Objective: Neurons in the cochlear nucleus show different response patterns to the short tone bursts. Because of the limitations of animal experiments, it is hard to explore the principle. Therefore, using a model to ...Objective: Neurons in the cochlear nucleus show different response patterns to the short tone bursts. Because of the limitations of animal experiments, it is hard to explore the principle. Therefore, using a model to simulate CN neurons will be a feasible way. Methods: Based on the initial model mentioned in the previous study, we proposed an improved CN model in MATLAB R2012b. Results: By modifying the parameters of the model we found the interchanges among "primary-like", "chopper",and "onset" response patterns. Furthermore, we simulated the "pauser" response pattern by adding an extra input in our model. Conclusion: The results indicate that the synaptic integrations and the input modes can give rise to different characteristics of CN neurons, which eventually determine the response patterns of CN neurons.展开更多
We have delivered viral vectors containing either Chop2 fused with GFP, Channelrhodopsin-2 （ChR2）, or Halorhodopsin （HaloR） fused with mCherry （to form light gated cation channels or chloride pumps, respectively...We have delivered viral vectors containing either Chop2 fused with GFP, Channelrhodopsin-2 （ChR2）, or Halorhodopsin （HaloR） fused with mCherry （to form light gated cation channels or chloride pumps, respectively）, into the dorsal cochlear nucleus （DCN）. One to eighteen months later we examined the CN and inferior colliculus （IC） for evidence of virally transfected cells and processes. Production of ChR2 and HaloR was observed throughout the DCN. Rhodopsin localization within neurons was determined, with elongate, fusiform and giant cells identified based on morphology and location within the DCN. Production of ChR2 and HaloR was found at both the injection site as well as in regions projecting to and from the DCN. Light driven neuronal activity in the DCN was dependent upon the wavelength and intensity of the light, with only the appropriate wavelength resulting in activation and higher intensity light resulting in more neuronal activity. Transfecting cells via viral delivery of rhodopsins can be useful as a tract tracer and as a neuronal marker to delineate pathways. In the future rhodopsin delivery and activation may be developed as an alternative to electrical stimulation of neurons.展开更多
Objective： To demonstrate the performance benefit of the Automatic Scene Classifier （SCAN） algorithm available in the Nucleus 6 （CP900 series） sound processor over the default processing algorithms of the previou...Objective： To demonstrate the performance benefit of the Automatic Scene Classifier （SCAN） algorithm available in the Nucleus 6 （CP900 series） sound processor over the default processing algorithms of the previous generation Nucleus 5 （CP810） and Freedom HybridTM sound processors. Methods： Eighty-two cochlear implant recipients （40 Nucleus 5 processor users and 42 Freedom Hybrid processor users） listened to and repeated AzBio sentences in noise with their current processor and with the Nucleus 6 processor. Results： The SCAN algorithm when enabled yielded statistically significant non-inferior and superior performance when compared to the Nucleus 5 and Freedom Hybrid sound processors programmed with ASC ＋ ADRO. Conclusion： The results of these studies demonstrate the superior performance and clinical utility of the SCAN algorithm in the Nucleus 6 processor over the Nucleus 5 and Freedom Hybrid processors.展开更多
By numerical simulations on frequency dependence of the spiking threshold, i.e. on the critical amplitude of periodic stimulus, for a neuron to fire, we find that bushy cells in the cochlear nuclear exhibit frequency ...By numerical simulations on frequency dependence of the spiking threshold, i.e. on the critical amplitude of periodic stimulus, for a neuron to fire, we find that bushy cells in the cochlear nuclear exhibit frequency selec- tivity behaviour. However, the selective frequency band of a bushy cell is far away from that of the preferred spectral range in human and mammal auditory perception. The mechanism underlying this neural activity is also discussed. Further studies show that the ion channel densities have little impact on the selective frequency band of bushy cells. These findings suggest that the neuronal behaviour of frequency selectivity in bushy cells at both the single cell and population levels may be not functionally relevant to frequency discrimination. Our results may reveal a neural hint to the reconsideration on the busily cell functional role in auditory information processing of sound frequency.展开更多
