Auditory brainstem responses to tonal stimuli in young and aging rats

Hearing Researeh. 43 (1990) 17[ ~|g0 Else~le~

17~

HEARF~ 01303

Auditory brainstem responses to tonal stimuli in young and aging rats W i l l i a m A. C o o p e r , Jr. i J a m e s P . C o l e m a n ~ a n d E l i z a b e t h H. N e w t o n ~* Deparfments of t Ctm~m,mtcat,~e Dtsarders. a~d :' P~,chotogT and Physiology, DR? Un¢t~erfa(Vo/,v~-~dth C~r'ol,~a~ ColI~I~ L South Carolina, US, A, (Received 21 June 1989: e~x:eptexl 16 ~ugust 1989,~

The auditory brmn stem reslxmse (~,BR) was stud~ed m young adult "and aged rats using 3. 8 and ~} kHz t~me f~ps. The cxlx~cled inverse relationship between frequency and tatcncv ~'a~ observed in the younger grcrap for ~,aves I. 11 and Iil. whi~ the re~t~gmse to the higb~t frequency stimulus had the longest latency at wa~e V. Ab~_.o|ute ta~e~cies for waves ] tt~'o~agh V e ~ h showed age-related i ~ t s with more pronounced changes c ~ u r i n g to 3 and 40 k i l t stimuli than to the fre~ent~, of maximum sensid~4ty {8 kHzL Threshold increases with age for thee high~sl fre~ucnoy al~proxJmate~y doubled tt-~,,e f t . the ~wer frequencies, E~eranation of inlet'peak intervals (IP!) f i l l , Iil-V and I-V revealed ag/ng e¢f~'~g, The largest IPl i-V increment occurred to 3 kH.z s(imulation ~hwh r¢fk:cts change.~ at both I-ill and llI-V sub-imeo,'Ms. These result:, demonstrate dectrophysioiog~cal correlatc~ ~f aging due to transformztions in the peripheral ai.~dtto~ system coupled with alterations in brainstem auditory pmthways.

Auaitory brainstem; Tonal stimuli: .Aging: Rat: Later~cy: I n ~ k

I n ~

Hearing capacity in mammals is known to decline as a result of aging. Age-related hearing loss typically is manifested first in the h~ghcr frequencies and may eacroach on lower frequencies over time (cir. Giorig et al.. 1957: Corso, 1963;). Corresponding anatomical and physiological changes have been obse~,ed at nearly every level of the auditor3' system in aging animals ~'Hanson ~nd Reske-Niel~n, 1965; Crowley et al, 1972, 1973: Vaughn, 1976; Vaughn and Vit~cenL 1979; llenry and Chole, 1980; Casey and Fddman, 1982; Kcithle~ and Fddman, 1982; London et al., 1983; Clerici and Coleman, 1987; Hoeffding and Feidman, 1988; Willott et al.. 1988L Age-relat~xl changes are most commonly associated "~th

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Pre~m¢ a d d ~ : A~d*oto~ aeaJ S p t ~ Pa~hok~gy S ~ v ~ ¢ V¢~teran~ Adrrnn~tratMm M ~ z i C e n ~ A u ~ t , ~ (LA

interval

cochlear pathology. The reported structural, metabolic and deczroph~ologic alterations of the central pathways may reflect peripheral dysfunction or may constitute further senescem changes of the auditory brainstem or associated neural structures. The aaditory brainstem re~por~se (ABR) "has been used to invc-stig2~lethe effects of aging in various mammals (Harrison and B~hwa|d~ 1982; Simpson et al., 1985) including humans (Rosen.hamei el al.. 1980; Rowe, 1980: Otto and M o Candleg¢ 1982; Chu, 1985). Wave c o m e t s of the ABR reflect underlying peripheral and central activity (cf. Moiler, 1983; Moller and Jannetta, 1985: Achor and Start-, 1980L The latency of ABR Wave 1 is prohmged in heaitny aging humans relative to y~:mr~gadult subjects (R~x,cenh~rt~er et aL 19~0; Rowe, 1980; Otto and McCandless, 1982; Chu, 1985). Since wave I represents the distal portion of the eighth nerve in humans (Molle, and lane~etta_ 1985L the latency protonxgation may be attributed to peripheral pall~)tcgy. Similar htency shifts of wave I as a luneticai of age ha*,,,, been reported in cat by Harri.~on and Buchwald (1982) and in rat by Simpson el a!. {i985L 'l~e~, and other studies

