Optical Imaging of Cat Auditory Cortex Cochleotopic Selectivity Evoked by Acute Electrical Stimulation of a M ult i-chan nel Cochlear I m plan t

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1 Europen Journl of Neuroscience, Vol. 9, pp , Europen Neuroscience Assocition Opticl Imging of Ct Auditory Cortex Cochleotopic Selectivity Evoked y Acute Electricl Stimultion of M ult i-chn nel Cochler I m pln t Huert R. Dinse, Ben Godde, Thoms Hilger, Gunter Reuter', Sven M. Cords', Thoms Lenrzl nd Werner von Seelen lnstitut fur Neuroinformtik, Theoretische Biologie, Ruhr Universitt Bochum, ND 04, D Bochum, Germny 'Medizinische Hochschule Hnnover, Experimentelle HNO, D Hnnover, Germny Keywords: intrinsic signls, receptive fields, representtionl mps, isofrequency representtion, chrcteristic frequency, corticl plsticity, hering ids Astrct We mesured reflectnce chnges y mens of opticl imging of intrinsic signls to study the effects of cute electricl cochler stimultion on the topogrphy of the ct uditory cortex. After single-pulse electricl stimultion t selected sites of multichnnel implnt device, we found topogrphiclly restricted response res representing minly the high-frequency rnge in Al. Systemtic vrition of the stimultion pirs nd thus of the cochler frequency sites reveled systemtic nd corresponding shift of the response res tht mtched the underlying frequency orgniztion. Intensity functions were usully very steep. Incresingly higher stimultion currents evoked incresingly lrger response res, resulting in decresing sptil, i.e. cochleotopic, selectivity; however, we oserved only slight positionl shifts of the focl zones of ctivity. Electrophysiologicl recordings of locl field potentil mps in the sme individul nimls reveled close correspondence of the loctions of the corticl response res. The results suggest tht the method of opticl imging cn e used to mp response res evoked y electricl cochler stimultion, therey mintining profound cochleotopic selectivity. Further experiments in chroniclly stimulted nimls will shed more light on the degree of functionl nd reorgniztionl cpcities of the primry uditory cortex nd could e eneficil for our understnding of the tretment of profound defness. Introduction Cochler prostheses re incresingly used to provide sound perception in ptients with profound defness of sensorineurl origin. By electricl stimultion of the coustic nerve fires, their uditory system cn e ctivted in systemtic wy tht restores to considerle degree their cpcity for hering. It hs een shown tht such devices re cple of ctivting the centrl uditory pthwys over mny yers. As consequence of n incresing usge, the question of how they ffect the mture centrl nervous system gins n incresing importnce. Since the introduction of the technique of cochler implnttion (cf. Merzenich nd White, 1977), there hve een mny studies focusing on the investigtion of dischrge ptterns of the uditory nerve fires fter electricl stimultion of the cochler nucleus or uditory midrin with n implnted device (Hrtmnn et l., 1984; Snyder et l, 1991; Brown et l, 1992). There hve een few studies ddressing the question of properties of corticl responses fter cochler stimultion (Rggio et l, 1992; Rggio nd Schreiner, 1994; Fiseifis nd Scheich, 1995; Schreiner nd Rggio, 1996). Bsed on extensive electsophysiologicl mpping studies using multiple microelectrode penetrtions nd receptive field mesure- ments, mps of the primry uditory cortex of the ct re chrcterized y differentilly rodly tuned receptive fields, resulting in firly strict cochleotopic representtion long the cudl-rostr1 dimension (Merzenich et l., 1975), which is expressed s n increse in the chrcteristic frequency of neuronl frequency tuning curves (Fig. 1). While the representtion of single tones within the frmework of corticl mps is firly well understood (Schreiner, 1991, 1995), little is known out the nture nd the degree of the topogrphic spects of the representtion of cochler stimultion within corticl mps. During recent yers, new methods hve een developed to record opticlly from the exposed cortex in order to otin the twodimensionl reflectnce chnges tht hve een shown to correspond to the sptil distriutions of the underlying neuronl mps (Frostig et l., 1990; Grinvld et l, 1991). These reflectnce mesurements hve the dvntge of llowing repeted nd multiple mesurements of functionl mps following sensory stimultion in the sme niml, with sptil resolution of up to 50 km (Frostig et l., 1990). While the usefulness of this method hs een demonstrted in the nlysis of the visul (Bonhoeffer nd Grinvld, 1991, 1993; Mlonek et l., 1994) nd more recently lso of the somtosensory cortex (Gochin Correspondence to: Huert R. Dinse, s ove Received 18 Mrch 1996, revised 29 August 1996, ccepted 9 Septemer 1996

