CHAPTER FOUR

Introduction

Auditory development after cochlear implantation inchildren with early onset deafness is inferred throughbehavioral improvements in speech perception skills.However, these outcomes can be highly variable andmay depend on numerous factors ranging from the de-lay to implantation, to the child’s IQ, to family structureor even the educational environment (Geers and Bren-ner 2003; Geers, Brenner and Davidson 2003; Niparko2007). At the most basic level, the cochlear implant is de-signed to stimulate activity in the central auditory sys-tem, which is anticipated, in children, to lead to develop-ment of the auditory pathways.

In this paper we will provide evidence that the audi-tory system is formed even in the absence of significantactivity in children with early onset/congenital deaf-ness, but that the pathways require auditory input to de-velop. If deprived of activity bilaterally, the auditory thal-amus and cortex will likely be driven by non-auditory in-puts including those from the visual pathways (Finney,Fine and Dobkins 2001; Finney, Clementz, Hickok andDobkins 2003; Fine, Finney, Boynton and Dobkins 2005)which could compromise their use for auditory process-ing post-implantation (Giraud, Price, Graham, Truy andFrackowiak 2001; Lee et al. 2001; Lee et al. 2007). Theauditory brainstem has comparatively less competitiveinfluences than the auditory thalamus and cortex andconsequently remains virtually unchanged, or “frozen”,

during the period of auditory deprivation. We haveshown that development in the auditory brainstem canproceed in children with severe-profound sensorineuralhearing loss once a cochlear implant is provided. How-ever, this unilateral input may drive development whichalters the plasticity of the contralateral pathways. Fi-nally, we will show that stimulation from bilateralcochlear implants can be integrated in the auditorybrainstem, but that the patterns of integration can becompromised by a period of unilateral implant use. Ourresults to date indicate that there may be at least two sen-sitive periods during auditory development: the firstfrom a delay between onset of deafness in early child-hood to cochlear implantation, which compromises thal-amo-cortical development with implications for speech-language acquisition, and the second due to a delay be-tween unilateral and bilateral input which may alter de-velopment of binaural auditory processing.

Effects of Auditory Deprivation on theDeveloping Central Auditory Pathways

Neural pathways, including those of the central au-ditory system, form in the developing fetus prior to theonset of hearing through inherent mechanisms that arelikely mediated genetically. Once the cochlea developsand becomes functional, these pathways are available torespond albeit in an immature way. With age, the path-ways develop becoming more adult-like; more periph-eral portions of the central auditory system appear tohave shorter developmental time courses than relativelycentral portions, which can extend throughout child-hood into adolescence. Much of this information hasbeen learned from measuring auditory evoked poten-tials from different levels of the system in children withnormal hearing. These responses change over time, be-

51

Auditory Development Promoted by Unilateral and Bilateral Cochlear Implant Use

Karen Gordon

Address correspondence to: Karen A. Gordon, PhD., Assistant Professor, Department of Otolaryngology, University of Toronto, Director of Research, The Cochlear Implant Program, The Hospital for Sick Children, Rm. 6D08, 555 University Avenue, Toronto, ON, M5G1X8, karen.gordon@utoronto.ca

A Sound Foundation Through Early Amplification52

coming more clearly detectable and changing in both la-tency and amplitude (Eggermont 1985; Eggermont1988; Ponton, Moore and Eggermont 1996; Sharma,Kraus, McGee and Nicol 1997; Ponton, Eggermont,Khosla, Kwong and Don 2002). Whilst some develop-mental processes likely occur inherently (through ge-netic instruction), others require input or experience.

For children with early onset deafness, any develop-ment of the auditory pathways prior to the use of an audi-tory prosthesis occurs in the absence of significant input.Our research focuses on the effects of deafness on thepathways originally intended to carry sound to the brainand on the ability to stimulate these neural connec-tions with a cochlear implant. We focus on discrete areasof the pathways using evoked potential recordings and cancompare the responses we find in children using cochlearimplants with those recorded in normal hearing children.

