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Auditory brainstem activity in children with 9–30 months of bilateral cochlear implant use
Hearing Research
Hearing Research 233 (2007) 97–107
www.elsevier.com/locate/heares
Research paper
Auditory brainstem activity in children with 9–30 months of bilateral cochlear implant use K.A. Gordon a
a,b,c,*
, J. Valero a, B.C. Papsin
a,b
Cochlear Implant Laboratory, The Hospital for Sick Children, Room 6D08, 555 University Avenue, Toronto, ON, Canada M5G 1X8 b The Department of Otolaryngology-Head and Neck Surgery, University of Toronto, ON, Canada M5G 2N2 c Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8 Received 2 May 2007; received in revised form 29 July 2007; accepted 1 August 2007 Available online 9 August 2007
Abstract Bilateral cochlear implants aim to restore binaural processing along the auditory pathways in children with bilateral deafness. We assessed auditory brainstem activity evoked by single biphasic pulses delivered by an apical or basal electrode from the left, right and both cochlear implants in 13 children. Repeated measures were made over the first 9–30 months of bilateral implant use. In children with short or long periods of unilateral implant use prior to the second implantation, Wave eV of the auditory brainstem response was initially prolonged when evoked by the naı¨ve versus experienced side. These differences tended to resolve in children first implanted <3 years of age but not in children implanted at older ages with long delays between implants. Latency differences were projected to persist for longer periods in children with long delays between implants compared with children with short delays. No differences in right versus left evoked eV latency were found in 2 children receiving bilateral implants simultaneously and their response latencies decreased over time. Binaural interaction responses showed effects of stimulating electrode position (responses were more detectable when evoked by an apical than basal pair of implant electrodes), and duration of delay between implants (measured by latency delays). The trends shown here suggest a negative impact of unilateral implant use on bilateral auditory brainstem plasticity. Ó 2007 Elsevier B.V. All rights reserved. Keywords: Deafness; Auditory brainstem response; Binaural interaction component; Binaural difference response; Evoked potential; Auditory development and plasticity
1. Introduction We assessed auditory brainstem responses in children who were provided with bilateral cochlear implants either simultaneously or sequentially. Based on our previous work in which EABR wave latencies were found to decrease over the first year of implant use (Gordon et al., 2003, 2006, 2007), we expected that: (a) responses evoked by either implant would show latency differences in children implanted sequentially but not simultaneously; (b) *
Corresponding author. Address: Cochlear Implant Laboratory, The Hospital for Sick Children, Room 6D08, 555 University Avenue, Toronto, ON, Canada M5G 1X8. Tel.: +1 416 813 7259 (Main)/6683 (Lab); fax: +1 416 813 5036. E-mail address: [email protected] (K.A. Gordon). 0378-5955/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.heares.2007.08.001
decreases in wave latencies with implant use would occur in ears with <1 year implant experience; and (c) children with long delays between implants would show minimal changes in wave latencies evoked in the experienced ear (>2 years of implant use). Given the importance of relative timing in responses evoked by either ear on the latency of the normal binaural difference wave (Furst et al., 1985; Goksoy et al., 2005; Riedel and Kollmeier, 2006), we also expected that latency differences in wave eV evoked by left versus right cochlear implants in children with long or short delays between implants would be associated with latency delays in electrically evoked binaural difference responses. Central auditory development can be promoted with consistent use of a single cochlear implant in children with
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early onset deafness. Using electrophysiological responses, we have shown that wave latencies and interwave latencies decrease with implant use in such children (Gordon et al., 2003, 2005, 2006) reflecting activity-dependent processes which may include myelination and/or improvements in synaptic efficacy (Eggermont, 1988). These changes appear to occur at many levels of the auditory pathways including the auditory nerve, brainstem, thalamus and cortex as shown by decreasing wave latencies in early, middle and later latency responses (Gordon et al., 2005, 2006; Sharma et al., 2002b; Thai-Van et al., 2007). Although there may be subtle differences in the timing between the waves as compared to normal responses, responses in the rostral portion of the brainstem show similar degrees of latency decrease as occur in normal development (Gordon et al., 2006). The time course of these changes are thought to be the same (Thai-Van et al., 2007) or slightly shorter than normal (Gordon et al., 2006). Our data suggests that latency decreases in the electrically evoked auditory brainstem response (EABR) are largely complete by the end of the first year of implant use (Gordon et al., 2006). If latency decreases are dependent upon evoked activity, we would expect that EABRs evoked by the non-stimulated ear would not change in latency. Children receiving a second cochlear implant after a period of unilateral implant use should thus show prolonged EABR wave latencies evoked by the naive ear relative to responses evoked by the experienced ear. In a recent report, we show that this is true; at initial stages of bilateral implant use, response latencies evoked in the newly implanted ear were later than in responses evoked by the more experienced ear and similar to latencies evoked at initial implant use in agematched unilateral implant users (Gordon et al., 2007). In contrast, children receiving bilateral cochlear implants simultaneously did not show a mean latency difference in responses evoked from either side. In the present study, we assess results from 13 children followed for at least 9 months after bilateral implantation. Based on the time course of EABR latency changes shown in unilateral implant users, we expected that ears with greater than 1 year of implant experience would show little change in latency. We also expected that the time for differences between the ears to resolve would be dependent upon the duration of delay between the first and second implants and on the age of the child at the time of first implant. Although behavioral and cortical measures of auditory development after cochlear implantation have been shown to be related to the age at implantation (Connor et al., 2006; Gordon et al., 2005; Harrison et al., 2005; Sharma et al., 2002a), there appears to be little influence of age at implantation on EABR latency changes after unilateral cochlear implantation (Gordon et al., 2003, 2006; ThaiVan et al., 2007). We hypothesize that, for children with early onset deafness, the lack of age effect is a result of bilateral auditory deprivation of the auditory brainstem in the period prior to implantation. Whereas the deaf auditory cortex is susceptible to reorganization promoted by
input from other sensory systems including the somatosensory and visual systems (Doucet et al., 2006; Giraud et al., 2001; Lee et al., 2001), the auditory brainstem pathways receive little input from other sensory modalities thus limiting the potential for this ‘‘cross-modal’’ plasticity. In the absence of significant input, development of the auditory brainstem, including the sensitive period of development, may be arrested. If true, unilateral implant use would promote auditory brainstem development thus reinitiating a sensitive period. It is not clear, however, to what extent human auditory brainstem development is altered by unilateral (as compared to bilateral) input. Evidence from animal models suggests that a lack of binaural input during development results in extensive reorganization of the auditory brainstem pathways; connections from the cochlear nucleus to the ipsilateral inferior colliculus (IC) increase and connections to the contralateral inferior colliculus decrease (Illing et al., 1999; Nordeen et al., 1983). These changes are thought to result from a lack of competition from one side in brainstem nuclei which would normally receive inputs from either ear (Silverman and Clopton, 1977). Pathway reorganization in the brainstem is likely to affect more central areas of the auditory system. Indeed differences in cortical responses, reflecting altered patterns of response, have been shown in both adults and children with unilateral hearing loss (Ponton et al., 2001; Schmithorst et al., 2005). It is possible then that unilateral stimulation from a cochlear implant promotes reorganization of the auditory pathways during a sensitive period in development and that these changes might be difficult to reverse once the sensitive period is over. Based on our findings that the auditory brainstem response is largely mature after 1 year of unilateral cochlear implant use (Gordon et al., 2006), we hypothesized that children with long periods of unilateral cochlear implant use (>2 years) prior to receiving a second implant would be less likely to show developmental changes in the auditory brainstem (as measured by EABR) than children with shorter (<1 year) or no delays between implants. Any limitation in development of the second ear might compromise the ability of the two ears to integrate information and this was examined using electrophysiological measures. Evidence from normally hearing children and adults indicate that auditory brainstem responses evoked by binaural stimulation show amplitude and latency changes compared with the summation of responses evoked by each ear independently. This difference between the binaural and summated responses is typically plotted over the recording interval and referred to as the binaural difference (BD) response or binaural interaction component (BIC). The underlying mechanism for this phenomenon has been proposed to involve binaural processes in the superior olivary complex (Goksoy et al., 2005; McPherson and Starr, 1993; Melcher, 1996; Riedel and Kollmeier, 2006; Zaaroor and Starr, 1991). Interaural timing and level changes appear to affect both the latency and amplitude of the difference waveform (Furst et al., 1985; Riedel and
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1, all children used nucleus cochlear implants bilaterally and all had early onset deafness. None of the children showed any developmental delays. All were in auditory verbal therapy programs after bilateral implantation and wore their devices consistently.
Kollmeier, 2006; Ungan et al., 1997) correlating with psychophysical measures of sound lateralization (Furst et al., 1985, 1990, 1995, 2000). A similar response has now been shown in response to electrical stimulation from independent cochlear implants in cats (Smith and Delgutte, 2007) and we have demonstrated that it can also be recorded in children using bilateral implants (Gordon et al., 2007). In that paper, we showed that the binaural difference response of the EABR, measured at the first day of bilateral implant activation, is delayed in latency (relative to the latency of wave eV evoked by the ear first implanted) in children with long or short delays between implants but not in children who receive simultaneous bilateral implants (Gordon et al., 2007). In the present study, we show results from children with longer term bilateral implant use to assess the presence and parameters of the binaural interaction response.
