Effect of Cochlear Implantation on the Endocochlear Potential and Stria Vascularis.

HYPOTHESIS: Animals with cochlear implantation-induced hearing loss will have a lower endocochlear potential (EP) and decreased strial vascular density. BACKGROUND: The cause of residual hearing loss following cochlear implantation remains poorly understood. Recent work from our lab has shown a correlation between vascular changes in the cochlear lateral wall and postimplantation hearing loss, suggesting a role of the stria vascularis and EP. METHODS: Fourteen young, normal-hearing male albino guinea pigs underwent cochlear implantation using either a cochleostomy (CI-c, n = 9) or an extended round window (CI-eRW, n = 5) approach. Hearing sensitivity was assessed pre- and postoperatively using auditory brainstem response thresholds. Three weeks after implantation, EP measurements were obtained from the first and second turns. Hair cell counts and stria vascularis capillary density measurements were also obtained. RESULTS: The implanted group experienced significant threshold elevations at 8 to 24 kHz (mean threshold shift 9.1 ±â€Š1.1 dB), with a more robust threshold shift observed in the CI-eRW group compared to the CI-c group. Implanted animals had a significantly lower first turn EP (81.4 ±â€Š5.1 mV) compared with controls (87.9 ±â€Š6.1 mV). No differences were observed in the second turn (75.8 ±â€Š12.0 mV for implanted animals compared to 76.5 ±â€Š7.0 mV for controls). There were no significant correlations between turn-specific threshold shifts, EP measurements, or strial blood vessel density. CONCLUSIONS: Reliable EP measurements can be obtained in chronically implanted guinea pigs. Hearing loss after implantation is not explained by changes in strial vascular density or reductions in EP.

Binaural Pitch Fusion in Children With Normal Hearing, Hearing Aids, and Cochlear Implants.

OBJECTIVES: Binaural pitch fusion is the perceptual integration of stimuli that evoke different pitches between the ears into a single auditory image. Adults who use hearing aids (HAs) or cochlear implants (CIs) often experience abnormally broad binaural pitch fusion, such that sounds differing in pitch by as much as 3 to 4 octaves are fused across ears, leading to spectral averaging and speech perception interference. The main goal of this study was to measure binaural pitch fusion in children with different hearing device combinations and compare results across groups and with adults. A second goal was to examine the relationship of binaural pitch fusion to interaural pitch differences or pitch match range, a measure of sequential pitch discriminability. DESIGN: Binaural pitch fusion was measured in children between the ages of 6.1 and 11.1 years with bilateral HAs (n = 9), bimodal CI (n = 10), bilateral CIs (n = 17), as well as normal-hearing (NH) children (n = 21). Depending on device combination, stimuli were pure tones or electric pulse trains delivered to individual electrodes. Fusion ranges were measured using simultaneous, dichotic presentation of reference and comparison stimuli in opposite ears, and varying the comparison stimulus to find the range that fused with the reference stimulus. Interaural pitch match functions were measured using sequential presentation of reference and comparison stimuli, and varying the comparison stimulus to find the pitch match center and range. RESULTS: Children with bilateral HAs had significantly broader binaural pitch fusion than children with NH, bimodal CI, or bilateral CIs. Children with NH and bilateral HAs, but not children with bimodal or bilateral CIs, had significantly broader fusion than adults with the same hearing status and device configuration. In children with bilateral CIs, fusion range was correlated with several variables that were also correlated with each other: pure-tone average in the second implanted ear before CI, and duration of prior bilateral HA, bimodal CI, or bilateral CI experience. No relationship was observed between fusion range and pitch match differences or range. CONCLUSIONS: The findings suggest that binaural pitch fusion is still developing in this age range and depends on hearing device combination but not on interaural pitch differences or discriminability.

Morphological correlates of hearing loss after cochlear implantation and electro-acoustic stimulation in a hearing-impaired Guinea pig model.