A typical cochlear implant, both internal and exter-nal components, is shown in figure 1. Electrical pulsesare delivered by electrodes, which are implanted alongan array into the scala media of the cochlea. As we willdiscuss, these electrical pulses are highly effective instimulating the auditory nerve and consequently stimu-lating the central auditory system.

Figure 2 displays evoked responses from the audi-tory nerve and brainstem evoked by stimulation from abasal implant electrode in a child with early onset deaf-ness. Because the first wave of the electrically evokedauditory brainstem response (EABR) is obscured by ar-tifact, we also measure the electrically evoked com-pound action potential (ECAP) of the auditory nerve us-

Figure 1. The cross section of the cochlea shows the electrode arraysurgically placed in the scala tympani. The implant converts acousticsound to electrical pulses that stimulate the auditory nerve. Acousticinput enters the microphone, which is worn on the ear, and is sent tothe speech processor for analysis of intensity in a number of set fre-quency bands. The resulting information is sent from the externallyworn transmitting coil to the subcutaneous receiver-stimulatorthrough FM waves. These components are held together by a pair ofmagnets so that they are separated only by the thickness of the skinflap. Each frequency band is assigned to a particular electrode alongthe implanted array (mimicking the normal basal-to-apical organiza-tion of high to low frequencies in the cochlea). If instructed, this arraywill provide a biphasic electrical pulse to stimulate the auditory nerve.The magnitude of the pulse provided by any one electrode will dependon the acoustic intensity within the assigned frequency band and thedynamic range of current (minimum to maximum) programmed forthat electrode. This figure appears in (Papsin and Gordon 2007) as fig-ure 1 on page 2382.

Figure 2. (A) Characteristic peaks of the auditory brainstem re-sponse evoked by an acoustic click in a normal hearing adult areshown. (B) Early latency EABR wave peaks, including wave eI gener-ated by primary auditory neurons, are obscured by stimulus artifactbut waves eIII and eV are visible. ECAP eN1 latency was used to as-sess the response of primary neurons in place of eI latency. Part B ofthis figure appears in (Gordon et al. 2006) page 10.

A

B

Auditory Development Promoted by Unilateral and Bilateral Cochlear Implant Use 53

ing the device’s telemetry system to record from an in-tracochlear implant electrode. The close proximity ofthe recording electrode to the neurons being activated,and the use of a subtraction paradigm to eliminate stim-ulus artifact, allows this response to be recorded as pre-viously described (Abbas et al. 1999).

In combination, we can assess interwave latenciesbetween the eN1 of the ECAP and the EABR waves tomeasure the time of neural conduction along the audi-tory brainstem in children using cochlear implants. Theinterwave latencies also allow a comparison betweenelectrically evoked responses in children using implantsand acoustically evoked responses in normal hearing in-dividuals. In figure 3, ECAP and EABR wave latenciesare compared with published ABR values suggestingsimilar latency and interwave latencies for the earlywaves but shorter eIII and eV values compared to theacoustic homologues (III and V, respectively).

Initial Auditory Activity: Effects of Bilateral Auditory Deprivation

We are particularly interested in the responses ob-tained immediately following cochlear implant activationbecause they: a) confirm that neural pathways are pres-ent, can be stimulated by the implanted device and areorganized in an expected way; b) provide a measure ofthe effects of deafness on the auditory pathways; and

c) are a baseline for any changes realized with ongoingcochlear implant use. ECAP and EABR wave latenciesand amplitudes evoked by a basal electrode at initial de-vice activation are shown in figure 4. Of the 50 childrenincluded in this study cohort, 47 (94%) had clear EABRsat initial activation (in two children a large myogenic re-sponse was recorded, possibly obscuring a presentEABR and, in one child, EABRs were recorded at latertime points in response to stimulation with wider pulsewidths). As shown in figure 3, no significant relationshipbetween wave latencies, maximum amplitudes or theslope of amplitude growth (with increasing intensity)were found with respect to age at testing. Given thatthese children all had early onset (typically congenital)deafness, their age at this time was equivalent to their du-ration of bilateral deafness. The lack of significantchange of latency or amplitude values with respect to thistime period suggests that: a) developmental changes inthe auditory nerve and brainstem do not occur in the ab-sence of significant input; and b) if degenerative changesoccur during this period, they are not large enough to bedetected by the evoked potential measures.