2.2. Electrophysiological recordings Our parameters for recording electrically evoked auditory brainstem responses have been reported previously (Gordon et al., 2006, 2007). Briefly, we recorded evoked potential responses at center midline of the head (Cz) referenced to both earlobes [recording channel A1 (left earlobe) and A2 (right earlobe)] with a ground on the forehead using a NeuroScan Synamps and Scan 4.3 software. Single biphasic monopolar electrical pulses were delivered at 11 Hz from the left implant or the right implant, or from both simultaneously using the SPEAR processor and software developed by Dr. Richard van Hoesel, CRC-HEAR, Melbourne, Australia. This software allows precise control of timing of stimulation provided to the two cochlear implants but was not available at initial stages of device use for most of the 13 children included in this study. Prior to use of the SPEAR processor and software, the same stimuli presentation was directed to the left or right implants using Cochlear Corporation WinDPS (for N24M, RCS and CA devices) and/or Custom Sound EP (for N24RE devices) software. This meant that binaural interaction responses could not be measured in many of the children until they had had at least 3 months of bilateral implant experience. Pulses were delivered from an apical (#20) and a basal (#3) implant electrode in all children. Stimulation levels were increased to a level at which the electrophysiological response was clear and the child remained comfortable. Levels were kept constant from the first day of device activation through subsequent recording sessions. Children were not sedated and sat alone or on a parent/caregiver’s lap. They were kept occupied
2. Material and methods 2.1. Subjects Of the children receiving bilateral cochlear implants in our center, 13 children have been followed for at least 9 months. All children and/or families consented to participate in this study as approved by the Hospital for Sick Children’s Research Ethics Board which adheres to the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. Two children received bilateral cochlear implants simultaneously at young ages (1.0 year and 1.8 years). Eight of the children were initially implanted at ages <3 years in the right ear (mean 1.23 ± 0.43 years) and then received an implant in the left ear after a long (n = 3, mean 3.54 ± 1.47 years) or short (n = 5, mean 0.76 ± 0.13 years) delay. Three children received their first implant in the right ear at older ages (mean 4.37 ± 0.85 years) and were implanted in the left ear after a long delay (mean 5.50 ± 0.19 years). As detailed in Table
Table 1 Demographic information Patient
Onset of HL
Etiology
Age at activation 1st Implant
Simultaneous 1 Simultaneous 2 Short Delay 1 Short Delay 2 Short Delay 3 Short Delay 4 Short Delay 5 Long Delay 1 Long Delay 2 Long Delay 3 Older Long 1
Congenital Congenital Congenital Congenital Congenital Congenital Congenital Congenital Congenital Congenital Congenital
Older Long 2 Older Long 3
Congenital Congenital
Connexin 26 Unknown Connexin 26 Connexin 26 Usher’s syndrome Unknown Unknown Unknown Unknown Connexin 26 Connexin 26 Heterozygote Unknown Connexin 26
Ear (1st Implant)
2nd Implant
Device Right
Left
Duration of bilateral CI use (months)
1.1 1.7 0.8 1 0.8 1.3 2 0.9 1.4 1.7 4
1.1 1.7 1.7 1.8 1.6 2.2 2.7 3.8 3.9 6.1 9.6
Right Right Right Right Right Right Right Right Right Right Right
N24RE N24RE N24CA N24CA N24CA N24CA N24CA N24RSC N24RCS N24M N24M
N24RE N24RE N24RE N24RE N24RE N24RE N24RE N24CA N24CA N24CA N24CA
15 15 12 15 9 15 15 30 30 24 30
5.4 4
10.8 9.5
Right Right
N24M N24M
N24CA N24CA
24 18
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throughout the test by a second tester and/or by watching a movie. The same recordings were completed in 5 children (Short Delay 1, Short Delay 3, Long Delay 3, Older Long Delay 2, Older Long Delay 3) at some point(s) during their period of unilateral N24M or RCS use. Data collection was the same; monopolar biphasic pulses were presented at 11 Hz from an apical (#20) and basal (#3) electrode at comfortably loud levels and recorded using the same equipment, recording montage and parameters. A prior version of NeuroScan software (version 4.0) was used with the same amplifier and other hardware. 2.3. Analyses Because changes in wave eV with implant use are likely due to neurological rather than peripheral changes (ThaiVan et al., 2007), we focused on this wave for the purpose of the present paper. The amplitude peak of wave eV was marked using Matlab 6.5.2 (The Mathworks, Natick, MA) by an observer blinded to the patient, stimulating electrode, and duration of bilateral implant use. Extreme outliers were remeasured. Linear regression analyses were completed using SPSS 14.0. 3. Results 3.1. Comparisons of responses evoked by each implant over time Results evoked by individual implants are shown for each child in Figs. 1 and 2. Responses from the simultaneous bilateral implant group (n = 2) and the short delay group (n = 5) are included in Fig. 1. Responses from children with long delays are shown in Fig. 2; children first implanted at young ages (<3 years; n = 3) are delineated from children who received their first implant at older ages (n = 3). Data from each group are combined in Fig. 3. Figs. 1 and 2 show waveforms evoked by the apical implant electrode in either implant (from the recording channel in which the ipsilateral earlobe was used as reference) in each child at each recording session. A plot of wave eV latency for each response is shown to the right for each set of waveforms. As shown in Fig. 1, the 2 children who received simultaneous bilateral cochlear implants had very similar eV latencies at device activation. Latencies in both ears decreased in both children over time although the eV latency evoked by Simultaneous 2’s left implant seemed to remain fixed through months 3–12. The 5 children implanted at young ages with the first implant in the right ear and then with the second after a short delay of unilateral implant use are also shown in Fig. 1. Data was available from the first implanted ear (right) at initial stages of unilateral implant use in Short Delay 1 and 3. In these 2 children, the right ear response showed decreases in eV latency over the first months of unilateral implant use and only subtle latency changes thereafter. Similarly the
other 3 children in this group showed only small changes in wave eV evoked by the experienced ear over the period of bilateral implant use. Responses evoked from the newly implanted left side were initially prolonged relative to the more experienced right side in 4 of the 5 children (left and right evoked latencies were similar in Short Delay 3). With bilateral implant use, 4 of the 5 children showed clear changes in eV latency evoked by the left device during this time (Short Delay 5 did not show eV changes over time in responses evoked by either implant). Interestingly, Short Delay 2 showed large initial response differences between sides as compared with the other children. In this child, despite clear decreases in eV latency evoked in the left ear, response latency differences between the ears were not resolved even after a year of bilateral implant use. Fig. 2 displays the same data from children who had long delays between implants; 3 children received their first implants at young ages (<3 years) and 3 received their implants at older ages (P4 years). In the former group of children (long delay group), wave eV latency changed very little when evoked in the right (experienced) ear. Responses from the newly implanted left ear decreased in latency from initial values but little thereafter in Long Delay 1 and 2. Long Delay 3 showed the smallest difference between ears at initial bilateral activation and over time of bilateral implant use. Interestingly, that child also demonstrated small changes in response latencies evoked by the first implant over the first year of unilateral implant use. In the children who were implanted in the right ear at ages P4 years and who also had long periods of unilateral use before receiving the second implant (older long delay group), wave eV latency did not appear to change in responses evoked by either ear and latency differences between the ears remained with ongoing bilateral implant use. Data for Older Long Delay 3 over the first year of unilateral implant use was available and indicates a clear decrease over time in contrast to the lack of change noted on the left side during the first 2 years of bilateral implant use. Group trends for responses evoked by the apical and basal implant electrode are shown in Fig. 3. Wave eV latency data from the ipsilateral recording electrode in both right and left evoked responses are plotted with respect to duration of bilateral implant use for each group. The linear regression lines indicate different patterns of latency change in each group confirming the trends noted in the individual data shown in Figs. 1 and 2. These analyses suggest that children receiving simultaneous bilateral implants tend to have similar wave eV latencies in responses evoked by either ear which decrease with ongoing bilateral implant use. Latencies in the experienced ear show small changes in children having short periods (6–12 months) of unilateral use but little change in children with longer durations of unilateral use (>2 years). Responses in the newly implanted ear were prolonged relative to the experienced ear at early stages of bilateral implant use in all groups of children receiving sequential bilateral implants. This difference is projected by linear regression to resolve in the children with
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Fig. 1. Auditory brainstem responses evoked by the apical electrode in the right and left cochlear implants in 2 children who received simultaneous bilateral implants and 5 children who used a unilateral implant in the right ear for a short period prior to implantation of the left ear. Wave eV latencies are indicated by the dashed lines over the period of bilateral implant use and plotted for each child. Responses recorded during the period of unilateral implant use are shown for children referred to as Short Delay 1 and 3. D = day, M = month, U = unilateral.
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Fig. 2. Auditory brainstem responses evoked by the apical electrode in the right and left cochlear implants in 6 children who received a cochlear implant in the left ear after a long period of unilateral implant use in the right; 3 were first implanted at young ages < 3 years (long delay group) and 3 at older ages (older long delay group). Wave eV latencies are indicated by the dashed lines over the period of bilateral implant use and plotted for each child. Responses recorded during the period of unilateral implant use are shown for children referred to as Long Delay 3 and Older Long Delay 3. D = day, M = month, U = unilateral.
short delays by approximately 1.5–2.0 years whereas differences in children with long delays are predicted to take longer than 2.5 years. Children provided with their first implant at ages >3 years and who had long delays between implants show no trend toward a decrease in the difference between ears. 3.2. Binaural difference responses The binaural difference response was calculated by addP ing the responses evoked by either implant [ (L + R)] and then subtracting the binaurally evoked response from this sum. Three examples of this process are shown in Fig. 4. These are responses from the child named Simultaneous 1 after 15 months of simultaneous implant use, from Short Delay 1 after 12 months of bilateral use (in addition to 9
previous months of unilateral use on the right side) and from Older Long Delay 1 after 30 months of bilateral implant use (sequentially implanted after a period of 5 years of unilateral use on the right side). In all three examples, a clear difference wave can be observed in both recording channels. Fig. 5 shows the most recent binaural difference waves for each child evoked by apical and basal electrode pairs. The detectability of the interaction response was better when evoked by apical electrodes (present in 11 of 13 children) compared to the basal electrode (present in only 6 of the 13 children). The incidence of the interaction response by group is shown in Table 2. As indicated in Table 2, the interaction response evoked by the pair of apical implant electrodes tends to increase in latency (relative to the right ear) as the duration of delay increases.
