Exp Brain Res (1991) 85:537-542
Experimental BrainResearch 9 Springer-Verlag1991
Generator study of brainstem auditory evoked potentials by a radiofrequency lesion method in rats T.-J. Chen and S.-S. Chen Department of Neurology and Physiology,Graduate Institute of Medicine, KaohsiungMedical College, Kaohsiung 80708, Taiwan, Republic of China Received August 9, 1990 / Accepted March 14, 1991
Summary. The generators of brainstem auditory evoked potentials (BAEPs) in rats were investigated experimentally. Discrete lesions of the brainstem auditory pathway were made unilaterally using a stereotaxic radiofrequency coagulation method, and the BAEPs were recorded before and after the lesions to observe the alterations. The waves of the BAEPs were affected by the lesions as follows: (1) all of the BAEP waves were attenuated or eliminated by a lesion of the auditory nerve; (2) wave II was abolished or attenuated in amplitude following a lesion of the cochlear nucleus; (3) marked reduction or abolition of wave III occurred with some effect on waves IV and V following lesions of the superior olivary complex; (4) the following trough in the wave III was significantly attenuated by lesions of the lateral lemniscus that were associated with inconsistent changes in waves IV and V; (5) no waves were affected significantly by a lesion of the inferior colliculus. The method of radiofrequency lesion using stereotaxic localization proved to be a simpler and more rapid procedure for determining the generators of BAEPs in animals than other surgical lesion methods. Key words: Generators Brainstem auditory evoked potentials - Stereotaxic radiofrequency coagulation Rat
Introduction The brainstem auditory evoked potentials (BAEPs) are considered to reflect the far-field volume conducted potentials recorded from scalp electrodes in human beings or animals during the first 10 ms following an acoustic stimulus. The generators of the BAEP peaks have been attributed to specific portions of the brainstem auditory pathway on the basis of latency correlations between surface- and depth-recorded activity (Jewett Offprint requests to: S.-S. Chen (address see above)
1970; Achor and Starr 1980a, b; Moller et al. 1981; Moller and Jannetta 1982; Legatt et al. 1986), as well as changes in the BAEPs accompanying experimental brainstem lesions in animals (Buchwald and Huang 1975; Achor and Starr 1980b; Wada and Starr 1983a-c). Also, there has been a correlation between abnormalities of BAEPs recorded in patients with brainstem disorders, and the site of brainstem lesions defined by CT scan or autopsy (Start and Achor 1975; Start and Hamilton 1976; Narayan et al. 1981). There is a description, still controversial among researchers, that the principal generators for the BAEPs in human beings and cats are: peak I, the auditory nerve (AN); peak II, the cochlear nucleus (CN); peak III, the superior olivary complex (SOC); peak IV, the lateral lemniscus (LL); and peak V, the inferior colliculus (IC). However, the precise generator of each component is uncertain. Some investigators suggest that just one structure, probably a nuclear group or fiber tract, contributes primarily to each component (Jewett 1970; Buchwald and Huang 1975). In contrast, Achor and Starr (1980a) concluded that most of the components of the BAEPs in cats may have resulted from several brainstem sites, and that each structure may also contribute to the formation of several components. The BAEPs have been shown to be invaluable in detecting otological defects in infants and in uncooperative children (Galambos and Despland 1980), as well as in the detection of brainstem or otogenic lesions in the adult (Start and Hamilton 1976; Kjaer 1980; Ciganek et al. 1984). So an understanding of the origin of the BAEP wave components should be of great importance to its clinical application. Thus, animal experiments, which present less obstacles while studying the generators of the BAEPs, can contribute greatly to the understanding the origins of BAEP generators. Rats are preferred in our laboratory because they are less expensive, much more easily controlled, and have similar acoustic pathways to that of the cat and human being. The rat model of BAEP study has been well established and a series of studies have already been done using rats