The “frozen” state of the auditory nerve and brain-stem prior to implantation is not mirrored in more cen-tral areas of the auditory system. We assessed thalamo-cortical activity at device activation in awake children byrecording electrically evoked middle latency responses(EMLR). A sample response is shown in figure 5. Inter-

Figure 3. Mean ECAP/EABR latencies and mean ABR latencies froma previous study by Jiang et al. (1991) are plotted along a continuum inwhich waves eN1 and I are at 0 ms latency for comparison purposes.The EABR wave eIII and interwave eII-eIII are shorter than the ABRIII and II-III and eIII-eV is both longer than III-IV and shorter than III-V. This figure appears in (Gordon et al. 2006) page 17.

Figure 4. Wave parameters from recordings made at initial stimula-tion plotted as a function of age at implantation on a logarithmic scale.There was no correlation between A) minimum wave latency, B) max-imum wave amplitude or C) linear slope of amplitude growth and ageat implantation for waves eN1, eIII, and eV (p > 0.05). This figure ap-pears in (Gordon et al. 2003) page 491.

A Sound Foundation Through Early Amplification54

estingly, we found that children older than 8 years of age(who also experienced eight years of deafness) weremore likely to show detectable EMLRs (> 60% present)than children younger than this (< 40% present) at initialimplant use. This suggests that, unlike the auditorybrainstem, the thalamo-cortical pathways undergochange during the period of deafness. We do not yetfully understand what changes are occurring, but bothnormal and/or abnormal developmental processescould be involved. Because there is no significant audi-tory input to drive these changes, these could beprocesses that are activity-independent (perhaps genet-ically mediated) or processes driven by non-auditory in-put. The latter argument is supported by evidence thatthe auditory cortex undergoes reorganization duringthe period of deafness, which is driven by non-auditoryactivity including input from the visual and somato-sen-sory systems (Finney et al. 2001; Finney et al. 2003; Fineet al. 2005) and that the auditory cortex can be reorgan-ized by experimentally connecting retinal neurons

the target neuron would be strengthened, while theother, less successful inputs would be eliminated (Hebb1949). Because cortical neurons receive connectionsfrom multi-sensory neural pathways, it is possible thatthose inputs carrying auditory information are dormantin bilateral deafness and therefore eliminated or weak-ened, whereas non-auditory inputs are more successfuland thus are abnormally strengthened in traditionallyauditory dominant areas of the cortex. In contrast, neu-rons in the auditory brainstem receive the majority oftheir inputs from the left and right ears. Without signif-icant input from either side, we hypothesize that theseneurons are left virtually without input and thus do notshow any change as measured by evoked potentials dur-ing the period of bilateral auditory deprivation. We fur-ther hypothesize that a period of unilateral auditory in-put will drive connections from the stimulated side atthe expense of those from the unstimulated side.

In the following sections, effects of unilateral stimu-lation from a single cochlear implant on the central au-ditory system will be addressed. Further discussion willthen focus on how chronic unilateral stimulation duringdevelopment might impact contralaterally evoked re-sponses after bilateral cochlear implantation.

Changes with Unilateral Cochlear Implant Stimulation

Our studies have examined development promotedby unilateral cochlear implant use by following a largecohort of children with early onset deafness over thefirst year of implant use. A typical example of repeatedECAP and EABR recordings evoked by an apical andbasal cochlear implant electrode is shown in figure 6;wave latencies appear to decrease with implant use. Thisis confirmed by the group data shown in figure 7; signif-icant decreases in both wave and interwave latencieswere found. Decreasing EABR wave and interwave la-tencies reflect increasingly rapid neural conductionthrough the auditory brainstem with ongoing cochlearimplant use. Similarly, the acoustically evoked AuditoryBrainstem Responses (ABR) undergoes latency de-creases over the first year of life in normal hearing in-fants (Beiser, Himelfarb, Gold and Shanon 1985; Pon-ton, Eggermont, Coupland and Winkelaar 1992; Jiang1995; Ponton et al. 1996). These changes have been ex-plained by increased myelination and improved synap-tic efficiency through processes such as that proposedby Hebb (Eggermont 1985; Eggermont 1988). Synapticchanges alone might explain the evoked potential find-

Figure 5. Characteristic amplitude peaks of the electrically evoked mid-dle latency response are shown as evoked by a biphasic electrical pulsedelivered from an electrode at the apical end of the cochlear implant ar-ray. In the early portion of the recording window, the device’s power-uppulses are evident immediately prior to the large stimulus artifact.