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Fig. 3. Wave eV latencies evoked by the right and left implants are plotted over duration of bilateral implant use for each group. On the left are plotted response latencies evoked by apical implant electrodes and on the right are response latencies evoked by basal implant electrodes. Linear regression lines and associated Pearson co-efficient are shown.
Fig. 4. Responses evoked from the apical electrodes in either implant and both implants simultaneously from 3 children are shown. The binaural P interaction response was calculated by adding the responses evoked by either implant [ (L + R)] (shown by dashed lines) and subtracting the binaurally evoked response from this sum. A clear difference wave can be observed in both recording channels in all three examples.
4. Discussion 4.1. Differences in response latencies evoked in either ear As predicted, auditory brainstem response latencies evoked from chronically stimulated ears were found to be shorter than those evoked from naı¨ve ears. This was shown in most of the individual data sets in Figs. 1 and 2. A similar finding was initially noted by Thai-Van and colleagues in two children receiving sequential bilateral cochlear implants (Thai-Van et al., 2002) and we recently confirmed it in a systematic and controlled group study of responses recorded at initial stages of bilateral implant use (Gordon et al., 2007). In that report, we showed that the latency dif-
ferences between ears were not present at initial device activation in the group of children who received simultaneously implanted bilateral cochlear implants. The differences in response latencies evoked by either implant shown in both the previous and present studies span up to 0.65 ms which is considerably larger than differences in responses evoked by left versus right ears in normal neonates (0.051–0.070 ms) as reported by Sininger and ConeWesson (2006). We previously showed that there was no statistical difference between responses evoked by the naı¨ve ears of bilateral users and those from the naı¨ve ears in agematched unilateral controls. This finding further confirms that brainstem development reflected by decreasing EABR latencies is dependent upon activity. In the absence of
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Fig. 5. Binaural difference waves calculated in each child after at least 9 months of bilateral implant use are shown. Detectable responses observed in both recording channels are indicated by arrows. Further details are provided in Table 2.
Table 2 Incidence and latency of binaural interaction responses
Simultaneous Short Delay Long Delay Older Long Delay
Duration of BI use (months)
Apical electrode Incidence of BIC
Latency of BIC (ms)
Incidence of BIC
Latency of BIC (ms)
12 ± 4 12 ± 3 28 ± 3 24 ± 6
2/2 5/5 2/3 2/3
0.09 ± 0.00 0.07 ± 0.22 0.15 ± 0.07 0.35 ± 0.35
2/2 1/5 2/3 1/3
0.32 ± 0.11 0.45 0.10 ± 0.07 0.55
significant input, latencies remain delayed suggesting a relative immaturity of the auditory brainstem as evoked in a newly implanted ear. The functional implications of this
Basal electrode
abnormal disparity in response timing between implanted ears are not known. It is possible that these ‘‘internal’’ interaural time differences disrupt or add to ‘‘external’’
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interaural timing differences which are normally used to localize low frequency sounds. If true, children receiving sequential bilateral implants might not be able to use timing cues effectively or accurately for sound localization at initial stages of device use even if both devices functioned in perfect synchrony. Because bilateral cochlear implants presently consist of two individual devices each with their own internal and external components, the timing of inter-implant stimulation cannot be controlled. The lack of co-ordination of stimulation provided by the two electrode arrays might further add to difficulties in perceiving interaural timing differences. In this study, we addressed the potential for the initial ‘‘internal’’ interaural timing differences to resolve with ongoing bilateral implant use. Trends shown in Fig. 3 suggest that the experienced ear in children receiving sequential bilateral implants changes very little after bilateral implantation. This was expected given that maturation of the auditory brainstem in children using a single cochlear implant is largely complete by 6–12 months of implant use (Gordon et al., 2006). The very slight decrease in wave eV latencies in children who had 6–12 months of unilateral implant use is further evidence of this developmental time course. Wave eV latencies evoked by the newly implanted ear showed different trends for each group over time of bilateral implant use. While eV latency appeared to decrease with bilateral implant use in children with short delays between implants, children with long delays between implants showed trends for a slower rate of change (when the first implant was at a young age) or very little change (for children who received their first implant at older ages). This reflects a change in developmental plasticity in children with long term unilateral implant use at the level of the auditory brainstem. These early trends are an interesting departure from our previous findings in which the brainstem’s ability to change upon unilateral implant use as measured by decreasing wave latencies showed no age dependency (Gordon et al., 2003, 2006). This has been recently confirmed (Thai-Van et al., 2007) and suggests that any changes occurring in the auditory brainstem during the period of bilateral deprivation are small compared to the significant changes promoted by implant stimulation. In contrast, the trends shown in the present study suggest that the maturation of the brainstem from stimulation on one side either restricts or changes the course of maturation evoked by the second side. Recent evidence suggests that limitations to auditory development after cochlear implantation is the result of competition from other modalities; ‘‘cross-modal’’ plasticity has been implicated in reorganization of the auditory cortex during the period of deafness (Lee et al., 2001) and is thought to restrict the ability of auditory activity, stimulated by cochlear implant use, to reestablish normal cortical connections. The auditory cortex appears to be vulnerable to inputs carrying visual (Fine et al., 2005; Lambertz et al., 2005) or perhaps other sensory information.
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The auditory brainstem is likely less vulnerable to competition from non-auditory projections as it primarily receives inputs from either ear. Thus, in the absence of bilateral input, there is little to promote activity-dependent processes in the auditory brainstem which likely accounts for the similarity in evoked potentials in children with early onset bilateral deafness regardless of the duration of deafness (Gordon et al., 2003). Once stimulation is provided from one ear, however, processes requiring activity can be initiated and there may be implications of this unbalanced activity in the auditory brainstem. Animal models with experimentally induced unilateral cochlear lesions suggest that one stimulated ear can dominate brainstem development at the expense of pathways innervating the other side. Without competition from one side during development, there is an expansion of excitatory projections from the ipsilateral cochlear nucleus to the ipsilateral IC (Nordeen et al., 1983) and a loss of binaural activity in the ipsilateral IC (Silverman and Clopton, 1977). The contralateral IC receives an expansion of projections from the ipsilateral cochlear nucleus (Nordeen et al., 1983) and demonstrates increased inhibitory activity (Silverman and Clopton, 1977). Unilateral loss induced in mature animals does not yield similar effects as in younger animals. There was no effect of unilateral hearing loss on connections to the IC if the onset of the loss occurred after 60 days in cats (Clopton and Silverman, 1977) and no effect on cell size in brainstem nuclei in CBJ/A mice if the unilateral loss did not include all or part of a range of post-natal development days (12–24 days) (Webster, 1983). It is thus possible that unilateral cochlear implant use in children with early onset deafness not only strengthens connections innervating that ear but also allows for abnormal expansion of these connections. The trends shown in the present study require statistical validation (which will be done once we have followed sufficient numbers of children using bilateral implants over the long term). If confirmed, these trends would suggest that, like the animal data, there is a period of unilateral deprivation in early development after which auditory plasticity is altered. We expected that bilateral auditory development would proceed in children receiving two cochlear implants simultaneously at young ages. Indeed, responses from the 2 children in this group, shown in Fig. 1, indicate a decrease in latency in both ears with ongoing bilateral implant use suggestive of developmental changes in the auditory brainstem. Interestingly, these changes are very similar when evoked from either ear in the child named Simultaneous 1. On the other hand, responses evoked in Simultaneous 2’s left ear showed a period of some months in which no changes were realized while the right ear responses showed regular decreases in latency over time. This suggests that in young children receiving simultaneous bilateral implants: (a) there is some independence between pathways which respond to right versus left implant stimulation and (b) effects of deafness or activity-dependent developmental processes may not necessarily be uniform between ears.
