Dissociated Representation of Binaural Cues in Single-Sided Deafness: Implications for Cochlear Implantation

Example raster plots from representative units in one hearing control (top) and one congenitally (binaurally) deaf cat (bottom). Shown are the sensitivity to interaural time differences (left) and interaural level differences (right) of the same unit. In the hearing control, the unit responded preferentially to crossed-earlier and crossed stronger conditions. In the deaf cat, the responsiveness to both ITD and ILD was reduced and more similar for both crossed and uncrossed stimulation. The gray bar corresponds to the blanked region of the stimulus artifact. For a detailed analysis of the ITD responses in HCs and CDCs, see Tillein et al. (2010).

Representative unit responses in two uCDCs (one with the right, the other with the left hearing ear) showing flat ITD function and ILD tuning favoring the hearing ear irrespective of recording hemisphere. A, Responses to binaural cues for the hearing ear on the right side, recorded either from the ipsilateral (uCDC_i, top) and contralateral (uCDC_c, bottom) cortices. The ITD (left) and ILD (right) results were both from the same unit. While ITDs in both hemispheres showed a flat ITD sensitivity response, the ILDs resulted in a strongly preferred ear—the hearing ear (blue legend). The response to the deaf ear (red legend) was weak. Note that the comparison within the same hemisphere is for the same unit. B, Representative unit responses in an uCDC with left-ear hearing, recorded at the ipsilateral (top) and contralateral (bottom) cortices, respectively, in response to its hearing (blue) and deaf (red) ear earlier or stronger.

Grand mean ITD and ILD functions of all responsive units recorded in the study. A–C, Grand mean ITD function (mean ± standard errors; top panels) and pooled ITD data for uncrossed-earlier (less than −100 µs), balanced (−100 to +100 µs), and crossed-earlier (greater than −100 µs) condition (bottom panels). In hearing controls (A, blue frame), the firing rate significantly increased from uncrossed-ear earlier to crossed-ear leading stimulation. In congenitally deaf cats (B, red frame), the functions showed a small constant increase from uncrossed to crossed condition; however, it did not reach statistical significance. In uCDCs (C, pale blue/yellow frame), ITD functions were flat, however, at a higher overall firing rate than in CDCs. The dashed line depicts the overall mean firing rate in top panels, and the gray rectangles encompass the ILDs defined as “balanced” conditions. Two-tailed Wilcoxon–Mann–Whitney test with multiple comparisons corrected using Bonferroni’s procedure in bottom panels, ***∼p < 0.001. D–F, Grand mean ILD functions (mean ± standard errors; top panels) and pooled ILD data for uncrossed stronger (less than −2 dB), balanced (−2 to +2 dB), and crossed stronger (greater than −2 dB) condition (bottom panels). In hearing controls (D, blue frame), the firing rate increased with crossed-ear stronger stimulation (positive ILDs) and decreased with uncrossed-ear stronger stimulation. Pooling all data from balanced ILD conditions and comparing them with more-negative ILDs (uncrossed stronger) resulted in a significant difference, and the comparison to the more-positive ILDs (crossed stronger) was also statistically significant. In congenitally deaf cats (E, red frame), a significance was observed in the comparison between balanced and uncrossed stronger, as well as the uncrossed stronger to crossed stronger condition. In uCDCs (F, pale blue/yellow), the mean ILD function was flat. Correspondingly, no effect was observed in the statistical analysis. Two-tailed Wilcoxon–Mann–Whitney test with multiple comparisons corrected using Bonferroni’s procedure, ***∼p < 0.001.