Current putative regeneration oriented studies express possible role of stem cell based implantation strategy in the restoration of fundamental perception of hearing. The present work utilizes a rat auditory nerve (AN...Current putative regeneration oriented studies express possible role of stem cell based implantation strategy in the restoration of fundamental perception of hearing. The present work utilizes a rat auditory nerve (AN) directed transplantation of human neural progenitor cells (HNPCs) as a cell replacement therapy for impaired auditory function. Groups of b-bungarotoxin induced auditory function compromised female rats were used to transplant HNPCs in the nerve trunk. In the treatment groups, brain derived neurotrophic factor (BDNF), peptide amphiphile nanofiber bioactive gel (Bgel) and Chondroitinase ABC (ChABC), a digestive enzyme that cleaves the core of chondroitin sulphate proteoglycans, were added along with HNPCs while the control groups were with PA inert gel (Igel) and devoid of ChABC. Six weeks post transplantation survival, migration, and differentiation of HNPCs were studied and compared. The groups treated with BDNF and Bgel showed improved survival and differentiation of transplanted HNPCs while the ChABC treated group showed significant migration of HNPCs along the AN and elongation of neuronal fibers along the nerve towards the cochlear nucleus (CN) which was characterized by immunocytochemical markers for human Nuclei (HuN), human mitochondria (HuM) and neuronal β-tubulin (Tuj1). These findings show that addition of BDNF and ChABC consisted Bgel environment facilitated HNPC survival, migration and differentiation along the transplanted rat AN towards the CN. This transplantation strategy provides unique experimental validation for futuristic role of cell based biomaterial consisted neurotrophic factor application in clinically transferable treatment of sensorineural hearing loss (SNHL) along with cochlear implants (CI).展开更多
Cochlear implants can successfully provide auditory information for bilaterally profoundly deaf patients by electrically stimulating auditory nerve fibres via an electrode array, which is surgically implanted into the...Cochlear implants can successfully provide auditory information for bilaterally profoundly deaf patients by electrically stimulating auditory nerve fibres via an electrode array, which is surgically implanted into the scala tympani of the cochlea. It is therefore important that the electrode array does not cause damage to the fine intracochlear structures during the process of insertion, as this can result in the loss of spiral ganglion cells, which are necessary for the implant to evoke auditory percepts. There is strong evidence that trauma and damage during insertion of electrode arrays into the human cochlea are related to the stiffness of the electrode array. Previous studies were conducted to experimentally determine the stiffness properties of electrode arrays using three-point flexural bending and buckling tests.In this paper, the design of nucleus straight electrode array is modified to give a greater flexibility to further reduce the risk of trauma to delicate structures of the cochlea during surgical insertion of the electrode array. This is achieved by reducing the cross-sectional area of the electrode array at selected positions over its length. Improvements in the flexibility of the new straight electrode array and the bending behavior at its tip have been demonstrated using finite element analysis. Loads applied to the tip of the electrode array at different angles with respect to the longitudinal axis of the electrode array showed that the modified design caused the tip to be more flexible and therefore better able to curl around the inner spiral of the scala tympani and thus less likely to penetrate the basilar membrane during insertion. Loads applied at other positions along the electrode array showed that bending occurred more readily using the modified design thereby reducing the friction and shear stresses at the contact interface between the electrode array and the delicate cochlea structures.展开更多
The auditory brainstem implant(ABI)was originally developed to provide rehabilitation of retrocochlear deafness caused by neurofibromatosis type 2(NF2).Recent studies of the ABI have investigated outcomes in non-NF2 c...The auditory brainstem implant(ABI)was originally developed to provide rehabilitation of retrocochlear deafness caused by neurofibromatosis type 2(NF2).Recent studies of the ABI have investigated outcomes in non-NF2 cohorts,such as patients with cochlear nerve aplasia or cochlear ossification and more recently,intractable tinnitus.New technologies that improve the ABI-neural tissue interface are being explored as means to improve performance and decrease side effects.Innovative discoveries in optogenetics and bioengineering present opportunities to continually evolve this technology into the future,enhancing spatial selectivity of neuronal activation in the cochlear nucleus and preventing side effects through reduction in activation of non-target neuronal circuitry.These advances will improve surgical planning and ultimately improve patients1 audiological capabilities.ABI research has rapidly increased in the 21st century and applications of this technology are likely to continually evolve.Herein,we aim to characterize ongoing clinical,basic science,and bioengineering advances in ABIs and discuss future directions of this technology.展开更多
基金National Natural Science Foundation of Chinagrant number:31171059
文摘Objective: Neurons in the cochlear nucleus show different response patterns to the short tone bursts. Because of the limitations of animal experiments, it is hard to explore the principle. Therefore, using a model to simulate CN neurons will be a feasible way. Methods: Based on the initial model mentioned in the previous study, we proposed an improved CN model in MATLAB R2012b. Results: By modifying the parameters of the model we found the interchanges among "primary-like", "chopper",and "onset" response patterns. Furthermore, we simulated the "pauser" response pattern by adding an extra input in our model. Conclusion: The results indicate that the synaptic integrations and the input modes can give rise to different characteristics of CN neurons, which eventually determine the response patterns of CN neurons.