2 114 Opticl imging of cochler implnt stimultion in cts L4 L8 posterior medil t I d 10 mm II FIG. 2. Schemtic illustrtion of n intrcochler multichnnel electrode s used in our ct experiments. Ech electrode contined eight ipolr electrode pirs. Electrode 1 ws locted most distl to the round window. Four of the electrode pirs were inserted vi cochleostomy close to the round window. - 1 rnm I \es low frequencies 0.5 khz 50 khz high frequencies FIG. 1. Top pnel shows the lyout nd prcelltion of uditoiy corticl fields in the ct. AAF, nterior uditory field; AI, primry uditory cortex; AII, secondry uditory field; es, nterior ectosylvin sulcus; Is, lterl sulcus; PAF, posterior uditory field; pes, posterior ectosylvin sulcus; sss, suprsylvin sulcus. Loction of the frme usully used for opticl imging is indicted in the top nd ottom pnels. At the ottom is n enlrged view together with schemtic drwing of the rostrocudl frequency grdient. Modified from Imig nd Rele (1980). et l., 1992; Msino et l., 1993; Nryn et l., 1994; Godde et l., 1995, ), sptilly highly resolved mps sed on intrinsic signls of the uditory cortex re rre (Hessp nd Scheich, 1995; Bkin et l., 1996), specificlly for the uditory cortex of the ct (Dinse et l., 1996). We therefore ddress the question of the effects of cute electricl cochler stimultion on the orgniztion of the cochleotopic mps in the uditory cortex of dult cts y mens of opticl recording of intrinsic signls. Mteril nd methods Generl niml preprtion A totl of seven cts were studied. They were nesthetized for surgery with 25 mgkg ketmine hydrochloride (Vetlr, Prke Dvies) in comintion with 1.5 mglkg xylzine hydrochloride (Rompun, Byer). Tretment of ll nimls ws ccording to the US Ntionl Institutes of Helth Guide for Cre nd Use of Lortory Animls (revised 1987). In rief, crniotomy ws performed over the lterl cortex nd the dur ws removed. All pressure points nd wound mrgins were infiltrted with locl nesthetic (xylocine). During the experiment, the niml ws continuously infused with 3-9 mg/h of pentoritl (Nemutl) together with dextrose nd electrolytes (Sterofundin, Brun). The ody temperture ws kept t C nd the electrocrdiogrph ws monitored. The nimls were cutely defened y intrcochler injection of neomycin sulphte solution (0.1 ml, 50 mg/ml) in oth ers through the round window. Electrode plcement After cochleostomy distl to the round window, four pirs of pltinum-iridium lls of humn multichnnel implnt electrode, consisting of totl of eight electrodes, were inserted into the scl tympni. The insertion hole ws filled with connective tissue. Inside the ull tympni one, the electrode ws fixed y glss ionomer cement (Ionos, Seefeld). The other end of the electrode, which contined the glvnic plug connector, ws led freely through the skin. A reference electrode ws plced under the skin of the occipitl one. The totl length of the inserted electrode prt ws -8 mm, nd the men distnce etween electrode sites ws -1.8 mm (Fig. 2). In some cses, the position of the electrode ws ssessed post mortem y roentgenogrphy. Electrophysiologicl controls Conventionl electrophysiologicl controls were mde in three cts fter the opticl imging session y recording extrcellulrly ction potentils following electricl stimultion of different electrode sites from smll clusters of neurons t depths of pm using glss microelectrodes (1-2 MR) filled with 3 M NC1. The signls were low-pss filtered to record locl field potentils (LFPs) following electricl stimultion of selected electrode positions of the implnt device. The sptil distriution of ctivity (LFP mps) ws computed t vrious levels of LFP mplitude. Electricl cochler stirnultion Cochler stimultion ws performed using iphsic current pulses of 75 or 100 ps durtion per phse nd were delivered vi WPI 365 stimulus isoltor. Electrode impednce ws checked regulrly nd ws in the rnge of 5-50 kr. Electricl current levels were expressed in db reltive to 100 FA. Topogrphy of ctivity In order to mesure the possile underlying topogrphy of ctivity following cochler implnt electricl stimultion, we stimulted