Representations of binaural cues in uCDCs resorted relative to the deaf and the hearing ear. Grand mean ITD and ILD functions shown as mean ± standard error. A, B, Pooling the results relative to the hearing and deaf ears did not reveal any significance in ITD sensitivity, similar to the crossed/uncrossed alignment. Sorting the ILD sensitivity relative to the hearing and deaf ears (C, D), however, changed the mean ILD function substantially. Here, the deaf ear stronger condition resulted in a weaker response, whereas the hearing ear stronger condition resulted in a stronger response, generating an ILD tuning preferring the previously hearing ear. Correspondingly, all differences in statistical comparisons were significant in such resorted ILD functions (D). E, Pairwise differences in the subset of units (see text) that showed sensitivity to both ITD and ILD. The firing rates were normalized to the maximum of each function. Shown are the grand mean ITD–ILD differences ± standard errors of the mean. Only the uCDC data show several successive data points in the grand mean well beyond 0.1 relative difference (pale gray horizontal stripe). F, Statistical comparison between the mean difference values, demonstrating a systematic difference between ITD and ILD tuning only in uCDCs. Two-tailed Wilcoxon–Mann–Whitney test, multiple comparisons corrected by Bonferroni’s procedure, ***∼p < 0.001.

Variable ABI paradigm focused on the analysis of excitation–inhibition balance. A, An individual unit example from an HC shows a monotonically increasing firing rate with an increasing current level. The arrow shows the +6 dB condition. B, Adding the uncrossed ear to the crossed-ear stimulation at 6 dB resulted either in an unchanged firing rate (black bullets, neutral interaction), an increasing firing rate (gray triangles, excitatory interaction), or a reduced firing rate (white pentagons, inhibition). The −2 dB stimulation at the uncrossed ear and +6 dB at the crossed ear (denoted by the asterisks) defines the “−2 dB condition” and corresponds to a response to an effective crossed stimulation with 6 dB. The mean of +8, 9, and 10 dB above the threshold at the uncrossed and +6 dB at the crossed ear (gray rectangles) will be termed as “binaural maximum” in subsequent text. C, Relating the firing rate to the −2 dB condition clearly sorts the neutral, excitatory, and inhibitory interactions. Statistical comparison (Wilcoxon–Mann–Whitney test, α = 5%) of all pooled values relative to zero for each unit response allows us to define excitation, inhibition, and neutral interactions. D, Statistical comparison of the proportion of the recording sites (units) expressing excitation and inhibition. Binaural inhibition was typically observed by ∼40% of the units in HCs. In uCDC_i, there were essentially no inhibitory interactions, whereas in uCDC_c, these were not different from HCs. E, The results for excitation were reciprocal to those of inhibition in uCDCs. F, Neutral interactions showed only a significant difference between CDCs and uCDC_i. Kruskal–Wallis test with Tukey–Kramer post hoc significance difference criterion. *∼p < 0.05; **∼p < 0.01; ***∼p < 0.001.

ABI variable paradigm results. A, The mean response from all units at 6 dB (above the threshold) at the crossed ear and −2 dB (below the threshold) at the uncrossed ear. HCs and uCDC_c demonstrated strong responses, while CDCs and uCDCi showed the weakest. B, Increasing the uncrossed level to the maximum current substantially increased the uCDCi response, whereas the HCs and uCDC_c responses tended to be suppressed. C, The firing rate change (difference between the mean firing rate of the three largest current levels and the firing rate at −2 dB level) illustrates that in both HCs and CDCs, there was a mixed excitation–inhibition effect, whereas the uCDC_i showed a mean excitation and uCDC_c showed a mean inhibition. The gray rectangle shows the 15 ms that were evaluated for firing rate analysis. D, Firing rate at 6 dB above the threshold at the crossed ear and −2 dB at the uncrossed ear. The highest firing rates were confirmed for HCs and uCDC_c. E, Same data for the maximum current level at the uncrossed ear and 6 dB at the crossed ear. F, Analysis of the change in firing rate. The gray rectangle shows the ±0.2, the margin around zero that is considered the “occlusion” or “neutral” interaction (Tillein et al., 2016). It shows that in three-quarters of the units in uCDC_i, the excitation was beyond that margin and thus represents a genuine excitatory effect. In uCDC_c (as in HCs), the suppression was in approximately half of the units within the “occlusive” margin and only ∼25% in the suppression range, suggesting that the strength of inhibition is moderate. Kruskal–Wallis test with Tukey–Kramer post hoc significance difference criterion, *∼p < 0.05; **∼p < 0.01 and ***∼p < 0.001.