children conform to the developmental trends which have been reported, and whether children show characteristic and stable response patterns which might serve as an index of individual development. This laboratory has described the maturation of the auditory evoked potential (AEP) based on data obtained in cross-sectional study of normal sleeping children ranging in age from near birth to three years (Barnet and Goodwin 1965; Ohlrich and Barnet 1972, Barnet et al. 1975). Components of the vertex recorded AEP with post stimulus latencies of 30 to 1000 msec were examined. Latencies of c o m p o n e n t s occurring after

150 msec were found to decrease with age, the most rapi d decrease being in the first year of life. AEP amplitudes also showed significant age related changes. AEP parameters were influenced n o t only by age b u t also by the child's state along the sleep/wake continuum. Although significant age trends were discovered, the responses were also highly variable. Age and sleep stage accounted for less than half of the variability. The purposes of the present study were to see to what degree the findings reported in the cross-sectional study (Barnet et al. 1975) could be replicated; to examine individual patterns of cortical AEP maturation; to determine if longitudinal data would show substantially less variability than crosssectional data; to further measure the effects of stage of sleep on the AEP; and to assess possible influences of other factors such as sex and stimulus order. To this end, we examined AEPs for 16 normal children who were tested repeatedly between the ages of approximately two weeks and three years. Thirteen of these children were represented once each in the cross-sectional study (Barnet et al. 1975). The thirteen AEPs which appeared in both studies were widely distributed over the three year age range.

The research reported here was supported by PHS Grants HD 02296 and K2MH45472.

Five females and 11 males were tested in recording sessions which t o o k place at approxi-

Methods Subjects

412

mately bi-weekly intervals through 6 months of age, at 3-month intervals from 6 to 18 months, and then at 6-month intervals until age 3. All children missed some sessions for various reasons, b u t each child is represented by data obtained during 8 to 18 sessions. All 16 of the children were tested until one year of age, 10 of the 16 until 2 years of age, 5 until 21A years and 3 until 3 years of age. Nine of the children, 8 white and one black, were living at home, and 7 children, all black, resided in child care institutions during the time period during which they were tested for this study. Pediatric and neurological examinations performed on all the subjects indicated no significant abnormalities. Scores on the Bayley Scales of Infant Development fell in the normal range. The Children were all products of full-term uncomplicated pregnancies and normal deliveries, had birth weights of 2500 g or more and had Apgar scores of 8 or above (Apgar 1953). The EP procedures were carried out only when the child appeared to be in good physical health. Procedure

The EEG was recorded with Grass silversilver chloride or gold electrodes attached to the scalp with electrode jelly and collodionsoaked absorbent cotton. Periorbital and submandibular electrodes were used to monitor variables related to subject state and technical adequacy of the recording. Results from an electrode at the vertex (Cz) referred to joined mastoids are reported here. The stimuli were sets of 100 65 dB SL* (108 dB SPL) clicks, presented through a loudspeaker once every 2.5 seconds. The 65 dB sets were interspersed among other sets of auditory and visual stimuli. If possible, i.e., if the child t o o k a long enough nap, the 65 dB set was repeated. Details of the procedures are * In dB above t h e m e a n t h r e s h o l d values for n o r m a l hearing adults t e s t e d u n d e r t h e c o n d i t i o n s used for t h e children. See Ohlrich a n d B a r n e t (1972) for f u r t h e r s p e c i f i c a t i o n o f t h e stimulus.

