The maturation and interrelationship of EEG patterns and auditory evoked responses in premature infants

367

Electroencepha!ography and Clinical Neurophysiolo~'. 1974. 36: 367 375 ~7 Elsevier Scientific Publishing Company. Amsterdam - Printed in The Netherlands

THE

MATURATION

AND AUDITORY

AND

EVOKED

INTERRELATIONSHIP RESPONSES

LEONARD J. GRAZIANI, LEONARD KATZ, ROGER ELLIOTT D . WEITZMAN

OF EEG PATTERNS

IN PREMATURE

Q. CRACCO,

INFANTS ~

JOAN B. CRACCO AND

Saul R. Korey Deparonent ~I Neurohnly and the Ro.~e F. Kemledy Center .lor Re.wurch 01 Mental Rerar&ition and thereto Derelopmem. Albert Einstehl C,dle.qe o] Medicbte. Bronx. New i~rk and the Department ol :~'euroh~gy. Je/ter.~,m Medical Colleqe ¢!I 7ilomas J~:[lbrson Unh'ersity. Philadelphia. Petal. 19107 ¢U.S.A./ [Accepted for publication: October t I. t 973 }

Auditory evoked responses {AERs)and electroencephalographic l EEG I activity recorded from the scalp of neonatal infants provide objective int'ormation related to the maturation of the immature nervous system not otherwise obtainable, The uset'ubaess and reliability of such studies are presently limited by the lack of quantitative methods for the visual analysis of immature EEG and by the unexplained variability of neonatal AERs. Previous studies of lull term and premature infants suggested that characteristics of the neonatal AER are in part related to background EEG or to sleep state although such relationships h~we been inconsistent, uncertain or difficult to establish {Barrier and Goodwin 1965; Weitzman et al. 1965: Weitzman and Graziani 1968: Akiyama et al. 1969; Engel and Young 1969; Hrbek et aL 1969; Monod and Garma 1971). A quantitative method which permits a more reliable visual analysis of neonatal EEG patterns was previously described by Katz et al. (1972), and was used in the present study to determine the relationship of EEG activity to the latency and amplitude of AERs recorded in premature infants during the neonatal period. The influence of maturation on the occurrence of the EEG patterns and on the relationship of EEG patterns to AER characteristics was also studied.

SUBJF~('TS ANt) METHODS

EEGs and summed AERs were recorded simultaneously every 2 weeks during sleep from 23 premature infants who, at the time of the recordings, were witl'tout evidence of neonatal complications and were between 28 and 41 weeks post-conception. Birth weights of the su[~ects ranged from !100 to 2200 g, and gestational ages from 27 to 37 weeks. Gestational age, which is length of pregnancy, and pestconceptional age. which is gestational plus post-natal age, were calculated from the first week of the maternal last normal menstrual period. Infants with birth weights below the 10th percentile for gestation were excluded from the analysis. A total of 78 recordings of 60--74 min each were analyzed. The infants were placed in a research isolette and humidity and temperature kept constant. Midline recording electrodes, Ag-AgCI discs, were applied to the alcohol cleansed scalp, held in place with either collodian or adhesive tape, and connected via cable to a Grass 16 channel EEG. The EEG amplifiers were used in the frequency range of !-70 c/sec. Electrodes applied to both ears were combined and connected to grid 1 as reference. Resistances of less than 10,000 t) were obtained. The stimuli were auditory clicks every 4 sec t This investigation v.:as supported by Research Grants with a peak intensity of 90 dB with reference to No. HD04174. H.D.-01405. NB-05325. NB-5114. NB-03356. NB-04174. 5 TO1 NS05135-14. from the National Institutes 0.0002 dynes/cm 2 as measured by an impact noise analyzer. Evoked responses to 100 clicks of Health. Public Health Service.

