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Cortical Plasticity and Reorganization in Pediatric Single-sided Deafness Pre- and Postcochlear Implantation: A Case Study

Sharma, Anu*; Glick, Hannah*,†; Campbell, Julia*,†; Torres, Jennifer; Dorman, Michael; Zeitler, Daniel M.§

doi: 10.1097/MAO.0000000000000904
NASHVILLE CI PAPERS

Hypothesis: The purpose of this study was to examine changes in cortical development and neuroplasticity in a child with single-sided deafness (SSD) before and after cochlear implantation (CI).

Background: The extent to which sensory pathways reorganize in childhood SSD is not well understood and there is currently little evidence demonstrating the efficacy of CI in children with SSD.

Methods: High-density 128-channel electroencephalography (EEG) was used to collect cortical auditory evoked potentials (CAEP), cortical visual evoked potentials (CVEP), and cortical somatosensory evoked potentials (CSSEP) in a child with SSD, pre-CI and at subsequent sessions until approximately 3 years post-CI in her right ear which occurred at age 9.86 years. Behavioral correlates of speech perception and sound localization were also measured.

Results: Pre-CI, high-density EEG showed evidence of delayed auditory cortical response morphology, auditory cortical development strongly contralateral (to the normal hearing ear), evidence of increased cognitive load, and cross-modal reorganization by the visual and somatosensory modalities. The post-CI developmental trajectory provided clear evidence of age-appropriate development of auditory cortical responses, and decreased cross-modal reorganization, consistent with improved speech perception and sound localization.

Conclusion: Post-CI, the child demonstrated age-appropriate auditory cortical development and improved speech perception and sound localization suggestive of significant benefits from cochlear implantation. Reversal of somatosensory recruitment was clearly apparent, and only a residual amount of visual cross-modal plasticity remained postimplantation. Overall, our results suggest that CI in pediatric SSD patients may benefit from a highly plastic cortex in childhood.

*Department of Speech, Language, and Hearing Science and Institute of Cognitive Science, University of Colorado, Boulder

Denver Ear Associates, Englewood, Colorado

Department of Speech and Hearing Science, Arizona State University, Tempe, Arizona

§Virginia Mason Medical Center, Seattle, Washington, U.S.A.

Address correspondence and reprint requests to Anu Sharma, Ph.D., Department of Speech, Language, and Hearing Science, University of Colorado, 2501 Kittredge Loop Road 409 UCB, Boulder, CO 80309, U.S.A.; E-mail: anu.sharma@colorado.edu

This research was supported by the National Institutes of Health [R01DC006257].

The authors disclose no conflicts of interest.

Single-sided deafness (SSD) refers to normal hearing in one ear and a severe-profound sensorineural hearing loss in the contralateral ear. The prevalence of unilateral hearing loss (UHL) is estimated to affect between 3 and 8.3% of the general population, with the incidence increasing as children progress to adolescence (1,2). Individuals with SSD experience difficulties that include sound localization and speech perception in background noise (3–7). In addition, children with UHL are at greater risk for developmental delays in speech and language, educational delays, and behavioral problems, highlighting the need for effective and timely intervention (1).

Treatment options for UHL include hearing aids, contralateral routing of signal (CROS) hearing aids, bone-anchored hearing devices, and frequency-modulated (FM) systems (2). In the case of SSD, success with these devices is limited since adequate amplification allowing for speech perception improvements is not often achievable. Moreover, the ability for true sound localization is not possible with currently available devices. Although FDA approval for cochlear implantion (CI) as a treatment for SSD has not yet been established in the United States, several studies show promising results in adults and children with SSD and other nontraditional implant candidates (i.e., asymmetric hearing loss) (8–14).

In bilaterally deaf children, CI has proven successful when implantation occurs within a sensitive period for central auditory development, wherein the auditory pathways are maximally plastic (15). The benefits of early implantation are sustained by electrophysiological (15–19) and behavioral data (20–22), which demonstrate optimal cortical development and speech and language outcomes in early- compared with late-implanted children.

In the case of bilateral congenital deafness, there is growing evidence that poor outcomes in cochlear implanted patients may be explained by cross-modal reorganization, whereby a sensory modality (i.e., vision and somatosensation) may recruit another sensory system (i.e., audition) as compensation for deficits in the deprived modality (20–30). Such reorganization of cortical auditory areas by other sensory systems may be maladaptive in nature, inhibiting an individual's ability to make use of incoming auditory information via the implant (29). Cross-modal plasticity in the case of SSD has never been documented. Further, it is unknown whether cross-modal changes, if present, are reversible after CI.