E.S. OHLRICH ET AL. presented in Ohlrich and Barnet (1972) and Barnet et al. (1975). All the data were collected while the children were sleeping; no sedation was used. Sleep stage ~was scored frQm the polygraph records using'the criteria of Anders et al. (1971) for the younger subjects and Rechtschaffen and Kales (1968) from about 3 months onward. The EPs were averaged on line by an electronic averager (CAT 400B), or offline by a Packard Bell 250 c o m p u t e r or PDP-11 computer. For most AEPs, amplitude and latency measurements were made from X-Y plots of the AEPs using a micrometer. Those EPs averaged on the PDP-11 were measured, after visual inspection, using an electronic cursor. The parameters of the vertex recorded A E P discussed in this report are the latencies of the most prominent and consistent positive (P) and negative (N) peaks of the one-second EP, and the amplitudes between these peaks. Those were: No, a small sharp negative deflection with a latency of 15--60 msec; P1, a positive deflection between No and N1 with a latency greater than 35 msec; NI; the trough preceding the rise to the positive P2 peak or a clear discontinuity in this slope. P2 was defined as the most prominent peak occurring with a post-stimulus latency of approx. 100--300 msec and N2 as the lowest negative deflection following P2. P3 ~vas the major positive wave following N2. P3 could have the P3A form, a prominent positive deflection followed by a negative trough, or the P3B form, a broad positive wave lacking a well defined peak. A P3A wave could be followed by a P3B wave of greater positivity. When a single measure of P3 was used, it was P3B, if present, and otherwise, P3A. Components are labeled in Fig. 1. Occasionally peaks selected by these rules did not appear to be homologous to peaks given the same label in other records. Rigid adherence to the criteria overemphasized within-subject variability to some extent; but we considered this preferable to the possibility of introducing a subjective bias in choosing peaks which might create an age trend where there was none.

A U D I T O R Y EP DEVELOPMENT: A L O N G I T U D I N A L STUDY

413

O

Z A ,

,

i

i

j

I

I

i

°¢~

"6

O

II

3.7 1.6 9.8 22.5 28.2 7.7 9.7

38 88 116 234 543 660 848 843

0.16 0.24J't 0.04 0.23"~t 0.08 0.54tt 0.47tt

0.00 -0,19tt -0.11 -0.56tt -0.58tt -0.23tt -0.35~t -0.38tt

6.5 4.3 11.0 36.4 37.9 41.5 44.8

38 71 104 153 315 502 686 646

1.6 1.8 15.4 26.4 24.6 10.5 11.9

35 69 104 231 534 665 777 785

0.49tt 0.30tJ" -0.40tJ0.23Tj0.24t~" 0.58t"t 0.51tt

-0.07 0.02 -0.01 -0.61t~ -0.67tt -0.28tt -0.28tt -0.41tt

7.4 5.0 6.2 37.7 48.4 40.6 51.5

33 70 104 154 318 540 671 627

36 Mo.

4.5 2.0 10.8 30.9 38.8 11.4 15.4

35 95 123 234 582 744 910 874

0.5 Mo.

0.10 0.20 0.02 0.07 -0.05 0.44tt 0.37it

0.12 -0.24~T -0.17 -0.62tt -0.69tt -0.45tt -0.54tt -0.48tt

r

6.4 4.5 11.4 35.8 33.6 42.2 45.3

40 69 99 153 287 453 623 603

36 Mo.

1.8 2.3 15.9 30.1 29.9 11.7 14.6

35 69 105 234 559 700 798 787

0.5 Mo,

0.41tt 0.19 -0.37tT 0.08 0.09 0.58tt 0.50tt

-0.08 0.05 -0.00 -0.60tt -0.74tt -0.41tt -0.41tt -0.43tt

r

Cross-sectional'~

6.9 4.2 6.6 33.8 36.3 39.3 43.9

33 72 105 156 300 501 655 632

36 Mo.

* All sleep stages combined : Statistics incorporate EPs from various stages of sleep. ** Stage 2 sleep: Only EPs collected during time subject was determined to have been in stage 2 sleep (or SWS or TA sleep for youngest subjects) were included in this analysis. *** Longitudinal: Statistics based upon the longitudinal data described in this report. Data collected from 254 EPs obtained by repeatedly testing 16 subjects. t Cross-Sectional: Statistics based upon cross-sectional data described in previous report (Barnet et al. 1975). Data collected from 130 EPs collected from 130 different subjects from 2 weeks to 3 years of age. t t r significant, P < 0.05.