368

L.J. GRAZIAN!et aL

P2

NI N2 20,uV 500 msec. Fig. I. Summed auditory evoked response to lO0 moderate intensity clicks, recorded fi'om vertex in premature infant at 36 weeks post-conception. Reference electrode combined ears. Upward deflection indicates positivity at the active electrode.

were algebraically summed on line by a special purpose computer. CAT 400 A (Mnemotron Corp.). An analysis time of I sec on the computer was used following the stimulus, and the summed responses were plotted on graph paper using an X--Y plotter. Prior to each recording session and in some of the sessions prior to each stimulus, a square wave signal was processed in the same way as the evoked response and used to calibrate the computer. Peak latencies and amplitudes of the first late negative wave, N t, and the following positive wave, P2, were noted by visual inspection of each summed response recorded from the vertex electrode at the interaural line (Fig. !). Peak amplitude was measured from the first late positive wave, Pt, to N t or when Pt was not well defined from baseline at the onset of the N t potential. The peak to peak amplitude of the N tP2 potential was also measured. The reliable identii'ication of every AER component is frequently difficult, and is not necessarily valid when polarity and latency are the only criteria, especially if the response configuration is atypical. Therefore, in this study, the N~ and P2 components onl,. were studied because both in very young and the more mature premature infants, either or both potentials can be readily identified, provided the response is typical for age postconception. In premature infants less than

32 weeks, the P2 w a v e is not as prominent as in the older infants or may be absent (Weitzman and Graziani 1968). In these subjects, the N~ wave only, which is very prominent, was analyzed. The monopolar tracings from 4 or 6 midline electrodes placed at equidistant intervals between Fz and Pz were used in the visual analysis of the EEG activity from most of the subjects. In all instances, the electrode from which the AER was summed was included in the visual analysis. Since the EEG activity from all midlineelectrodes was synchronous between Fz and Pz, the number or location of the midline electrodes did not influence the resultsof the analysis. Each 20 sec epoch of EEG activity during each summed AER recording of 6.7 min was classified into 1 of 6 patterns according to criteria related to frequency, amplitude and continuity or intermittency of activity (Table I). Reliability between two a u ~ o r s was tested and found to be 74 ''~ /'qt} in agreement, with most errors in pattern Tc. When more than 20"J. of the EEG epochs during a summed response were classified as "'U'" due to movement artifact, the AER or EEG from that recording was not used in analysis of the results. The 20 sec epoch was chosen largely because that amount of tracing can be visually inspected and measurements made conveniently. The relationship of each EEG pattern to the amplitude and latency of the N ~ and P2 waves was determined by regression analysis. The effect of maturation on E EG patterns and on the relationship between EEG and AER was also determined, Two-tailed tests were used in the statistical tests for significance. To determine whether the auditory stimuli influenced the occurrence of the pmterns, EEGs without click stimuli were recorded in 8 infants t'rom 34 to 40 weeks post-conception during 14 sessions of 3--6 h each. The association between EEG pattern and sleep state was also determined by inspection of the tracings from these subjects on which respirations, eye movements, body movements, chin EMG and behavioral observation were also recorded. If less than 3 of the 4 physiologic measurements, excluding the EEG tracing, were concordant for a sleep state, the 20 sec epoch was classified as transitional. Active or quiet sleep states were defined by 3 or 4 of the

EEGS AND AERS IN PREMATURES

369

TABLE i Criteria for classifying each _'20sec epoch o f EEG tracing into I o f 6 possible patterns. PaUern

per cent of epoch

Amplitude ~V)

Continuous duration

(secl

Frequency

(c sec)

Immature (1) Suppression Bursts (+_)

<50 < 50

< I0 > 30

> 6 < 4

o.A+~.fl

Immature transitional {it) Suppression Bursts

> 50 < 50

> 20 > 30

>4

0.A_+.,.fl

5f,--85 15-50

> 30 < 15

>2

Transitional continuous {Tc) Continuous or bursts Suppression

50--85 15--,50

> 40 > !5

>2

Continuous (C)

> 85

>40

> 10

Low Voltage Irregular (LVi) Continuous

> 85

2040

> 10

Undassifiable (U Artihet

> 50

Transitional intermittant Continuous or burnts Suppression

(Ti)

4 physiologic measurements but excluding the EEG pattern and according to the criteria described by Anaers et al. (1971). A detailed analysis relating each of the physiologic measurements to each of the EEG patterns was not done. RESULTS

A typical AER recorded from a premature infant is illustrated in Fig. 1 and the 6 EEG patterns recognized according to the criteria listed in Table I are illustrated in Fig. 2. The occurrence of each pattern at each 2 week interval between 28 and 41 weeks post-conception was calculated by scoring all the EEG tracings obtained during the recording of AERs, and the mean value with its standard deviation calculated from the pooled data (Fig. 3). The results suggested a decreasing occurrence in 3 and an increasing occurrence in 2 patterns with age. The I pattern, which decreased with age, was virtually absent after 34 weeks post-conception while LVI, which increased