The purpose of this study was to examine developmental cortical neuroplasticity in a child with SSD before and after CI. The findings presented in this article track auditory, visual, and somatosensory neuroplasticity and behavioral performance over time with the child's continued use of the implant. Since a CI for children with SSD is not currently approved in many countries, data from case studies are valuable in assessing the efficacy of CI in this population.

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MATERIALS AND METHODS

Subjects

The subject was a female child who had a progressive idiopathic hearing loss in her right ear beginning at age 5 years. She underwent trials with a CROS hearing aid and FM system. However, when her hearing loss progressed to severe she was no longer benefiting from their use. Because of complications with insurance coverage, she was denied the FDA approved bone-anchored hearing device. Unaided audiometric thresholds indicated a severe-profound hearing loss in the right ear (masked air conduction thresholds at 250, 500, 1000, 2000, 4000, 8000 Hz were 85, 90, 90, 90, 80, 90 dB HL) and normal hearing in the left ear (masked air conduction thresholds at 250, 500, 1000, 2000, 4000, 8000 Hz were 0 dB HL). Her unaided speech awareness threshold was 80 dB HL in the right ear and speech recognition threshold was 5 dB in the left ear. At the age of 9.86 years, the child received a CI in her right ear.

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EEG Recording

Evoked potentials are a noninvasive technique to record electrical activity in response to sensory stimulation. Cortical auditory evoked potentials (CAEPs), cortical visual evoked potentials (CVEPs), and cortical somatosensory evoked potentials (CSSEPs) were recorded from the patient's scalp using a 128-channel electrode net (Electrical Geodesic, Inc., Eugene, OR). Informed consent was obtained as per the University of Colorado institutional review board.

For the CAEP recordings in the pre-CI condition, a speech syllable, /ba/, was presented via insert earphones to the patient's normal hearing (left) ear at 65 dB HL (31) and the SSD (right) ear at 100 dB HL and post-CI, the /ba/ was presented to the normal hearing (left) ear at 65 dB HL via a speaker located at 45 degrees to the left ear, with the right ear implant turned off. Post-CI, the speech sound was presented to the SSD (right) ear at a level of 65 dB HL with her implant turned on. The left normal hearing ear was plugged with a deep insertion disposable earplug over which an earmuff was placed. Masking noise was not used because of potential for the noise to distort the CAEP recording. Although we acknowledge the possibility of cross-over, our results suggest that the morphology of the CAEP response from the two ears was clearly distinct. The subject was asked to ignore the stimulus while watching a movie with subtitles, to ensure she remained awake and alert. Each /ba/ stimulus was 90 milliseconds (ms) in duration and was presented at an interstimulus interval of 610 ms; 1200 sweeps were collected for each ear at each session. For the CVEP recordings, the patient was shown a high contrast sinusoidal concentric grating morphing into a radially modulated grating or circle-star pattern (32) providing the percept of apparent motion and shape change (32). A total of 300 stimulus sweeps were recorded. The child was instructed to direct her gaze to the center of the star/circle at a black dot and to not shift gaze during testing.

For the CSSEP recordings, a 250 Hz tone was presented via a bone oscillator adhered to the right index finger. Throughout the recording, steady-state noise was presented through a speaker to mask audibility of the bone oscillator (33). The subject confirmed that the stimulus was felt and not heard. A total of 1200 sweeps were collected. The subject was asked to ignore the stimulus while watching a movie, with the sound off and subtitles on, to ensure the subject remained awake and alert.

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EEG Analysis

Postprocessing of the EEG data included baseline correction, eye-blink and artifact rejection, bad channel rejection and interpolation of bad channels, and averaging. Data were pruned according to amplitudes and latencies for all obligatory CAEP peaks (i.e., P1, N1, and P2), CVEP peaks (i.e., P1, N1, and P2), and CSSEP peaks (P50, N70, P100, N140). For CAEP recordings the cochlear implant artifact was minimized using previously described procedures from our laboratory (34).

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Current Density Reconstructions

CAEP, CVEP, and CSSEP data were baseline corrected, artifact rejected, and down-sampled to 250 Hz. An independent component analysis (ICA) was performed on the concatenated EEG sweeps, allowing for observation of spatially fixed and temporally independent components underlying the evoked potential. Pruned waveforms were used for source modeling. Current density reconstruction (CDR) was conducted via the sLORETA algorithm using the boundary element method for each component. The activations are represented by a graded color scale superimposed on an average MRI.