172 (Thompson et al., 1978; Jerker and Hall, 1980) imve also reported latency incre ~ses for later waves of the ABR. Since peripheral deficits contribute to alterations of wave 1 latency, ,he~ same changes contribute to increments of subsequent latencies of central components. The relative contribution, if any, of aging of central auditory structures to increased latency of later waves (e.g., waves ll-V) remains unclear. Central effects, which can be detected by increases in intetpcak latency of the ABR, have not been consistently observed in humans. Rowe (1980), Allison et al. (1983). Chu (1985) and Rosenhall et al. (1986) all showed prolongation of interpeak latencies relative to younger subjects. However, Beagley and Sheldrake (1978), Harkins (1981) and Otto and McCandless (1982) failed to demonstrate increased interpeak latencies with age. The paucity of interpeak changes as a function of age has aim been reported in non-human mammals (Harrison and Buchwald 1982; and Simpson el al.+ 1985). Some of the discrepancies in the ABR literature may be relattxl to the effects of loss of peril~heral ,sensitivity as well as with central changes associated with aging per se. Activity of the brainsten,, as monitored by basal metabolism of the cochlear nuclei and inferior colli,'-!us, does not decline with age, although there are differences in metabolic responses to long-duration tonal auditory, stimuli (Clerici and Coleman, 1987; WiUott et al., 198e). A problem with previous ABR research in aging humans and animals is the use of a broad-band click stimulus in conjunction with va~ing degrees of high-frequency hearing loss. Coats and Marlin (1977) have demonstrated in humans that hearing loss in the 4-8 kHz region results in a prolongation of the eighth nerve actitm potential (AP) buL paradoxically, shortens the interval betweg.n tbe first AP peak and wave V when using click stimuli. By using widely separated frequency-specific st~muh, peak and interpeak lateacies in young and old subjects can be compared at lower frequen-~eg which have relatively little peripheral hearing loss, and for high-frequency stimuli for which the older subjects would be expected to have a rnc~e sJabstantial hearing less. Although tonc-bur~*, stimuli have been us~xt with humans to a s ~ t h~,.d;oVd (Davis and Hirsh, 1976; Woo~ et al.~ 1979; Gocga et aI., 1988) and binaural interections (Ito el al..

1988L these stimtdi do not appear to have been used for stL~die, of ag~g Tone-burst stimuli have been employed recently in our laborato~ to identify differential ABR responses in the developing rat (Blatchley el al.. 1987, 1989) and to examine the interaction of frequency and rate of stimulation in the 'adult rat (Newton et aL 1987). These stimuli provide much more di~rete information than the widely-uscxl broad-hand click stimuli, The rat has been a useful non-hun.an/m~det for ABR studies since the pioneering work of Jewett and Romano (1972). Latencies and amplitudes of ABR components have been stuGed in developing and aging ra~ populations (Jewett and Romano. 1972; Simp~,t e~ al. 19~5: Blatchle~ et al.. 1987, i989), q~ ~,~!
Subjects Twenty adult Sprague-Dawley rats were divided into two groups: twelve young adults ranging in age from 10-14 months, and eight old adults ranging from 24-29 laonths. Oto~opic examination of ai! animals revea!ed that ear canals were free of debris and tympanic mmnbranes appeared normal in tx~tor arm oriealtation. Nor,'aal rats in these age groups do no: show differences L~ nrdddle ear pr~/sures nor do they. differ markedly in maximum compliance (Clerici and Coleman, 1987). The non-test ear was plugged with ear-impression material to reduce its participation in the experiment. The animals ~ r e injected with atrooin¢ sulphate and anesthetized with sodium pcr~tobarbital. Body temperature was maintained at 37°C by a rectal thermometer and associated Harvard Bioscience regulating electric blanket+

Test Apparatus Stimulus

A Bio-logic Traveler ABR unit ptovit~ed the triggc, fen, stimulus presentation and

acquisit,on, analysis and display of all data. Stimuli were 90 dB Peak equivalent Sound Prc~are Level tone-bur~ts t / 3 , 8 and 4{i) kitz w~ih n~e,,"fati lime~ of 0.5 ms and 1 ms at maximum a.mpt~ude presented at randoh phase 20 times per .,~c,ond. Presentation at a constant 25 dB above thr~hoAd was attempted, but the magPJtude of hearing loss in several members of the older gronp and equipment limitath~ns precluded compretum~i,¢e evaluation at these levels. Tones were produced by a Hewt~tt-Paclmrd oscillator {Model 239-A) and were limed and shaped by Coulboum modular programming apparatus. The signal was amplified and delivered to a 4-inch Herald speaker located at 90", 2 cm from the concha of the stimulated ear. Frequencies were measured with a Tektronix 503A Universal Counter/Timer and maintained witmn I% of the i n t ~ value. The intensity w~s c~mtrolled with a pair of Hewle.tt-Packard 350D attenuators and was verified periodically with a Brad & Kjaer 2203 Sound Level Meter, Model 1613 Octave "Band Analyzer and l l 8 t h inch microphone. The frequency response of the calibra. tion assembly was flat to 50 kHz. A Bruel & Kjaer Modal 2033 S p e o m m Analyzer was used in conjunction with the SLM to confirm that the 3 and 8 Id~z acoustic stimuli had the characteris~tic splatter centered about the test f r e q ~ wfftich is associated with brief tones of rapid onset. The 40 kHz tone burst was examined with an oscilloscolx and the SLM and no distortion m the wavefora,n was discernable.

Results

The typica| r~:,~rtmg from yo~n~ adult ~nimal~ using the stimulus and recc,rding paramelers ~ tioned above results in a ~ries of at |east five repr(~ucible ~aves depending on fre~en{;y of ~timulalion. Fig I (topl ,~ho~+~ ~ ' a ~ oblairmd from one young animal at ~ dB Peak equivalent ~ u n d Pressure Le~d for e a ~ of the three test frequencies, Respon~ to 8_ and 4t) kHz stimuti ~t~ow wave t to be tripl-m.sic while at 3 kHz only one wave I compement appea,~. In m u i t i - p ~ i c waves, the latency of the firsl peak was a ~ t e d z~s the data-point. *g~aves II and 111 u)mel{me~ appear to b¢ a "co~:~plex" le~s clearly ~epa~ahle from
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40 kHZ

Recording.