Amph (~V) NoPI P2N2 N,P 2 P2N2 N~P3A N2P3B N2P~

Lat. (msec) No P~ N~ P2 N2 P3A P3B P3

r

0.5 Mo.

0.5 Mo.

36 Mo.

Longitudinal***

'Cross-sectional*

Longitudinal*** r

Stage 2 sleep**

All sleep stages combined*

Predicted values for each EP component at 0.5 and 36 months of age and the coefficients of correlation (r) for the value vs. log age regressions

TABLE I

0

AUDITORY EP DEVELOPMENT: A LONGITUDINAL STUDY Results

60-

Overall Results: 16 subjects, 194 sessions, 254 EPs. Results for the whole group will be considered first in order to develop a basis for comparison for the responses of individual subjects and also in order to ascertain to what extent the results of the present study confirm those of the cross-sectional study (Barnet et al. 1975). To define the relationship between AEP components and age, the regression of latency and amplitude measures on age and on log age and the corresponding coefficients of correlation were computed. As in the 1975 study, most of the relationships seemed to be better approximated b y the logarithmic function and the reported results are from the log age analyses. Relationships which are reported w i t h o u t c o m m e n t in the text were significant at P < 0.05. Latencies of P2 and subsequent components decreased over age for the total data (all sleep stages combined), and also when only EPs from stage 2 sleep were considered. Table I shows the correlation 1000 -

LONGITUDINAL . . . .

900 -

800

CROSS S E C T I O N A L

-

700 -

--

600

~

500-

Z

-

400 -

30°

-t........

PL

200 -

P1

1000 0.5

415

I

I

I

I

1

2

4

8 10

AGE

I

I

l

20

40

(months)

Fig. 2. Regressions of latencies of P1, P2, N2 and P3 on log age for AEPs from 16 longitudinally studied subjects and 130 subjects in a previously reported cross sectional study (Barnet et al. 1975).

LONGITUDINAL m - -

~

CROSS S E C T I O N A L /

SO

f

7

-"

,N

10 P1N1 0

0.5

I

I

I

I

I

I

I

1

2

4

8

10

20

40

AGE

Fig.

3.

Regressions

of

(months)

amplitudes

of PINi,

P2N~

and N2P3 on log age for AEPs from the longitudinal and cross sectional studies.

coefficients (r), and the intercepts at 0.5 and 36 months for the EP components for both the cross-sectional and longitudinal studies. The regression lines for P1, P2, N2, and P3 are shown in Fig. 2. P3A and P3B regressions were similar to that shown for P3. For the 27 EPs obtained during stages 3 and 4 sleep, only the latencies of N2, P3, and P3B varied significantly over age (r's = - 0 . 4 5 , 0.68 and 0.60, respectively). For the 21 EPs obtained during stage REM sleep, only P2 latency showed a significant change over age (r = - 0 . 6 2 ) . P1N,, P2N2, N2P3 and N2P3B amplitudes increased with age when EPs taken in all stages of sleep were considered (Table I, Fig. 3). When the analysis was restricted to subjects in stage 2 sleep, only N2P3 and N2P3B amplitudes were found to increase with age. Differences in results between Barnet et al. (1975) and the present study are summarized in Table I. The previously reported N2P3A increase over age f o r pooled data was primarily due to an increase in N2P3A amplitude as sleep stage varied from stages 1 to 4 and a simultaneous increase in frequency of stages 3 and 4 among older subjects. The strong coupling of P3A waves and stage 3--4 sleep observed in the cross-sectional data was n o t

E.S. OHLRICH ET AL.

416 evident in longitudinal sample in which Pag waves were found to occur as often in stage 2 as in 3--4 sleep. Overall, fewer P3A waves were present in the longitudinal sample (37%) than in the cross-sectional (55%). The 27 EPs recorded in stages 3 and 4 showed an increase over age in N2P3B amplitude but in no other amplitude. During stage REM sleep (21 EPs) only N2P3 and N2P3B amplitudes increased with age. REM EP amplitudes were lower than those recorded during stage 2 (18 vs. 33 gV for P2N2; 12.8 vs. 33 pV for N2P3). These differences persisted with the data were corrected for a difference in mean age between EPs collected in REM and stage 2. Amplitudes tended to be smaller for stage 2 EPs than for the EPs from stages 3 and 4 (33.8 vs. 37.5 pV). The longitudinal study confirmed the previously noted heavy preponderance of P3B waves in 1 REM (95%) and in the neonatal sleep stages TA and SWS (93%). Separate analyses of female and male subjects revealed that both males and females showed decreases over age in the latencies of P2, N2, P3 and P3B; P1 was found to decrease only in the males. No differences in mean latency were found between males and females for any peaks except P3 and P3B. The latencies for females for these peaks were somewhat shorter (P = 0.05). Both females and males showed increases in NEP3 and N2P3B amplitudes over age. For the males, there was also an increase in PINt amplitude. The data were also examined for the effect of race and rearing status, variables which in this study were almost completely confounded. All of the white children were living at home (H) and all but one of the black children were living in institutions (I) for dependent children. The data with respect to these variables were analyzed for the first year of life since the largest comparison group was available for this period. P2, N2 and P3 latencies decreased in both H and I groups, and N2P3B amplitudes increased. The I group had slightly longer latencies for P3 and P3B and smaller amplitudes for NoP1, PIN1, PEN2 and N2P38. Thirteen of the 16 subjects had one or

