Eur Arch Otorhinolaryngol (1992) 249 : 325-328

European Archives of

Oto-RhinoLaryngology © Springer-Verrag 1992

Maturation of binaural interaction components in auditory brainstem responses of young guinea pigs with monaural or binaural conductive hearing loss M. Laska, M. Walger, I. Schneider, and H. von Wedel HNO-Universit~tsklinik KOln, Joseph-Stelzmann-Strasse 9, W-5000 Cologne 41, Federal Republic of Germany Received January 27, 1992 / Accepted June 16, 1992

Summary. Reversible conductive hearing loss created during the first 4 weeks post partum caused marked alterations in the maturation of binaural interaction components in the auditory brainstem responses of guinea pigs. In untreated control animals all three components investigated demonstrated postnatal development in terms of latency shortening that was completed during the first 3 weeks of life. Plugging of both external ear canals caused a significant delay in the maturation of the late component DN2, where latency values of the controls were reached only 2 weeks after the end of the treatment, i.e. after 6 weeks of life. Monaural deprivation likewise led to a retarded development of peak latencies during the phase of imbalanced sensory imput. After the end of the one-sided conductive hearing loss the maturation process was markedly enhanced, even resuiting in latency values for DN2 and DP1 that were significantly shorter than those of the controls. This phenomenon persisted until the end of the study period and was the case for both plugged and untreated ears in this group of animals. The time course of latencies in two other groups of experimental animals which were deprived in the same way as adults suggests that the effects observed are due to a sensitive period in the maturation process of the auditory pathway. Key words: Auditory maturation - Binaural interaction components - Auditory brainstem responses - Conductive hearing loss - Guinea pigs

Introduction During the early development of the human auditory system, non-genetic factors such as antibiotics, noise trauma or conductive hearing loss may result in irreversible damage to speech perception and speech development [6, 18]. In this respect, the recording of auditory evoked Correspondence to: M.Laska, Institut fiir Medizinische Psychologie, Goethestrasse 31, W-8000 Munich 2, Federal Republic of Germany

potentials [auditory brainstem responses (ABR); middle latency responses (MLR)] represents an important tool for the diagnosis of hearing disorders in children [5, 15, 20]. In man, binaural interaction components (BIC) can be recorded from the 1st day of life by subtracting the summed monaurally evoked from the binaurally evoked ABR. This reflects the activity of binaurally innervated neurons within the brainstem which are sensitive to interaural intensity and phase differences and therefore are essential for localizing a sound source in space. Thus, recording of BICs may be important in the early detection of central processing disorders [7]. As can be observed in the ABR, BICs undergo a postnatal maturation in terms of latency shortening which indicates increasing myelinization of central auditory neurons. Animal studies on the effects of early deprivation also point to a plasticity of the central auditory system if partial or total auditory restriction give rise to an acoustic imbalance between the two ears. Single neurons of the inferior colliculus which are sensitive to binaural acoustic input (EE, EI neurons) change their discharge patterns after unilateral ligature of the external auditory meatus or destruction of the cochlea in young bats and rats [2, 8, 12, 16]. However, these changes were found only after monaural but not binaural deprivation. Possible effects of peripheral hearing disorders, such as frequently occurring otitis media, on the maturation of BICs have not been studied so far. For this reason, the purpose of our study was to evaluate the effects of a reversible conductive hearing loss on the development of BICs in A B R by comparing recordings from monaurally or binaurally deprived young guinea pigs with equally treated adult animals and untreated young controls.

Materials and methods The experiments were carried out in 30 pigmented guinea pigs. BICs of the ABR were evaluated by recording the ABRs to monaural and binaural stimulation (500 sweeps with a repetition rate of 21 alternating clicks/s, recorded every 3 days at 20 dB above threshold) and using the algorithm BIC = Bin

-

(Monipsi +Mon

...... )

326

~" 6E Bin

DN2 o ~ 5"

>

Mon

AA

ipsi

c a)

DP1

-~4-

DN1

Mon i

i

i

i

I

i

1

i

i

i

i

1 4 7 10131619222528 i

i

i

i

i

i

i

i

i

i

i

i

i

i

i

i

i

i

i

i

i

i

i

1 4 7 101316192225263542495684

i

Days

2 ms / Div.