Subcutaneous needle electrod~ ~,ere located at vertex ( + ) and chin (-) arvJ the ~aimal greamded at the base of the I~io The amplifier gain was set to 100.000 and band*pass f,lu.':r~ from 0.1 to 3 kHz witch the notch filter enat ted. A sampling rate of 20 kHz and a time frame o" I0.24 ms was used. Two runs of I000 presemation ~were obtained for each stimulus condition+

The principal waves of tl~ ABR were identified as previo~isly described (B|atcMey. (cooper ~ Coleman. 1987, 198~L Univari.~t~ a n a l v ~ of age and f r e q ~ , eff~ts ~as appl~e~l Io e~:/h wave and 1o the interwave lateexies of I-!!1, III-V arm I-V. Po~t-hoc anAy~s w-as con., ducted using Tuk~"s test,

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w+ve !, ++'hi~:h are pronounc~;d in the y o u n g adult, a r e often not dtscrimtnable m oRI.~+ iinimPl~, T h e ~I'+h0+btlity af the resp~m~es at this intensity, hove+ wet+ are uadir+u~iBhed with age+ Across w,~lves a n d ffequem+e+ the ~ o u p of older sub%~ts often cx+ M N t e d gr+;mtet v a n a b i h t y than the ~ounger group. Jnsgmctk+m of Table I reveMs that the difference it+ the standard dev+a~sm u;f the older g r o u p occa+a:m++lly re++ched two,+, to four+ times that of the y~mnger group { e g wave 1, 3 kiL{; +rave il, kHz}+ Latency/'+nten~i~ty function~ for e;+ch freq,,+cncy revealed thai the ~*-:+ve 11+,1tf +,:~m~plc*+ ~ah [hc

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inherent varlabdity of the appearance of A B R as a predictor ,+f hearing s++n+qtMty, LalenO +

T h e latency of wave 1 for y o u n g adult rats fo}~ows the expected tonotoptc order of tra~tsduclion m the cochlea (Table I and Fig. 2}, T h e

l ABLF 2 MiANS. AND ,&~SO(tATt'I) STANDARD DI(.ViATIONS {H+ 'Ill[ 'TI|RIF-SHOLD~L+ IN dB PF~'~+K EQUIVALENT SOL~NI) PiaFSSURF L} VEt. I:,N'I+M ++FEDBY 'THI AUDI I('H~Y BRAINS+I | M RI;SI~)NSI - ~-OR T H F Y{)UN{i~ AND ~';IL;~]~S F(IR ILA('II O F Till: TIIRI-I! ,~II,MUt.L~S I R[~:O(t~:P~ !~S ALSO [ ) [ S P L A Y I ; D ARE t~}'lt: Dtl [ t : K t N ( ' F S B~ I w F | N I t t i : FW(}(IR(++I.!I+5ANt() ¢ }I I) + /J~i)(~|., I

t h r e s h o l d te~-ct~ Mc+++r+ghresh,~+ld% amd the a++++o+.++ ated mla.d;~+'d dry+st+oct% +c+'(+~+eigh! a++imal,~ f r o m

each g~:mp are displayed i : Table It0 For youngadult animals m a x i m u m sen~iti~it2+ ~. ~>h++cfved at 8 kFIz wh|lL

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~+idc+ +m+mab+ re|row ~hc ieasl a + c . l d a t e d h>~+ ot r~|~:,ll~ ~;¢Psiliv~ty al ]t kH~ it3+75 till ~hifl) aad lh¢ ~/'catesl chang~~ ~ 4+.~ ki++Iz +32 2.3 d ~ +,,li~l'|} {(,}no oMcr a m m a I did ++++Ii+,+?und ;d % dBo the m++m+mun't hmiv~ of the +ppat+~u'++ ++t 40 ~+i/ +rod wa~ +,~++ed +:++++ ',h+e+~hoid ~,f lO+~+~i+++) \I+ M++e+,+h++ld ~++l+ft m w+ih "++¢ +++'¢ ++g+++f+++~+l t { ~:' " 1) (++) I +r+{: V+iri + ~bIlv1y r i o t e d

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Io 10o ~ttf. ~Ut'NCi (kl~,O 2~ T}~il l ! l t l i l iai~ti~y lt~ tia~ O| e~li ~atc for ~¢h group .~ ~itun,liOn ot slilnul~ls frequencyis pr~nI~.~l.