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Independence of the ears may be of benefit during development as suggested by Sininger and Cone-Wesson (2006). 4.2. Binaural interaction responses We have previously shown that binaural difference responses are present at initial stages of bilateral cochlear implantation in children (Gordon et al., 2007). These responses show unexpected delays in latency relative to the first implanted ear in children receiving the second implant after a long or short period of unilateral implant use but are similar in latency to responses evoked by either implant in children receiving simultaneous bilateral implants. In that report, we also showed that binaural interaction responses were more likely to be detected when evoked by apical versus basal implant electrode stimulation. Very similar findings were seen in the binaural responses measured after at least 9 months of bilateral implant use. As shown in Fig. 5, the interaction responses were more likely evoked by a pair of apical electrodes than a pair of basal electrodes. This reflects weaker or absent interaction between neurons stimulated by a pair of basal electrodes. This could be explained by peripheral factors which influence the spread of current differently in the base relative to more apical areas of the cochlea and/or to differences in neural integrity along the cochlea. This could also be explained by potential maturational changes in binaural processing evoked by stimulation from basal ends of the cochlea. The ability to record binaural difference components using high versus low frequency acoustic stimuli is not impaired in normal hearing adults (Polyakov and Pratt, 1999) or neonates, however, there might be an amplitude change with age. High versus low frequency stimuli evoke larger amplitude difference components in adults (Polyakov and Pratt, 1999) and smaller amplitudes in neonates (Cone-Wesson et al., 1997). If immaturity underlies the poor detectability of binaural difference responses evoked by the basal electrode, we would expect in future studies to find an improvement in detectability with chronic bilateral cochlear implant use. As for the latencies of the apically evoked interaction response, the data shown in Table 2 indicate that these responses are prolonged relative to responses from the experienced ear (right ear) in children who receive bilateral implants after a long period of unilateral implant use (0.15 ± 0.07 ms for long delay group and 0.35 ± 0.35 ms in the older long delay group) despite significant bilateral implant use (at least 12 months). This is consistent with a lack or slow rate of change in response latencies evoked by either ear in these groups of children. The association between delayed latencies of binaural interaction responses and function in cochlear implant users are as yet unknown, however, latency increases in the binaural interaction response have been shown to occur when interaural timing and level differences are increased in normal hearing adults (Furst et al., 1985; Riedel and Kollmeier, 2006) and infants (Furst et al., 2004). Thus, the latencies of the binaural
interaction responses might also support the presence of an ‘‘internal’’ interaural timing difference between auditory brainstem activity evoked by one implant relative to the other. Children receiving simultaneous bilateral implants and those with only short delays between implants showed binaural responses more similar to latencies of the right ear (0.09 ± 0.00 ms for the simultaneous group and 0.07 0.22 ms in the short delay group) after many months of bilateral implant use. It is therefore possible that, after chronic bilateral stimulation, interaural timing cues may be more accurately processed in the auditory brainstem in these children. Further analyses of how the binaural difference responses change with bilateral implant use might provide insight into the development of binaural processing in the auditory brainstem. 5. Conclusions The early findings of auditory brainstem plasticity evoked by chronic bilateral electrical stimulation in children with early onset deafness suggest a negative impact of a period of unilateral implant use. Short delays between implants appeared to be less restrictive to development of pathways innervated by the second ear than long delays, however, the time course of development may be prolonged relative to that promoted by the first implant. Binaural interaction responses were present in children receiving bilateral cochlear implants simultaneously or sequentially but were more detectable when evoked by a pair of apical implant electrodes than a pair located at the basal end in the latter group. The data shown here suggests a trend toward increased latency delay of the binaural interaction response in children with long versus short periods of unilateral implant use prior to implantation of the second ear. Simultaneous bilateral implantation, on the other hand, resulted in evoked potential responses of similar latency when evoked by either implant, decreases in response latency with bilateral implant use, and binaural interaction response of expected latencies. Acknowledgements We acknowledge grant support provided by the Canadian Institutes of Health Research and the SickKids Foundation and our collaboration with Dr. Richard van Hoesel. We also thank the children and their families for their contributions of time and effort. References Clopton, B.M., Silverman, M.S., 1977. Plasticity of binaural interaction. II. Critical period and changes in midline response. J. Neurophysiol. 40, 1275–1280. Cone-Wesson, B., Ma, E., Fowler, C.G., 1997. Effect of stimulus level and frequency on ABR and MLR binaural interaction in human neonates. Hear. Res. 106, 163–178. Connor, C.M., Craig, H.K., Raudenbush, S.W., Heavner, K., Zwolan, T.A., 2006. The age at which young deaf children receive cochlear
K.A. Gordon et al. / Hearing Research 233 (2007) 97–107 implants and their vocabulary and speech-production growth: is there an added value for early implantation? Ear Hear. 27, 628–644. Doucet, M.E., Bergeron, F., Lassonde, M., Ferron, P., Lepore, F., 2006. Cross-modal reorganization and speech perception in cochlear implant users. Brain 129, 3376–3383. Eggermont, J.J., 1988. On the rate of maturation of sensory evoked potentials. Electroencephalogr. Clin. Neurophysiol. 70, 293–305. Fine, I., Finney, E.M., Boynton, G.M., Dobkins, K.R., 2005. Comparing the effects of auditory deprivation and sign language within the auditory and visual cortex. J. Cogn. Neurosci. 17, 1621–1637. Furst, M., Levine, R.A., McGaffigan, P.M., 1985. Click lateralization is related to the beta component of the dichotic brainstem auditory evoked potentials of human subjects. J. Acoust. Soc. Am. 78, 1644–1651. Furst, M., Eyal, S., Korczyn, A.D., 1990. Prediction of binaural click lateralization by brainstem auditory evoked potentials. Hear. Res. 49, 347–359. Furst, M., Levine, R.A., Korczyn, A.D., Fullerton, B.C., Tadmor, R., Algom, D., 1995. Brainstem lesions and click lateralization in patients with multiple sclerosis. Hear. Res. 82, 109–124. Furst, M., Aharonson, V., Levine, R.A., Fullerton, B.C., Tadmor, R., Pratt, H., Polyakov, A., Korczyn, A.D., 2000. Sound lateralization and interaural discrimination. Effects of brainstem infarcts and multiple sclerosis lesions. Hear. Res. 143, 29–42. Furst, M., Bresloff, I., Levine, R.A., Merlob, P.L., Attias, J.J., 2004. Interaural time coincidence detectors are present at birth: evidence from binaural interaction. Hear. Res. 187, 63–72. Giraud, A.L., Price, C.J., Graham, J.M., Truy, E., Frackowiak, R.S., 2001. Cross-modal plasticity underpins language recovery after cochlear implantation. Neuron 30, 657–663. Goksoy, C., Demirtas, S., Yagcioglu, S., Ungan, P., 2005. Interaural delay-dependent changes in the binaural interaction component of the guinea pig brainstem responses. Brain Res. 1054, 183–191. Gordon, K.A., Papsin, B.C., Harrison, R.V., 2003. Activity-dependent developmental plasticity of the auditory brainstem in children who use cochlear implants. Ear Hear. 24, 485–500. Gordon, K.A., Papsin, B.C., Harrison, R.V., 2005. Effects of cochlear implant use on the electrically evoked middle latency response in children. Hear. Res. 204, 78–89. Gordon, K.A., Papsin, B.C., Harrison, R.V., 2006. An evoked potential study of the developmental time course of the auditory nerve and brainstem in children using cochlear implants. Audiol. Neurootol. 11, 7–23. Gordon, K., Valero, J., Papsin, B.C., 2007. Binaural processing in children using bilateral cochlear implants. Neuroreport 18, 613–618. Harrison, R.V., Gordon, K.A., Mount, R.J., 2005. Is there a critical period for cochlear implantation in congenitally deaf children? Analyses of hearing and speech perception performance after implantation. Dev. Psychobiol. 46, 252–261. Illing, R.B., Cao, Q.L., Forster, C.R., Laszig, R., 1999. Auditory brainstem: development and plasticity of GAP-43 mRNA expression in the rat. J. Comp. Neurol. 412, 353–372. Lambertz, N., Gizewski, E.R., de Greiff, A., Forsting, M., 2005. Crossmodal plasticity in deaf subjects dependent on the extent of hearing loss. Brain Res. Cogn. Brain Res. 25, 884–890.
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Lee, D.S., Lee, J.S., Oh, S.H., Kim, S.-K., Kim, J.-W., Chung, J.-K., Lee, M.C., Kim, C.S., 2001. Deafness: cross-modal plasticity and cochlear implants. Nature 409, 149–150. McPherson, D.L., Starr, A., 1993. Binaural interaction in auditory evoked potentials: brainstem, middle- and long-latency components. Hear. Res. 66, 91–98. Melcher, J.R., 1996. Cellular generators of the binaural difference potential in cat. Hear. Res. 95, 144–160. Nordeen, K.W., Killackey, H.P., Kitzes, L.M., 1983. Ascending projections to the inferior colliculus following unilateral cochlear ablation in the neonatal gerbil, Meriones unguiculatus. J. Comp. Neurol. 214, 144– 153. Polyakov, A., Pratt, H., 1999. Contribution of click frequency bands to the human binaural interaction components. Audiology 38, 321–327. Ponton, C.W., Vasama, J.P., Tremblay, K., Khosla, D., Kwong, B., Don, M., 2001. Plasticity in the adult human central auditory system: evidence from late-onset profound unilateral deafness. Hear. Res. 154, 32–44. Riedel, H., Kollmeier, B., 2006. Interaural delay-dependent changes in the binaural difference potential of the human auditory brain stem response. Hear. Res. 218, 5–19. Schmithorst, V.J., Holland, S.K., Ret, J., Duggins, A., Arjmand, E., Greinwald, J., 2005. Cortical reorganization in children with unilateral sensorineural hearing loss. Neuroreport 16, 463–467. Sharma, A., Dorman, M.F., Spahr, A.J., 2002a. A sensitive period for the development of the central auditory system in children with cochlear implants: implications for age of implantation. Ear Hear. 23, 532–539. Sharma, A., Dorman, M., Spahr, A., Todd, N.W., 2002b. Early cochlear implantation in children allows normal development of central auditory pathways. Ann. Otol. Rhinol. Laryngol. Suppl. 189, 38–41. Silverman, M.S., Clopton, B.M., 1977. Plasticity of binaural interaction. I. Effect of early auditory deprivation. J. Neurophysiol. 40, 1266–1274. Sininger, Y.S., Cone-Wesson, B., 2006. Lateral asymmetry in the ABR of neonates: evidence and mechanisms. Hear. Res. 212, 203–211. Smith, Z.M., Delgutte, B., 2007. Using evoked potentials to match interaural electrode pairs with bilateral cochlear implants. J. Assoc. Res. Otolaryngol. 8, 134–151. Thai-Van, H., Gallego, S., Truy, E., Veuillet, E., Collet, L., 2002. Electrophysiological findings in two bilateral cochlear implant cases: does the duration of deafness affect electrically evoked auditory brain stem responses? Ann. Otol. Rhinol. Laryngol. 111, 1008–1014. Thai-Van, H., Cozma, S., Boutitie, F., Disant, F., Truy, E., Collet, L., 2007. The pattern of auditory brainstem response wave V maturation in cochlear-implanted children. Clin. Neurophysiol. 118, 676–689. Ungan, P., Yagcioglu, S., Ozmen, B., 1997. Interaural delay-dependent changes in the binaural difference potential in cat auditory brainstem response: implications about the origin of the binaural interaction component. Hear. Res. 106, 66–82. Webster, D.B., 1983. A critical period during postnatal auditory development of mice. Int. J. Pediatr. Otorhinolaryngol. 6, 107–118. Zaaroor, M., Starr, A., 1991. Auditory brain-stem evoked potentials in cat after kainic acid induced neuronal loss. I. Superior olivary complex. Electroencephalogr. Clin. Neurophysiol. 80, 422–435.
