Brain-stem auditory evoked response (BAER): normative study in children and adults

Brain-stem auditory evoked response (BAER): normative study in children and adults

Electroencephalography and clinical Neurophysiology, 1987, 6 8 : 4 7 9 - 4 8 4 Elsevier Scientific Publishers Ireland, Ltd. 479 E E G 03360 Short c...

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Electroencephalography and clinical Neurophysiology, 1987, 6 8 : 4 7 9 - 4 8 4 Elsevier Scientific Publishers Ireland, Ltd.

479

E E G 03360

Short communication

Brain-stem auditory evoked response (BAER): normative study in children and adults Jacques Thivierge and Robert CSt6 Centre de Recherche Laval - Robert Giffard, 2601, Chemin de la Canardibre, Quebec G1J 2G3 (Canada) (Accepted for publication: 25 June, 1987)

Summary The influences of age and sex on the BAER latency values are analysed in a non-clinical sample of adults and children. We found (1) that BAER values vary according to age and sex, but for the I I I - V interpeak latency (IPL); (2) that the age effect is more important than the sex effect on absolute latency (AL) II, III and V; (3) that there is a significant sex effect on the l - I I I IPL. Comparisons to other studies are made: we find differences but no contradiction. This is briefly discussed. Key words: Brain-stem auditory evoked response

The major goal of this paper is to look at the influence of age and sex on the BAER values both through our own data and the pertinent literature that has been reviewed. The subject matter is important as regards clinical interpretations and research questions where BAER values are used as indexes of central nervous system dysfunctions. For some BAER values that we looked at, the answer to the question of age and sex influence seems to be straightforward whereas for others, there seem to be m a n y confounding factors standing in the way of a clear answer. We have tried to throw some light on these confounding factors in terms of identifying some of them, and also, more specifically, in terms of trying to illustrate how one of them, namely statistical testing, might operate for confounding the issues.

Methodology (A) Sample Our sample (N = 142) was drawn from a non-clinical population and was recruited through our hospital personnel, their families and their friends. Table I illustrates its gender and age characteristics. Eleven subjects were excluded from our norm computation because of our following exclusion criteria:

Correspondence to: Dr. Jacques Thivierge, Centre de Recherche Laval - Robert Giffard, 2601, Chemin de la Canardi+re, Quebec G1J 2G3 (Canada).

(1) Firstly on account of medical history elements: we excluded all subjects showing a previous or current neurological or ENT diagnosis or important intervention (Bell palsy, epilepsy, cerebral commotion, tympanoplasty, migraine hypothyroidia). A simple history of otitis in infancy without any further complication was not taken as an exclusion criterion. We also excluded subjects currently being on any kind of medication. Ten subjects were so excluded.

TABLE I Sample gender and age characteristics.

Children

Age

Female

Male

4- 5 6-7 8- 9 10-11 12-13

5 5 11 6

1 3 10 5 2

1 8 15 16 8

27

21

48

9 1 30 6 4

8 1 12 10 2

17 2 42 16 6

50

33

83

77

54

131

Sub-total Adults

Sub-total Total

0168-5597/87/$03.50 © 1987 Elsevier Scientific Publishers Ireland, Ltd.

14-19 20-29 30-39 40-49 50-59

Total

480

J. T H I V I E R G E , R. COTE

TABLE II

base 10 msec. The recording site was at Cz, the reference at the ipsilateral mastoid and the ground at FP z. There was contralateral masking ( - 30 dB). The low and high bandpasses were respectively set at 75 and 3000 Hz. Two thousand sweeps were taken in test and in retest.

Kolmogorov's goodness-of-fit test for normality (n = 13). Values

D: normal

P > D

I II III IV V I-III III-V I-V

0.1498 0.0849 0.0594 0.0560 0.0699 0.1018 0.0599 0.0837

< 0.01 * 0.024 * > 0.15 > 0.15 0.126 < 0.01 * > 0.15 0.028 *

(C) Research question and data analysis The variables that have been retained for analysis are: (1) the absolute latencies (ALs) of waves I up to V; (2) the I - I I I , I I I - V and I - V interpeak latencies (IPLs). We used the data related to the left ear monoaural stimulation. We asked the question: are age and sex characteristics having any effects on these variables and can one observe an a g e / s e x interplay? In order to choose between parametric and non-parametric tests, it is important to make sure that the assumptions required by these tests be met. As an example the Student ' t ' test and the Fisher-Snedecor F test require, among other things, the normality of the data. Using the Kolmogorov goodness of fit test, we assessed the normality of the eight sets of data. Results are reported in Table I I.