0,A±a.fl

0.A± ~.fl A± 0.z.l~ o.:~.fl ++A

with age, was virtually absent prior to 34 weeks. This suggestion of maturational change was supported by the individual regressions of EEG occurrence in 13 infants with 3 or more recording sessions, the first before 34 weeks post-conception (Table II); the median and mean regressions are estimates of the rate of change in occurrence of each EEG pattern with increasing age. Inspection of the data from each subject and the mean occurrences of EEG patterns did not suggest any change in rate of maturation between 28 and 41 weeks so that straight line regressions only were calculated. The relative occurrences of the 6 EEG patterns during the sleep recordings without click stimuli were not significantly different from the mean occurrence of patterns obtaired during AER recordings. I, It and Ti patterns occurred during all sleep stages but were associated significantly (P<0.05) more frequently with quiet than with active and transitional sleep. During each of the 78 recording sessions, 9-12 summed evoked responses to 100 clicks

L. J. GRAZIAN! e l a[.

370 R-, R" i

-~,

• ~..

..............

IMMATURE (I) PATTERN

R-3

R-2

,~

"%,,

,j

TRANSITIONAL CONTINUOUS (To) PATTERN

i

..,

R-3

R-, ~,.r~-'------~'~V~

.

STIM. i

STIM.

-

R-2

~

R-3

~

R-4

~

l

i

*

- -

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I

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t

•

R-2 ~

IMMATURE TRANSITIONAL (It) PATTERN

''-~-'--~

,

~

~

CONTINUOUS {C) PATTERN

~ l

~

R-3 ~

%

~

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J

~

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~

%

~

f

~

~

R-4 ~ i

STIM.

R-, ~ TRANSITIONAL

R'2

INTERMITTENT (Ti) PATTERN

"

R-3 R-4

R

i

-

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i

-

3TIM.

- -

-

" - -~" ~

~,,,_,...~....~..._.,_..~ , ~ . ~ , ' ~ . ~ - ~ -

LOW VOLTAGE IRREGULAR

_

(LVI) PATTERN

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50

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Fig. 2. Examples of each o1' 6 EEC} patterns recognized in the present study according to the criteria listed in Table !. I ~"~,

,

,

.

It i

!

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i

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,

Ti 1

i

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!

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AGE POST-CONCEPTION (WEEKS) Fig. 3. Means and S.D. of occurrences (percentages) of each EEG pattern during 78 recording sessions in 23 premature infants studied longitudinally. Gestational ages ranged from 27 to 37 weeks. Age post-conception at time of recording as noted. 31 is I, It and Ti patterns combined.

were obtained. Straight line regressions (least squares method) between the occurrence (percentage) of each EEG pattern and each of the 4 AER measurements (latencit.: and amplitudes of N, and P2) w e r e ,:ietermined anu, for purposes of clarity, will be termed AER-EEG regression coefficients. Since these regressions were fitted using data obtained within a single recording sescion, the variability due to electrode placement and subject differences was thereby reduced.

The AER-EEG regression coefficients from all recording sessions were pooled according to age post-conception and the mean values calculated for the various age intervals (Table lII). The AER-EEG regression coefficients o f l and It did not differ significantly (P < 0.05 t test) from each other and neither did those of It and Ti; thus the data reported in Table III are limited to that related to the combined occurrence of these 3 intermittent patterns and to the continuous

371

EEGS AND AERS IN PRE,~LA'rURES TABLE II

Age related changes in EEG 9atterns. Values shown are regressions of occurrence of EEG patterns from 28 to 41 weeks post-conception, and represent median and mean percent change in EEG pattern per week. 31 EEG pattern is I, It and Ti patterns combined. EEG pattern I

it

Ti

31

Tc

C

LV!

- 3,4*

- 1,8*

- 2,0"

- 5, ! *

0,7

1. I *

0.8*

-2,6+0,6

- !,8+2,1

- i,6_+ !,5

- 4 , 0 ± 2.5

0,7±2.3

I).8_+ !.2

!.! _+ 1.0

Median regression Mean regression

• Sign. positive or negati~.'e, of tke median regression is statistically significant. P < 0.01, signed rank lest.

TABLE i l i Relationships of EEG patterns to AER characteristics from 30 to 41 xveeks post-conception. 31 EEG pattern is !, It and Ti combined, ABe, ~x't'eks post-conception 3031

32-33

34-35

36 37

38 39

41) 41 .