538 for e x p l o r i n g v a r i o u s n e u r o l o g i c a l p r o b l e m s ( C h e n et al. 1988; H s u et al. 1989; P a n et al. 1989; Chert a n d Chert 1990). W h i l s t t h e r e h a s b e e n f r e q u e n t use o f rats as a n i m a l m o d e l s in B A E P s studies, there is a l a c k o f d i r e c t literature w h i c h p r o v i d e s e n o u g h i n f o r m a t i o n to i d e n t i f y the g e n e r a t o r s o f the r a t B A E P s (Jewett a n d R o m a n o 1972; P l a n t z et al. 1974; F u n a i a n d F u n a s a k a 1983; S h a w 1988), so a n a t t e m p t was m a d e to c o n f i r m the identificat i o n a n d n o m e n c l a t u r e o f each c o m p o n e n t o f B A E P s in o u r r o d e n t m o d e l . T h e r e f o r e , the p u r p o s e o f the p r e s e n t s t u d y was to e x a m i n e a n d define the g e n e r a t o r s o f the B A E P s in the r a t d e r i v e d f r o m the effects o f discrete lesions o f the b r a i n s t e m a u d i t o r y p a t h w a y u p o n B A E P s . N u m e r o u s lesion m e t h o d s c a n be used, i n c l u d i n g elect r o l y t i c lesion b y c a t h o d a l c u r r e n t ( A c h o r a n d S t a r r 1980b; W a d a a n d S t a r r 1983c), r a d i o f r e q u e n c y a n d o t h e r t h e r m o c o a g u l a t i o n techniques ( G r e e n b e r g et al. 1981; L u m e n t a et al. 1986), s u c t i o n o r a s p i r a t i o n o f n e r v o u s tissue ( B u c h w a l d a n d H u a n g 1975; C a i r d a n d K l i n k e 1987), i n j e c t i o n o f a local a n e s t h e t i c such as p r o c a i n e ( W a d a a n d S t a r r 1983a) o r a n e x c i t o t o x i c a m i n o a c i d such as k a i n i c a c i d ( G a r d i a n d B l e d s o e 1981), surgical section o f a specific locus ( W a d a a n d S t a r r 1983b, c) o r t r a n s e c t i o n o f a c r o s s e d b u n d l e ( O - U c h i et al. 1982). R a d i o f r e q u e n c y c o a g u l a t i o n was e m p l o y e d in the p r e s e n t s t u d y b e c a u s e it c o u l d give w e l l - c i r c u m s c r i b e d lesions. W h e n the e l e c t r o d e c u r r e n t flows t h r o u g h the b r a i n tissue, h e a t is g e n e r a t e d in the tissue a n d n o t in the tip o f the electrode, a n d e v e n t u a l l y e v e r y t h i n g c o m e s to therm a l e q u i l i b r i u m a n d the tip t e m p e r a t u r e a p p r o a c h e s t h a t o f the h o t t e s t p a r t o f the h e a t e d tissue. Thus, this m e t h o d supplies a d i r e c t m e a s u r e o f m a x i m u m tissue h e a t i n g a n d a n excellent m e a n s o f q u a n t i t a t i n g the c o a g u l a t i o n s .
as the inferior colliculus, three lesions were performed at the same X-Y coordinates with a depth interval of 0.04 mm in order to create a larger lesion.
Material and methods
Classification and quantification of BAEP changes after lesion
Animal preparation Forty-seven adult male Long-Evans rats, weighing between 300 and 400 gm, were prepared. The animals were anesthetized intraperitoneally with sodium pentobarbital 50 mg/KgBW. The deep rectal temperature was maintained between 37.0-37.5 ~ C throughout the experiment with a thermoregulator. To place the recording electrodes, a dental drill was used to make holes in the skull overlying the right mastoid and the left frontal bone. Two stainless steel screws were then placed in the holes to serve as the permanent recording electrodes. In addition, one needle electrode was attached to the left mastoid to serve as the ground.