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Behavioral Testing

At 33 months post-CI the patient was tested with a battery of speech perception tests. In a single-loudspeaker, audiometric booth environment, speech understanding in quiet using the AzBio sentence material was tested using direct, cable input to the cochlear implant. The patient was also tested in an 8-loudspeaker “surround sound” environment (35). In this environment, directionally appropriate restaurant noise was presented from each loudspeaker. In one condition, sentences in noise were presented from the loudspeaker on the side of the patient's CI. In this condition, the CI signal processor was turned off and performance was a function of the normal-hearing ear. In another condition, the cochlear implant was activated and the signal was directed again to the loudspeaker on the side of the cochlear implant. At issue was the gain in performance when the patient had access to information from her CI in addition to her normal hearing ear. In yet another test, sound source localization was assessed with methodology described by Dorman et al. (36).

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RESULTS

EEG Results

Figure 1 shows CAEP responses at age 9.86 years, shortly before the child received a CI in her right ear. The patient's normal hearing (left) ear shows clear P1, N1, and P2 responses with normal morphology and peak latencies falling within normal limits for the child's chronological age (left panel), suggestive of age-appropriate development of the central auditory pathways in response to stimulation of the normal hearing ear. However, the child's SSD (right) ear shows a delayed CAEP response with abnormal morphology dominated by a single (P1) component (right panel); N1 and P2 components are absent from the response, suggestive of immature development of the pathways in response to stimulation of the SSD ear.

FIG. 1

FIG. 1

Figure 2 depicts current density reconstructions (CDR) for the P1, N1, and P2 components, pre-CI, when stimulating the patient's normal hearing ear. As observed in Figure 2, the P1, N1, and P2 components activated auditory areas in the contralateral (right) superior temporal gyrus, medial temporal gyrus, inferior frontal gyrus, frontal gyrus, and insula. It is noteworthy that we saw primarily contralateral temporal cortex activation, suggesting that the activation of the cortex ipsilateral to the normal hearing (left) ear was significantly weaker and therefore not apparent in the CDR, consistent with reports in animal studies (37–39). This finding is also consistent with Gordon et al. (40) showing similar results in children with long periods of unilateral CI use before bilateral implantation, where there was a reduction in normal dominance of contralateral input in the auditory cortex. In addition to auditory temporal cortical areas of activation, inferior frontal gyrus was also activated when sound was presented to the subject's normal hearing ear. Activation of frontal areas is consistent with evidence of increased cognitive load and listening effort during auditory processing in hearing impaired listeners (41–43).

FIG. 2

FIG. 2

Figure 3 depicts the developmental trajectory of the subject's SSD (right) ear, pre-CI and at 3, 8, and 14 months post-CI. As observed in Figure 3, P1 latency in the right ear decreases within a 3-month span post-CI. By 8 months post-CI, there is a clear morphological change in the CAEP response, marked by the emergence of the N1 and P2 response, reflecting an age-appropriate waveform morphology 14 months after implantation.

FIG. 3

FIG. 3

Figure 4 shows the changes in current density reconstructions for the P1 CAEP pre-CI (left panel) and 14 months post-CI (right panel) when the auditory stimulus was presented to the patient's SSD (right) ear. Although pre-CI we saw temporal and frontal activation of primarily the right hemisphere, i.e., ipsilateral to SSD ear, at 14 months post-CI we see robust contralateral activation of only auditory temporal areas in superior and medial temporal gyrus. The decrease in frontal activation post-CI is suggestive of a decrease in listening effort and the robust contralateral activation suggests more typical development of auditory pathways postimplantation.

FIG. 4

FIG. 4

Figure 5 shows cortical activation (CDR) for visual stimuli pre-CI (upper left panel) and 27 months post-CI (upper right panel). Pre-CI, the subject showed activation of left frontal gyrus, and auditory areas in inferior temporal gyrus, and medial temporal gyrus consistent with cross-modal recruitment of temporal areas for visual processing. However, post-CI, the subject showed activation of activation of higher order visual areas including fusiform gyrus, consistent with more normal processing of these stimuli (33,44) as well as some residual activation in auditory areas of left superior and middle temporal gyrus. This response pattern suggests that although some auditory processing regions are still being recruited for visual processing in this patient post-CI, the dominant activation occurs in visual processing regions, suggesting a significant (but not complete) reversal of the visual cross-modal plasticity relative to the pre-CI condition. This result is consistent with recent findings from our laboratory showing that compensatory cross-modal recruitment of auditory processing areas by vision persists in children after cochlear implantation (33,44).