* P < 0.05, normality rejected.

(2) Secondly on account of wave identification problem: in one subject, waves I and II could not be elicited in either ear. The subject was excluded.

(B) Recording procedure and parameters The recordings were made in a sound-proof Faraday Cage. Prior to recording the hearing level of both ears was tested in every subject. It has been found within standards for all of our subjects. We used sensation levels instead of normalized hearing levels in order to maximize to our best the comparability of the data across subjects, and between ears for the same subject. The recording parameters were unfiltered rarefaction clicks (100 #sec). The rate was l l . 1 / s e c , intensity 70 dB SL and time

Results To verify the age and gender effects on those sets of normally distributed data (AL III, IV, V and I I I - V IPL), we used a Student ' t ' where the homogeneity of the variances has

TABLE III Effect on the III, IV, V AL and I I I - V IPL using a 2-tailed Student t test. Values

N

~

s

Ho: 02 = 02

Ho:

82 48 80 48 81 47 81 47

3.72 3.64 4.95 4.85 5.60 5.49 - 1.88 - 1.85

0.15 0.17 0.20 0.21 0.22 0.17 0.182 0.146

F = 1.32 ( e = 0.26) F = 1.02 ( e = 0.93) F = 1.66 ( P = 0.06) F = 1.55 ( P = 0.10)

t= (e t= (P t= (P t= (P

N

~

o

H0:

Ho:

Female Male Female Male Female Male Female

77 53 76 52 76 52 76

3.65 3.75 4.87 4.98 5.52 5.62 - 1.87

0.15 0.16 0.19 0.22 0.22 0.17 0.17

Male

52

- 1.87

0.16

F = 1.20 ( P = 0.46) F = 1.24 ( P = 0.39) F = 1.58 ( P = 0.08) F = 1.22 ( P = 0.45)

,l'ta = }/'c

Age III AL IV AL V AL I I I - V IPL

Adults Children Adults Children Adults Children Adults Children

2 O"v? _ -- 0 M

2.49 - 0.01) 2.48 = 0.014) 2.85 = 0.005) -0.74 = 0.45) M F = M M

Gender III AL IV AL V AL I I I - V IPL 2

t= (P t= (P t= (P t= (P

- 3.76 = 0.0003) - 2.91 = 0.004) -2.58 = 0.011) - 0.155 = 0.87)

oG and ~G stand respectively for the variance and the mean of the G population indexed by letter G (for group).

BAER: STUDY IN CHILDREN

481

AND ADULTS

w e used the n o n - p a r a m e t r i c W i l c o x o n r a n k s u m s test ( T a b l e

T A B L E IV Effect on the I, II A L a n d I - I I I , I - V I P L using the W i l c o x o n r a n k s u m s test. Variables

IV). T h e r e are no m e d i a n differences b e t w e e n sex a n d age on I - V IPL. H o w e v e r , we f o u n d a n age effect for w a v e I I A L (adults longer) (W s = 2389.50; P < 0.01) a n d a sex d i f f e r e n c e for the I - I I I I P L (females shorter) (W~ = 2648.50; P < 0.01). T h e p r o b l e m r e m a i n s of a possible i n t e r p l a y of age a n d sex

Sex

Age

Mvs. F

Yvs. O

AL I

W~ = 3587.50 P = 0.3182

W~ = 2667.00 P = 0.0268 *

o n the B A E R values. In o r d e r to explore this possibility, we successively used o u r 4 g r o u p s ( y o u n g e r age, o l d e r age, male, female) as o u r d e p e n d e n t v a r i a b l e a n d c o m p a r e d within each

A L II

W s = 3209.50 P = 0.9645

W~ = 2389.50 P = 0.0007 * *

w i t h i n every age g r o u p a n d a c c o r d i n g to age within e v e r y sex

IPL I-III

W~ = 2648.50 P = 0.0004 * *

W~ = 3409.00 P = 0.1593

g r o u p . W e used a n o n - p a r a m e t r i c test of significance, the W i l c o x o n r a n k sums (test (see T a b l e V).