Experimental lesion After the baseline recording of BAEPs, the animals were placed in a stereotaxic frame. According to the location decided by an atlas of stereotaxic coordinates (Paxinos and Watson 1982), a hole was drilled at the appropriate site in the skull to accommodate the radiofrequency lesion electrode. Then the lesion electrode was introduced vertically to the desired lesion site. A radiofrequency current generator was used (model RFG-4A, Radionics Inc., Burlington, Massachusetts) to control the lesion electrode, which was a Radionics type TCZ temperature-monitoring electrode. Radiofrequency coagulation was carried out unilaterally on the right side with a radiofrequency current of 500,000 cps for 60 s at a temperature of 90 ~ C. In the case of some anatomical structures such
BAEP recording BAEPs were recorded using a Signal Processor, 7 S l l A (San-Ei Company, Japan). Synchronization was achieved using an acoustic stimulator (San-Ei Company, Japan). The audiosignals were monaural clicks with an alternative polarity, delivered at a repetitive rate of 13.3/s via an earphone (Dynamic receiver, type DR-531, Elega Acous, Japan) positioned 5 cm from the animal's ear. The stimulation intensity was set at 90 dBSPL. The evoked signals were then amplified and filtered with a bandpass of 80 to 3000 Hz, and passed to the signal processor for averaging. Each BAEP recordings averaged from 1024 click-evoked responses for the first 10 ms period following the stimulation. The analogue output was revealed on an oscilloscope, and then plotted on graph paper by a X-Y recorder. The BAEPs were recorded in 2 epochs : prior to the experimental lesion and immediately after a lesion had been performed to a discrete portion along the brainstem auditory pathway. To compare the changes in the BAEPs between the two epochs, special attention was paid to the disappearance of or any alteration in the waveform, a delay in the latency, or a reduction of the amplitude.
Histology When the experiment was terminated, the rats were given a lethal dose of sodium pentobarbital and decapitated immediately after death. Their brains were removed and fixed by liquid-nitrogen cooled isopentane solution. Serial transverse 20 gm frozen sections were made using a freezing microtome and stained with toluidine blue. All sections were examined for the exact lesion site and signs of the electrode's entry into the brain stem. In this study, a lesion was defined as that area of brainstem tissue which was destroyed to such an extent that the brain tissue was obviously "coagulated" and this was indicated by an area of infarction with absence of staining, surrounded by a hyperemic and an edematous areas.
The amplitudes and latencies of the BAEP waves were measured for pre- and post-lesion tracings and compared with each other. Amplitude was measured as the distance from the positive peak to the succeeding negative peak, and the amplitude effects were then expressed as a percentage of the pre-lesion control values. Latency was measured as the time from stimulus onset to a wave's peak. While any change in latency was expressed as an absolute value.
Results T h e initial five p o s i t i v e w a v e s o f B A E P s in r a t s were c o n s i s t e n t a n d were n a m e d w a v e I, II, III, IV a n d V respectively. U s u a l l y w i t h rats, w a v e I split i n t o t w o c o m p o n e n t s n a m e d I A a n d IB. T h e c o m p o n e n t s a f t e r w a v e V were e v i d e n t in even fewer r e c o r d i n g s a n d were t h e r e f o r e n o t e v a l u a t e d . T h e B A E P s were v e r y s t a b l e in b o t h a m p l i t u d e a n d l a t e n c y d u r i n g the p r e - l e s i o n c o n t r o l r e c o r d i n g p e r i o d . I n general, the v a r i a b i l i t y in the l a t e n c y was l i m i t e d to 150 gs o r less a n d in the a m p l i t u d e it was l i m i t e d to 10% o r less ( A c h o r a n d S t a r r 1980b). E x p e r i m e n t a l lesions b y r a d i o f r e q u e n c y c o a g u l a t i o n were m a d e u n i l a t e r a l l y in the A N , C N , S O C , L L a n d I C w i t h a lesion e x t e n t o f 0.5-4.2 m m 3 in the b r a i n tissues.
539
Lesions of the auditory nerve (AN) The loci of lesions were selected in the A N nearby the CN. A unilateral lesion of the A N attenuated or eliminated all of the neural components of the BAEPs to ipsilateral stimulation while no effect was present to contralateral stimulation. In one animal, the lesion abolished all of the components of the BAEPs which became isoelectric. In another 3 animals, the BAEPs following the stimulation of the ear ipsilateral to the lesion showed a reduction in amplitude to a m i n i m u m value of 36% in waves I to V, and also a prolongation in
latency for waves IA and IB. In the other 4 animals, the lesion abolished wave I and attenuated waves II V during the ipsilateral stimulation. Histologic findings showed that the lesions were restricted to the A N without revealing significant damage to the other brainstem auditory structures (Fig. 1A).
Lesions of the cochlear nucleus (CN) Lesions in the loci of the C N in 12 rats led to a m o n o phasic wave I which unified IA and IB with a latency between that of waves I A and IB, and the loss o f waves I I - V in one animal. In eight animals, wave I became monophasic and there was an attenuation of waves I I - V by 17%-97%. In another three rats, there were attenuations of waves I I - V by 24%-91% associated with an increase in the amplitude of wave IB of over 38%. Peak latency was prolonged by more than 150 Its f r o m wave II on. All these BAEP changes were restricted to the stimulation of the ear ipsilateral to the lesion, but there was no change in BAEP while stimulating the contralateral side. Histologic findings showed that the radiofrequency lesion sites involved both the ventral and dorsal cochlear nuclei in all 12 rats (Fig. 1B).