FIG. 5

FIG. 5

Figure 5 also shows cortical activation (CDR) for somatosensory stimuli pre-CI (lower left panel) and elicited 27 months post-CI (lower right panel). Pre-CI, the subject shows activation of somatosensory regions (pre- and postcentral gyrus, inferior parietal lobule, superior parietal lobule) in addition to activation of temporal regions (middle temporal gyrus) and the insula. This suggests recruitment of auditory regions for somatosensory processing and is evidence of cross-modal plasticity. Post-CI, the subject shows left somatosensory activation of pre- and postcentral gyrus, inferior and superior parietal lobule, which is consistent with normal processing of these stimuli (33,45–47). No auditory areas are being recruited for somatosensory processing post-CI, suggesting a complete reversal of cross-modal recruitment of auditory areas for somatosensory processing after cochlear implantation (33).

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Behavioral Perception Results

As observed in Figure 6 (left panel), speech perception testing at 33 months post-CI revealed a sentence score of 95% correct in the CI-only condition. This score is at the 90th percentile of scores on this test for adults fit with a cochlear implant (48). (Middle panel) Testing in the surround sound environment revealed a 25-percentage point improvement in performance when the CI was used in addition to the normal hearing ear. This improvement score is within the range of scores achieved by adult SSD subjects who have received a CI tested in the same environment. (Right panel) Sound localization testing showed a root mean score error of 14 degrees. This score is just outside the range of normal-hearing adults [95th percentile for young normal hearing adults is approximately 10 degrees of error (49) but the patient's score as good, or better than, for example, subjects fit with bilateral cochlear implants (49)]. Overall, the subject's excellent behavioral perception scores are consistent with the child's subjective perception of improved benefit with the CI.

FIG. 6

FIG. 6

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DISCUSSION

In this study we provide a first description of developmental neuroplasticity following CI in a pediatric case of SSD. A clear developmental difference in the CAEP waveforms between the two ears was evidenced pre-CI. Although the patient's normal hearing ear showed an age-appropriate CAEP response with normal P1 morphology and developmentally appropriate emergence of higher-order (N1 and P2) components, stimulation of the SSD ear showed an immature response marked by a single P1 component occurring at a delayed latency (Fig. 1). Such a present, but delayed, CAEP response in the SSD (right) ear is conceivably because of the child's early experience with sound in the deaf ear before the hearing loss progressed and/or potential preservation of plasticity because of stimulation of crossed pathways arising from the normal hearing ear (37–39,50,51).

Pre-CI, stimulation in each ear activated the right hemisphere, i.e., contralateral to the normal ear and ipsilateral to the SSD ear (Fig. 2; Fig. 4, left panel). In normal hearing subjects, monaural auditory stimulation results in bilateral activation with greater activation in the contralateral cortex to the ear stimulated, displaying asymmetrical activation of the central auditory system and dominance of contralateral pathways at the level of the cortex (50,51). Studies in animal models of congenital and early-onset SSD show a massive reorganization in aural preference for the normal hearing ear (37,38). That is, though bilateral activation is still present, the cortex contralateral to the normal hearing ear shows a strengthened response when either the normal hearing (left) ear or SSD (right) ear is stimulated (37,38). In our study, the fact that we did not see bilateral activation can be explained by the fact that in the context of a dominant underlying neural source, simultaneously active, less robust sources may not be visible using the sLORETA algorithm (52). Pre-CI, we saw representational dominance of contralateral cortex to the normal hearing ear, in that, stimulation of either the normal hearing ear or SSD ear resulted in activation of right auditory cortex. These results converge with the animal and human studies, showing clear changes in cortical auditory activation in preference of the normal hearing ear (37,38,40,53). Importantly, we saw a reversal of this dominance for the normal hearing ear once auditory stimulation was restored with the CI, with the patient demonstrating primarily contralateral activation when stimulating the CI ear (Fig. 4, right panel). This demonstrates a restoration of cortical auditory activation patterns more typical of what would be expected in normal hearing.