IPL I-V

W~ = 2892.00 P = 0.0675

Ws = 3339.00 P = 0.1012

g r o u p our d e p e n d e n t variables ( B A E R values) a c c o r d i n g to sex

Discussion

* P < 0.05. * * P < 0.01. M = male; F = female; Y = y o u n g e r ; O = older.

T a b l e VI shows the c o m p a r i s o n across studies. It shows the

also b e e n tested ( T a b l e I I I ) v i a the F i s h e r - S n e d e c o r F test. O n the A L of w a v e s III, I V a n d V, the c h i l d r e n m e a n is statistically significantly less t h a n adult's, a n d f e m a l e ' s t h a n m a l e . It is also s h o w n that age a n d sex b o t h h a v e n o effect on the I I I - V IPL. T o verify the age a n d g e n d e r effect o n the I, II A L a n d I - I I I , I - V IPL, w h e r e the n o r m a l i t y a s s u m p t i o n does not hold

statistically significant differences that h a v e b e e n f o u n d for the usual latency values as r e g a r d s age a n d sex. Basically it shows (1) w h e t h e r or not a d i f f e r e n c e has been shown, (2) the direction of the d i f f e r e n c e w h e n present. T h e first striking thing in this table is that there are no conflicting results across studies in the directions of the differences. O n a given value, one s t u d y m a y find a d i f f e r e n c e a n d the o t h e r not b u t w h e n e v e r two or m o r e studies d o find a difference, the d i f f e r e n c e is a l w a y s in the s a m e direction w i t h o u t a n y exception. T o be m o r e specific, w h e n e v e r there is a sex

TABLE V A g e / s e x i n t e r p l a y using the W i l c o x o n r a n k s u m s test. O

Variables

Y

I II III

Ws = 569.0 W~ = 519.0 Ws = 620.5

P = 0.2545 P = 0.9335 P = 0.0279 *

W~ = 1318.0 W S = 1160.0 W~ = 1 6 0 7 . 5

P = 0.6507 P = 0.9959 P = 0.0079 *

IV V

W~ = 619.0 W s = 593.5

P = 0.0303 * P = 0.0147 *

W~ = 1447.0 W s = 1482.5

P = 0.0590 P = 0.1000

I-III III-V

W s = 422.5 Ws = 472.5

P = 0.0567 P = 0.8801

W s = 980.0 W~ = 1344.0

P = 0.0047 * P = 0.7606

I-V

W~ = 396.0

P = 0.0719

W s = 1149.5

P = 0.2972

M vs. F

M vs. F

F

M

Yvs. O

Yvs. O

I II

W~ = W~ =

882.0 788.5

P = 0.0681 P = 0.0047 *

W s = 480.5 Ws = 441.5

P = 0.1551 P = 0.0655

III IV V

W~ = Ws = Ws =

806.0 853.5 835.0

P = 0.0084 * P = 0.0438 * P = 0.0266 *

W S = 487.0 W s = 496.0 Ws = 419.5

P = 0.1472 P = 0.2623 P = 0.0381 a

I-III III-V I-V

W s = 1188.0 W~ = 1094.0 W S = 1188.0

P = 0.1505 P = 0.5575 P = 0.1067

W s = 501.0 W s = 542.5 W s = 554.0

P = 0.4011 P = 0.8212 P = 0.5178

* P < 0.05. M = male; F = female; Y = y o u n g e r ; O = older.

482

J. THIVIERGE, R. COTI~

TABLE VI Age and sex comparison across studies * Studies

Age/sex

Present

A-S (4-59) N=134

Rosenhamer et al. (1980)

A-S (20-65) N = 61

Mochizuki et al. (1982) Robier and Reynaud (1984) Rowe (1978) Kjaer (1979) Rosenhall et al. (1985) Chu (1985) Johannsen and Lehn (1984)

IPL

Y
8-11:

Beagly and Sheldrake (1978) McClelland and McCrea (1979) O'Donovan et al. (1980)

Latencies

F
III

IV

F
F
F
F
I-III F
III-V

I-V

F
F
F
S N = 70

F
(9-34) S N =119

F
A-S (5-11) N = 70 S S

A-S A-S A-S (A)-S

(NN-20) N = 200 (19-30) N = 20 (17-74) N = 50 (10-69) N = 40 (5-75) N = 268 (18-76) N-156

F
,L2 months F
F
F
Y
A (25 vs. 63) N=?