more sessions during which repeat AEPs to the 65 dB click were o b t a i n e d later in the session. In approx. 75% of the comparisons, amplitudes for P2N2 and the N2P3 waves were lower for the AEP obtained later in the session. AEP latency did n o t appear to vary systematically with the stimulus order factor. A complex interaction was found among stimulus order, the rearing/ race factor, and EP values. The difference in EP values between the first and second stimulus sets tended to be a function of both the rearing/race factor and which EP component was considered. The total data base was re-analyzed for the relationships of age to each EP measure, while sex, rearing/race status, stimulus order, laboratory site and equipment were held constant. Except for PEN2 amplitude which failed to show significant age relationships when certain combinations of those factors were held constant, the results were essentially the same as those reported for the data as a whole. The P2NE-age relationship had previously been shown to be weak in data restricted to stage 2 sleep. Changes in background EEG and/or sleep stage seemed to be responsible for much of the apparent change of P2N2 amplitude with age. The age related changes found for the other EP components, however, persisted through the various analyses of the data.

Individual subjects The relationships of age to the EP measures for each child were examined in order to determine whether the group findings for developmental trends applied to individual children. Table II gives the percentage of children who conformed to the group trends. P2 latency was found to decrease significantly with age in the largest percentage (81%) of subjects, while N2 and P3 decreased in 56%. NEP3B and N2P3 increased significantly in 50% and 38% of the children respectively. In contrast to the findings of the cross-sectional study, N1P2 amplitude for the pooled longitudinal data did not decrease with age although 63% of the 16 subjects did show a decrease.

417

A U D I T O R Y EP DEVELOPMENT: A LONGITUDINAL STUDY TABLE II Slopes of regression of EP values on age Slopes of all subjects combined* msec or uV per log unit age

Direction of change with age for 16 individual subjects Percent** subjects with + sloper

Percent*** subjects with - sloper 44 75 (13) 63 94 (81) 94 (56) 75 (19) 81 (38) 88 (56)

No P1 N~ P2 N2 P3A P3B P3

NS -9 NS -43 -122 -85 -88 -106

56 25 37 6 6 25 19 12

N0P 1 PIN, N,P 2 P~N 2 N2P3A N2P3B N2P 3

NS +1.5 NS +7.5 NS +18 +18.9

60 75 37 56 44 94 94

(0) (19) (50) (38)

40 25 63 44 56 6 6

* Slope for the regression of EP value on log age using total data base of 254 EPs from 16 subjects. Values are significant at P < 0.05 unless NS is entered. ** Percentage of subjects in whom the slope (of a given component over age) was positive. *** Percentage of subjects in whom the slope (of a given component over age) was negative. J- Percentages of individual subjects in whom the regressions on age were significant at P < 0.05 is given in parenthesis.

The n u m b e r of EP components showing significant changes with age varied from child to child. Zack, for example, has seven components which were age related, while Elaine had only one (Fig. 1). The amount and even occasionally the direction of change with age varied from child to child, as did the strength of the relationship as measured by the coefficient of correlation.

Sources o f AEP variability The data were examined in order to estimate the relative contributions o f the factors discussed in the previous sections, i.e., age, sleep stage, sex, the rearing/race factor, stimulus order and individual Subjects, to the overall variance for each AEP measure. Since the experimental design on which this report

is based did not sufficiently approximate a latin square to permit a formal analysis of variance, rough estimates were made of the contribution of the various factors by the following method: The total variance was calculated for each of the 15 amplitude and latency measures. The portion of the variance due to log age (r ~) was subtracted, leaving the total non-age-related variance. The contribution of the various other factors was then estimated through successive restrictions of the data to the appropriate subset of AEPs; i.e., those from (a) stage 2 sleep; (b) males; (c) females; (d) institutionalized subjects; (e) home reared subjects; (f) the first 65 dB click set of a given test session; (g) through (v) each of the 16 individual subjects in stage 2 sleep. By subtracting the non-age variance ob-

418

E.S. OHLRICH ET AL.