Fig.1. Examples of auditory brainstem responses (ABRs) at 20 dB above threshold level, click-evoked by binaural stimulation (Bin) or monaural stimulation of the ipsilateral side (monipsi) or the contralateral side (Mon~o,,t~) relative to the recording electrode. The binaural interaction components (BIC) DNI, DP1 and DN2 were calculated according to the algorithm shown in the text

Fig. 3. Development of latencies of the BICs DN1, DP1 and DN 2 for the groups of binaurally sound-deprived young guinea pigs (dashed lines) and untreated controls (solid lines). Mean values from n = 12 ears per group. Open arrows indicate the beginning and filled arrows the end of a period of significant differences between the experimental and control groups. The line parallel to the abscissa indicates the 4-week of deprivation in the experimental group

~" 6" E DN2 ~ 5" o

DP1

c

v~"

DN2

5'

DN1

DP1 J

4i

i

4

i

i

t

J

i

t

J

7 10131619222528

i

i

J

1

4

t

i

i

t

i

t

J

J

i

=

t

t

.

~

_

~

.

_

.

~"...

DN1

t

7 101316192225283542495684

Days

Fig. 2. Development of latencies of the BICs DNx, DP1 and DN2 for the untreated young control animals (mean _+ SD; n = 12 ears; standard deviations are represented one-sided). The line parallel to the abscissa indicates the 4-week period of deprivation in the experimental groups

with BIC representing binaural interaction components; Bin, binaural stimulation; Monipsi, monaural stimulation on the ipsilateral side relative to the recording electrode; and Moncontr,, monaural stimulation on the contralateral side relative to the recording electrode. The course of latencies of the BIC peaks DNa, DP1 and DNz is shown in Fig. 1. This was compared in a control group of 6 young untreated animals from the 1st day of life to the 4th month with those from four experimental groups. In 6 animals both ears were occluded from the 1st day of life through a period of 4 weeks. This was done by using plugs consisting of sterile surgical cotton and a 3-mm layer of a dental plastic (Pala Press). Both plugs were then exchanged every 3 days after disinfecting the ear canals with alcohol. Using the same method, another group of 6 guinea pigs was subjected to a monaural conductive hearing loss during the first 4 weeks post partum. In order to discriminate true developmental effects from artifacts due to the experimental method, two groups of animals were also subjected to the same treatment of a 4-week monaural or binaural ear plugging at the age of 4 months. In all four experimental groups, a control measurement was recorded immediately prior to the deprivation phase (i.e., day 0 values in Figs. 3-6). Data of all experimental groups were compared using the Mann-Whitney U-test and, when not otherwise stated, an alpha values of 0.01 was taken as the level of significance.

I

3

,

0

i

i

i

i

i

i

i

i

t

4 7 10131619222528

i

i

]

i

J

i

i

i

i

J

i

i

i

i

i

1 4 7 101316192225283542495684

Days

Fig.4. Time course of latencies of the BICs DN1, DP1, and DN2 for the group of binaurally sound-deprived adult guinea pigs. Solid lines, Right ears; dashed lines, left ears; mean values from n = 6 animals. The line parallel to the abscissa indicates the 4-week period of deprivation in the experimental group

7"

~" 6" E

v

o~

DN2

5"

0) "

DP1 4"

DN1

i

i

i

i

i

i

J

i

J

i

i

1 4 7 10131619222528

i

i

i

i

i

i

i

i

i

i

i

i

i

i

1 4 7 101316192225283542495684

Days

Fig.5. Development of latencies of the BICs DN1, DP1 and DN2 for the groups of monaurally deprived young guinea pigs (dashed lines, deprived ears; dotted lines, untreated ears) and untreated controls (solid lines). Mean values from n = 6 animals per group. Open arrows indicate the beginning and filled arrows the end of a period of significant differences between experimental and control groups. The line parallel to the abscissa indicates the 4-week period of deprivation in the experimental group

327 6 ..~

........"..~.. DN2 ~=

5

•

.

~,

o

.4

.

4

............ ~

3

i

~

i

i

~ .

i

~

"

.

i

i

i

"

.

i

1 4 7 10131619222528

E

'

" - ....... ....

"'" •........... DN1

"

i

I

1 4

i

DP1

i

i

i

i

~

i

i

1

i

i

7 101316192225283542495684

Days Fig. 6. T i m e c o u r s e of latencies of t h e B I C s D N I , DP1 a n d DN2 f o r t h e g r o u p of m o n a u r a l l y d e p r i v e d a d u l t g u i n e a pigs. Solid lines,

Deprived ears; dashed lines, untreated ears; mean values from n = 6 animals. The line parallel to the abscissa indicatesthe 4-week period of deprivation in the experimentalgroup