latency to 40 kHz stimulation is the shortest ~nd thai for 3 kHz is ih~ longest, Tukey's le~t indic~tles that the i~tency Of respong f~,r ¢~ch frequency of stimulation is different ( P < 0 . 0 5 L Unlike the young animals, in aging subjects the reponses to 8 a~d 40 kHz are not different from one ~nother, although both are faster than the response to 3 kHe. (Fig, 2L Ill the older group of ~ubjects wave I exhibits a longer latency averaged acre.s frequency ( P < 0~001) than o b ~ r v e d in the young animals, The appaicnt respon~ lalency differences between age groups for 3 ann 40 kHz stimuli is confirl, ntat ( P ~ 0,05) but noi a~ 8 k i l t , For young animals, die ~ave Ii latency 'by frequency f~.m~:thm is parallel to thai for wave I. The latency of the respon,~ to 40 kHz is shorter than h)l the other frequencies which are rlol different from e~wb other. Tukey's test indicates thai for older subjects~ response to 3 kHz shows a longer latency ,~h~lli for 8 kHz ( P < 0.05). AIIhou/ll thcr,e is ~t main effect fo~ age ;lcro~s

frequency, the differcnce~ b¢fwe¢ii age gro~p,~ tire a¢~;¢nluated at tile highest ~lnd lowell le~l fit*qiten> ,te~ ( P < 0.{:)5; Fig, 2 and T,Tlblc I). Fr~r wave iii, the slope (ff the, hliiction in young animals continues in the expe~ ~ d dire,Aion where the r~spon~- to 40 kHz cxmlinucs to h,~ve a shorter latency than resr~,nse to 3 kt!~ (P < 0,05). For older amntals the response IO 8 kltz continu:s to tx~ur sooner than response to 3 kHz. The ~tp: parent age-related difference, l~l latency is signifio cant ( P < 0,001; Table I). The increase in latency ~is a function of a8¢ is significant at :.1 and 40 kHz ( P < 0.05)~ The slope of the freqtlt, ncy by latency function in young animals rio longer represents the ¢s,. pectcd eochleotopic order at wave IV 'lh~ re., spons¢ latency In ~.) kH~ i~ not fa~ler thiln re., l ~ n ~ s in tile other tC~I frequencies, POt older animltls the response to 8 kHz i+~ fl.r the first time faster than for both other test frequencies ( P < 0.05). The overall effect of age continues to be observed for wave 1V ( P < 0,05~ with significant increments for the highest and lowest test frequert., cies as noted +n e~rlier waves ( P < 0,05), The s l o | t of the I~*ency.frcquency function i~rt young adults is further altered at wave V, The response latency in the h/giws~ te~t frequency is now hmger than the respon~, to lower test fi'e~ quem;i¢~, For the older animal~, the I~tencyfrequency function for wave V sho~s the same pattern ob,..erved at wave IV with the response latency at 8 kHz shorter than the re~,porlse~ in higher and lower frequcnci¢~ ( P ,, IL()5), A!~ with all elirlicr wav¢~, wllv¢ %; ~liow~ ml over,Ill ltl~,c' effect (P < IL(~tOI ), The effect i~ ftir lhc fii~t time ~;ig!'~ifiCatil ~il cat:h test frequeflcy (P .....0,05; Fig, 2L

Imerpeak /~tet:cws Interpeak interval (IPI) latencic,~ wcm es~ amined to determine central condu~:ticn d~-fivien,ties separate from the effects of peripheral h~arin~ Ios~ noted in Table 11. Fig, 3 and Table I plesem the intcrpeak latencie~ for Ihe two group~ at each test frequency, For the young rat there ~lPl~C,.'~r.~tt~ be no difference in cen'.ral condt,tclio|i tinic fronl waves | to II! :~s a lunctlon of freqocncy ()n the contrary, the 4() k i l t b i l l I Pl appcar.~ longer th;m lhe lPl tor other lest frcquetlt:ics in lilt? ,'],~cr

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in Ihe a u d i t o r y ~/>tern using the ABR+ A m o n g the changes noted were thre'+ho!d shills+ i t ' ~ in ! a t e n c i ~ o f c(~mponeai r~-+l~mSes, i ~ ' r e a ~ in ink+rsubject variahilty and i a c r e a ~ s m +~e!cct~M in+ |e+peak laten~+y shltt+L

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0.(}5} l'he m++++m+++,< Ill V llq :~ +++ klI~ +, +,3 m , loI+}~+r tP+++l+lh+H [~+) ++ [.ll/ +l+ +++m++grat,, ~',h+lc the +l+Ifer+++++ +++ +|el he+ + +~m+ ~ k i d a:c Ic~+~ 0++m I ++)+ I+++ PIw ~,Idm+r a m m a l + ~hc IPl l~'+ 40 ktlz rome+me longer thaa to X k|'iz+ wl'lllc the IPI to 3 I~Hz. ha~ subslae+lL,dls murc,~,+ed l'hc e f f e c t (~f agr<" ++++,igmifwm++>++~,+ al ~ k i l l ~] .... O1)+{} Wh<++ th++ +++)+~,~ ,,~ i ++, I l l ,++,++ ' ; l

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+~+++m+cd {+++te++l+++~+ t ~t+ V~ +he+e ++Pc b~*th age P < 0 +)+u~)6} +end f + q u c n c y t i' - 0 ( ~ ) I ) eff+:~:t,, F++, ]+ +h~3+A'~ +hi| I-V l["I~I~P+'++i} Zt{ 4+[) ~ . + t g +m++'++~J+ ++~,+++¢+1~¢++ hit lh+~ yo+i++gc+ ,mimed, ih+ ++hbor +++++++++h,++b+o ~+how +) +]L~++P~++~]++ ~+,?+ +t~~++~+I~++++PI+++C~:+ l>e;w~++~ the iatc,qc+c ~, +++ ~+++~++++X k }l/, While ~hc 3 a++d 8 k}lz +r+l~ ++re:appro~in)a~cly the same u+ +h~" !;++~)r++cr +~+++mab,++be +++++or +++r+lmab,u+++nilc+,~ +~+ng,cr