(from the visual system) to the central auditory system(von Melchner, Pallas and Sur 2000).

Donald Hebb’s notion of neural development mighthelp to explain why non-auditory inputs stimulate the au-ditory cortex after many years of bilateral deafness, aswell as why there is relatively little change occurring inthe auditory brainstem during this period of auditorydeprivation. It is known that abundant connections be-tween neurons are made during development, but thatonly some of these connections survive (Huttenlocherand Dabholkar 1997). Hebb explained this phenomenonby proposing that those connections which provide co-ordinated signaling resulting in successful activation of

Auditory Development Promoted by Unilateral and Bilateral Cochlear Implant Use 55

ings in both the developing ABR in normal hearing chil-dren (Ponton et al. 1996) and the EABR in pediatriccochlear implant users. The developmental time coursefor the EABR eIII-eV interwave latency in children withearly onset deafness was calculated to span over the firstyear of implant use, meaning that the unilaterally elec-trically stimulated auditory brainstem should be ap-proaching maturation around the first year anniversaryof device activation.

We have also examined changes in the EMLR overtime. As plotted in figure 8, the ability to detect theEMLR increased dramatically over the first six monthsof implant use in children implanted at ages < 8 years,whereas less change was observed in children im-planted at least 8 years of age. However, the more re-stricted change over this period in the oldest group ofchildren might be associated with the increased abilityto detect this response at initial stimulation. A similar

Figure 6. Measures completed over the first year of implant use in a child with pre-lingual deafness implanted at 3 years of age. The electricallyevoked compound action potential is shown in the top panel and the electrically evoked auditory brainstem response in the panel below. Responsesevoked by apical electrodes have noticeably shorter latencies than those evoked by basal electrodes. Decreasing latencies with implant use can alsobe seen. This figure appears in (Gordon et al. 2007b) on page 1679.

Figure 7. Mean wave latency and inter-latency data during the duration of implant use. Error bars indicate ±1SE. Repeated measures ANOVA performed on complete datasets indicate a significant decrease in wave latency for waves eN1, eIII, and eV. Significant decreases in interwave latency were found for eN1-eIII reflecting neural conduction time in the lower brain stem, and eIII-eV reflecting neural conduction time in the upperbrain stem. These figures appear in (Gordon et al. 2003) on pages 492 and 493.

igure

A Sound Foundation Through Early Amplification56

finding has been reported by Sharma and colleagueswho found that late latency cortical responses in chil-dren implanted “late” had shorter wave latencies com-pared to children implanted at younger ages andchanged relatively little compared to the younger group(Sharma, Dorman and Kral 2005). As discussed above,it is possible that the auditory thalamo-cortex, as as-sessed by EMLR and late latency responses, changes ei-ther through activity-independent mechanisms or un-dergoes abnormal development promoted by non-audi-tory input during extended periods of bilateral auditorydeprivation in childhood. In either case, normal audi-tory development might not be reestablished aftercochlear implantation. Ponton and Eggermont havesuggested that children using cochlear implants mightnever develop normal adult-like cortical responses(Ponton and Eggermont 2001; Ponton 2006), which inturn would reflect persistent differences in the electri-cally driven auditory cortex. This will only be com-pletely resolved as we follow children implanted atyoung ages/short durations of deafness into adulthood.

Studies examining behavioral responses in childrenusing unilateral cochlear implant show that there aremany factors which contribute to post-implant out-comes, including speech perception abilities, speechand language acquisition, and reading. Age at implanta-tion appears to be one of these predictors in childrenwith early onset deafness, and this supports the ideathat bilateral auditory deprivation in early years of lifecompromises a sensitive period in auditory develop-ment. Based on our previous and current work, we sug-gest that there may be more than one sensitive period inauditory development. In the following section, we will

examine the possibility that a sensitive period for bilat-eral input is present in the developing auditory system.