基金supported by Ralph Wilson Foundation(to A.G.H)Capita Foundation(to A.G.H)
文摘We have delivered viral vectors containing either Chop2 fused with GFP, Channelrhodopsin-2 （ChR2）, or Halorhodopsin （HaloR） fused with mCherry （to form light gated cation channels or chloride pumps, respectively）, into the dorsal cochlear nucleus （DCN）. One to eighteen months later we examined the CN and inferior colliculus （IC） for evidence of virally transfected cells and processes. Production of ChR2 and HaloR was observed throughout the DCN. Rhodopsin localization within neurons was determined, with elongate, fusiform and giant cells identified based on morphology and location within the DCN. Production of ChR2 and HaloR was found at both the injection site as well as in regions projecting to and from the DCN. Light driven neuronal activity in the DCN was dependent upon the wavelength and intensity of the light, with only the appropriate wavelength resulting in activation and higher intensity light resulting in more neuronal activity. Transfecting cells via viral delivery of rhodopsins can be useful as a tract tracer and as a neuronal marker to delineate pathways. In the future rhodopsin delivery and activation may be developed as an alternative to electrical stimulation of neurons.
文摘Objective： To demonstrate the performance benefit of the Automatic Scene Classifier （SCAN） algorithm available in the Nucleus 6 （CP900 series） sound processor over the default processing algorithms of the previous generation Nucleus 5 （CP810） and Freedom HybridTM sound processors. Methods： Eighty-two cochlear implant recipients （40 Nucleus 5 processor users and 42 Freedom Hybrid processor users） listened to and repeated AzBio sentences in noise with their current processor and with the Nucleus 6 processor. Results： The SCAN algorithm when enabled yielded statistically significant non-inferior and superior performance when compared to the Nucleus 5 and Freedom Hybrid sound processors programmed with ASC ＋ ADRO. Conclusion： The results of these studies demonstrate the superior performance and clinical utility of the SCAN algorithm in the Nucleus 6 processor over the Nucleus 5 and Freedom Hybrid processors.
文摘By numerical simulations on frequency dependence of the spiking threshold, i.e. on the critical amplitude of periodic stimulus, for a neuron to fire, we find that bushy cells in the cochlear nuclear exhibit frequency selec- tivity behaviour. However, the selective frequency band of a bushy cell is far away from that of the preferred spectral range in human and mammal auditory perception. The mechanism underlying this neural activity is also discussed. Further studies show that the ion channel densities have little impact on the selective frequency band of bushy cells. These findings suggest that the neuronal behaviour of frequency selectivity in bushy cells at both the single cell and population levels may be not functionally relevant to frequency discrimination. Our results may reveal a neural hint to the reconsideration on the busily cell functional role in auditory information processing of sound frequency.
基金supported by The Swedish Research Council no.2008-2822,Marianne and Marcus Wallenbergs Foundation,Petrus and Augusta Hedlunds Foundation,The Swedish Association of Hard of Hearing People,Acta Otolaryngologica’s Foundation,The Foundation Tysta Skolan,Ollie and Elof Ericssons Foundation for Medical Research and Karolinska Institutet Foundationssupported by the Medical faculty and Lund University.