Hearing Research 233 (2007) 97–107
www.elsevier.com/locate/heares
Research paper
Auditory brainstem activity in children with 9–30 months of bilateral cochlear implant use K.A. Gordon a
a,b,c,*
, J. Valero a, B.C. Papsin
a,b
Cochlear Implant Laboratory, The Hospital for Sick Children, Room 6D08, 555 University Avenue, Toronto, ON, Canada M5G 1X8 b The Department of Otolaryngology-Head and Neck Surgery, University of Toronto, ON, Canada M5G 2N2 c Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada M5S 1A8 Received 2 May 2007; received in revised form 29 July 2007; accepted 1 August 2007 Available online 9 August 2007
Abstract Bilateral cochlear implants aim to restore binaural processing along the auditory pathways in children with bilateral deafness. We assessed auditory brainstem activity evoked by single biphasic pulses delivered by an apical or basal electrode from the left, right and both cochlear implants in 13 children. Repeated measures were made over the first 9–30 months of bilateral implant use. In children with short or long periods of unilateral implant use prior to the second implantation, Wave eV of the auditory brainstem response was initially prolonged when evoked by the naı¨ve versus experienced side. These differences tended to resolve in children first implanted <3 years of age but not in children implanted at older ages with long delays between implants. Latency differences were projected to persist for longer periods in children with long delays between implants compared with children with short delays. No differences in right versus left evoked eV latency were found in 2 children receiving bilateral implants simultaneously and their response latencies decreased over time. Binaural interaction responses showed effects of stimulating electrode position (responses were more detectable when evoked by an apical than basal pair of implant electrodes), and duration of delay between implants (measured by latency delays). The trends shown here suggest a negative impact of unilateral implant use on bilateral auditory brainstem plasticity. Ó 2007 Elsevier B.V. All rights reserved. Keywords: Deafness; Auditory brainstem response; Binaural interaction component; Binaural difference response; Evoked potential; Auditory development and plasticity
1. Introduction We assessed auditory brainstem responses in children who were provided with bilateral cochlear implants either simultaneously or sequentially. Based on our previous work in which EABR wave latencies were found to decrease over the first year of implant use (Gordon et al., 2003, 2006, 2007), we expected that: (a) responses evoked by either implant would show latency differences in children implanted sequentially but not simultaneously; (b) *
Corresponding author. Address: Cochlear Implant Laboratory, The Hospital for Sick Children, Room 6D08, 555 University Avenue, Toronto, ON, Canada M5G 1X8. Tel.: +1 416 813 7259 (Main)/6683 (Lab); fax: +1 416 813 5036. E-mail address: [email protected] (K.A. Gordon). 0378-5955/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.heares.2007.08.001
decreases in wave latencies with implant use would occur in ears with <1 year implant experience; and (c) children with long delays between implants would show minimal changes in wave latencies evoked in the experienced ear (>2 years of implant use). Given the importance of relative timing in responses evoked by either ear on the latency of the normal binaural difference wave (Furst et al., 1985; Goksoy et al., 2005; Riedel and Kollmeier, 2006), we also expected that latency differences in wave eV evoked by left versus right cochlear implants in children with long or short delays between implants would be associated with latency delays in electrically evoked binaural difference responses. Central auditory development can be promoted with consistent use of a single cochlear implant in children with
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early onset deafness. Using electrophysiological responses, we have shown that wave latencies and interwave latencies decrease with implant use in such children (Gordon et al., 2003, 2005, 2006) reflecting activity-dependent processes which may include myelination and/or improvements in synaptic efficacy (Eggermont, 1988). These changes appear to occur at many levels of the auditory pathways including the auditory nerve, brainstem, thalamus and cortex as shown by decreasing wave latencies in early, middle and later latency responses (Gordon et al., 2005, 2006; Sharma et al., 2002b; Thai-Van et al., 2007). Although there may be subtle differences in the timing between the waves as compared to normal responses, responses in the rostral portion of the brainstem show similar degrees of latency decrease as occur in normal development (Gordon et al., 2006). The time course of these changes are thought to be the same (Thai-Van et al., 2007) or slightly shorter than normal (Gordon et al., 2006). Our data suggests that latency decreases in the electrically evoked auditory brainstem response (EABR) are largely complete by the end of the first year of implant use (Gordon et al., 2006). If latency decreases are dependent upon evoked activity, we would expect that EABRs evoked by the non-stimulated ear would not change in latency. Children receiving a second cochlear implant after a period of unilateral implant use should thus show prolonged EABR wave latencies evoked by the naive ear relative to responses evoked by the experienced ear. In a recent report, we show that this is true; at initial stages of bilateral implant use, response latencies evoked in the newly implanted ear were later than in responses evoked by the more experienced ear and similar to latencies evoked at initial implant use in agematched unilateral implant users (Gordon et al., 2007). In contrast, children receiving bilateral cochlear implants simultaneously did not show a mean latency difference in responses evoked from either side. In the present study, we assess results from 13 children followed for at least 9 months after bilateral implantation. Based on the time course of EABR latency changes shown in unilateral implant users, we expected that ears with greater than 1 year of implant experience would show little change in latency. We also expected that the time for differences between the ears to resolve would be dependent upon the duration of delay between the first and second implants and on the age of the child at the time of first implant. Although behavioral and cortical measures of auditory development after cochlear implantation have been shown to be related to the age at implantation (Connor et al., 2006; Gordon et al., 2005; Harrison et al., 2005; Sharma et al., 2002a), there appears to be little influence of age at implantation on EABR latency changes after unilateral cochlear implantation (Gordon et al., 2003, 2006; ThaiVan et al., 2007). We hypothesize that, for children with early onset deafness, the lack of age effect is a result of bilateral auditory deprivation of the auditory brainstem in the period prior to implantation. Whereas the deaf auditory cortex is susceptible to reorganization promoted by
input from other sensory systems including the somatosensory and visual systems (Doucet et al., 2006; Giraud et al., 2001; Lee et al., 2001), the auditory brainstem pathways receive little input from other sensory modalities thus limiting the potential for this ‘‘cross-modal’’ plasticity. In the absence of significant input, development of the auditory brainstem, including the sensitive period of development, may be arrested. If true, unilateral implant use would promote auditory brainstem development thus reinitiating a sensitive period. It is not clear, however, to what extent human auditory brainstem development is altered by unilateral (as compared to bilateral) input. Evidence from animal models suggests that a lack of binaural input during development results in extensive reorganization of the auditory brainstem pathways; connections from the cochlear nucleus to the ipsilateral inferior colliculus (IC) increase and connections to the contralateral inferior colliculus decrease (Illing et al., 1999; Nordeen et al., 1983). These changes are thought to result from a lack of competition from one side in brainstem nuclei which would normally receive inputs from either ear (Silverman and Clopton, 1977). Pathway reorganization in the brainstem is likely to affect more central areas of the auditory system. Indeed differences in cortical responses, reflecting altered patterns of response, have been shown in both adults and children with unilateral hearing loss (Ponton et al., 2001; Schmithorst et al., 2005). It is possible then that unilateral stimulation from a cochlear implant promotes reorganization of the auditory pathways during a sensitive period in development and that these changes might be difficult to reverse once the sensitive period is over. Based on our findings that the auditory brainstem response is largely mature after 1 year of unilateral cochlear implant use (Gordon et al., 2006), we hypothesized that children with long periods of unilateral cochlear implant use (>2 years) prior to receiving a second implant would be less likely to show developmental changes in the auditory brainstem (as measured by EABR) than children with shorter (<1 year) or no delays between implants. Any limitation in development of the second ear might compromise the ability of the two ears to integrate information and this was examined using electrophysiological measures. Evidence from normally hearing children and adults indicate that auditory brainstem responses evoked by binaural stimulation show amplitude and latency changes compared with the summation of responses evoked by each ear independently. This difference between the binaural and summated responses is typically plotted over the recording interval and referred to as the binaural difference (BD) response or binaural interaction component (BIC). The underlying mechanism for this phenomenon has been proposed to involve binaural processes in the superior olivary complex (Goksoy et al., 2005; McPherson and Starr, 1993; Melcher, 1996; Riedel and Kollmeier, 2006; Zaaroor and Starr, 1991). Interaural timing and level changes appear to affect both the latency and amplitude of the difference waveform (Furst et al., 1985; Riedel and
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1, all children used nucleus cochlear implants bilaterally and all had early onset deafness. None of the children showed any developmental delays. All were in auditory verbal therapy programs after bilateral implantation and wore their devices consistently.
Kollmeier, 2006; Ungan et al., 1997) correlating with psychophysical measures of sound lateralization (Furst et al., 1985, 1990, 1995, 2000). A similar response has now been shown in response to electrical stimulation from independent cochlear implants in cats (Smith and Delgutte, 2007) and we have demonstrated that it can also be recorded in children using bilateral implants (Gordon et al., 2007). In that paper, we showed that the binaural difference response of the EABR, measured at the first day of bilateral implant activation, is delayed in latency (relative to the latency of wave eV evoked by the ear first implanted) in children with long or short delays between implants but not in children who receive simultaneous bilateral implants (Gordon et al., 2007). In the present study, we show results from children with longer term bilateral implant use to assess the presence and parameters of the binaural interaction response.