3 Opticl imging of cochler implnt stimultion in cts 115 different pirs of electrode sites with current pulses db ove threshold. The different electrode pirs corresponded to different positions in the cochle nd thus to different distnces from the round window, resulting in different frequency domins to e stimulted. In some cses, we stimulted selected sites using ground s reference. Six stimuli were pplied t repetition rte of 3 Hz. Effects of current mplitude To mesure the effect of incresing stimultion current on the topogrphy of the ctivity distriution, we systemticlly vried stimultion currents etween threshold nd 20 db ove threshold. Electricl uditory rin stem responses In three nimls, electricl uditory rin stem responses (EABRs) were recorded for ech electrode pir y mens of suderml steel needle electrodes t the forehed, mstoid nd neck (ground). Current mplitude nd pulse width (75 pslphse) were set y wve genertor (Wvetek@, model 175) t frequency of 30 Hz. Recordings were differentilly mplified (X ) nd nd-pss filtered 100 Hz to 1.5 khz y n nlogue-digitl converter smpling rte of 25 khz for period of 20 ms following stimulus onset (Westr', model ERA QSl2). Opticl recording For opticl mesurements, we used Lightstr I1 imging nd cquisition system (Lvision, Gottingen) with 2 MHz nloguedigitl converter nd Peltier-cooled, slow-scn 12 it digitl CCD cmer. The CCD ws controlled y 486 PC with 64 MB RAM. Imges were otined with n cquisition time of 80 ms durtion. Averging ws chieved y dding intertril sequences consisting of five imges of 80 ms durtion, which were verged to six tnls (Godde et L, 1995, ). Ech tril ws seprted y puse of 40 s to void intertril interference. The cortex ws illuminted with 546 nm light source. Controls (non-stimulus conditions) were tken s lnk imges prior to ech stimulus presenttion. Imges were computed y sutrcting stimulus from non-stimulus condition. Dt nlysis ws performed on Sun worksttions using custommde nlysis softwre written in IDLTM. The sptil distriutions of reflectnce chnges were colour-coded nd quntittively computed in terms of corticl re for 25, 50 nd 75% of the mximl reflectnce chnges. Results Electricl uditory rin stem responses In three of the seven nimls we mesured EABRs prior to opticl imging, using conventionl recording techniques. This llowed the ssessment of the thresholds of the different electrode pirs nd documenttion of their effectiveness. We found ltency rnge of ms for pek I1 nd ms for pek IV. Thresholds were etween 100 nd 200 PA. Opticl reflectnce chnges following intrcochler stimultion We otined 300 complete opticl mps of reflectnce chnges following different stimultion protocols of the cochler implnt device in seven cts. Ech mp consisted of sequence of 12 imges of 400 ms durtion providing informtion out the time course of the signls. Accordingly, totl of 3600 single mps were recorded. For further nlysis, the frme contining mximl reflectnce chnges, usully occurring during 2 nd 3 s fter stimulus onset, ws used for further nlysis. As rule, during the temporl development of the opticl signl we oserved differences in mplitude ut not in topogrphy. Electricl stimultion of rdil pirs elicited topogrphiclly restricted distriutions of opticl signls (Fig. 3). On verge, the mplitude of the intrinsic signls, i.e. the reltive reflectnce chnge mesured for the 546 nm light source, ws in the rnge of %. The re of the two-dimensionl signl distriution incresed firly linerly with signl mplitude. We found n verge corticl territory of 0.39 t 0.32 mm2 t 75% of the mximl reflectnce chnges, 2.76 i 1.91 m2 t 50% nd mm2 t 25% (n = 170, mps mesured t similr current levels). Generlly, the opticlly otined distriutions of signls were non-homogeneous nd often multipeked, especilly in the non-mximl prts of the signls, resulting in complex, ptchy ptterns of ctivity. As cn e clculted from the length of the electrode, the position of the stimultion sites nd the individul intrcochler position, the frequency rnge eing stimulted ws estimted to e etween 6 nd 50 khz (see Discussion). According to the position of the implnts in the cochle, response res in A1 were indeed restricted to the high-frequency representtions. Electrophysiologicl controls: LFP mps The sptil extent of the underlying neuronl response distriutions following single-pulse cochler electricl stimultion ws studied y conventionl LFP mppings using up to 40 penetrtions in the sme niml. These mesurements reveled LFP mps of ctivity distriutions tht were in remrkle ccordnce with the sptil reflectnce distriutions of the opticl dt imged in the sme niml (Fig. 3A). For this prticulr recording, we found res of ctivtion for the 25, 50 nd 75% levels of 10.3 versus 10.6 mm2 (opticl imging versus LFP), 5.6 versus 4.5 mm2, nd 1.8 versus 1.9 mm2 corticl surfce. Compring ll recorded opticl imging nd LFP mps (seven mps in three cts) reveled similr correspondence ( versus 10.1? 