TABLE III Means, standard deviations and estimates of percentage of variance accounted for by age and other factors; 254 AEPs of 16 subjects recorded over the first three years of life.

N, P2 N2 P~B NtP 2 P2N~ N2P3B

Means

S.D.

(msec or uV)

(msec or uV)

109 186 409 757 11 31 27

30 35 100 121 7 15 16

Percent of variance due to Age

Sleep stage

Sex

Rearing/ race

Stim. order

Subjects

Residual

1 31 34 12 0 5 29

0 25 13 6 0 0 0

(15)* (6) (0) 0 (0) (0) 0

(3) (2) 0 (10) (0) (0) 0

2 0 2 5 0 (0) 0

(25) (17) (50) (34) (60) (43) (48)

54 19 1 33 40 52 23

* Percentage variance is reported in parenthesis for factors which yielded substantially different values for the different levels. For sleep stage, only one level, stage 2, was analyzed. For subjects, 16 levels, i.e., one for each subject, were analyzed and values for the median are given. See text for further explanation.

tained for each subset of the data (a through v) from the total variance, the proportion of variance accounted for by each of the possible sources was estimated. Table III summarizes the estimated percent of the total variance due to each factor.* For certain factors (e.g., sex), the variance obtained for one level {e.g., males) differed from that obtained from the other level. In those cases the percent of variance accounted for b y the factor was assigned by taking the mean of the respective variances associated with the various levels of the factor. For those EP measures in which such interactions were found, the variance is reported in parenthesis in Table III. Since there were striking differences among the variances calculated for the data from individual subjects, the percentage variance due to the factor 'subjects' {Table III) was approximated by using a hypothetical 'typical' subject. This subject was defined as one with the median value for r (the coefficient of correlation for log age and EP measure) and ~he median value for variance. The contribu* In order to avo.id a 15 column table, the results only for 'major' EP components are presented. Information on the other components is available on request from the authors.

tion of the variance of the factor 'subjects' was then found by subtracting the variance for the 'typical' subject from the total variance. The variance of the factor 'subjects' is a measure of the among-subjects contribution to the total variance found in the 254 EPs records from the 16 children. For the longitudinal data considered as a whole, the percent of total variance accounted for by age varied according to which measure was being considered, from near 0% for No latency to 34% f o r N2 latency. These percentages are similar to those found for the cross-sectional data. Thus, effects other than age accounted for m o s t of the total variance for the group data. For the 16 subjects there were striking individual differences in the proportion of variance accounted for by age. The median values were 61% for P2 and N2 latencies and 50% for P3 latency; therefore, in more than half of the individual subjects, age accounted for at least half of the total variance in these latency measures over the first three years of life. Since latency varied substantially from subject to subject, the variance due to the factor 'subjects' reduces the coefficient of correlation for age vs. latency in the group analyses. For age-

AUDITORY EP DEVELOPMENT: A LONGITUDINAL STUDY

amplitude relationships, however, coefficients or correlation (and therefore the percent of variance accounted for by age) were low, b o t h within and among subjects. When the data were restricted to AEPs obtained in stage 2 sleep, variance for the latency measures was reduced by as much as 25%. Stage 2 AEP amplitudes, however, had variances which were not smaller than those found for the data as a whole, despite the differences in values for mean amplitudes found between REM recorded AEPs and the other sleep stages. The disparate findings may be related to the small number (n = 21) of REM EPs. Overall, sex, the rearing/race factor and stimulus order appeared to contribute little to the total variance (Table III). For the EP latencies, I subjects showed higher variances than H subjects. Males showed higher variances for some Of the latencies, and females for others. For EP amplitude, females and H subjects c o n s i s ~ n t l y showed higher variability than males and I subjects, respectively. The factor 'subjects' (Table III) accounted for from 17 to 60% of the total variance, depending on which c o m p o n e n t was considered. A high proportio n of the "error variance' i.e., that portion of the EP variability not accounted for by age, sleep stage, sex, the rearing/race factor and stimulus order, was eliminated when the data analyzed were confined to those from the 'typical' subject. The 16 individual subjects, however, differed greatly from one another in the a m o u n t of error variance in their respective EPs. The reduction in error variance for a given component which was affected by considering the subjects individually ranged from 0% to 100% of the total estimated error variance for the group. Of course, there was a strong tendency for those EP measures which were highly age dependent in particular subjects to show low error variance. The 'residual' variance shown in Table III is a measure of the error variance found in individual subjects. It is partly due to true within-subject EP variability, b u t it also