A similar change was observed at 8 months postimplantation in the morphology of the CAEP response, where previously absent N1 and P2 components became identifiable and age-appropriate (Fig. 3). The dramatic changes in morphology and cortical activation indicate a significant potential benefit of CI in SSD. This result is in line with our previous studies that have shown that it takes approximately 6 to 8 months of implant use for important developmental landmarks to become apparent (54).

Overall the results of this study show that a very high degree of neuroplasticity was apparent in the auditory cortex even after implantation at age 9.86 years, well after the brief sensitive period previously described for deaf children who receive cochlear implants (31,55,56). It is possible that the progressive nature of the hearing loss may have restricted deterioration of the central auditory pathways, preserving plasticity well into the school-age years. Future studies are needed to determine the time limits for a sensitive period for CI in congenitally deaf children with SSD.

The CDR results showing activation of cortical sources further sheds light on how unilateral auditory deprivation affects cortical resource allocation. Pre-CI, auditory stimulation of the patient's normal hearing ear resulted in temporal and frontal activation only in the contralateral cortex to this ear. As discussed above, this is consistent with patterns observed in normal hearing individuals, in which stimulation of one ear results in greater activation of the contralateral hemisphere (50,51). However, the presence of frontal cortical activation pre-CI in response to auditory stimulation seems to reflect compensatory plasticity indicative of increased cognitive load. The presence of frontal activation is consistent with previous fMRI and EEG studies in adults with hearing loss (41–43) in which pre-frontal and frontal activation was correlated with increased listening effort measured through tasks of executive function and working memory. Our results suggest that untreated SSD results in increased listening effort, which may not be easily captured using traditional audiological testing. CDR results post-CI do not show frontal cortex activation by sound (Fig. 4, right panel) suggesting a decrease in listening effort with the CI.

Our results suggest that CI in SSD may also reverse cross-modal reorganization from other modalities. In this case study, we saw a reversal of cross-modal recruitment of temporal areas for somatosensory processing by 27 months post-CI (Fig. 5, lower left and right panels). However, visual stimulation at 27 months post-CI continued to show some residual recruitment of auditory temporal areas for visual processing (Fig. 5, upper left and right panels) at 27 months post-CI. That is, by 27 months post-CI, visual stimulation resulted in activation of typical cortical visual processing regions, with only a small amount of residual cross-modal activation of temporal cortical areas traditionally associated with auditory processing including left superior and middle temporal gyrus. This is in line with recent results from our laboratory which show that, as a group, CI children who have worn their implant for several years continue to show evidence of cross-modal recruitment of auditory temporal areas by visual stimulation (33,34). Overall, this result is consistent with previous findings that cochlear implanted children as a whole are more attentive to visual stimulation compared with normal hearing peers (57). Our results also suggest that although compensatory plasticity from both visual and somatosensory modalities is present in auditory deprivation, reversal of visual cross-modal reorganization may take longer (compared with somatosensory reorganization) because of the functional role of visual processing in every day human communication and may even be considered beneficial as the auditory cortex adapts to a cochlear implant (58).

Finally, as predicted by the high degree of experience-driven neuroplasticity (described above) at 33 months post-CI, rigorous behavioral testing revealed that our patient was an excellent user of her cochlear implant. As can be observed from the results in Figure 6, she showed clear improvement from the addition of the cochlear implant and depicted adult levels of performance in speech perception and sound localization tasks.

In summary, in this case study of SSD, we describe evidence of deficits in cortical auditory development apparent in the delayed latency of the P1, absence of the N1/P2 components of the CAEP and cortical auditory activation showing a clear aural preference for pathways contralateral to the normal hearing ear. After cochlear implantation at a relatively late age (9.86 yrs) in childhood, we observed significant benefit as indicated by development of typical CAEP morphology, cortical activation contralateral to the implanted ear, decreased listening effort, reversal of somatosensory cross-modal plasticity, and only residual visual cross-modal plasticity. Results from a single case should be interpreted with caution, and there is a clear need for larger studies using more subjects with rigorous statistical analyses to describe changes in cortical reorganization after cochlear implantation in SSD. Nevertheless, in our case report, results suggest that cochlear implantation in pediatric SSD cases can provide significant benefit by taking advantage of the high degree of neuroplasticity in childhood.

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Keywords:

Cochlear implant; Cortical neuroplasticity; Cross-modal reorganization; Electrophysiology; Pediatric; Single-sided deafness

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