2.18; versus 4.5? 1.17; versus 1.8? 0.46) nd ws further sustntited y liner regression nlysis (r = , P < ). Cochleotopic selectivity In order to demonstrte tht the electricl stimultion of multichnnel cochler implnt preserves cochleotopic selectivity, i.e. evokes response res tht mtch the underlying frequency-specific orgniztion in AI, we mpped the uditory cortex with intrinsic reflectnce mesurements for vriety of different stimultion sites. In the exmple shown, the reflectnce mesurements were otined to electricl stimultion of rdil electrode pirs 1-2, 3-4 nd 5-8 (Fig. 3C). There ws systemtic shift of the response res towrds more nterior sites, which re known to represent successively higher frequencies. There ws no overlp etween the response res evoked y stimulting sites 1-2 versus 34, nd restricted overlp etween the stimultion sites 3 4 versus 5-8. In Figure 3C, the response res of ech of the three stimultion sites re colour-coded for n mplitude level of 50%, illustrting cler cochleotopic selectivity (comintion mp). A similr pttern of cochleotopic selectivity ws oserved when the reference electrode ws not one of the implnt sites ut the generl ground. In the exmple shown in Figure 3B, opticl mps for stimulting site 3 versus ground nd site 8 versus ground re illustrted. Effects of intensity of electricl stimultion Electricl thresholds for generting opticl mps were usully in the rnge of pa (3.5-8 db), ut could differ etween different

4 116 Opticl imging of cochler implnt stimultion in cts A c c c mx C nil n e FIG.3. (A) Comprison of the opticlly mesured sptil reflectnce chnges of intrinsic signls with the sptil distriution of electricl ctivity of multiple LFP recordings. Electricl stimultion of electrode positions 1-3 ws with 250 PA. Scle r, 1 mm. () Video imge of the corticl surfce. () Topogrphiclly restricted reflectnce distriution of n opticlly recorded imge following intrcochler stimultion. (c) LFP mp superimposed on n imge of the corticl surfce sed on recordings t 35 penetrtion sites (electrode penetrtion sites re mrked). (B) Cochleotopic selectivity s result of imging response mps using two electrode positions tht were stimulted with ground s reference. () Video imge of the corticl surfce. (, c) Mp of reflectnce chnges. () Stimultion of electrode 3 versus ground. (c) Stimultion of electrode 8 versus ground. Stimultion current, 12 db. Scle r, 1 mm. (C) Cochleotopic selectivity s result of imging response mps using three electrode positions. () Video imge of the corticl surfce. () Comintion mp of three different stimultion sites (cf. c-e) otined for reflectnce chnges of 50% mximl ctivity. Blue, electrode pir 1-2; green, electrode pir 3 4 ; red, electrode pir 5-8. (c-e) Mp of reflectnce chnges. (c) Stimultion of electrode pir 1-2. (d) Stimultion of electrode pir 3 4. (e) Stimultion of electrode pir 5-8. Stimultion current ws 15 db for 1-2 nd 3 4, nd 18 db for 5-8. Scle r, 1 mm. electrode pirs. Figure 4 shows n exmple of the effect of incresing stimultion current on the sptil distriution of the evoked opticl mps of reflectnce chnges. The resulting intensity functions were firly steep. In the exmple illustrted, 0.5 dl3 increse resulted in two-fold enlrgement of the response re. At db ove threshold, mximl re of excittion ws reveled. This enlrge-

5 Opticl imging of cochler implnt stimultion in cts 117 e d e f h i FIG.4. Effects of incresing stimultion current on the sptil distriution of reflectnce chnges to stimultion of electrode pir 1-3. Current is indicted s db reltive to 100 PA. () Video imge of the corticl surfce. () 3.5 db. (c) 4.2 db. (d) 4.5 db. (e) 4.7 db. (f) 4.9 db. (g) 9.5 db. (h) 14 db. (i) 17 db. Scle r, 1 mm. ment, prllel to the increse in stimulting current, which ws due to incresing recruitment of corticl response res, reflected the decresing cochleotopic selectivity of the electricl stimultion. At the sme time, during high current stimultion the regions of mximl ctivity seen during low current stimultion shifted to positions most proly corresponding to uditory fields outside A1 (Fig. 4e-Q.This enlrgement of response res prllel to the increse of stimulting current reflects decresing selectivity of the electricl stimultion. However, there were only slight shifts in the overll position nd loction of the focl zones of ctivity emerging during low current stimultion. Insted, the effect of incresing