419

contains a proportion of error from factors such as incorrect identification or measure. ment of components by the experimenters. In our experience these problems were more likely to arise with No, P1 and NI, partly because the recording parameters which hac been chosen (amplification, digitization rate, display) were not optimal for the characteriza tion of these waves. Experimenter error wa, less likely to occur for the components P: and N2, which were relatively unambiguous In fact the residual error variance was quit~ low. for the latencies of these component, (19% and 1%); however, for the amplitud~ of P2N2, a measurement which could be made with ease, there was still a high within-subjecl error variance (52%). This contrast betweer latency and amplitude error variances of th~ same peak probably reflects the inherentl3 greater sensitivity of EP amplitude to m o m e n t b y - m o m e n t within subject changes in level o~ consciousness and similar variables related tc state.

Signature EPs Certain subjects produced EPs which wer, remarkably similar from session to session Traci's responses (Fig. 1) were characterizec by high amplitude sharp P2, N2 and P3 peaks Her P~ was nearly always of the P3A form Elaine almost always showed a notched P2 Zack was a subject who showed less charac teristic response morphology than some o the others. Zack's peak latencies and amplit udes were strongly age-related, while Elaine' were not. Morphological consistency an( age-relatedness of peaks did n o t alway coexist in the same child. Because of thei characteristic morphology, EPs from abou one-third of the subjects could be classifie( with reasonable accuracy by an experience( observer as having been produced by tha child.

Discussion The developmental changes found in thi

420

longitudinal study were very similar to those reported previously for a cross-sectional study of children in the same age range, with mean values obtained for amplitude or latency of a given c o m p o n e n t at a'given age often within a few milliseconds or microvolts (cf. Table I). In b o t h studies P2, N2, P3A, P3B and P3 latencies decreased with age; P1N1, P2N~, N2P3B amplitudes increased with age; and No and N~ latencies did n o t show age-related changes. The results of b o t h studies were similar with respect to the regression of the values for the AEP components on log age, coefficients of correlation and sleep stage effects. There were some differences found. The longitudinal group as a whole had a significant decrease in P1 latency with age. This effect was n o t evident in the cross-sectional group. Two statistically significant age-amplitude relationships which were present in the cross-sectional group were n o t seen in the longitudinal group: an increase in NoP1 over age and a decrease in N1P2. The failure to replicate changes with age for NoP~ and N~P2 seemed to be. due to errors caused b y sampling and small size of the l~ingitudinal subject population. The EP values for individual subjects were distributed across a large range, resulting in a frequency distribution histogram which did n o t approximate a normal distribution. Estimates of statistics based on the pooled longitudinal data are therefore likely to be biased. To the extent that the median values for the coefficient of correlation and standard deviation can be taken to represent those for a 'typical subject', the findings of the present longitudinal study with respect to NoP1 and N1P2 are in essential agreement with those of the cross-sectional study. These statistics cannot be expected to apply to individual subjects, however, since subjects display .age trends differing greatly from one subject to another. In b o t h studies all AEPs were obtained during sleep, mostly stage 2. Sleep has been shown in these and other studies (Williams et al. 1962; Ornitz et al. 1967; Tanguay et al. 1973; Graziani et al. 1974; Ellingson et al.

E.S. O H L R I C H E T AL.