.

.

.

Rehtthmship {d31 EE(I A ERo,EEG ret,lrcsxiott coct/h,icnt I l~ttlll'D!/0," Ampl, Ampl, Lat. Lat.

Nt P, Nt P2

0,1 ±0,1" 0,1 + 0,07" 0.3±0.6 0.1 ±0,2

0,1 ±0,1" 0 1 + 0. I 0.2+0,4* --0.2+0,5

0.1 ±ILl* 0.1 ±0.1" 0.3+_0.1" 0.2±0.1"

0.1 ± 0 . 1 ' 0.1 ±ILl* 0.2±0.7 0.4±0.1"

0.1±0,2 0.1±0,2 -0.1±0.3" -0.2±0,3

-0.1±0.1" -0.1±0.1" 0.1±0.9 -0.1±0.1"

-0.4±0.1" -0.2±0.3* -0.1±0.3" -0.3±0.4*

0.3±1).1' 0.1 ±0,02* 0.4±0.2* 0.4_+0.3*

0.5±0.2* 0.2±0.1" 0.4±0.9 0.6±0.3*

Relationship of C EEG paltertls to: Ampi. Ampl, Lat. Lat.

Nt Pz Nt P2

-0.1±0.1 -0.1±0.1" 0.3±0.8 0.2±0.5

-0.2±0.3* -0.3±0.1" -0.3±0.4* -0.2±0.2*

-0.5±0.8 -0.34,0.1" -05±0.7* -0.4±0.6*

t Values shown are mean and standard deviations of ~.ER EEG regression coefficients (see text) calculated from data obtained from 23 infants during 78 recording sessions. * Sign of the mean value, positive or negative, is statistically significant. P < 0.05 signed rank test.

pattern. Since the occurrence of the LVI pattern was relatively small (Fig. 3) and since only very few of the AER-EEG regression coefficients related to LVI and to Tc were significant (sigaed rank test) their means are not summarized. The results suggest that in infants older than 34 weeks the latencies and amplitudes of both N~ and P2 are positively correlated with the intermittent patterns I, It and Ti and negatively with pattern C. The mean AER-EEG regression coefficients at 2 week intervals are estimates of the average relationship between a unit change in percentage of each EEG pattern and the change in amplitude or latency of the AER potentials. The suggestion

in Table III that maturation influences the correla;ions is supported by the sigaificant trends of AER-EEG regression coefficients related to increasing gestationai age (Table IV). The trends of the AER-EEG regression coefficients related to age post-conception did not differ significantly (t test) from the trends of the AER-EEG coefficients related to gestational age, suggesting that age post-conception as well as gestational age influences the relationships between AER and EEG patterns. The trends of the AER-EEG regression coefficients with increasing post-natal age were not si~ificant so that extrauterine development itself did not

372

L.J. GRAZIANIet aL

TABLE IV Age related trends of A E R - E E G regression coefficients as gestational age increases from 29 to 37 v,'eeks. Calculated from data obtained at the ! st recording session within 8 days of birth in each of 17 premature intants. 31 EEG pattern is i, it and Ti combined. EEG patterns

AE R characteristics Ampl. Nt Ampl. P2 Lat. NI Lat. P.,

31

C

Trends +* +* +* +*

-* -* -* -ns

• Trend. positive or negatixc, differs significantly from O: P < 0.05 t test. ns. not significant.

independently affect this bioelectric maturation. All trends azere estimated by least squares fit between AER-~EEG regression coefficients and age in weeks. Regardless of EEG pattern, AERs recorded from infants 28-33 weeks post-conception were less likely (P < 0.05) to contain a P2 wave than those from infants 36-41 weeks. Thus the presence or absence of P2 was related to age but not to EEG pattern, suggesting that maturation also has an independent effect on waveform of the AER, as described previously {Weitzman and Graziani 1968). In the present study, the ranges of absolute latencies and amplitudes did not differ from those reported previously (Weitzman and Graziani 1968; Akiyama et al. 1969; Engel and Young 1969; Monod and Garma 1971 ) and are not therefore further described. DISCUSSION

