Three-dimensional models of cochlear implants : a review of their development and how they could support management and maintenance of cochlear implant performance

Three-dimensional (3D) computational modelling of the auditory periphery forms an integral part of modern-day research in cochlear implants (CIs). These models consist of a volume conduction description of implanted stimulation electrodes and the current distribution around these, coupled to auditory nerve fibre models. Cochlear neural activation patterns can then be predicted for a given input stimulus. The objective of this article is to present the context of 3D modelling within the field of CIs, the different models and approaches to models that have been developed over the years, as well as the applications and potential applications of these models. The process of development of 3D models is discussed, and the article places specific emphasis on the complementary roles of generic models and user-specific models, as the latter is important for translation of these models into clinical application.http://tandfonline.com/toc/inet202017-05-31hb2016Electrical, Electronic and Computer Engineerin

Qualitative effect of tissue heterogeneity and modiolus porosity on the transmembrane potential of type-1 spiral ganglion neurons in the human cochlea: a simulation study

Electric stimulation of auditory nerve by cochlear implants has been a successful clinical intervention to treat the sensorineural deafness. However, various micro-anatomical factors have not been considered in the state of the art models while studying the interaction between the applied electric field and the auditory nerve. The present finite element modeling study suggests that the modiolus porosity and tissue heterogeneity significantly alter the electric field distribution in the Rosenthal’s canal and thereby affect the cochlear implant functionality

Restoring Sensation of Gravitoinertial Acceleration through Prosthetic Stimulation of the Utricle and Saccule

Individuals with bilateral vestibular hypofunction suffer reduced quality of life due to loss of postural and ocular reflexes essential to maintaining balance and visual acuity during head movements. Vestibular stimulation has demonstrated success in restoring sensation of angular head rotations using electrical stimulation of the semi-circular canals (SCCs). Efforts toward utricle and saccule stimulation to restore sensation of gravitoinertial acceleration have been limited due to the complexity of the otolith end organs and otolith-ocular reflexes (OORs). Four key pieces of technology were developed to extend prosthetic stimulation to the utricle and saccule: a low-noise scleral coil system to record binocular 3D eye movements; a motion platform control system for automated presentation of rotational and translational stimuli; custom electrode arrays with fifty contacts targeting the SCCs, utricle and saccule; and a general-purpose neuroelectronic stimulator for vestibular and other neuromodulation applications. Using these new technologies, OORs were first characterized in six chinchillas to establish OOR norms during translations and static tilts. Results led to creation of a model that infers the axis of head tilt from measured binocular eye movements and thereby provides a context and means to assess the selectivity of prosthetic utricle and saccule stimulation. The model confirms the expectation that excitation of the left utricle and saccule primarily encodes tilts that bring the left ear down. Three of the chinchillas were implanted with electrode arrays in the left ear. Step changes in pulse rate were delivered to utricle and saccule electrodes near the maculae while measuring 3D binocular eye movements with the animal stationary in darkness. These stimuli elicited sustained ocular counter-roll responses that increased in magnitude as pulse rate or amplitude increased. Bipolar stimulation via neighboring electrodes elicited slow-rising or delayed onset of ocular counter-rolls (consistent with normal translational OOR low-pass filter behavior). Two chinchillas showed different direction of electrically-evoked ocular counter-roll between utricle versus saccule stimulation. Only near-neighbor bipolar electrode combinations elicited eye responses compensatory for tilts other than the ‘usual’ left ear down, suggesting the need for distributing multiple bipolar electrode pairs across the maculae to achieve selective stimulation and restore 3D sensation of gravitoinertial acceleration

The Role of Connexin and Pannexin Large-Pore Channels in Hearing

Connexin and pannexin large-pore channels allow the regulated passage of small molecules at sites of cell-cell contacts, and from the cytosol to the extracellular milieu, respectively. Since it has been known for many years that Cx26 and Cx30 gap junction proteins are crucial in hearing we propose that Cx43 might also be important in hearing. Here we used two different genetically modified mouse lines that contain systemic Cx43 gene mutations that reduces gap junctional intercellular communication (GJIC) to examine whether Cx43 is also important for proper hearing function. Furthermore, since pannexins have also been postulated to be involved in auditory function we used three different Panx global knock-out mice to evaluate their hearing profiles. We showed that Cx43 mutant mice that had severe loss of Cx43 channel function had hearing loss, while mutant mice with a modest loss of Cx43 function exhibited normal hearing. Surprisingly, Panx1-/-, Panx3-/-, and double knock-out (dKO) mice did not have hearing loss, suggesting that pannexins do not play an important role in hearing. To evaluate whether large-pore channels played a role in noise-induced hearing loss (NIHL), we challenged Cx43 mutant and pannexin knock-out mice with a loud noise-exposure and examined their permanent hearing loss. Interestingly, only Panx3-/- and Panx dKO mice were slightly protected against permanent hearing damage. Finally, organotypic cochlear cultures from Cx43 mutant mice and a CRISPR Cas9 Cx43 ablated cochlear-derived cell line, revealed that GJIC does not exacerbate drug-induced hearing loss but does cause supporting cell reorganization. Collectively, our results highlight the importance of Cx43 GJIC in hearing function, but not noise- or drug-induced ototoxicity. Furthermore, our studies support the notion that Panxs are not involved in baseline hearing, but loss of Panx3 may lead to slight protection against permanent NIHL

Frameshift mutations at the C-terminus of HIST1H1E result in a specific DNA hypomethylation signature

BACKGROUND: We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern. RESULTS: Methylome analysis from peripheral blood samples of six affected subjects led us to identify a specific hypomethylated profile. This "episignature" was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity and specificity in detecting subjects with Rahman syndrome. Applying this model to a cohort of undiagnosed probands allowed us to reach diagnosis in one subject. CONCLUSIONS: We demonstrate an epigenetic signature in subjects with Rahman syndrome that can be used to reach molecular diagnosis