1974) to m o d i f y AEP characteristics. The actual values which describe the age-AEP relationship (e.g., latency or amplitude of a peak at a given age, or a m o u n t of change in an AEP measure over age) were affected by sleep stage in a manner consistent with that d~scribed previously by Barnet et al. (1975) and by other investigators as well. In both longitudinal and cross-sectional studies, the apparent age-related change in the amplitude of P2N2 seemed to be determined by an age-related increase in amount of time spent in stages 3 and 4 sleep (Roffwarg et al. 1964; Clemente et al. 1972). P:N2 tends to be larger in stages 3 and 4 than in other sleep stages (cf., for example, Table II in Barnet et al. 1975). When sleep stage was held constant to stage 2, P2N2 was found to show no change in amplitude with age. N2P3A waves were not seen in early infancy. After their appearance at t w o to three months of age, their amplitude did not change significantly with age when sleep stage was held constant to stage 2. Schenkenberg (1970) who studied subjects ranging from 5 years to old age found longer N100 and P200 latencies for males than for females. Similar findings were reported b y Engel et al. (1968) for neonatal visual EPs. Such sex differences failed to emerge from either the cross-sectional or longitudinal data reported here. In Schenkenberg's study one measure of AEP amplitude (cumulative voltage) indicated certain sex differences, b u t measurements for individual components did not. This latter result is similar to our own. We and others have reported that decrements in EP amplitudes occur over time during sleep (Barnet et al. 1971; Westenberg and Weinberger 1976). In the present experiment as well, decreased amplitudes for longer latency components were found for stimulus sets presented later in the recording session. No differences in age trends were found related, to what we have termed a rearing/race factor. There were, however, small b u t consistent differences in mean values for amplitudes and latencies of most EP components. Some differences which were asso-

AUDITORY EP DEVEI~OPMENT: A LONGITUDINAL STUDY ciated with race were founfl in a neonatal population b y Engel et al. (1968). In that study blacks were f o u n d to have shorter latencies than whites, a result opposite to the finding of the present study. The language and social development of some of the subjects who participated in our study was shown to be affected b y a rearing factor {home vs. institution) (Lodge et al. 1970). The EP study, however, was n o t designed in such a way that the effect of rearing on EPs could be independently assessed. There was considerable variation in the degree to which each of the 16 children studied conformed to the overall trends with respect to age. In one subject (Zack, Fig. 1) 7 o u t of the 15 coefficients of correlation of age with EP measure were statistically significant. One subject had no c o m p o n e n t significantly correlated with age. In the latter subject and in some others as well, negative results appeared to be due to small n's. Certain subjects tended to produce very complex responses in which labeling of components was sometimes arbitrary (cf., Elaine, Fig. 1); thus, trends in the data may have been obscured by measurement artefacts. In some subjects certain components varied with age in the direction opposite to that for the group data. For only one subjectc o m p o n e n t combination, however, was such a relationship statistically significant. P2 latency was most closely related to age in the largest n u m b e r of subjects, confirming the prediction of Ellingson (1974) that this c o m p o n e n t would be useful for characterizing the individual and for inter-subject comparisons. Individt~al differences will be examined in more detail in a later report from this laboratory (Weiss et al., in preparation). Table III indicates that the factors age, sleep stage, and subjects are the most important determinants of AEP characteristics. The data also reveals that very little of the variance due to subjects is caused by the rearing/race factor or by sex. The relatively low residual variance of N2, P2 and N2P3B is an indication of EP stability during a developmental period

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in which non-monotonic changes in brain functions are known to occur. Other EP measures, e.g., N1 and P2N2, show less longrange stability. The logarithmic relationship between EP parameters and age is o n l y an approximation of the true developmental changes in the AEp of the first years of life. During this time, a complex set of maturational variables are operative which probably introduce non-linear effects. These nonlinearities may cause spuriously low estimates for the effects of age on EP measures; nevertheless, it is likely that factors other than age determine a large portion of the variance. The factors listed in Table III are some of those which we assumed might contribute substantially to total variance. Many other factors, of course, could have been considered; e.g., the time of day the test was performed, the interval between test sessions, the child's adaptation to the laboratory setting, and variables related to cognitive and perceptual development and style. Some of these factors may make sizeable contributions to the 'error' variance reported in the study.