In sleeping infants at term, the most prominent evoked responses to auditory stimuli are obtained at the vertex and adjacent scalp areas with ears or occipital region as reference (Ellingson 1967). Summing or averaging techniques are necessary for reliable analysis of AER waveform, and consistently satisfactory recordings are obtained without undue difficulty o~..y in sleeping infants. AERs in infants and adults have characteristics that suggest they are non-specific although Vaughn and Ritter (1970) have suggested a

source of a late AER component originating from within t h e primary auditory projection cortex. The maturation of the late components of summed AERs to loud clicks in the neonatal period was described previously (Weitzman and Graziani 1968). Generally, a decreasing latency of most waves, with changing waveform and topography as a function of age post-conception was noted. The effect of sleep and background EEG on characteristics of evoked responses has been evaluated in several neonatal and infant studies {Barnet and Goodwin 1965; Weitzman et al. 1965; Rapin and Graziani 1967; Akiyama et al. 1969; Hrbek et al. 1969; Ornitz et ak 1969; Taguchi et al. 1969; Engel and Milstein 1971: Monod and Garma 1971). Weitzman and Graziani (1968} noted that in low birth weight infants the variability of the AER during a recording session was considerable and in part appeared to be related to the background EEG. There was no relationship of EEG to latencies of N 2 waves or to iatencies of any wave recorded from posterolaterally placed electrodes: amplitude relationships were not determined in that study. A general agreement among the various authors regarding the relationships of EEG or sleep state to AER latency or amphtude, however, has not, been noted (Graziani and Weitzman 1972). Differences in recording techniques, stimulus parameters, criteria for defining EEG or sleep stage, maturation and whether or not subjects are studied longitudinally are factors which probably contribute to the variable results reported. In the present study, we attempted to reduce some of these factors which might interfere with obtaining consistent relationships among AERs, EEG, and maturation. Two relatively constant waves of the AER recorded from a vertex electrode were analyzed for latency and amplitude. Relatively reliable and objective criteria for scoring EEG patterns which were tested in a previous report (Katz et aL 1972) were utilized and finally a lon#tudinal study with intra-subject and intra-session analysis of the data was carried out. Since similar EEG patterns may occur in both active and quiet sleep (Parmelee et al. 1968), we have considered EEG and sleep state separately in this study and have analyzed the data primarily with regard to EEG patterns.

EEGS^ND ,ea~RSIN PRE,S~TL'RES Also, a relatively large proportion of sleep in infants less than 37 weeks post-conception is classified as transitional, reflecting the uncertainty in defining active and quiet sleep in young premature infants. The regressions of the 6 EEG patterns with age post-conception as well as some ofthe relationships of EEG to AE R were significant ~ithout regard to sleep state suggesting that EEG and sleep state may be considered separately in analysis of bioelectric information, at least in this young age group. In the present study, maturation influenced some of the relationships between AER and EEG characteristics (Tables Ill and IV), but extrauterine development as measured by postnatal age did not influence these relationships independently of age post-conception. The amplitude of the EEG patterns did not determine the amplitude ofthe AER waves since the N, and Pa amplitudes were related negatively to the C EEG pattern and positively to patterns of predominantly lower amplitude than C including Ti and It. The neurophysiologic mechanisms responsible for the interrelationships of EEG patterns, AER characteristics and maturation are conjectural. With increasing post-conceptional age, variations in cerebral excitability reflected by changes in spontaneous EEG activity may increasingly affect the responsivity of peripheral and central elements of the AER. Alternatively or additionally, common subcortical neural systems which modify both spontaneous EEG activity and some AER characteristics may become increasingly operative with maturation. Visual analysis of EEG patterns in studies of neonatal infants has bee.1 previously described (Parmelee et al. 1968; Dreyfus-Brisac 1970, Schulte et al. 1971). Using bipolar recordings from scalp and objective criteria for scoring, Parmelee et al. (1968), considered i0 and Dreyfus-Brisac (1970) 4 EEG patterns. The 6 patterns described in this study were obtained by monopolar recordings but are, in general, similar to those reported by Parmelee et al. (1968). For all patterns except Tc, regressions of occurrence related to age were statistically significant, so that the criteria used for identification of at least 5 of the patterns may be useful in further studies of neonatal bioelectric activity. The total amount

373 of EEG tracing necessary to obtain reliable scores of the 6 EEG patterns was not determined in the present study: however, the maturational age of the infant is not likely to be over-estimated if 60-StJ min of recording which will include at least one period of quiet sleep are analyzed, since the more immature patterns I, It, and Ti were associated predominantly with quiet sleep. The data obtained from infants studied without AERs suggest that click stimuli did not affect the relative amounts of the 6 EEG patterns. The results of the present study suggest that, in the neonatal period, the variability of AER characteristics is related partially to the occurrence of EEG patterns, and that these relationships are influenced by age post-conception. Hopefully. further quantitative studies will aid the development of clinical application of AER and EEG recordings in the neonatal period. SUMMARY