文摘Current putative regeneration oriented studies express possible role of stem cell based implantation strategy in the restoration of fundamental perception of hearing. The present work utilizes a rat auditory nerve (AN) directed transplantation of human neural progenitor cells (HNPCs) as a cell replacement therapy for impaired auditory function. Groups of b-bungarotoxin induced auditory function compromised female rats were used to transplant HNPCs in the nerve trunk. In the treatment groups, brain derived neurotrophic factor (BDNF), peptide amphiphile nanofiber bioactive gel (Bgel) and Chondroitinase ABC (ChABC), a digestive enzyme that cleaves the core of chondroitin sulphate proteoglycans, were added along with HNPCs while the control groups were with PA inert gel (Igel) and devoid of ChABC. Six weeks post transplantation survival, migration, and differentiation of HNPCs were studied and compared. The groups treated with BDNF and Bgel showed improved survival and differentiation of transplanted HNPCs while the ChABC treated group showed significant migration of HNPCs along the AN and elongation of neuronal fibers along the nerve towards the cochlear nucleus (CN) which was characterized by immunocytochemical markers for human Nuclei (HuN), human mitochondria (HuM) and neuronal β-tubulin (Tuj1). These findings show that addition of BDNF and ChABC consisted Bgel environment facilitated HNPC survival, migration and differentiation along the transplanted rat AN towards the CN. This transplantation strategy provides unique experimental validation for futuristic role of cell based biomaterial consisted neurotrophic factor application in clinically transferable treatment of sensorineural hearing loss (SNHL) along with cochlear implants (CI).
文摘Cochlear implants can successfully provide auditory information for bilaterally profoundly deaf patients by electrically stimulating auditory nerve fibres via an electrode array, which is surgically implanted into the scala tympani of the cochlea. It is therefore important that the electrode array does not cause damage to the fine intracochlear structures during the process of insertion, as this can result in the loss of spiral ganglion cells, which are necessary for the implant to evoke auditory percepts. There is strong evidence that trauma and damage during insertion of electrode arrays into the human cochlea are related to the stiffness of the electrode array. Previous studies were conducted to experimentally determine the stiffness properties of electrode arrays using three-point flexural bending and buckling tests.In this paper, the design of nucleus straight electrode array is modified to give a greater flexibility to further reduce the risk of trauma to delicate structures of the cochlea during surgical insertion of the electrode array. This is achieved by reducing the cross-sectional area of the electrode array at selected positions over its length. Improvements in the flexibility of the new straight electrode array and the bending behavior at its tip have been demonstrated using finite element analysis. Loads applied to the tip of the electrode array at different angles with respect to the longitudinal axis of the electrode array showed that the modified design caused the tip to be more flexible and therefore better able to curl around the inner spiral of the scala tympani and thus less likely to penetrate the basilar membrane during insertion. Loads applied at other positions along the electrode array showed that bending occurred more readily using the modified design thereby reducing the friction and shear stresses at the contact interface between the electrode array and the delicate cochlea structures.
基金Swiss National Science Foundation,Grant numbers:W81XWH-17-NFRP-IIRASinergia Neuroprosthetic Platform for Personalized and Impantable Systems,US Department of Defense Grant numbers:W81XWH-17-NFRP-IIRA.
文摘The auditory brainstem implant(ABI)was originally developed to provide rehabilitation of retrocochlear deafness caused by neurofibromatosis type 2(NF2).Recent studies of the ABI have investigated outcomes in non-NF2 cohorts,such as patients with cochlear nerve aplasia or cochlear ossification and more recently,intractable tinnitus.New technologies that improve the ABI-neural tissue interface are being explored as means to improve performance and decrease side effects.Innovative discoveries in optogenetics and bioengineering present opportunities to continually evolve this technology into the future,enhancing spatial selectivity of neuronal activation in the cochlear nucleus and preventing side effects through reduction in activation of non-target neuronal circuitry.These advances will improve surgical planning and ultimately improve patients1 audiological capabilities.ABI research has rapidly increased in the 21st century and applications of this technology are likely to continually evolve.Herein,we aim to characterize ongoing clinical,basic science,and bioengineering advances in ABIs and discuss future directions of this technology.