Hybrid or electro-acoustic stimulation (EAS) cochlear implants (CIs) are designed to provide high-frequency electric hearing together with residual low-frequency acoustic hearing. However, 30-50% of EAS CI recipients lose residual hearing after implantation. The objective of this study was to determine the mechanisms of EAS-induced hearing loss in an animal model with high-frequency hearing loss. Guinea pigs were exposed to 24 h of noise (12-24 kHz at 116 dB) to induce a high-frequency hearing loss. After recovery, two groups of animals were implanted (n = 6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no stimulation during this time frame. A third group (n = 6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem responses were recorded biweekly to monitor changes in hearing. The organ of Corti was immunolabeled with phalloidin, anti-CtBP2, and anti-GluR2 to quantify hair cells, ribbons and post-synaptic receptors. The lateral wall was immunolabeled with phalloidin and lectin to quantify stria vascularis capillary diameters. Bimodal or trimodal diameter distributions were observed; the number and location of peaks were objectively determined using the Aikake Information Criterion and Expectation Maximization algorithm. Noise exposure led to immediate hearing loss at 16-32 kHz for all groups. Cochlear implantation led to additional hearing loss at 4-8 kHz; this hearing loss was negatively and positively correlated with minimum and maximum peaks of the bimodal or trimodal distributions of stria vascularis capillary diameters, respectively. After chronic stimulation, no significant group changes in thresholds were seen; however, elevated thresholds at 1 kHz in implanted, stimulated animals were significantly correlated with decreased presynaptic ribbon and postsynaptic receptor counts. Inner and outer hair cell counts did not differ between groups and were not correlated with threshold shifts at any frequency. As in the previous study in a normal-hearing model, stria vascularis capillary changes were associated with immediate hearing loss after implantation, while little to no hair cell loss was observed even in cochlear regions with threshold shifts as large as 40-50 dB. These findings again support a role of lateral wall blood flow changes, rather than hair cell loss, in hearing loss after surgical trauma, and implicate the endocochlear potential as a factor in implantation-induced hearing loss. Further, the analysis of the hair cell ribbons and post-synaptic receptors suggest that delayed hearing loss may be linked to synapse or peripheral nerve loss due to stimulation excitotoxicity or inflammation. Further research is needed to separate these potential mechanisms of delayed hearing loss.

Changes in Gene Expression and Hearing Thresholds After Cochlear Implantation.

HYPOTHESIS: Gene expression changes occur in conjunction with hearing threshold changes after cochlear implantation. BACKGROUND: Between 30 and 50% of individuals who receive electro-acoustic stimulation (EAS) cochlear implants lose residual hearing after cochlear implantation, reducing the benefits of EAS. The mechanism underlying this hearing loss is unknown; potential pathways include mechanical damage, inflammation, or tissue remodeling changes. METHODS: Guinea pigs were implanted in one ear with cochlear implant electrode arrays, with non-implanted ears serving as controls, and allowed to recover for 1, 3, 7, or 14 days. Hearing threshold changes were measured over time. Cochlear ribonucleic acid was analyzed using real-time quantitative reverse transcription-polymerase chain reaction from the following gene families: cytokines, tight junction claudins, ion and water (aquaporin) transport channels, gap junction connexins, and tissue remodeling genes. RESULTS: Significant increases in expression were observed for cochlear inflammatory genes (Cxcl1, IL-1ß, TNF-α, and Tnfrsf1a/b) and ion homeostasis genes (Scnn1γ, Aqp3, and Gjb3). Upregulation of tissue remodeling genes (TGF-ß, MMP2, MMP9) as well as a paracrine gene (CTGF) was also observed. Hearing loss occurred rapidly, peaking at 3 days with some recovery at 7 and 14 days after implantation. MM9 exhibited extreme upregulation of expression and was qualitatively associated with changes in hearing thresholds. CONCLUSION: Cochlear implantation induces similar changes as middle ear inflammation for genes involved in inflammation and ion and water transport function, whereas tissue remodeling changes differ markedly. The upregulation of MMP9 with hearing loss is consistent with previous findings linking stria vascularis vessel changes with cochlear implant-induced hearing loss.

Factors associated with hearing loss in a normal-hearing guinea pig model of Hybrid cochlear implants.