In a longitudinal neonatal study, biweekly EEGs and summed auditory evoked responses (AERs) were recorded during sleep from 23 premature infants between the ages of 28 and 41 weeks post-conception. Seventy-eight EEG tracings were obtained and 60-74 rain of each were visually analyzed. Each 20 sec epoch was classified into one of 6 EEG patterns according to specific criteria relating to amplitude, frequency. and persistence or intermittancy of activity. With increasing post-conceptional age, the relative and absolute occurrences of 3 patterns decreased and 2 patterns increased significantly in a general linear fashion. During each EEG session, 9-12 summed AERs to loud click stimuli were recorded from the vertex with combined ear~ as the reference electrode. The amplitude and latency of the N. and P2 potentials were, in general, positively related to 3 intermittent, relatively immature EEG patterns, and negatively related to a high voltage continuous pattern, but significant relationships were noted mainly in subjects older than 34 weeks post-conception. Post-conceptional and gestational age but not post-natal age influenced the relationship between EEG patterns and AER measurements. The average regression coefficients between AER measurements and

374 some EEG patterns were determined for every 2 week age period permitting a quantitative estimate of these relationships related to age post-conception. The intra-subject, intra-recording variability in amplitude and latency of 2 major waves of the neonatal AER recorded from premature infants was therefore related to two measurable variables, background EEG and age post-conception. RESUME LA MATURATION ET L'INTERRELATION DES PATTERNS EEG ET DES REPONSES EVOQUEES AUDITIVES CHEZ LES ENFANTS PREMATURES

Au cours d'6tudes n6o-natales longitudinales, des EEG bi-hebdomadaires et des AERs somm6s ont 6t6 enregistr6s au cours du sommeil chez 23 enfants pr6matur6s de 28 '~ 41 semaines d'fige conceptionnel. Soixante dix-huit trac6s EEG ont 6,6 obtenus dont 60 ~ 74 min ont 6t6 analys6es visueilement pour chacun d'eux. Chaque 6poquc de 20 sec a 6t6 class6e en Fun des 6 patterns EEG d6finis suivant des crit~res sp6cifiques tenant compte de l'amplitude, de la fr6quence et de la perisistance ou de I'intermittence de I'activit6. Avec I'accroissement de l'age post-conceptionnel les survenues relatives et absolues de 3 de ces patterns diminuent et 2 patterns augmentent significativement d'une faqon ggn6ralement lin6aire. Au cours de chaque session EEG, 9 "h 12 rgponses 6voqu6es auditives somm6es /t des stimuli sonores graves ont 6t6 enregistr6es au niveau du vertex reli6/~ des 61ectrodes de r6fgrence situ6es sur les oreilles. L'amplitude et la latence des potentieis N t et Pz sont en g6n6ral li6es positivement/~ 3 des patterns EEG intermittents relativement immatures et de faqon n6gative fi un pattern continu de haut voltage, mais des relations significatives ont 6t6 not6es principalement chez des sujets fig6s de plus de 34 semaines d'fige post-conceptionnel. L'fige gestationnel et postconceptionnel influence les relations entre les patterns EEG et les mesures des AERs mais non l'fige post-natal. Les coefficients moyens de rggression entre les mesures des AERs et certains patterns EEG ont 6t6 d6termin6s pour chaque p6riode d'fige de deux semaines, permettant une estimation quantitative de ces relations par

L.J. GRAZIANIet aL rapport/l l'~ge post-conceptionnel. La variabilit6 intra-sujet et intra-enregistrement de l'amplitude et de la latence des deux ondes principales de I'AER n6o-natal enregistr6e chez des enfants pr6matur6s est ainsi li6e /~ deux variables mesurables, I'activit6 de fond EEG et l"~ge postconceptionnel. The authors wish to thank Dr. Hyman Menduke for his invaluable assistance in the statistical analysis of the data. We also wish to acknowledge with gratitude the technical assistance of Miriam Heebner. and the cooperation and help of the nursing staffofthe premature nursery, Bronx Municipal Hospital. and the intensive care nursery. Thomas Jefferson University Hospital.

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