Thr<+h+,td~ Yhr .)~r.>hotd~ ohlaincd by Ih¢ ABR mcth(~l mdtcale lha there i~ a +~ii~ilivii~ Iof+~ al all l ~ l ffequL'nci~s wtlh adv~ncin 8 age+ T h e d~ta of S+mp~o++ ct al. (!98~) ,¢vca!¢d an 18 d|) lh~sh~dd shifl for t~h~k +~Umtdt in aged rats. Thai is approxim a t d y the amoun! of shill p r o d u c e d b y the two Iowo frequencms in the present study ~nd ~ub+ ~tantia|ly le~s than the Io~, at 40 k H z O2.2 dB)+ The t+realer ehaagc fin the mghe~t f~cquency and the lea~| Io,~ a| the frequency ~f ~rt~lest ~nsiliv+{y +++ the VO~m~ (8 kHs,) was riot unsaFe'tied (e,g+ (Jlor)g el +tto, 1953'), [One of the older ,~mmal~ did m)t r ~ p t m d to ~} ktt~ a| the limils o f our ape para{um (95 dB PeSPL) and one had a thresrtold of ~5 OB P~'SPI++ Thus, latency data at that [rcqu¢~=y ++ h~+~d on seven rather than eight animals,) +l'he+ frcquenc~ related diffcrences are not likely io have+ ,wcurrcd duc to a conductive pathok~gy: ;here was m, ¢.~,tcrna[ or middle ear p a | h o t o g y obvious hy +++',+++tlm~[~lic~n; ptevIOU+ o|'l+~rvation~ 0[ old rais iY~m+ our c o h m +, rcvcakmt mobile lympanlc mere+ |++ mc~ ~+~ a m b w n t air pressure (Clerici and Cole+ n,+n, I+,~?}. Kcid++tc> and Feldm+m (1982) dem+m+ ~!+a~+:d that hair cell to+m in aging rat co,.:hlca~ was <++lca+,r++ in ~hc ba++al +++d a l i h o u ~ substantive p+~thol,+++5 +++~ ++b+u o h , c r v z d at the a|~+x [:urthct+ +n~++~: m ++~+~ .'i~,~ihc prc~omcd ~abslrate [0r +++,~c +, the at+dM++r++' ++crvc, ¢++ldelg,t+% r¢ductic+a in ,heath and +p+r;~I +++a,glm,+ degeneration (Kmlhlcy r,++~+J +: C!~I +++++++ i +'+<++ tl++ffdmg and Fctdm+m,

177

L~/cncT It has been derru'mstcated that in the adult t:he ba~l end of the cochlea is responsible for the mediation Of higher [r~,~t~ency stimuh and the apical end for the lower frequencies (c.;. Harris and Dallos, 1984). P~rker and Thornton (1970) and Zerlin (1969) ha~e shown that, for equivalent stimulus intensities, the frequency differences in latency of wave 1 arc ~ f i a l l y ~ , ~ a n t e d for by the differences in the time required for the travel* ling wave to traverse the c~x:hle~o The present study in rat ~xmfirms that for the f~¢quencies studied the expected tonotopic ocg~mi~atioa oh. rains for wave 1 of the ABR for y>ung animah. 1here is a linear decrca~,¢ in latent., with a logarithmic increase in frequency. The difference in respon~ latency between the old rod y~mng animals is greater at 3 and 40 kH~ , h ~ g~, g kltT'r ]'his may he related to the greater ¢ochkar d~g~n eration noted at the base and apical end:~ (KeittIcy and Feldman, 1982) and associated spiral gangli,3n changes (Keith_ley and Feldman, 1979}. In the young adult the latency relatonship across, frequer~cy changes significantly for the later waves. In contrast to waves !1 and I!1 which manifest the s~.~rrg: frequency-latency relationship as wave I, there arc no discriminable difkrenccs in latency by wave IV, At wave V, response latetg~y to the high-test frequency is actually longer than to the remaining t o t frequerg'ies. "Ibis phenomenon has b~m previously observed in developing and adult animals (Blatchley, C ~ p e r and Coleman, 1987, 1989; Newton. Cooper and Coleman, 1987, ltenry, 1979), The apparent slowing by w~ve IV of the respon~ to 40 kilt ~timuli relative to that of other frequencies n~ghl be partially explain~J by differences in neural path length or may reflect other par~mete~ such :~s pathway conduction vett~ilies or synaptic efficacy. The older rats ~how a generally greater increa~ in latency acr(~.s frequen~:y at each successive wave tha~ the younger ammals, This is particu~ larly exacerbated for rcspon~.~ to the highest and lowest te~t frequencies. Previous work in aged rat (Simp~n el al.~ !985) and eat (Harrist~n and Buchwa~d, 1982), employing acoustic click stimuli adjusted for sensation l~el, fc,und m~ age-related differences in lalenci~ of brainstem components. However. Simpson el aL (1985) repc,rted increased

latencies it~ old |at~, when stim~]aled ~tl ~he same SPI~ as young rats. Such click stimuli produce a broad pattern of excitation of the c~:hlear partition, while tone burst stimuli, such as employed in the peesent sludy, excite more, discrete portions of the cochlea. The older animals of the present study often exhibited greater variability in response latency than did the younger group. Part of this variability may be related simply to the mean threshold beino grc~ter in the older group, part to the larger d i f f ¢ r e n ~ in threshold among ~eznbers of that group ~han the younger group, arid part to central conduction differences associated with age. ttra/~t~rem condu¢'tiem