The Hybrid cochlear implant (CI), also known as Electro-Acoustic Stimulation (EAS), is a new type of CI that preserves residual acoustic hearing and enables combined cochlear implant and hearing aid use in the same ear. However, 30-55% of patients experience acoustic hearing loss within days to months after activation, suggesting that both surgical trauma and electrical stimulation may cause hearing loss. The goals of this study were to: 1) determine the contributions of both implantation surgery and EAS to hearing loss in a normal-hearing guinea pig model; 2) determine which cochlear structural changes are associated with hearing loss after surgery and EAS. Two groups of animals were implanted (n = 6 per group), with one group receiving chronic acoustic and electric stimulation for 10 weeks, and the other group receiving no direct acoustic or electric stimulation during this time frame. A third group (n = 6) was not implanted, but received chronic acoustic stimulation. Auditory brainstem response thresholds were followed over time at 1, 2, 6, and 16 kHz. At the end of the study, the following cochlear measures were quantified: hair cells, spiral ganglion neuron density, fibrous tissue density, and stria vascularis blood vessel density; the presence or absence of ossification around the electrode entry was also noted. After surgery, implanted animals experienced a range of 0-55 dB of threshold shifts in the vicinity of the electrode at 6 and 16 kHz. The degree of hearing loss was significantly correlated with reduced stria vascularis vessel density and with the presence of ossification, but not with hair cell counts, spiral ganglion neuron density, or fibrosis area. After 10 weeks of stimulation, 67% of implanted, stimulated animals had more than 10 dB of additional threshold shift at 1 kHz, compared to 17% of implanted, non-stimulated animals and 0% of non-implanted animals. This 1-kHz hearing loss was not associated with changes in any of the cochlear measures quantified in this study. The variation in hearing loss after surgery and electrical stimulation in this animal model is consistent with the variation in human patients. Further, these findings illustrate an advantage of a normal-hearing animal model for quantification of hearing loss and damage to cochlear structures without the confounding effects of chemical- or noise-induced hearing loss. Finally, this study is the first to suggest a role of the stria vascularis and damage to the lateral wall in implantation-induced hearing loss. Further work is needed to determine the mechanisms of implantation- and electrical-stimulation-induced hearing loss.

Circadian discrimination of reward: evidence for simultaneous yet separable food- and drug-entrained rhythms in the rat.

A unique extra-suprachiasmatic nucleus (SCN) oscillator, operating independently of the light-entrainable oscillator, has been hypothesized to generate feeding and drug-related rhythms. To test the validity of this hypothesis, sham-lesioned (Sham) and SCN-lesioned (SCNx) rats were housed in constant dim-red illumination (LL(red)) and received a daily cocaine injection every 24 h for 7 d (Experiment 1). In a second experiment, rats underwent 3-h daily restricted feeding (RF) followed 12 d later by the addition of daily cocaine injections given every 25 h in combination with RF until the two schedules were in antiphase. In both experiments, body temperature and total activity were monitored continuously. Results from Experiment 1 revealed that cocaine, but not saline, injections produced anticipatory increases in temperature and activity in SCNx and Sham rats. Following withdrawal from cocaine, free-running temperature rhythms persisted for 2-10 d in SCNx rats. In Experiment 2, robust anticipatory increases in temperature and activity were associated with RF and cocaine injections; however, the feeding periodicity (23.9 h) predominated over the cocaine periodicity. During drug withdrawal, the authors observed two free-running rhythms of temperature and activity that persisted for >14 d in both Sham and SCNx rats. The periods of the free-running rhythms were similar to the feeding entrainment (period = 23.7 and 24.0 h, respectively) and drug entrainment (period = 25.7 and 26.1 h, respectively). Also during withdrawal, the normally close correlation between activity and temperature was greatly disrupted in Sham and SCNx rats. Taken together, these results do not support the existence of a single oscillator mediating the rewarding properties of both food and cocaine. Rather, they suggest that these two highly rewarding behaviors can be temporally isolated, especially during drug withdrawal. Under stable dual-entrainment conditions, food reward appears to exhibit a slightly greater circadian influence than drug reward. The ability to generate free-running temperature rhythms of different frequencies following combined food and drug exposures could reflect a state of internal desynchrony that may contribute to the addiction process and drug relapse.