2.2. Electrophysiological recordings Our parameters for recording electrically evoked auditory brainstem responses have been reported previously (Gordon et al., 2006, 2007). Briefly, we recorded evoked potential responses at center midline of the head (Cz) referenced to both earlobes [recording channel A1 (left earlobe) and A2 (right earlobe)] with a ground on the forehead using a NeuroScan Synamps and Scan 4.3 software. Single biphasic monopolar electrical pulses were delivered at 11 Hz from the left implant or the right implant, or from both simultaneously using the SPEAR processor and software developed by Dr. Richard van Hoesel, CRC-HEAR, Melbourne, Australia. This software allows precise control of timing of stimulation provided to the two cochlear implants but was not available at initial stages of device use for most of the 13 children included in this study. Prior to use of the SPEAR processor and software, the same stimuli presentation was directed to the left or right implants using Cochlear Corporation WinDPS (for N24M, RCS and CA devices) and/or Custom Sound EP (for N24RE devices) software. This meant that binaural interaction responses could not be measured in many of the children until they had had at least 3 months of bilateral implant experience. Pulses were delivered from an apical (#20) and a basal (#3) implant electrode in all children. Stimulation levels were increased to a level at which the electrophysiological response was clear and the child remained comfortable. Levels were kept constant from the first day of device activation through subsequent recording sessions. Children were not sedated and sat alone or on a parent/caregiver’s lap. They were kept occupied
2. Material and methods 2.1. Subjects Of the children receiving bilateral cochlear implants in our center, 13 children have been followed for at least 9 months. All children and/or families consented to participate in this study as approved by the Hospital for Sick Children’s Research Ethics Board which adheres to the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans. Two children received bilateral cochlear implants simultaneously at young ages (1.0 year and 1.8 years). Eight of the children were initially implanted at ages <3 years in the right ear (mean 1.23 ± 0.43 years) and then received an implant in the left ear after a long (n = 3, mean 3.54 ± 1.47 years) or short (n = 5, mean 0.76 ± 0.13 years) delay. Three children received their first implant in the right ear at older ages (mean 4.37 ± 0.85 years) and were implanted in the left ear after a long delay (mean 5.50 ± 0.19 years). As detailed in Table
Table 1 Demographic information Patient
Onset of HL
Etiology
Age at activation 1st Implant
Simultaneous 1 Simultaneous 2 Short Delay 1 Short Delay 2 Short Delay 3 Short Delay 4 Short Delay 5 Long Delay 1 Long Delay 2 Long Delay 3 Older Long 1
Congenital Congenital Congenital Congenital Congenital Congenital Congenital Congenital Congenital Congenital Congenital
Older Long 2 Older Long 3
Congenital Congenital
Connexin 26 Unknown Connexin 26 Connexin 26 Usher’s syndrome Unknown Unknown Unknown Unknown Connexin 26 Connexin 26 Heterozygote Unknown Connexin 26
Ear (1st Implant)
2nd Implant
Device Right
Left
Duration of bilateral CI use (months)
1.1 1.7 0.8 1 0.8 1.3 2 0.9 1.4 1.7 4
1.1 1.7 1.7 1.8 1.6 2.2 2.7 3.8 3.9 6.1 9.6
Right Right Right Right Right Right Right Right Right Right Right
N24RE N24RE N24CA N24CA N24CA N24CA N24CA N24RSC N24RCS N24M N24M
N24RE N24RE N24RE N24RE N24RE N24RE N24RE N24CA N24CA N24CA N24CA
15 15 12 15 9 15 15 30 30 24 30
5.4 4
10.8 9.5
Right Right
N24M N24M
N24CA N24CA
24 18
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throughout the test by a second tester and/or by watching a movie. The same recordings were completed in 5 children (Short Delay 1, Short Delay 3, Long Delay 3, Older Long Delay 2, Older Long Delay 3) at some point(s) during their period of unilateral N24M or RCS use. Data collection was the same; monopolar biphasic pulses were presented at 11 Hz from an apical (#20) and basal (#3) electrode at comfortably loud levels and recorded using the same equipment, recording montage and parameters. A prior version of NeuroScan software (version 4.0) was used with the same amplifier and other hardware. 2.3. Analyses Because changes in wave eV with implant use are likely due to neurological rather than peripheral changes (ThaiVan et al., 2007), we focused on this wave for the purpose of the present paper. The amplitude peak of wave eV was marked using Matlab 6.5.2 (The Mathworks, Natick, MA) by an observer blinded to the patient, stimulating electrode, and duration of bilateral implant use. Extreme outliers were remeasured. Linear regression analyses were completed using SPSS 14.0. 3. Results 3.1. Comparisons of responses evoked by each implant over time Results evoked by individual implants are shown for each child in Figs. 1 and 2. Responses from the simultaneous bilateral implant group (n = 2) and the short delay group (n = 5) are included in Fig. 1. Responses from children with long delays are shown in Fig. 2; children first implanted at young ages (<3 years; n = 3) are delineated from children who received their first implant at older ages (n = 3). Data from each group are combined in Fig. 3. Figs. 1 and 2 show waveforms evoked by the apical implant electrode in either implant (from the recording channel in which the ipsilateral earlobe was used as reference) in each child at each recording session. A plot of wave eV latency for each response is shown to the right for each set of waveforms. As shown in Fig. 1, the 2 children who received simultaneous bilateral cochlear implants had very similar eV latencies at device activation. Latencies in both ears decreased in both children over time although the eV latency evoked by Simultaneous 2’s left implant seemed to remain fixed through months 3–12. The 5 children implanted at young ages with the first implant in the right ear and then with the second after a short delay of unilateral implant use are also shown in Fig. 1. Data was available from the first implanted ear (right) at initial stages of unilateral implant use in Short Delay 1 and 3. In these 2 children, the right ear response showed decreases in eV latency over the first months of unilateral implant use and only subtle latency changes thereafter. Similarly the
other 3 children in this group showed only small changes in wave eV evoked by the experienced ear over the period of bilateral implant use. Responses evoked from the newly implanted left side were initially prolonged relative to the more experienced right side in 4 of the 5 children (left and right evoked latencies were similar in Short Delay 3). With bilateral implant use, 4 of the 5 children showed clear changes in eV latency evoked by the left device during this time (Short Delay 5 did not show eV changes over time in responses evoked by either implant). Interestingly, Short Delay 2 showed large initial response differences between sides as compared with the other children. In this child, despite clear decreases in eV latency evoked in the left ear, response latency differences between the ears were not resolved even after a year of bilateral implant use. Fig. 2 displays the same data from children who had long delays between implants; 3 children received their first implants at young ages (<3 years) and 3 received their implants at older ages (P4 years). In the former group of children (long delay group), wave eV latency changed very little when evoked in the right (experienced) ear. Responses from the newly implanted left ear decreased in latency from initial values but little thereafter in Long Delay 1 and 2. Long Delay 3 showed the smallest difference between ears at initial bilateral activation and over time of bilateral implant use. Interestingly, that child also demonstrated small changes in response latencies evoked by the first implant over the first year of unilateral implant use. In the children who were implanted in the right ear at ages P4 years and who also had long periods of unilateral use before receiving the second implant (older long delay group), wave eV latency did not appear to change in responses evoked by either ear and latency differences between the ears remained with ongoing bilateral implant use. Data for Older Long Delay 3 over the first year of unilateral implant use was available and indicates a clear decrease over time in contrast to the lack of change noted on the left side during the first 2 years of bilateral implant use. Group trends for responses evoked by the apical and basal implant electrode are shown in Fig. 3. Wave eV latency data from the ipsilateral recording electrode in both right and left evoked responses are plotted with respect to duration of bilateral implant use for each group. The linear regression lines indicate different patterns of latency change in each group confirming the trends noted in the individual data shown in Figs. 1 and 2. These analyses suggest that children receiving simultaneous bilateral implants tend to have similar wave eV latencies in responses evoked by either ear which decrease with ongoing bilateral implant use. Latencies in the experienced ear show small changes in children having short periods (6–12 months) of unilateral use but little change in children with longer durations of unilateral use (>2 years). Responses in the newly implanted ear were prolonged relative to the experienced ear at early stages of bilateral implant use in all groups of children receiving sequential bilateral implants. This difference is projected by linear regression to resolve in the children with
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Fig. 1. Auditory brainstem responses evoked by the apical electrode in the right and left cochlear implants in 2 children who received simultaneous bilateral implants and 5 children who used a unilateral implant in the right ear for a short period prior to implantation of the left ear. Wave eV latencies are indicated by the dashed lines over the period of bilateral implant use and plotted for each child. Responses recorded during the period of unilateral implant use are shown for children referred to as Short Delay 1 and 3. D = day, M = month, U = unilateral.
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Fig. 2. Auditory brainstem responses evoked by the apical electrode in the right and left cochlear implants in 6 children who received a cochlear implant in the left ear after a long period of unilateral implant use in the right; 3 were first implanted at young ages < 3 years (long delay group) and 3 at older ages (older long delay group). Wave eV latencies are indicated by the dashed lines over the period of bilateral implant use and plotted for each child. Responses recorded during the period of unilateral implant use are shown for children referred to as Long Delay 3 and Older Long Delay 3. D = day, M = month, U = unilateral.
short delays by approximately 1.5–2.0 years whereas differences in children with long delays are predicted to take longer than 2.5 years. Children provided with their first implant at ages >3 years and who had long delays between implants show no trend toward a decrease in the difference between ears. 3.2. Binaural difference responses The binaural difference response was calculated by addP ing the responses evoked by either implant [ (L + R)] and then subtracting the binaurally evoked response from this sum. Three examples of this process are shown in Fig. 4. These are responses from the child named Simultaneous 1 after 15 months of simultaneous implant use, from Short Delay 1 after 12 months of bilateral use (in addition to 9
previous months of unilateral use on the right side) and from Older Long Delay 1 after 30 months of bilateral implant use (sequentially implanted after a period of 5 years of unilateral use on the right side). In all three examples, a clear difference wave can be observed in both recording channels. Fig. 5 shows the most recent binaural difference waves for each child evoked by apical and basal electrode pairs. The detectability of the interaction response was better when evoked by apical electrodes (present in 11 of 13 children) compared to the basal electrode (present in only 6 of the 13 children). The incidence of the interaction response by group is shown in Table 2. As indicated in Table 2, the interaction response evoked by the pair of apical implant electrodes tends to increase in latency (relative to the right ear) as the duration of delay increases.