Effects of Unilateral Cochlear Implant Stimulation on ContralaterallyEvoked Responses after Bilateral Cochlear Implantation

Recently we have been conducting studies asking ifa period of unilateral implant use compromises develop-ment of the contralateral auditory pathways. This hasparticular implications for children who receive a sec-ond cochlear implant a number of years following im-plantation of the first ear. We hypothesized that the au-ditory brainstem would be most plastic during the pe-riod of auditory brainstem development as measured bychanges in the EABR. We therefore examined plasticityin the contralaterally stimulated auditory brainstem inchildren who had over two years of unilateral implantuse (and likely a mature auditory brainstem as mea-sured by EABR); children who had less than one year ofunilateral use prior (EABR still undergoing change);and children with no unilateral implant experience priorto bilateral implantation. In children using bilateralcochlear implants, we have measured the EABR evoked

Figure 8. EMLR detectability over duration of implant use for completedata in each of four groups of children defined by the age at implanta-tion. The eMLR is detected more frequently in the oldest group of chil-dren (8–17 year olds shown in black) at device activation and changesover the first year of implant use are small in this group. This figure appears in (Gordon et al. 2005) page 83.

Figure 9. In each panel, auditory brainstem responses evoked by theright and left implants are shown first (each referenced to the ipsilateralearlobe). The bilateral responses with the calculated sum of left andright evoked responses from both recording channels are then shown.The bottom waveforms are the difference between bilateral andsummed responses in both channels. Child A, responses in a 2-year-oldchild who received bilateral implants simultaneously. Wave latencies aresimilar in all responses. Child B, responses from a child implanted in theright ear at12 months and in the left at 6 years of age. Left evoked wavepeaks are prolonged in latency. There is an observable difference wavein responses evoked by the apical but not the basal electrode. This fig-ure appears in (Gordon et al. 2007a) page 614.

Auditory Development Promoted by Unilateral and Bilateral Cochlear Implant Use 57

by the cochlear implant on the right and on the leftsides, as well as by bilateral cochlear implant stimula-tion. Responses recorded from the first day of bilateraldevice activation are shown in figure 9 for Child A whoreceived both cochlear implants in the same surgery (si-multaneous implantation) and Child B who received asecond implant in the left ear five years after the implan-tation of the right ear (sequential implantation after along delay between implants). Responses evoked by theright implant are shown in black and the left in gray.While there are no clear differences between responsesevoked by either implant in Child A, wave latencies inChild B’s newly activated left implant are prolongedcompared to those evoked by the experienced rightside. Predicted binaural responses, the sum of the leftand right responses, are shown for two recording chan-nels by the dashed line, and the measured binaurallyevoked response is shown by a solid line. The difference

Figure 10. Mean latencies (±1SE) of wave eV and interwave eIII-eV latencies evoked in the left ear at initial device activation were not significantly different in each bilateral implant group than age-matched uni-lateral users at the same stage of implant use (p > 0.05). Response latencies in the right ear are not significantly different from the left in the si-multaneous group (n = 9) (p > 0.05), slightly shorter in the short delay group (n = 15) (p > 0.05), and significantly shorter in the long delaygroup (n = 15) (p < 0.05). This figure appears in (Gordon et al. 2007a) on page 615.

Figure 11. Wave eV is indicated and appears prolonged in the less experienced left ear in the child on the right. Both children had used their bilateral im-plants for 3 months. Responses were evoked by the right implant, the left implant and binaurally. The binaural difference response is present in each record-ing channel for each child. In the bottom left panel, mean wave eV latencies evoked by the left implant are plotted relative to the right evoked eV latencyfor four groups of children at three separate time intervals. Children initially implanted at under 3 years of age had either long (> 2 years), short (6–12 months) or no inter-stage delays and a small group (n=4) of children initially implanted at over 3 years of age had long inter-stage intervals. Leftevoked eV was prolonged in all groups of children other than the simultaneous group. This difference decreased over time (but was still present in thetwo groups with long delays) and resolved by 9 months in the group with a short inter-stage interval. At the bottom right, the mean latency of the binau-ral difference response is plotted relative to the right evoked eV latency. The same trend is shown; the difference response remains prolonged in childrenwith long inter-stage intervals but is resolved at the 9-month time point in children with short delays. This figure appears in (Papsin and Gordon, in press).