Summary Serial recordings of auditory evoked potentials (AEPs) to clicks were obtained using a vertex-mastoid derivation from 16 normal children during sleep over an age span from near birth to age 3. The AEP components studied were: No (38 + 10 msec), P1 (79 -+ 24 msec), N1 (109 + 39 msec), P2 (186 -+ 35 msec), N~ (409 + 97 msec), P3A (554 -+ 116 msec), P3B (757 + 121 msec) and P3 (728 + 128 msec). Amplitudes and latencies of the components were calculated and regressions of the measures on age were c o m p u t e d for the group as a whole, for each subject and for subsets of the data based on sleep stage, sex, order of stimulus presentation and a rearing/race factor. For the group as ~ whole the latencies of P1, P2, N2, P3, and P3B decreased with age. The amplitudes of P,N, and the N2P3 waves

422 increased with age. Most change occurred during the first year of life. In general, the changes with age were also found to hold across all of the factors examined, although individuals varied widely in the degree to which they conformed to the trends found for the data as a whole. The a m o u n t contributed by each of the factors mentioned above to the total variance was estimated. The proportions varied for different EP components but, in general, age, sleep state, and subject factors other than rearing/race and sex accounted for most variance. One half to 5/6 of the unexplained variance in AEP latencies and amplitudes (i.e., that not due to age, sleep state, etc.) occurred across rather than within subjects. For both the group as a whole and for individual children, P2 and N: latencies were found to exhibit the greatest stability across time. The results of the longitudinal study reported here were in good agreement with those of a previous study from this laboratory which utilized a cross-sectional design. Rdsumd

Developpement du potential dvoqud auditif dans la petite enfance. Etude longitudinale Des enregistrements en sdrie des potentiels dvoquds auditifs (AEPs) a des clicks ont dte obtenus au cours du sommeil fi l'aide d'une ddrivation Vertex-Mastoide chez 16 enfants normaux d o n t l'~ge va de la pdriode ndonatale 3 ans. Les composantes d'AEP dtudides ont ~te: No (38 + 10 msec), P~ (79 + 24 msec), N1 (109 +_ 39 msec), P2 (186 + 35 msec), N2 (409 +_ 97 msec), P3A (554 + 116 msec), P3B (757 + 121 msec) et P3 (728 + 128 msec). Les amplitudes et les latences des composantes ont dtd calculdes et les rdgressions des mesures par rapport el l'~ge ont dtd calculdes pour l'ensemble du groupe, pour chaque sujet, et pour des sous-groupes de donndes basds sur le stade de sommeil, le sexe, l'ordre de prdsentation du stimulus, et un facteur dducation/race. Pour l'ensemble du groupe, les latences de

E.S. OHLRICH I~T AL. P1, P2, N2, P3 et P3B diminuent avec l'~ge. Les amplitudes de PIN1 et de N2P3 augmentent avec l'~ge. La plupart des modifications surviennent au cours de la premidre annde de la vie. En gdndral, les modifications avec l'~ge persistent quels que soient les facteurs examinds, bien que les individus varient considdrablement quant a leur degr~ de conformitd aux tendances observdes pour l'ensemble des donnees. La proportion dans laquelle chacun des facteurs ci-dessus mentionnes contribue la variance totale a dtd estimde. Cette proportion varie pour les diffdrentes composantes des EP mais en gdndral l'~ge, le stade de sommeil et les facteurs individuels autres que les facteurs education/race et sexe, rendent compte de la plupart de la variance. La moitid 5/6dine de la variance inexpliqude dans les latences et les amplitudes de I'AEP (c'est-fidire celle qui n'est pas due fi l'~ge, au stade de sommeil, etc.) est interindividuelle plut6t que intraindividuelle. Aussi bien pour le groupe dans sa totalite que pour chaque enfant pris individuellement, les latences de P2 et de N: m o n t r e n t la plus grande stabilite avec le temps. Les rdsultats de l'dtude longitudinale rapportes ici sont en bon accord avec ceux d'une dtude anterieure du mSme laboratoire qui utilisait un protocole d'dtude transversale. We thank Ann Lodge, Ph.D., who administered behavioral tests to many of the children and Howard Wolfe and Clive Newcomb, who provided technical assistance. We are grateful to the parents and children who participated faithfully in the project over a period of years. References Anders, T., Erode, R. and Parmelee, A. (Eds.), A Manual of Standardized Terminology, Techniques and Criteria for Scoring of States of Sleep and Wakefulness in Newborn Infants. NINDS Neurological Information Network, Los Angeles, 1971, 40 p. Apgar, V.A. proposal for a new method of evaluation of the newborn infant. Curr. Res. Anesth., 1953, 32: 260--267.

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