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Fig. 3. Wave eV latencies evoked by the right and left implants are plotted over duration of bilateral implant use for each group. On the left are plotted response latencies evoked by apical implant electrodes and on the right are response latencies evoked by basal implant electrodes. Linear regression lines and associated Pearson co-efficient are shown.
Fig. 4. Responses evoked from the apical electrodes in either implant and both implants simultaneously from 3 children are shown. The binaural P interaction response was calculated by adding the responses evoked by either implant [ (L + R)] (shown by dashed lines) and subtracting the binaurally evoked response from this sum. A clear difference wave can be observed in both recording channels in all three examples.
4. Discussion 4.1. Differences in response latencies evoked in either ear As predicted, auditory brainstem response latencies evoked from chronically stimulated ears were found to be shorter than those evoked from naı¨ve ears. This was shown in most of the individual data sets in Figs. 1 and 2. A similar finding was initially noted by Thai-Van and colleagues in two children receiving sequential bilateral cochlear implants (Thai-Van et al., 2002) and we recently confirmed it in a systematic and controlled group study of responses recorded at initial stages of bilateral implant use (Gordon et al., 2007). In that report, we showed that the latency dif-
ferences between ears were not present at initial device activation in the group of children who received simultaneously implanted bilateral cochlear implants. The differences in response latencies evoked by either implant shown in both the previous and present studies span up to 0.65 ms which is considerably larger than differences in responses evoked by left versus right ears in normal neonates (0.051–0.070 ms) as reported by Sininger and ConeWesson (2006). We previously showed that there was no statistical difference between responses evoked by the naı¨ve ears of bilateral users and those from the naı¨ve ears in agematched unilateral controls. This finding further confirms that brainstem development reflected by decreasing EABR latencies is dependent upon activity. In the absence of
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Fig. 5. Binaural difference waves calculated in each child after at least 9 months of bilateral implant use are shown. Detectable responses observed in both recording channels are indicated by arrows. Further details are provided in Table 2.
Table 2 Incidence and latency of binaural interaction responses
Simultaneous Short Delay Long Delay Older Long Delay
Duration of BI use (months)
Apical electrode Incidence of BIC
Latency of BIC (ms)
Incidence of BIC
Latency of BIC (ms)
12 ± 4 12 ± 3 28 ± 3 24 ± 6
2/2 5/5 2/3 2/3
0.09 ± 0.00 0.07 ± 0.22 0.15 ± 0.07 0.35 ± 0.35
2/2 1/5 2/3 1/3
0.32 ± 0.11 0.45 0.10 ± 0.07 0.55
significant input, latencies remain delayed suggesting a relative immaturity of the auditory brainstem as evoked in a newly implanted ear. The functional implications of this
Basal electrode
abnormal disparity in response timing between implanted ears are not known. It is possible that these ‘‘internal’’ interaural time differences disrupt or add to ‘‘external’’
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interaural timing differences which are normally used to localize low frequency sounds. If true, children receiving sequential bilateral implants might not be able to use timing cues effectively or accurately for sound localization at initial stages of device use even if both devices functioned in perfect synchrony. Because bilateral cochlear implants presently consist of two individual devices each with their own internal and external components, the timing of inter-implant stimulation cannot be controlled. The lack of co-ordination of stimulation provided by the two electrode arrays might further add to difficulties in perceiving interaural timing differences. In this study, we addressed the potential for the initial ‘‘internal’’ interaural timing differences to resolve with ongoing bilateral implant use. Trends shown in Fig. 3 suggest that the experienced ear in children receiving sequential bilateral implants changes very little after bilateral implantation. This was expected given that maturation of the auditory brainstem in children using a single cochlear implant is largely complete by 6–12 months of implant use (Gordon et al., 2006). The very slight decrease in wave eV latencies in children who had 6–12 months of unilateral implant use is further evidence of this developmental time course. Wave eV latencies evoked by the newly implanted ear showed different trends for each group over time of bilateral implant use. While eV latency appeared to decrease with bilateral implant use in children with short delays between implants, children with long delays between implants showed trends for a slower rate of change (when the first implant was at a young age) or very little change (for children who received their first implant at older ages). This reflects a change in developmental plasticity in children with long term unilateral implant use at the level of the auditory brainstem. These early trends are an interesting departure from our previous findings in which the brainstem’s ability to change upon unilateral implant use as measured by decreasing wave latencies showed no age dependency (Gordon et al., 2003, 2006). This has been recently confirmed (Thai-Van et al., 2007) and suggests that any changes occurring in the auditory brainstem during the period of bilateral deprivation are small compared to the significant changes promoted by implant stimulation. In contrast, the trends shown in the present study suggest that the maturation of the brainstem from stimulation on one side either restricts or changes the course of maturation evoked by the second side. Recent evidence suggests that limitations to auditory development after cochlear implantation is the result of competition from other modalities; ‘‘cross-modal’’ plasticity has been implicated in reorganization of the auditory cortex during the period of deafness (Lee et al., 2001) and is thought to restrict the ability of auditory activity, stimulated by cochlear implant use, to reestablish normal cortical connections. The auditory cortex appears to be vulnerable to inputs carrying visual (Fine et al., 2005; Lambertz et al., 2005) or perhaps other sensory information.
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The auditory brainstem is likely less vulnerable to competition from non-auditory projections as it primarily receives inputs from either ear. Thus, in the absence of bilateral input, there is little to promote activity-dependent processes in the auditory brainstem which likely accounts for the similarity in evoked potentials in children with early onset bilateral deafness regardless of the duration of deafness (Gordon et al., 2003). Once stimulation is provided from one ear, however, processes requiring activity can be initiated and there may be implications of this unbalanced activity in the auditory brainstem. Animal models with experimentally induced unilateral cochlear lesions suggest that one stimulated ear can dominate brainstem development at the expense of pathways innervating the other side. Without competition from one side during development, there is an expansion of excitatory projections from the ipsilateral cochlear nucleus to the ipsilateral IC (Nordeen et al., 1983) and a loss of binaural activity in the ipsilateral IC (Silverman and Clopton, 1977). The contralateral IC receives an expansion of projections from the ipsilateral cochlear nucleus (Nordeen et al., 1983) and demonstrates increased inhibitory activity (Silverman and Clopton, 1977). Unilateral loss induced in mature animals does not yield similar effects as in younger animals. There was no effect of unilateral hearing loss on connections to the IC if the onset of the loss occurred after 60 days in cats (Clopton and Silverman, 1977) and no effect on cell size in brainstem nuclei in CBJ/A mice if the unilateral loss did not include all or part of a range of post-natal development days (12–24 days) (Webster, 1983). It is thus possible that unilateral cochlear implant use in children with early onset deafness not only strengthens connections innervating that ear but also allows for abnormal expansion of these connections. The trends shown in the present study require statistical validation (which will be done once we have followed sufficient numbers of children using bilateral implants over the long term). If confirmed, these trends would suggest that, like the animal data, there is a period of unilateral deprivation in early development after which auditory plasticity is altered. We expected that bilateral auditory development would proceed in children receiving two cochlear implants simultaneously at young ages. Indeed, responses from the 2 children in this group, shown in Fig. 1, indicate a decrease in latency in both ears with ongoing bilateral implant use suggestive of developmental changes in the auditory brainstem. Interestingly, these changes are very similar when evoked from either ear in the child named Simultaneous 1. On the other hand, responses evoked in Simultaneous 2’s left ear showed a period of some months in which no changes were realized while the right ear responses showed regular decreases in latency over time. This suggests that in young children receiving simultaneous bilateral implants: (a) there is some independence between pathways which respond to right versus left implant stimulation and (b) effects of deafness or activity-dependent developmental processes may not necessarily be uniform between ears.