E~,u~ h~|ion of Fig. 3 ~nd ra~qe I ~ho~,,~ an overall el:"eet of aging fo~ IPl blll, t|]~V and bV, Reported central auditory ci~aages ~'~ rut, includ.~ ink loss of ¢c[I bodies and synaptic terminals {Ca~y and Fc|dlaan 1982, 198t~), likely ~.o~tribute to the observed ~.~ ~.~:~e in mterpeak ir~tervals, Structl~ral changes la the auditory brainstem have al.~ be,:n reported in humans (Kirikae et aL, 1964; Hansen and Reske~Nielson. 1965; Konigsm~rk and Murphy. 1972)~ Aging effe2ts on central auditory structl.cs, as shown by the increa~d interpe~k la:encies of the ABR, have bc,'n dca~onstrated in hur~ans (Rowe. 1980; Alligm et a k 1983; Chu, 1985). tlowevcr, other studies using lhe ABR metht~ in humans have repotted no cer;tral deficils (Beaglcy and Sheldrake~ ~,978; Harking, 1981: ()tt~ and Mc('andle~s, 1q82; Rosenhall ~| al., 1~5)~ All of the above studies relied upon click ~tn~mlalion, a~ did smlilar ~tudies in animals (ltarrison and Bach+ wald, 1982; Simpson e~ aL, 1985). The data of Harrison and Buchwald (1982) in cat in~icz~te that IP! is indepe~dant of stimuh~; intensity level. The aging effects on IPI remained the ~,ante wheltaer the two groups of animals were sih~lulated ai equal SPL or ai equal levels above threshold 1t wemtd appear then that the IPl data control~ for differences in threshold and con~'quent w~:~ve i latency shier:, between groups when assessing age o related central effects. Allhough aging affected the ~ensilivity thresholds and lateucies of wave 1 respooses a| all ~c~ frequencies, IPI data were dificre~tially af~

I?+ reeled by t¢.~t fr+qu+ticy. At b i l l IP!+ + k ! l z r e ~ n ~ + wet+ affected by ~tpng whi|+ only 3 kH~, r~spon+em were dranmiic+lty delayed 8* IPI Ill V, F| 8, 3 +Up+~e+l++lhat |]PI+ IPI dc|*i¢it+ r+h)|+:J +,+ :++++" lit the IOwe~I t¢+I freq¢~+ncy +m:+ur in t +h the towt)r ~nd hq~her t~i+)u~ o~ the m+~i+~oC> +,rain~o l+m neur+im, The mgc ¢+i+t+ iPi change+ +t the hi~ ffqtl~llCy tested ~pl~al ` tO be a ~ i a t e d w i t h the l o w ~ ~ i o n o f the paOrway, T h e obl~l~ved difference++ between g r o u p s in threihold and in lhe latency o f wave I indicate thal the att¢tltory periphery is clearly aff~ted by a$e+ ~ e relative cm+ttribulionm of changes in IPl secondary to r¢~d~tced inpt~I from t h e m portions o f the m)n~!ory apparalu;+ which show palhological ~terat~cms in older animals and of c h a n $ ~ duc to a ~ n g of b m i n s t c m pathwa~vs perry, l~ unknown, Future sludie+ of a ~ n 8 ~ u b j ~ t s usi. g A B R to )T)~sut¢ ab+olu|c tatcnci¢,~ and i n t e r l i n k intel~al~ ~,+" ~cspo~ses should incl~tde fiequency specific stimuli, while +it)dies of indlvidtml auditory t~i~instem ~ttuetures requi,e an anaiyms of [ ~ i + riot+ I¢ie+d+n~ ch+mges related to to~tc)topic orgm+tiz+ho+) ~Wil|otl ct ~+l+,198~),.

We ~i:;h 1o tht, nk A m y You+tIt for assisll,rtcc in datit coll~ho¢~ ~+td M+trk Zrutl for ~iati~lical cam+ p~t+tlt~s)t, "Vhc r~¢arch was supportcd in part by USPFtS A G t7~4, Tt'+ Deafn¢ss Ftc+~c++~h Found+++ tiOtI t))+iti the V'ct+ran,~ Admim+|r++titm Rchabili+

~.~|~1 4~v~k~,n'~nt of audilor~ bram~,lcm re~m~e lal,cncy L ~ y + M,A+ tt~t F~Id~I~, M+L+ (|9#2)Agt. 8 ~rt the ¢~tl rat~J+al n.,~I~tt~ of lhe lr+tpe~t~td body+ I+ LiJhl m k ' + ~ l ~ . ~ettt~

(a~y, M,A, a~d Fek|m~n, M L (198~t} A~t~reL~led ~ o[ ~I~ilpI~ t~fPt~n#t~|ilthe r~| tl~II~ ~Ii~l~ Of the ff~llelohl (~tappa, K+H+ Otttd+tmte+ K J+ and Yotmi~ R.R+ 0979) Bra~l,em attdilory evok~dl ~ , ~ , + Similes of w~eform vail|ions iu 50 nomu,l human ~bjects+ Arch+NemmL3b,