F
Y3
F
F
F
F
F
F
F
F
F
Y
Y
Y
* Only statistically significant results are shown. Y = younger group; O = older group; 0 = difference magnitude in m s e c ; - = not analysed.

difference on AL or IPL values, everybody agrees that females have shorter values than males, the same being true for age differences, younger being shorter than older ones. The second thing about this table is that there are two values about which there is a remarkable agreement across the studies that analysed them: everybody agrees (1) that there is no variation according to age and sex on the I I I - V IPL; this one appears as the most stable of the BAER values; (2) that for

wave V AL females have shorter values than males. Regarding the latter we now know of many biological variables which show a statistically significant difference between males and females and for most of them the physiological meaning of that fact remains unknown. The same applies to the male/female difference on the wave V AL. What can be said at this point is that, considering the results of all known studies the wave V AL appears to be the strongest and most

BAER: STUDY 1N C H I L D R E N A N D ADULTS consistent BAER index of the difference between males and females. As for the former the fact that the I I I - V IPL appears as the most stable of the BAER values across studies might have a direct bearing on clinical interpretation: here is a robust component that seems unlikely to be distorted by the usual confounding factors of age and sex, and maybe by factors of other nature. If this fact stands, it would confer a special status to the I I I - V IPL in terms of the solidity of the clinical interpretation based on it: an abnormality on this particular value would tend to be taken more seriously and with more confidence as an index of neurophysiological dysfunction. Finally there are some disagreements on the other values across studies as to the influence of age and sex. These disagreements have to be explained. There are in fact so many factors that could reasonably account for the disagreements that one is amazed at the fact that some of the findings as we have just seen are homogeneous across studies. Let us mention some of these factors: sample bias, sample age differences, some inadequate exclusion criteria for normative studies, factors tied to the recording parameters and to the statistical testing. At the present time it is always very difficult and often impossible to tell which one of these factors does explain a particular difference in the results between studies. However, we have to try to know more about the interplay of these factors and we would like to comment on some of them on the basis of the results of the present study.

(1) Recording parameters As in the majority of other studies we have assumed that there would be no difference in the values of women compared to men or of one age group compared to another accounted for by the type of equipment or the recording parameters that we used. In other words we thought it reasonable to assume that equipment and recording parameters were invariant as regards sex and age values. It probably is largely so. But Rosenhamer et al. (1980) have presented intriguing results in this respect. For example he reported a significant I - V IPL sex difference at 80 dB ( P < 0.025) which had disappeared at 60 dB. Does this suggest that the sex difference on the value is dependent on the stimulus intensity level? It obviously needs replication. What about the effect of other recording parameters on age and sex groups? Could they account for some of the differences across studies?

(2) Key age battlements Let us consider the 3 following facts: (a) O'Donovan et al. (1980) have reported an absence of sex difference in the 5-7-year-old group. Unfortunately we have been unable to replicate this finding in our own sample because of an inadequate number of subjects in this age group at this point. (b) In the present study we found no sex effect on the wave I AL in the total sample but found one in the 8-11-year-old group (N = 3l). Moreover the two studies (Rosenhamer et al. 1980; Rosenhall et al. 1985) that found an age effect on A L I both compared similar age groups (25 vs. 60) including males and females.

483 (c) Kjaer (1979) reported latencies greater in the 10-14(female and male) and 50-69 (female) than in the 20-29-yearold group. These facts taken altogether do suggest the possibility of some key age battlements in regard to age and sex effect on the values. If this concept holds it would definitely explain some of the differences in findings across studies.