Lesions of the superior olivary complex (SOC) Lesions in the SOC in 10 rats were associated with the following changes. The alterations o f the BAEPs when stimulated ipsilaterally at the lesion site primarily included two conditions. One is the loss of wave I I I combined with a broadening of wave IV, which showed a Table 1. Waveform alterations of BAEPs following discrete lesions of the auditory structures in rat brainstems Lesion
Stimulation
Characteristics of BAEPs
N
AN (n = 8)
I
isoelectric - lost all waves lost wave I & reduced waves II-V reduced waves I-V
1 4 3
CN (n = 12)
I
unified wave I & lost waves II-V 1 unified wave I & reduced waves II V 8 elevated wave IB & reduced waves II-V 3
SOC (n = 10)
I
lost wave I I I & broader wave IV with a shorter latency and a reduced amplitude reduced waves III-V reduced wave III
4
reduced of wave changes reduced reduced reduced reduced reduced
6
C LL (n = 12)
I
C Fig. 1A-E. Frozen sections of the brainstem stained with toluidine blue (left) and the corresponding reconstruction of the histology (right) in which discrete lesions on the auditory pathway of rat were made. The lesion was made unilaterally on the right side. The regions of the lesions were: A the auditory nerve (AN); B the cochlear nuclei (CN); C the superior olivary complex (SOC) and the trapezoid body (Tz); D the lateral lemniscus (LL); E the inferior colliculus (IC). D: dorsal; V: ventral; L: lateral; M: medial
IC
I, C
the following trough I I I & inconsistent on waves IV-V waves III-IV waves IV-V wave III waves III-IV waves IV-V
no significant effects
6 4
3 3 7 3 1 5
(n = 5) Lesion: AN = auditory nerve; CN = cochlear nucleus; SOC = superior olivary complex; LL = lateral lemniscus; IC = inferior colliculus. Stimulation: I = ipsilateral; C = contralateral
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Fig. 2 A - D . A l t e r a t i o n s o f the B A E P s following discrete lesions o f the b r a i n s t e m a u d i t o r y structures 9 A L e s i o n s o f the a u d i t o r y nerve: a lost all waves; b lost wave I a n d r e d u c e d w a v e s IT-V; e r e d u c e d w a v e s I-V. B L e s i o n s o f t h e cochlear n u c l e u s : a unified wave I a n d lost w a v e s I [ - V ; b unified w a v e I a n d reduced w a v e s I I - V ; e
elevated w a v e IB a n d r e d u c e d w a v e s I I - V . C L e s i o n s o f the superior olivary c o m p l e x : a lost w a v e [1[ a n d dispersed w a v e I V ; b reduced w a v e s I I I - V . D L e s i o n s o f l a t e r a l l e m n i s c u s : a r e d u c e d t h e following t r o u g h o f wave III; b reduced waves I I [ - I V ; c r e d u c e d waves I V - V
shorter latency and a reduction in amplitude of m o r e than 25%, in four animals 9 Second is a reduction o f around 30-90% in the amplitudes of waves I I I - V in the other six animals 9 O f these animals, four showed a reduced amplitude in wave III when stimulated contralaterally at the lesion side. Six animals were not stimulated of the contralateral site, so the alterations of the BAEPs were unknown. Histologic findings showed that the lesions involved the SOC, as well as the nucleus and the decussating fibers of the trapezoid body in all ten rats (Fig. 1C).