81+87+ Ch., ~,+S. (1~;) ,~@rela~ed I m e ~ cbantte~ in the b r ~ + +ram

(+'|crri(i+WJ+ altd (JOI~ll~tn,J.R. (198+/) Reslm8 anti pt+re tot~ evoked ~e*~bot~: ~.~pon~ in th~ inh~ftor ¢olliCl)lu~of ~ n ~ ~httl ~tlt~l ~ s , ~ n t taI,~ kettrt~Jl, ASint~ 8, 171 ~lI?8 C<~I~, A, amt M~rtil*+ J. (1977) Human audil(~ry Iwr~,¢ ac0ol~ I:~rIUa|~ and brain ~ttem evoked re~pon~t. Arch. Otot,ryrt~oL t03, ~+672+ ('o~)t.,, J,IL ('1963) ASj~q~ ~nd ~udilory thre~tlmkls ht n~n ~ J wom~o, AI~h, E)w.~m, Hu|ih, 6+ 350+356+ Cr~,,wlcy+DEE+,Schr~mt~ V.L++Swill). R.~ and S~an+c.~ SeN. (197~) Analysis of ag~ti~tled chaP.aes in ele~tflc ~ s e s from +he inner eat of rats+ Ann, Olol, 8l, 739-7t6+ Crowkry, DEE+, ~hramm, V,L+, 5w~tin,I ~ E ~nd S ~ r ~ o ¢ SeN+ (1973) Atp++++relaloJwlv~fofm chm~,~ ot Vltllh nerve ~* (i~m l~tenti+ds in rat;, L~ryntI~.xq~ 8~, ~27~i+ Dmv~, Ha nnd flirt, KK+ (1q76) The attdlonwtric utilityof brlttI) stem I~tpOD~ iO iOW freqtlelli~ sound+. Audiol¢~y l~i, 181 + t9~, (Jh~+qb A,, Wheeler+ D. f.+l~ti~h++It., (]l+W,~tt+W,+ ~ad S~mn~ro field, A t I%7) 19~4 Wim+~op+.stnStale F~*.ir H~ilin$ S~rw~y+

H~n,~m. C£'. +tud R~'+i~¢+N+el~cn,t'.+(i%5) P~dx)k~cal ~tud. ++~m pr~m+'~+~++~.At+h. (~o|ar++n~l. tQ+ it ++ 132. ll+rkff++, S W ,

i+<~,~)) Ef[~I+ of pmntl~

+J+++ll~.,ntiaof ti~

A~)++n~+% ++>+~o++ hrt~h+~icm tr+nmrnt~m+ontime+ Inl, J.

+~+~++~++>+P+~tI+++~+r++~+~P%,F~+~]++'~++L#+++.+%)++?)~'++t+r+++r~m++))+++~>+

++m+~ ++t+k*++~t~.+++~+++b:l+++~++~+m ¢+~t+t+onh+ it+c, ~+~, ml+l b+~++++m+ ~mm)~mr++ EE(] (+is h+e~+i.t)phvmoL+5, 6l+.+k~+). ~P~+~+++, ++ +~+ m+4 +P+kI~P+~++ J ~

Ii~,++++, D M <~m] D~ihm, P, (|tJS4) O~uogcmc changes in ~*~+~+~y m~ppm~ of a mmmm~lmn car, ~+enc¢ 225. ?4~ +++i+ i;++++,m.+~+. J, ~++d ltt+hwmld, J, (19+2) A~ht~+ braining) ++++,p+m.+++)+++e,+d -~i, N+,+, .~ioi A~m~ !, I~I +,l+tl H¢.+ir~,, E ~ [~79} AtPjtIOt~ fi~r~ ltoit bfitht ++I~DIV~llt+~t4:+

~ l++?~+ |,).I+I'i~fi~t++++>++ ++

('~A.;
)I++)+,++ K ~++++)(h,)i<'+ R (|+++,0) (+emotyp++ diffe+¢rl+++~ it! ~++tl~+~imr+'+~+Jd~io~+yb++l)~++ca r+~+++~c to h+tl++J+l+m;+hH+ +h+ +mr +~+ +l++mI%+. 32, 74 +P+i

+~+¢+++++++'d+m+i~rt++~+)O~mi~ (he [+++I~+r+iorym~ma~+AmJ+ot(+~y

19+ ,/>9 ~+8+

179 Ho~ffdin¢ V+ a~t M.I. Fetd.~n (1~3~} (~nantp~ wllh ~ m lhe morphr~y ~ the c ~ a r r~ in r ~ : l ~ t rm.

tll ~ r ~ t ~ r l to brlk,t~tem ~.it~,~ ~voked I~n¢~l~ {tk,'tted by ffi~iit~+~tp~,fi¢ ~ l i ~ l l . Heir, ~ , 3~, 9+20, .lS'7+.391, jew~t~ D~L Md R ~ M.N. (1972) N e ~ l l a l dev¢.lopm~ uf audilory ~ , ~ IX~l~m~s iv~qled from Ih~ ~ t p of r~t

wa ~ vekv~it~ ~]~ul~tcd from the' d~riv~d ,~ompo~e;;t~ of ti~ c ~ h ~ n~r~e and brain+,~m e~k~i r ~ p o n ~ ot the h u ~ . ~udlm~r~~+t¢tn+ ~md:, AridlY, 7+ 67 ~70, Ro~lm~lL U, Ped~ersen+K. and |~,~v+dl,M+ 0986) f~ff~t+ of pw~is m~d ~h~r t ~ o( he~rlng Io,~ on aud, tory ~ai~¢~
R~¢, M+ III ( , ~ ' Normal v~mabt~ty of ~he bf~in~lmm ~ k o r ~ ~ k ~ l ~,~.,, ~ t, ~ounS ~,d old mlult ~ubje',t~