current is minly reflected in n incresing recruitment of corticl response res. For exmple, res more ventrl to A1 were sometimes ctivted, most proly corresponding to AII. Discussion The min difference etween coustic nd electricl stimultion is tht electriclly induced ctivity of the uditory nerve is chrcterized y high temporl coherence nd synchronicity, minly ecuse no trvel times or locl mechnicl resonnce oscilltions re involved in their genertion. In spite of the methodologicl differences, we were le to demonstrte tht y mens of opticl recording of intrinsic signls it is possile to imge the topogrphic representtion of cute cochler stimultion in A1 nd in surrounding uditory corticl fields, nd tht stimultion of selected loctions of multichnnel implnt corresponding to different intrcochler frequency loctions results in selective shifts of the evoked response res, which mtch the underlying frequency orgniztion, nd thus preserves the overll cochleotopy. Advntges of opticl imging of intrinsic signls There is generl greement out the reliility of opticl recording of intrinsic signls, which ws demonstrted either y correspondence of opticlly nd electrophysiologiclly mesured representtions or y repeted opticl mesurements reveling low overll vrince of the mps together with considerle stility of representtionl detils (Bonhoeffer nd Gnnvld, 1993). In ddition, opticl recording of intrinsic signls llows repeted mesurements in one niml, which is not possile when the 2-deoxyglucose method is used. This is of considerle importnce when prmetric studies, which require vrition of mny prmeters, re intended. We were le to mesure up to 80 mps in single niml y systemticlly vrying lrge numer of stimulus prmeters. In ddition, we were le to perform numer of repeted mesurements, which were used to ssess nd to demonstrte the reliility of the mesured mps. However, in contrst to mpping sed on receptive field mesurements, opticl recording provides mesures of the corticl point spred function

6 118 Opticl imging of cochler implnt stimultion in cts (Msino et l., 1993; Grinvld et l., 1994; Godde et l., 1995; Hilger et l., 1996). Our comprison of opticl imging nd LFP dt reveled not only close correspondence etween the loction nd the sptil distriution of the ctivted re, ut lso considerle mtch concerning the slopes of the ctivity distriutions. Similr results hve een found for the rt somtosensory cortex (Hilger et l., 1996). In this study, dditionl comprison of the opticl imging dt with the spiking point spred function reveled high correltion for the 50% mplitude level. In study of topogrphic overlp in the somtosensory cortex of the rt, we found close mtch etween the estimted width of the corticl point spred function derived from receptive field recordings nd the opticl signl distriution for the 50% mximl mplitude (Godde et l., 1995). Bsed on oth results, we ssume tht the 50% mplitude level provides more pproprite estimtion out the corticl point spred function thn the mximl reflectnce chnges. In study in the rrel cortex of the rt, the SO% level ws lso chosen for further nlysis y Msino et l. (1993). Electrode plcement nd intrcochler frequency correspondence A criticl issue concerns the exct loction of the stimulting electrodes within the scl tympni. On some occsions, the position could e determined post mortem y roentgenogrphy. Normlly, controls included electrode resistnce mesurements nd mesurement of the solute current thresholds. Norml vlues of electrode resistnce were in the rnge of 5-50 kr. Thresholds were considered norml when they were etween 100 nd 200 pa. Asolute vlues for uditory nerve fires threshold were reported to e in the rnge of pa (Hrtmnn et l., 1984; Jvel, 1989). In contrst, t the single-cell level of neurons in AI, men vlues etween 200 nd 350 pa hve een descried, depending on whether rdil or longitudinl pirs were stimulted (Rggio nd Schreiner, 1994). Moreover, in three nimls we mesured EABRs. Their ltency chrcteristics, together with pproprite thresholds, provided dditionl cues for the intctness nd proper plcement of the electrodes. We found the most prominent reflectnce chnges in the highfrequency representtion of AI. To provide some solute vlues out the frequency rnges stimulted y ech electrode, we mde use of verge dt on the length of the scl tympni nd their corresponding frequency sites (Schuknecht, 1960; Htsushik et l., 1990). Bsed on these dt nd ssuming n overll length of the inserted electrode portion of -8 mm, we estimte tht the frequency rnge most proly stimulted ly within the