(3) Statistical testing If we are to use parametric test of significance (Student 't,' analysis of variance ...), the normality of the data should be tested. The majority of the studies have not reported the results of their analysis in this regard. After the results of one study (Salamy et al. 1982) where this aspect is extensively investigated for BAER values, it would appear that for some given variables the normality may be accepted in one subgroup and not in another one which would suggest that every researcher should test the normality in his own sample. For example in our own sample, normality was rejected for the I - V IPL; consequently we used a non-parametric test of significance and found neither age nor sex effect on this variable. However, had we ran a ' t ' test on the same data disregarding the normality assumption (as we did for experimenting the idea), it would have turned out to be significantly affected by sex. Had we used this only test we would have confirmed the findings of other studies on this variable on which the t test was used (Kjaer 1979; McClelland and McCrea 1979; Rosenhamer et al. 1980; Mochizuki et al. 1982; Robier and Reynaud 1984; Chu 1985). These facts support the idea that the way statistics are done contribute to explain differences of findings across studies. These facts are puzzling. What conclusion should we draw? For instance, is the I - V IPL significantly affected by sex? In view of our own findings it is not but we used a non-parametric test of significance to answer the question because our data were not normally distributed. Other studies found a sex effect on the I - V IPL using parametric tests of significance (Student 't'). If the Student ' t ' was applied to non-normally distributed data, we can have doubt about the meaningfulness of the conclusion. If the Student ' t ' has been applied to normally distributed data verified as such, we can then have some confidence in the conclusion. One has to remember that: (1) If a given type of distribution has been reported for one component in a given sample, this does not mean that the distribution of this component in another sample will be the same; the type of distribution has to be verified in every sample; (2) in order to be meaningful the statistical test of significance to be used is one that applies to the actual type of distribution of the data; (3) the 'truth' will eventually emerge out of a general consensus from methodologically sound studies done on several samples.

Conclusion (1) Like others did we have found significant differences on some of the BAER values according to age and sex. On one hand there are remarkable points of agreement across studies on the influence of age and sex on some of the BAER values;

484 on the other hand there are differences but no contradiction. We can identify many factors for possibly explaining these differences but we do not have the total picture as yet. In this situation it certainly is advisable that every laboratory establishes its own norms according to the age and sex characteristics of its own normal population. (2) More specifically the data of the present study show (a) a variation of the BAER values according to age and sex but for the III-V IPL, (b) that for AL II, III and V the age effect is more important than the sex effect, this being additionally so only for females as regards AL II and III, (c) a significant sex effect for the I-III IPL. (Curiously a rather high incidence of abnormal and neurologically unexplainable increase of this l-III value has been reported (Chiappa 1982). Our data suggest that the sex bias could perhaps explain some of the unexplained variation on this value.) Of course these results have to be replicated in other samples. The authors wish to express their thanks to Pierrette Boutin, Edith Crt6 and Francois Hupp6 who diligently made the recordings, to all the personnel of the Hrtel-Dieu du SacrrCoeur who participated in this study and to Germaine Larose who typed the manuscript.

References

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J. THIVIERGE, R. COTE Johannsen, H.S. and Lehn, T. The dependence of early acoustically evoked potentials on age. Arch. Otorhinolaryng., 1984, 240: 153-158. Kjaer, M. Differences of latencies and amplitudes of brain stem evoked potentials in subgroups of a normal material. Acta neurol, scand., 1979, 59: 72-79. Kjaer, M. Recognizability of brain stem auditory evoked potential components. Acta neurol, scand., 1980; 62: 202-233. McClelland, R.J. and McCrea, R.S. Intersubject variabifity of the auditory-evoked brain stem potentials. Audiology, 1979, 18: 462-471. Mochizuki, Y., Go, T., Ohkubo, H., Tatara, T. and Motomura, T. Developmental charges of brainstem auditory evoked potentials (BAEPs) in normal human subjects from infants to young adults. Brain Develop., 1982, 4: 127-136. Mochizuki, Y., Go, T., Ohkubo, H. and Motomura, T. Development of human brainstern auditory evoked potentials and gender differences from infants to young adults. Progr. Neurobiol., 1983, 20: 273-285. O'Donovan, C.A., Beagly, H.A. and Shaw, M. Latency of brainstem response in children. Brit. J. Audiol., 1980, 14: 23-29. Robier, A. et Reynaud, J. Potentiels 6voqurs auditifs du tronc crrrbral et enregistrement dynamique du rrflexe stap~dien: variations interindividuelles. Audiology, 1984, 23: 490-497. Rosenhall, U., Bj6rkman, G., Pedersen, K. and Kall, A. Brainstem auditory evoked potentials in different age groups. Electroenceph. clin. Neurophysiol, 1985, 62: 426-430. Rosenhamer, H.J., Lindstrom, B. and Lundborg, T. On the use of click-evoked electric brainstem responses in audiological diagnosis. Scan& Audiol., 1980, 9: 93-100. Rowe, M.J. Normal variability of the brain-stem auditory evoked response in young and old adults subjects. Electroenceph, clin. Neurophysiol., 1978, 44: 459-470. Salamy, A., Mendelson, T. and Tooley, W.H. Developmental profiles for the brainstem auditory evoked potential. Early hum. Develop., 1982, 6: 331-339.