Results

The course of peak latencies in the group of unimpaired young controls shows that all three B1Cs underwent a postnatal maturation in terms of a latency shift that was completed approximately 3 weeks post partum (Fig. 2). At that time latencies reached the values of adult animals. The most distinct development was found in the late component DN2, where the shortening of latency values amounted to 0.9 ms. As show previously [19], binaural occlusion with the plugs caused a threshold shift of 35-50dB over a wide frequency range. Young guinea pigs with reversible conductive hearing losses of both ears showed a marked delay in maturation of the late component DN2 compared to the controls (Fig. 3) (P < 0.01 from day 4 to day 7 post-occlusion and P < 0 . 0 5 at day 13). During the phase of deprivation the maturation process was retarded but not completely stopped. The experimental animals did not reach the latency values of the controls until about 2 weeks after the end of the treatment, that is after 6 weeks of life. Figure 4 shows the course of latency values of BICs in adult guinea pigs during and after the 4-week period of binaural deprivation. The slight increase in latency values for all three components during the phase of conductive hearing loss was completely due to the physical sound conduction delay caused by the ear plugs. It disappeared immediately when the ear plugs were removed, with latencies returning to the values recorded prior to treatment. The maturation of the BICs in monaurally deprived young guinea pigs is shown in Fig. 5. This demonstrates that the postnatal development of the late component DN2 was significantly retarded in relation to the controls. Again, maturation took place during the phase of deprivation, but this process was markedly enhanced after the end of treatment. This rapid development led to a latency shift that was also significantly lower than the values for DP1 and DN2 of the controls and perisisted until the end of the study period. (ln DN2 P < 0.01 from day 4 to day 7 post-occlusion and from day 16 post-occlusion to day 84. In DP1 P < 0.01 from day 16 post-occlu-

sion to day 84). However, no significant differences were found in the course of latency development between the hearing-deprived and the untreated ears in the experimental group. Adult guinea pigs which were hearing-deprived monaurally did not show any changes in the course of their peak latencies (Fig. 6). The differences between the impaired and the untreated ears during the phase of ear plugging again illustrate the physical sound conduction delay. After the end of the 4 weeks of sound deprivation, latency values for all components returned to or remained at the level recorded prior to treatment.

Discussion

The BICs investigated in the present study reflect the summed activity of binaurally innervated neurons in the brainstem. The peak latencies of DN1, DPt, and DN2 correspond to the activity of neurons in the superior olivary complex, lateral lemniscus and inferior colliculus which perform the central processing of interaural phase and intensity differences. As described for the maturation of ABR and MLR [3], BICs experience a postnatal development in terms of a latency decrease of up to 0.9ms (DN2) within the first 3 weeks of life in unimpaired control animals. In our present studies, a reversible sound-conductive hearing loss of about 40 dB was found in our test animals over a wide frequency range during the first 4 weeks post partum. This led to a retarded development of BIC latencies in both monaurally and binaurally sound-deprived animals with differences of up to 0.5 ms for the late component DNo. However, control values were reached within 10 days after the ear plug was removed. This latency shift cannot be attributed only to the physical sound conduction delay of about 0.2 ms caused by the ear plug, since it was also found in young monaurally deprived animals on the unplugged side. The effects observed were only found in the young immature animals but not in adult animals where, depending on the treatment, ear plugging caused only a monaural or binaural sound conduction delay. The plasticity of central stations of the developing auditory pathway is indicated by the marked latency decrease of BICs DPt and DN2 after the end of the monaural deprivation phase in young animals, where the level of controls was significantly and persistently undercut. The fact that this phenomenon only occurred after monaural but not binaural deprivation shows that an acoustic imbalance has a stronger influence upon the maturation of binaurally innervated neurons compared to a symmetrical deprivation. The consequences of early auditory restriction on the maturation of the auditory system have been described in histological [4, 9, 14, 17] and electrophysiological studies in several species [2, 8, 13, 16]. Unilateral ligature of the external auditory meatus, leading to a sound conductive hearing loss comparable to the one applied in our study, or unilateral destruction of the cochlea caused marked alterations in the discharge patterns of binau-

328 rally innervated n e u r o n s in the inferior colliculus. This n e u r o n a l plasticity in rats - loss of ipsilateral suppression in the ligated ear o f contralaterally e v o k e d activity - could only be observed during a "critical p h a s e " between days 10 and 30 after birth [2, 16]. In contrast to these findings, a loss of sensitivity of inferior colliculus n e u r o n s for interaural intensity differences after m o n aural deprivation has also b e e n r e c o r d e d in adult cats [131. T h e results p r e s e n t e d here are consistent with behavioral studies d e m o n s t r a t i n g disrupted localization behavior in y o u n g guinea pigs [1] and the rapid c o m p e n s a tion of s o u n d localization accuracy in y o u n g barn owls [10, 11] after unilateral s o u n d conductive hearing loss. T r a n s f e r r e d to h u m a n s , o u r data suggest that a s o u n d conductive hearing loss, as is typical for frequently occurring otitis media, m a y alter the m a t u r a t i o n of central c o m p o n e n t s of the auditory system and thus possibly impair speech d e v e l o p m e n t and c o m p r e h e n s i o n of speech in early childhood. H o w e v e r , a reversible acoustic imbalance m a y be c o m p e n s a t e d by n e u r o n a l plasticity during a further critical phase in d e v e l o p m e n t .