rnge 6-50 khz. By the sme token, ssuming distnce of -2 mm etween electrode pirs 1-2, 34, 5-6 nd 7-8, nd ssuming tht pir 1-2 ws locted most distl to the round window, frequency differences of 6-12, nd 2448 khz might e expected, i.e. the electrode pirs were presumly seprted in the frequency domin y -1 octve, thus covering totl rnge of -3 octves. However, it must e stted tht there ws considerle vrition from niml to niml, which ws proly due to differences in electrode plcement. This is reflected in the sustntil vrition in corticl seprtion distnces, in the rnge of 1-3 mm of corticl surfce for stimultion with different electrode pirs. Opticl imging using tone-urst stimultion in intct cts reveled men octve seprtion of mm (Dinse et l., 1996), which is in the rnge to e expected from single-cell mpping (Merzenich et l., 1975). Accordingly, the ove clcultions sed on verged frequency sites of the scl tympni cn only give rough estimte of the ctul electrode positions. Cochleotopic selectivity nd intensity functions We were le to demonstrte tht cute intrcochler stimultion t multiple sites preserves frequency-specific topogrphies t the level of the uditory cortex. In ll cses, electricl stimultion induced ptterns of ctivity tht were comptile with known fetures of the orgniztion of the uditory cortex: ptchiness t mximl mplitude levels, sptil orienttion in ccordnce with isofrequency domins t SO% mplitude, nd the overll size of ctivted res. Erlier studies using only single-site cochler electrodes were priori not le to ddress this question. A recent report using conventionl electrode mpping provided evidence for the correspondence of functionl topogrphies for coustic nd electricl stimultion (Rggio et l., 1992). Using the method of 2-deoxyglucose lelling performed in the inferior colliculus of the ct, lelling ws oserved following distl nd proximl intrcochler stimultion corresponding to the 12 nd khz nds cousticlly evoked from the ipsilterl er (Brown et l., 1992). We cn confirm from our mesurements tht the intensity function, i.e. the dependency of the signl on the mount of electric current, is very steep. A corresponding finding hs een reported for uditory nerve fires (vn den Honert nd Stypulkowski, 1987), in which firing rte increses rpidly with only smll increses in stimulus level. Specificlly during high-current stimultion, we were le to mesure widespred reflectnce chnges in corticl res surrounding AI, s estimted from the lyout of the corticl sulci, such s the nterior field, nd more ventrl to AI, most proly corresponding to A11 (Fig. 4e-f). These shifts in mximl ctivity, oserved t different current levels, suggest tht corticl regions outside A1 re chrcterized y higher thresholds. Bsed on electrophysiologicl mesurements, the high-threshold ehviour of single neurons to coustic stimultion hs een reported for A11 (Schreiner nd Cynder, 1984). As to the intensity ehviour of A1 (Fig. 4-c), there ppered to e only slight shifts in the overll position nd loction of the focl zones of ctivity emerging during low-current stimultion, while t higher currents new zones with even higher levels of ctivity cn evolve outside AI. Concluding remrks The rtionle ehind this study ws two-fold. (i) By mens of opticl imging techniques the effects of cute electricl stimultion with multichnnel cochler implnt cn e visulized. The resulting ctivity ptterns re comptile with known ctivity mps following coustic stimultion (Dinse et l., 1996). (ii) The dt presented re necessry seline for the study of the effects of chronic stimultion in nimls with hering experience nd in nimls tht re neontlly defened. In view of the well-documented plstic cpcities of corticl neurons, widespred reorgniztionl chnges following long-term stimultion might e expected, which in turn might provide the sustrte for the highly vrile improvement of open speech understnding with prctice often oserved in ptients with such hering ids (Clrk et l., 1987; Reuter et l., 1995). In ddition, the wy in which corticl systems rect to stimultion of cochler implnts cn shed light on the principles of corticl informtion processing strtegies, nd my therefore e eneficil for our understnding of the specific constrints of uditory processing s well s the development nd design of future implnts. Acknowledgements We grtefully cknowledge the support of the Institut fur Neuroinformtik. We thnk Drs M. Rggio nd C. Schreiner for criticl reding of the mnuscript. We re grteful to D. Moricke, M. Neef, M. Ziesmer nd

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