Lesions o f the lateral lemniscus ( L L )
Lesions o f the L L in 12 rats were accompanied by more complicated effects9 While the BAEPs were responsive to ipsilateral stimulation, there were six animals which showed a reduced amplitude in wave III. This particularly affected the following trough but not the peak of wave III. However the effect on waves IV and V was inconsistent. O f the six rats, five presented the same changes to the contralateral stimulation, and one animal presented a reduced amplitude for waves I I I and IV. Another three
541 animals showed reduced amplitudes, both for the peak and the following trough, in waves III and IV in response to ipsilateral stimulation. Of those three, one animal presented the same change to the contralateral stimulation, while two animals presented a reduced amplitude of wave III. The other three animals showed reduced amplitudes in waves IV and V to ipsilateral stimulation. One of these animals showed the same change to the contralateral stimulation, another presented a reduced amplitude in wave III, and the third showed reduced amplitude in waves III and IV. In summary, the effects o f a unilateral LL lesion were characterized primarily by marked attenuation beyond 60% of the following trough of wave Ill to both ipsilateral and contralateral stimulation. However the effect on waves IV and V was inconsistent. Histologic findings showed that the lesions involved both the nucleus and tracts of the L L in all 12 rats (Fig. 1D).
Lesions of the inferior colliculus (1(2) In five animals the unilateral IC were destroyed. There were no significant effects on any of the components of the BAEPs to either ipsilateral or contralateral stimulation. Histologic findings showed that the IC were almost completely involved in these five rats (Fig. 1E). The alterations of BAEPs following discrete lesions on the auditory brainstem structures are summarized in Table 1 and Fig. 2.
Discussion The results presented in this study indicate that the predominant effect of discrete brainstem lesion on the BAEPs is an attenuation in the amplitudes o f the components with only occasional increases in their latencies. These are summarized in Table 1. According to the results, a simple one-to-one relationship between a given anatomical site and a particular component of the BAEPs can be precluded, especially for the presentation of the wave III which was affected by lesions of both SOC a n d LL. In rats, wave I usually split into two components, which was documented by disappearance or attenuation of the first two waves following the lesion o f AN in the present study. It also corresponds to a study in cats, in which the components P0.8, N1.0, P1.2 and N1.5 of the BAEPs were unaffected by the lesions of the CN, but were affected by lesions of the A N (Achor and Starr 1980b). The higher amplitude of wave IB after lesions o f the C N probably resulted from the destruction of the COCB (crossed olivocochlear bundle). Some investigators have reported an inhibitory action of the COCB on the whole nerve action potential and single unit discharge rate of the cochlear nerve (Wiederhold 1970; Wiederhold and Kiang 1970). Therefore, augmentation of the auditory evoked responses from the cochlear nerve would be expected if the inhibitory action of the COCB on auditory
evoked potential disappeared following lesions of the CN. However, the action of the COCB is still contraversial, since some have reported an inhibitory action (Wiederhold 1970; Wiederhold and Kiang 1970), whereas others found no significant effect on the auditory evoked potentials (O-Uchi et al. 1982). The identity of the components following a lesion of the SOC is uncertain in some instances. This uncertainty is particularly relevant for the component which occurred around the time of the appearance of wave IV. Following the lesion, this component appeared at an earlier latency, it was broader in duration and showed a decreased amplitude when compared to the control wave IV. This phenomenon was similar to the result of a study which involved procaine injections into the trapezoid body (Tz) done by W a d a and Starr (1983a). Their paper suggested that the component in question might be a delayed wave I I I and that waves III and IV were fused, that wave IV shifted in latency or that it formed an entirely new component. However, the authors finally concluded that the component in question resembled wave IV rather than wave iII by evaluating the effects of variations in click intensity and click rate. Therefore, the wave in question which appeared following the lesion of the SOC in the