Acknowledgement. Financial support by the Deutsche Forschungsgemeinschaff is gratefully acknowledged.

References 1. Clements M, Kelly JB (1978) Auditory spatial response of young guinea pigs (Cavia porcellus) during and after ear blocking. J Comp Physiol 92 : 34-44 2. Clopton BM, Silverman MS (1977) Plasticity of binaural interaction. II. Critical period and changes in midline response. J Neurophysiol 40:1275-1280 3. Dum N (1984) Postnatal development of the auditory evoked brainstem potentials in the guinea pig. Acta Otolaryngol (Stockh) 97 : 63-68 4. Feng AS, Rogowski BA (1980) Effects of monaural and binaural occlusion on the morphology of neurons in the medial superior olivary nucleus of the rat. Brain Res 189: 530-534 5. Guerit JM (1985) Application of surface-recorded auditory evoked potentials for the early diagnosis of hearing loss in neonates and premature infants. Acta Otolaryngol 421 [Suppl] (Stockh) : 68-76

6. Henry KR (1983) Abnormal auditory development resulting from exposure to ototoxic chemicals, noise, and auditory restriction. In: Romand R (ed) Development of auditory and vestibular systems. Academic Press, New York, pp 273 : 308 7. Hosford-Dunn H, Mendelson T, Salamy A (1981) Binaural interactions in short-latency evoked potentials of neonates. Audiology 20 : 394-408 8. Jen PHS, Sun X (1990) Influence of monaural plugging on postnatal development of auditory spatial sensitivity of inferior colliculus neurons of the big brown bat, Eptesicus fuscus. Chin J Physiol 33:231-246 9. Killackey HP, Ryugo DK (1977) Effects of neonatal auditory system damage on the structure of the inferior colliculus of the rat. Anat Rec 187:624 10. Knudsen EI, Esterly SD, Knudsen PF (1984) Monaural occlusion alters sound localization during a sensitive period in the barn owl. J Neurosci 4:1001-1011 11. Knudsen EI, Knudsen PF, Esterly SD (1984) A critical period of the recovery of sound localization accuracy following monaural occlusion in the barn owl. J Neurosci 4 : 1012-1020 12. Moore DR (1983) Development of inferior colliculus and binaural audition. In: Romand R (ed) Development of auditory and vestibular systems. Academic Press, New York, pp 121-166 13. Moore DR, Irvine DRF (1981) Plasticity of binaural interaction in the cat inferior colliculus. Brain Res 208 : 198-202 14. Nordeen KW, Killackey HP, Kitzes LM (1983) Ascending projections in the inferior colliculus following unilateral cochlear ablation in the neonatal gerbil, Meriones unguiculatus. J Comp Neurol 214 : 144-153 15. Rotteveel JJ, Colon EJ, Notermans SLH, Stoelinga GBA, Visco YM (1985) The central auditory conduction at term and three months after birth. Scand Audiol 14:179-186 16. Silverman MS, Clopton BM (1977) Plasticity of binaural interaction. I. Effect of early auditory deprivation. J Neurophysiol 40 : 1266-1280 17. Trune DR (1982) Influence of neonatal cochlear removal on the development of mouse cochlear nucleus. I. Number, size, and density of its neurons. J Comp Neurol 209 : 409-424 18. Uziel A (1985) Non-genetic factors affecting hearing development. Acta Otolaryngol 421 [Suppl] (Stock) : 57-61 19. Walger M, Ferreira P, Laska M, Schneider I, Wedel H von (1989) EinfluB binauraler Schalleitungsst6rung auf die Reifung akustisch evozierter Potentiale (HSP, MLR) beim Meerschweinchen. Laryngol Rhinol Otol 68 : 626-631 20. Wedel H von, Schauseil-Zipf U, D6ring WH (1988) H0rscreening bei Neugeborenen und S~iuglingen mittels Ableitung akustisch evozierter Hirnstammpotentiale. Laryngol Rhinol Otol 67:307-311