Unilateral hearing during development: hemispheric specificity in plastic reorganizations

Abstract

The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing (unilateral deafness). The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved.

Keywords: cochlear implant; critical periods; development; plasticity; single-sided deafness.

Figure 1

Onset of unilateral hearing in ten animals (arrows) compared with the developmental time-line of deaf cat auditory system as reflected in the auditory cortex. The intensity of the color represents the extent of the given change. “Functional synaptogenesis” (development of synaptic function, measured by current source density analyses of evoked responses in the cortex, thus reflecting synaptic counts combined with synaptic function) in binaurally deaf animals has been shown to be delayed by 1.5 months compared to that in hearing animals, with a maximum of evoked synaptic currents around 3 months (Kral et al., , red). Previous studies in congenitally deaf cats demonstrated two sensitive periods: one for reorganization reflected at cortex ipsilateral to hearing ear (green), terminating between 3.5 and 4.2 months (Kral et al., 2013), the other sensitive period for increase in activated volume of tissue (“active area”) in the contralateral field A1 (and the corresponding response latencies; black), terminating between 5 and 6 months (Kral et al., ; Kral and Sharma, 2012). In the present study, distinction between early and late onset was based on sensitive period of aural preference (Kral et al., 2013), whereas sensitive period for expansion of the active area extends beyond this timeframe. Gray arrows: unilaterally congenitally deaf animals; black arrows: binaurally deaf animals, implanted with a unilateral cochlear implant at different postnatal times.

Figure 2

Hemispheric specificity of amplitude effects in cortical responses of a unilaterally congenitally deaf animal investigated at the ipsilateral and contralateral cortex. Insets indicate stimulation-recording configurations. In the inset, small loudspeaker indicates hearing side, and green spot the cortex in which recordings are made. Blue and red wires indicate ear stimulated with a cochlear implant. Largest peak amplitudes and peak latencies (color) are shown as a function of recording position. Responses below 50 μ V were not considered and are shown without coloring. (A) cochlear implant stimulation at the contralateral (deaf) ear, recording at hemisphere contralateral to hearing ear. Few responses above 50 μ V were observed. (B) in the same animal, stimulation of hearing ear extensively activated the whole contralateral primary auditory cortex. (C,D) at cortex ipsilateral to hearing ear, stimulation of both deaf (left) and hearing (right) ear resulted in strong activation of portions of auditory cortex.

Figure 3

Effect of stimulation duration (2 and 5 months) on morphology of mean local field potentials (LFPs) from hot spots in two early-implanted animals. Inset shows configuration: recording was at the ipsilateral cortex (green spot), stimulation of hearing and deaf ear. Response color denotes stimulation site (red: uncrossed stimulation, blue: crossed stimulation); shaded area is the temporally smoothed region of one standard deviation around mean. Gray bar below curve indicates statistical significance of difference between red and blue curve using a running two-tailed Wilcoxon-Mann-Whitney test (2 ms window, α = 0.001, corrected by the false detection rate procedure). Increasing stimulation duration increased overall amplitudes of responses, but more so for hearing ear. Additionally, latencies decreased with stimulation duration. Statistically significant portions are at P_b and N_b regions.

Figure 4

Crossed responses in a congenitally unilaterally deaf animal and a late-implanted animal (stimulation duration 5 months). Stimulation of hearing ear and recording at contralateral cortex shown in blue, for deaf ear and recording at the ipsilateral hemisphere in red, shaded area is the temporally smoothed region of one standard deviation around mean. Gray bars below curve indicate statistical significance of a running two-tailed Wilcoxon-Mann-Whitney test (α = 0.001, corrected by false detection rate procedure, 2 ms window). Ear-specific effects were observed in both animals; however, regions of statistical significance were larger in the congenital onset case. Maximum amplitudes in both compared animals were within 200–400 μV, as reported previously (Kral et al., 2009).

Figure 5

Comparison of crossed and uncrossed responses at both hemispheres in a congenitally unilaterally deaf animal (A,B) and a late implanted animal (C,D). Inset shows stimulus configuration; green spot shows recorded hemisphere. Crossed response is denoted in blue, uncrossed response in red; shaded area is the temporally smoothed region of one standard deviation around mean. Gray bar below curve indicates statistical significance of a running two-tailed Wilcoxon-Mann-Whitney test (α = 0.001, corrected by false detection rate procedure, 2 ms window). Morphology of LFPs shows temporal regions of significant difference in all configurations, but more so in the congenitally unilaterally deaf animal. Further, morphology is more different between hemispheres than within one hemisphere. Note differences in ordinate. Early-implanted animals had larger maximal amplitudes than congenital unilateral and late-implanted animals. The absolute LFP amplitude showed a high interindividual variability.

Figure 6

Dissimilarity index computed between mean LFPs within one hemisphere (gray) and between hemispheres (black). Interhemisphere comparisons result in significantly higher dissimilarity index than within-hemisphere comparisons. Two-tailed Wilcoxon-Mann-Whitney test, ^**p < 0.01.

Figure 7

Onset latency at the cortex contralateral to hearing ear in response to stimulation of hearing ear in two animals implanted at 3.5 months. One was stimulated for 2 months and the other for 5 months. Longer stimulation resulted in shorter-onset latency (two-tailed Wilcoxon-Mann-Whitney test, ^***~p < 0.001).

Figure 8

Onset latency for crossed responses; color denotes configuration. Blue denotes the hearing ear. In animals with early onset of unilateral hearing, crossed response for hearing ear was significantly shorter than that for the deaf ear (two-tailed Wilcoxon-Mann-Whitney test). This was not the case for late-onset animals. Onset latency for stimulation of deaf ear did not show any systematic dependence on onset of asymmetric hearing, whereas onset latency for hearing ear became longer in cases of late-onset asymmetric hearing. ^***~p < 0.001; ^*~p < 0.05.

Figure 9

Comparison of crossed and uncrossed responses for hearing ear. Color denotes hemisphere in which recordings are made (red: ipsilateral, blue: contralateral). In all early-onset animals, ipsilateral hemisphere showed a nominally smaller median onset latency, but difference was not statistically significant (two-tailed Wilcoxon-Mann-Whitney test). In all late-onset animals, contralateral hemisphere showed a smaller median latency, but in only two of three animals was the difference statistically significant (two-tailed Wilcoxon-Mann-Whitney test). Note that both ipsilateral and contralateral latencies were greater in late-onset animals. ^***~p < 0.001.

Figure 10

Difference between median latencies (uncrossed–crossed response) for hearing ear. All three early-onset animals had negative differences (uncrossed < crossed), whereas all late-onset animals had positive differences (uncrossed > crossed). Two-tailed Wilcoxon-Mann-Whitney test, p = 0.04 (^*~p < 0.05).

Figure 11

Graphical summary of results from this and two previous studies (Kral et al., 2009, 2013). In binaurally deaf animals, contralaterality was reduced. In early-onset unilaterally deaf animals, hearing ear resulted in reduced contralaterality (when assessed from crossed and uncrossed response for hearing ear), whereas deaf ear showed increased contralaterality (when assessed from crossed and uncrossed response for deaf ear) due to reduced uncrossed response.