present study was termed wave IV, because the histologic findings of our study also involved decussating fibers of Tz. However, the role of the Tz in the generation o f the BAEPs remains controversial (Shaw 1988). Caird et al. (1985) have argued that waves II and III in the cat arise in the ipsilateral and contralateral Tz, respectively. Nevertheless, it is unclear whether this structure is an intrinsic generator or merely a way station involved in the transmission of the afferent signal (Wada and Start 1983a, b). With the exception of lesions of the A N and the C N which altered the BAEPs only when stimulated ipsilaterally at the lesion site, unilateral lesions in particular regions of the brainstem auditory structures affected the BAEPs to stimulation of both sides. Some of the previous studies indicate that lesions of the SOC (Buchwald and H u a n g 1975; Achor and Starr 1980b) or the L L (Achor and Starr 1980b; Moller and Burgess 1986) only produced alterations of the BAEPs to stimulation contralateral to the lesion site. However, if the lesions involved more extensive areas, both ipsilateral and contralateral auditory evoked potentials were affected (Jewett 1970; Plantz et al. 1974; W a d a and Starr 1983c). In the present study, stereotaxic localization of discrete brain areas were performed and then lesions were made by radiofrequency coagulation. Such procedures did not require us to open the skull but only to drill a small hole in the skull in order to insert the lesion electrode. If the lesion is too small there may be little or no effcct even though correctly placed (Achor and Starr 1980b). So a larger lesion extension of a particular site was preferred for lesioning efficiently without causing damage to other auditory structures. Therefore the lesion effects on the BAEPs were more evident and were bilateral in the present study. As for the lesion of IC, no effect was showed on the BAEPs in the present study or in the study of W a d a and Starr (1983c). However, several studies have reported a significant reduction or inconsistent changes in wave V
542 a n d the f o l l o w i n g waves in cats ( C a i r d a n d K l i n k e 1987; A c h o r a n d S t a r r 1980b). T h e g e n e r a t o r s o f B A E P s h a v e been extensively s t u d ied in g u i n e a pigs a n d cats ( A c h o r a n d S t a r r 1980a, b; W a d a a n d S t a r r 1983a-c). S i m i l a r results in rats were o b t a i n e d in the p r e s e n t study. T h o u g h the p r e v i o u s invest i g a t i o n s were c o m p r e h e n s i v e , the lesion m e t h o d b y surgical o p e r a t i o n is m o r e c o m p l i c a t e d a n d time c o n s u m i n g , as well as r e q u i r i n g p r o f e s s i o n a l n e u r o s u r g i c a l techniques. I n c o n t r a s t , the p r e s e n t s t u d y used r a d i o f r e q u e n c y lesion v i a the a i d o f s t e r e o t a x i c l o c a l i z a t i o n , w h i c h p r o v e d to be a s i m p l e r a n d m o r e r a p i d p r o c e d u r e . So the p r e s e n t s t u d y p r o v i d e s a n easier lesion m e t h o d f o r invest i g a t i n g the g e n e r a t o r s o f the B A E P s , o r o t h e r c o r r e l a t ing studies. A l s o , this m e t h o d c o u l d be u s e d in studies in w h i c h the r a t survives after the lesion. A c c o r d i n g to the results o f the p r e s e n t study, the g e n e r a t o r s o f the B A E P s in o u r r a t m o d e l s were recognized, a n d the i d e n t i f i c a t i o n a n d n o m e n c l a t u r e o f each c o m p o n e n t were definitely confirmed.
Acknowledgements. This study was supported by grants NSC 80.0412-B-037-37 (National Science Council, Taiwan, R.O.C.) and by the Medical Research Council, Kaohsiung Medical College.
References Achor L J, Starr A (1980a) Auditory brain stem responses in the cat. I. Intracranial and extracranial recordings. Electroencephalogr Clin Neurophysiol 48 : 154-157 Achor LJ, Starr A (1980b) Auditory brain stem responses in the cat. II. Effects of lesions. Electroencephalogr Clin Neurophysiol 48:174-190 Buchwald JS, Huang CM (1975) Far-field acoustic response: origins in the cat. Science 189:382-384 Caird DM, Klinke R (1987) The effect of inferior colliculus lesions on auditory evoked potentials. Electroencephalogr Clin Neurophysiol 68:237-240 Caird D, Sontheimer D, Klinke R (1985) Intra- and extracranially recorded auditory evoked potentials in the cat. I. Source location and binaural interaction. Electroencephalogr Clin Neurophysiol 61 : 50-60 Chen TJ, Chen SS (1990) Brain stem auditory-evoked potentials in different strains of rodents. Acta Physiol