KB'Ik~, L, I~ ++ T. and S~i~mL, 11".(19~) Sludy in t w ~ 4 i~ ~ I ~ ~o l~mol~ 74, ~ 2 0 , KeiUtley+ ILM+ and F ~ M L (WTO) ~ ! t i g l o n ~;,e~l

Hi'~. ON+, Knight, R,'L Bra low~ky+ $. Pro~per~(~aPtri~+

~mnt~ i. ~m l t p ~ l p r ~ s~flt=~ of rat co~hl~ J. Colr~+ N~urot ISS~~ 4 ~ ; L K~itld~, ILM. ~ FeMm~. M,L (1982) Spiral ~ml~lio~ cell

O and ~abini+ D. (1983) e~¢~~ peripheral emd b~mnsl+m aud tocy ~r~lion in .g,ed rat+, ~r~ifl Res. ~8, 2g,o3~ Thom~a J. Te~ild~en, K. ~nd (hte~/mmm~l, P. (1~79) A~di~

NeuroL 18.8,4Zq-44|, Koniiptm~l~+ It+W+ ~ i MUIT~hy, E+& (1972) Volmm~ Of thl; ve~r~l e0~qdea~n~:teus i. ~,~'~: its ~ l a l k ~ h i p to r,euro. ~1 I~'-q)ulatio. ind =i"*'+J. N e ~ l ~ l , 'Exp. N~r~, ~1.

m~s+ ~,,,~d AudioL ?+ 179+183~ V~t~h~, D,W, (1~76) AS.e.~'~;l~t~ldeterioration ,q i,yramidal +:ell ha~l d~drile~ in r~| ~udilory cort,~x, J Comp. Neurol. 171. ~01 ~16+ VauBhn. D.W. and Vincent. J.M, (1979) Ull~+~tructure of flcuror'.s i~ th© ~u'ditOry ~ t e ~, of ~ j ~ r.~+~"~ m+~rph~h~.~.i~ c~l study. J. N~urcx:ylol,8, 215 228. WitlolL J+F., Hunter, K.P+ and Cot©rn.m~.JR+ {1988) Agin~ and presbucusis: E[f~rt~' Off 2-d¢oxy-~+$1tw~i~ uptake in the n~m~ a~]ilory brain ~tem in q,,i~t+ [:xp+ ~'J~'~1~fol, ~)~, 61~+621, Will.It. J.F+. P ~ k ~ , D. Hunter, K+P, ~md I~wdyh{tm M. ( 1 ~ ) Proj~l~m~ from the afit~rivr vcnff~l cochl+ ~r +~ueleu~ of th~ inf¢ri~ cotticulus in youn8 and al~lflg C57BL/6 mic¢~ J+ Comp~ NeutoL 2~7. ~4~+~5!. Wood+ MH+ ~ + M+R., ~.l~dJ~ob~)m J,T, 1079. Br~instcm tic, meal r ~ p o n ~ from ~lc~ted ~on¢ pip ~imuiL J. Am~ Aud+ Soe+ 5. 1~%+162. Zerlin. S. <1~'59) Travelling w~vc velocity in the huma~ co, hick, J~ Ac~,u~L . ~ Am, 46. !011 .i01~

l . ~ o m E.D,,Oh~t~ M.+ T~dkei.I1,+French, A.W, and P.ap~ porl, ,%1,(1983) RqJon~ c~¢~ral melalx~l~ rate for ~luco~ in ~ dop~ of diffe~t :~'l~ NturobioL AIP~ 4, i2i.+126+ M~ll~r, A+R. (1983) On ~ origin Of tL, ,~,mpound actlm+ l~tcrdi=b (N~+ N+)+ Of tl~ ~ of ,+ mr+ Exp. Negro+ M~ltr. A.R+ and Jurmetta, PJ, (19~5) Neur~d ~nrr.lors of lh¢ +mditory brain~Irm+ rt~pons~. Ira::J,T+ J~cob~on (E~L). The Auditory Brm++st+mR~mlxmm+,C~dl¢#e.liill Ptmm. ~ n Di+ ego. C & USA, pp, 13+!1+ NewiSh+ E,H++ C~X~r+ W+A, ~laj C~dem~fi. J.R, 14ill+ rand fr~lu~n~y int~miion+ in tl~ adult ra! ABIL Prm~din$+ of the Xth Biennial Inttr~t ~ymlx~ium Internat. Electric Respon~ Audiom~try Study Group. August 24+.+17. 1987. Ch~lo~t¢~vdle+ VA. U KA, Otu~. W,C+ and McCm~dl+++~G+A+(1982) A~ir,~ a~J the ~.d++ |ofy brain +t¢m +m+p:o~m+Audioh+y 21+ 46~+47].