A Sound Foundation Through Early Amplification58

between the measured and predicted binaural responseis displayed for two recording channels. This calculatedresponse, termed the binaural difference (BD) wave, inChildren A and B can be seen for responses evoked bythe apical but not the basal implant electrode.

Figure 10 displays the mean wave eV latency datafor either ear in a group of children with long delays (> 2 years); short delays (6–12 months); and no delaysbetween implantation of the first and second ears, asrecorded at initial device activation. The right ear wasthe ear first implanted in all children. Mean latencies fora group of age-matched unilateral cochlear implantusers recorded at initial device stimulation are also plot-ted. Response latencies evoked by the right experiencedear are significantly shorter in the children with longand short delays between implants, relative to theirnewly implanted left ears and responses evoked at thefirst unilateral stimulation in the age-matched unilateralgroup. These responses were recorded over the firstyear of bilateral implant use in all groups of children. Asplotted in figure 11, the prolongation of wave eV laten-cies evoked in the naïve relative to the more experi-enced ear was: a) not found in children with simulta-neous implants at any time point; and b) decreased inchildren with short but not long delays between im-plants. In both groups of children with long delays (chil-dren initially implanted > 3 or < 3 years of age), there ap-pears to be little change over time in the degree to whichresponses from the naïve ear lagged behind the experi-enced ear in latency. In this figure, the latency of the BDresponse is also plotted relative to the wave eV latencyof the experienced ear. In children with short delays, theBD at 9–12 months of bilateral implant use appears tohave decreased to latencies (relative to wave eV latencyevoked in the ear first implanted), which were similar tothose found in the children receiving simultaneous bilat-eral cochlear implants, whereas the BD in children withlong delays appears to remain prolonged (relative to eVevoked by the first implant). Thus, a period of unilateralimplant use, which extends beyond the time course ofelectrically evoked auditory brainstem response matu-ration, appears to alter the developmental potential ofthe contralaterally stimulated pathways. Moreover, theability of the contralateral pathway to integrate with theconnections stimulated by the first implanted side mightalso be compromised. Based on these data, we suggestthat in addition to sensitive periods missed during a pe-riod of bilateral deprivation in childhood, there may bea sensitive period for bilateral stimulation that is missedduring an extended period of solely unilateral auditory

input. Whereas the former may have implications forspeech and language acquisition, the latter is morelikely to affect binaural processes.

Summary and ConclusionsOur data suggest that experience has a major role in

shaping the developing central auditory system. Al-though the pathways form without significant input,they become refined based on the input they receive.We hypothesize that there is very little input to the audi-tory brainstem during the period of bilateral deafness inchildhood, which leaves the auditory brainstem imma-ture and virtually unchanged. In contrast, the thalamo-cortical pathways of the auditory system may be subjectto reorganization by non-auditory inputs that have con-nections to these areas. Our further work, based on thisHebbian view of neural development, showed that theintroduction of unilateral stimulation from a cochlearimplant promoted development of the auditory brain-stem regardless of the duration of deafness, but thatchanges in the thalamo-cortical areas were dependentupon the child’s age/duration of deafness. Althoughthese findings indicated a positive role of chronic stimu-lation by a cochlear implant, the unilateral input overseveral years was found to alter the potential for devel-opmental change in the contralaterally stimulated brain-stem pathways following sequential bilateral cochlearimplantation and for expected timing of binaural integra-tion as measured by the binaural difference response.This suggests a benefit of simultaneous bilateral implan-tation or sequential implantation after a short inter-im-plant interval. We therefore propose that there are atleast two sensitive periods in auditory development; thefirst depends on auditory input, having implications fordevelopment of speech-language, and the second de-pends on bilateral input, which has implications for de-velopment of binaural processing.

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