Scand 138:529-538 Chen TJ, Hsu HK, Chen SS (1988) Brain stem auditory evoked potentials in brain stem dysfunction. Kaohsiung J Med Sci 4: 238-247 Ciganek L, Smieskova A, Hruby M, Mladonicky P (1984) Processing and analysis techniques for brain-stem auditory evoked potentials with localization of brain-stem lesions. Electroencephalogr Clin Neurophysiol 57 : 92-96 Funai H, Funasaka S (1983) Experimental study on the effect of inferior colliculus lesions upon auditory brain stem response. Audiology 22: 9-19 Galambos R, Despland PA (1980) The auditory brainstem response (ABR) evaluates risk factors for hearing loss in the newborn. Pediat Res 14:159-163 Gardi JN, Bledsoe SC (1981) The use of kainic acid for studying the origins of scalp-recorded auditory brainstem responses in the guinea pig. Neurosci Lett 26:143-149 Greenberg RP, Stablein DM, Becker DP (1981) Noninvasive localization of brain-stem lesions in the cat with multimodality evoked potentials: correlation with human head-injury data. J Neurosurg 54:740-750 Hsu CC, Chen TJ, Jin SH, Chen SS (1989) Electrophysiological
studies of acute anoxic hypoxia. Kaohsiung J Med Sci 5: 670-675 Jewett DL (1970) Averaged volume-conducted potentials to auditory stimuli in the cat. Electroencephalogr Clin Neurophysiol 28 : 609-618 Jewett DL, Romano MN (1972) Neonatal development of auditory system potentials averaged from the scalp of rat and cat. Brain Res 36:101-115 Kjaer M (1980) Localizing brain stem lesions with brain stem auditory evoked potentials. Acta Neurol Scand 61 : 265-274 Legatt AD, Arezzo JC, Vaughan HG (1986) Short-latency auditory evoked potentials in the monkey. II. Intracranial generators. Electroencephalogr Clin Neurophysiol 64:53-73 Lumenta CB, Schober R, Sprick C, Bock WJ (1986) Findings confirming brainstem generators of auditory evoked potentials by stereotatic lesions in the rabbit. Neurol Res 8:114-116 Moller AR, Burgess J (1986) Neural generators of the brain-stem auditory evoked potentials (BAEPs) in the rhesus monkey. Electroencephalogr Clin Neurophysiol 65:361-372 Moller AR, Jannetta P (1982) Evoked potentials from the inferior colliculus in man. Electroencephalogr Clin Neurophysiol 53 : 612-620 Moller AR, Jannetta P, Bennett M, Moller MB (1981) Intracranially recorded responses from the human auditory nerve: new insights into the origin of brain stem evoked potentials (BSEPs). Electroenceph Clin Neurophysiol 52:18-27 Narayan RK, Greenberg RP, Miller JD, Enas GG, Choi SC, Kishore PRS, Selhorst JB, Lutz III HA, Becker DP (1981) Improved confidence of outcome prediction in severe head injury: a comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure. J Neurosurg 54:751-762 O-Uchi T, Igarashi M, Kulecz WB (1982) Transection of crossed olivocochlear bundle and auditory brain stem responses in the cat. Acta Otolaryngol 94:1-6 Pan CH, Chen TJ, Lin KS, Chen SS (1989) Brainstem auditory evoked potentials in head injury patients. Kaohsiung J Med Sci 5 : 569-577 Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, Sydney Plantz RG, Williston JS, Jewett DL (1974) Spatio-temporal distribution of auditory-evoked far field potentials in rat and cat. Brain Res 68 : 55-71 Shaw NA (1988) The auditory evoked potentials in the rat - a review. Prog Neurobiol 31 : 19-45 Starr A, Achor LJ (1975) Auditory brainstem responses in neurological diseases. Arch Neurol 32:761-768 Starr A, Hamilton AE (1976) Correlation between confirmed sites of neurological lesions and abnormalities of far-field auditory brainstem responses. Electroencephalogr Clin Neurophysiol 41 : 595-608 Wada SI, Start A (1983a) Generation of auditory brain stem responses (ABRs). I. Effects of injection of a local anesthetic (procaine HC1) into the trapezoid body of guinea pigs and cat. Electroencephalogr Clin Neurophysiol 56:326-339 Wada SI, Starr A (1983b) Generation of auditory brain stem responses (ABRs). II. Effects of surgical section of the trapezoid body on the ABR in guinea pigs and cat. Electroencephalogr Clin Neurophysiol 56:340-351 Wada SI, Starr A (1983c) Generation of auditory brain stem responses (ABRs). III. Effects of lesions of the superior olive, lateral lemniscus and inferior colliculus on the ABR in guinea pig. Electroencephalogr Clin Neurophysiol 56:352-366 Wiederhold ML (1970) Variations in the effects of electric stimulation of the crossed olivocochlear bundle on cat single auditorynerve-fiber responses to tone bursts. J Acoust Soc Am 48 : 966-977 Wiederhold ML, Kiang NYS (1970) Effects of electric stimulation of the crossed olivocochlear bundle on single auditory-nerve fibers in the cat. J Acoust Soc Am 48:950-965