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Independence of the ears may be of benefit during development as suggested by Sininger and Cone-Wesson (2006). 4.2. Binaural interaction responses We have previously shown that binaural difference responses are present at initial stages of bilateral cochlear implantation in children (Gordon et al., 2007). These responses show unexpected delays in latency relative to the first implanted ear in children receiving the second implant after a long or short period of unilateral implant use but are similar in latency to responses evoked by either implant in children receiving simultaneous bilateral implants. In that report, we also showed that binaural interaction responses were more likely to be detected when evoked by apical versus basal implant electrode stimulation. Very similar findings were seen in the binaural responses measured after at least 9 months of bilateral implant use. As shown in Fig. 5, the interaction responses were more likely evoked by a pair of apical electrodes than a pair of basal electrodes. This reflects weaker or absent interaction between neurons stimulated by a pair of basal electrodes. This could be explained by peripheral factors which influence the spread of current differently in the base relative to more apical areas of the cochlea and/or to differences in neural integrity along the cochlea. This could also be explained by potential maturational changes in binaural processing evoked by stimulation from basal ends of the cochlea. The ability to record binaural difference components using high versus low frequency acoustic stimuli is not impaired in normal hearing adults (Polyakov and Pratt, 1999) or neonates, however, there might be an amplitude change with age. High versus low frequency stimuli evoke larger amplitude difference components in adults (Polyakov and Pratt, 1999) and smaller amplitudes in neonates (Cone-Wesson et al., 1997). If immaturity underlies the poor detectability of binaural difference responses evoked by the basal electrode, we would expect in future studies to find an improvement in detectability with chronic bilateral cochlear implant use. As for the latencies of the apically evoked interaction response, the data shown in Table 2 indicate that these responses are prolonged relative to responses from the experienced ear (right ear) in children who receive bilateral implants after a long period of unilateral implant use (0.15 ± 0.07 ms for long delay group and 0.35 ± 0.35 ms in the older long delay group) despite significant bilateral implant use (at least 12 months). This is consistent with a lack or slow rate of change in response latencies evoked by either ear in these groups of children. The association between delayed latencies of binaural interaction responses and function in cochlear implant users are as yet unknown, however, latency increases in the binaural interaction response have been shown to occur when interaural timing and level differences are increased in normal hearing adults (Furst et al., 1985; Riedel and Kollmeier, 2006) and infants (Furst et al., 2004). Thus, the latencies of the binaural
interaction responses might also support the presence of an ‘‘internal’’ interaural timing difference between auditory brainstem activity evoked by one implant relative to the other. Children receiving simultaneous bilateral implants and those with only short delays between implants showed binaural responses more similar to latencies of the right ear (0.09 ± 0.00 ms for the simultaneous group and 0.07 0.22 ms in the short delay group) after many months of bilateral implant use. It is therefore possible that, after chronic bilateral stimulation, interaural timing cues may be more accurately processed in the auditory brainstem in these children. Further analyses of how the binaural difference responses change with bilateral implant use might provide insight into the development of binaural processing in the auditory brainstem. 5. Conclusions The early findings of auditory brainstem plasticity evoked by chronic bilateral electrical stimulation in children with early onset deafness suggest a negative impact of a period of unilateral implant use. Short delays between implants appeared to be less restrictive to development of pathways innervated by the second ear than long delays, however, the time course of development may be prolonged relative to that promoted by the first implant. Binaural interaction responses were present in children receiving bilateral cochlear implants simultaneously or sequentially but were more detectable when evoked by a pair of apical implant electrodes than a pair located at the basal end in the latter group. The data shown here suggests a trend toward increased latency delay of the binaural interaction response in children with long versus short periods of unilateral implant use prior to implantation of the second ear. Simultaneous bilateral implantation, on the other hand, resulted in evoked potential responses of similar latency when evoked by either implant, decreases in response latency with bilateral implant use, and binaural interaction response of expected latencies. Acknowledgements We acknowledge grant support provided by the Canadian Institutes of Health Research and the SickKids Foundation and our collaboration with Dr. Richard van Hoesel. We also thank the children and their families for their contributions of time and effort. References Clopton, B.M., Silverman, M.S., 1977. Plasticity of binaural interaction. II. Critical period and changes in midline response. J. Neurophysiol. 40, 1275–1280. Cone-Wesson, B., Ma, E., Fowler, C.G., 1997. Effect of stimulus level and frequency on ABR and MLR binaural interaction in human neonates. Hear. Res. 106, 163–178. Connor, C.M., Craig, H.K., Raudenbush, S.W., Heavner, K., Zwolan, T.A., 2006. The age at which young deaf children receive cochlear
K.A. Gordon et al. / Hearing Research 233 (2007) 97–107 implants and their vocabulary and speech-production growth: is there an added value for early implantation? Ear Hear. 27, 628–644. Doucet, M.E., Bergeron, F., Lassonde, M., Ferron, P., Lepore, F., 2006. Cross-modal reorganization and speech perception in cochlear implant users. Brain 129, 3376–3383. Eggermont, J.J., 1988. On the rate of maturation of sensory evoked potentials. Electroencephalogr. Clin. Neurophysiol. 70, 293–305. Fine, I., Finney, E.M., Boynton, G.M., Dobkins, K.R., 2005. Comparing the effects of auditory deprivation and sign language within the auditory and visual cortex. J. Cogn. Neurosci. 17, 1621–1637. Furst, M., Levine, R.A., McGaffigan, P.M., 1985. Click lateralization is related to the beta component of the dichotic brainstem auditory evoked potentials of human subjects. J. Acoust. Soc. Am. 78, 1644–1651. Furst, M., Eyal, S., Korczyn, A.D., 1990. Prediction of binaural click lateralization by brainstem auditory evoked potentials. Hear. Res. 49, 347–359. Furst, M., Levine, R.A., Korczyn, A.D., Fullerton, B.C., Tadmor, R., Algom, D., 1995. Brainstem lesions and click lateralization in patients with multiple sclerosis. Hear. Res. 82, 109–124. Furst, M., Aharonson, V., Levine, R.A., Fullerton, B.C., Tadmor, R., Pratt, H., Polyakov, A., Korczyn, A.D., 2000. Sound lateralization and interaural discrimination. Effects of brainstem infarcts and multiple sclerosis lesions. Hear. Res. 143, 29–42. Furst, M., Bresloff, I., Levine, R.A., Merlob, P.L., Attias, J.J., 2004. Interaural time coincidence detectors are present at birth: evidence from binaural interaction. Hear. Res. 187, 63–72. Giraud, A.L., Price, C.J., Graham, J.M., Truy, E., Frackowiak, R.S., 2001. Cross-modal plasticity underpins language recovery after cochlear implantation. Neuron 30, 657–663. Goksoy, C., Demirtas, S., Yagcioglu, S., Ungan, P., 2005. Interaural delay-dependent changes in the binaural interaction component of the guinea pig brainstem responses. Brain Res. 1054, 183–191. Gordon, K.A., Papsin, B.C., Harrison, R.V., 2003. Activity-dependent developmental plasticity of the auditory brainstem in children who use cochlear implants. Ear Hear. 24, 485–500. Gordon, K.A., Papsin, B.C., Harrison, R.V., 2005. Effects of cochlear implant use on the electrically evoked middle latency response in children. Hear. Res. 204, 78–89. Gordon, K.A., Papsin, B.C., Harrison, R.V., 2006. An evoked potential study of the developmental time course of the auditory nerve and brainstem in children using cochlear implants. Audiol. Neurootol. 11, 7–23. Gordon, K., Valero, J., Papsin, B.C., 2007. Binaural processing in children using bilateral cochlear implants. Neuroreport 18, 613–618. Harrison, R.V., Gordon, K.A., Mount, R.J., 2005. Is there a critical period for cochlear implantation in congenitally deaf children? Analyses of hearing and speech perception performance after implantation. Dev. Psychobiol. 46, 252–261. Illing, R.B., Cao, Q.L., Forster, C.R., Laszig, R., 1999. Auditory brainstem: development and plasticity of GAP-43 mRNA expression in the rat. J. Comp. Neurol. 412, 353–372. Lambertz, N., Gizewski, E.R., de Greiff, A., Forsting, M., 2005. Crossmodal plasticity in deaf subjects dependent on the extent of hearing loss. Brain Res. Cogn. Brain Res. 25, 884–890.
107
Lee, D.S., Lee, J.S., Oh, S.H., Kim, S.-K., Kim, J.-W., Chung, J.-K., Lee, M.C., Kim, C.S., 2001. Deafness: cross-modal plasticity and cochlear implants. Nature 409, 149–150. McPherson, D.L., Starr, A., 1993. Binaural interaction in auditory evoked potentials: brainstem, middle- and long-latency components. Hear. Res. 66, 91–98. Melcher, J.R., 1996. Cellular generators of the binaural difference potential in cat. Hear. Res. 95, 144–160. Nordeen, K.W., Killackey, H.P., Kitzes, L.M., 1983. Ascending projections to the inferior colliculus following unilateral cochlear ablation in the neonatal gerbil, Meriones unguiculatus. J. Comp. Neurol. 214, 144– 153. Polyakov, A., Pratt, H., 1999. Contribution of click frequency bands to the human binaural interaction components. Audiology 38, 321–327. Ponton, C.W., Vasama, J.P., Tremblay, K., Khosla, D., Kwong, B., Don, M., 2001. Plasticity in the adult human central auditory system: evidence from late-onset profound unilateral deafness. Hear. Res. 154, 32–44. Riedel, H., Kollmeier, B., 2006. Interaural delay-dependent changes in the binaural difference potential of the human auditory brain stem response. Hear. Res. 218, 5–19. Schmithorst, V.J., Holland, S.K., Ret, J., Duggins, A., Arjmand, E., Greinwald, J., 2005. Cortical reorganization in children with unilateral sensorineural hearing loss. Neuroreport 16, 463–467. Sharma, A., Dorman, M.F., Spahr, A.J., 2002a. A sensitive period for the development of the central auditory system in children with cochlear implants: implications for age of implantation. Ear Hear. 23, 532–539. Sharma, A., Dorman, M., Spahr, A., Todd, N.W., 2002b. Early cochlear implantation in children allows normal development of central auditory pathways. Ann. Otol. Rhinol. Laryngol. Suppl. 189, 38–41. Silverman, M.S., Clopton, B.M., 1977. Plasticity of binaural interaction. I. Effect of early auditory deprivation. J. Neurophysiol. 40, 1266–1274. Sininger, Y.S., Cone-Wesson, B., 2006. Lateral asymmetry in the ABR of neonates: evidence and mechanisms. Hear. Res. 212, 203–211. Smith, Z.M., Delgutte, B., 2007. Using evoked potentials to match interaural electrode pairs with bilateral cochlear implants. J. Assoc. Res. Otolaryngol. 8, 134–151. Thai-Van, H., Gallego, S., Truy, E., Veuillet, E., Collet, L., 2002. Electrophysiological findings in two bilateral cochlear implant cases: does the duration of deafness affect electrically evoked auditory brain stem responses? Ann. Otol. Rhinol. Laryngol. 111, 1008–1014. Thai-Van, H., Cozma, S., Boutitie, F., Disant, F., Truy, E., Collet, L., 2007. The pattern of auditory brainstem response wave V maturation in cochlear-implanted children. Clin. Neurophysiol. 118, 676–689. Ungan, P., Yagcioglu, S., Ozmen, B., 1997. Interaural delay-dependent changes in the binaural difference potential in cat auditory brainstem response: implications about the origin of the binaural interaction component. Hear. Res. 106, 66–82. Webster, D.B., 1983. A critical period during postnatal auditory development of mice. Int. J. Pediatr. Otorhinolaryngol. 6, 107–118. Zaaroor, M., Starr, A., 1991. Auditory brain-stem evoked potentials in cat after kainic acid induced neuronal loss. I. Superior olivary complex. Electroencephalogr. Clin. Neurophysiol. 80, 422–435.