Assessing non-invasive measures of neural health in cochlear implant users and the clinical implications

 描述（由申请人提供）：听觉神经的状况被认为是预测人工耳蜗植入（CI）结果的最重要因素之一。神经状况在植入的耳朵和耳朵内的耳蜗区域之间变化。如果基于对电极阵列上的植入耳朵的神经状况的评估，以对于每个个体最优的方式刺激听觉外围，则语音识别可以潜在地得到改善。通过建立与动物模型中螺旋神经节细胞密度相关的非侵入性测量，可以评估活体人类CI用户的神经状况。当前提案的目的是评估这些临床适用的神经健康措施在人类CI用户中的应用，并基于这些措施设计定制的刺激策略。在植入的豚鼠中，测试电极附近的螺旋神经节细胞计数与检测相关 低脉率时的阈值，以及阈值随脉率增加而降低的速率，称为多脉冲积分（MPI）。阈值较低和MPI斜率较陡的豚鼠往往有较高的螺旋神经节细胞密度。目的1评估这两个心理物理措施，以确定它们是否可以用来估计人类CI用户的神经密度。预测是，如果MPI函数的斜率或低速率阈值取决于神经密度，则该测量应预测人类神经兴奋（调谐）的位置特异性。目的2检验存活神经元的功能是MPI函数陡度的潜在机制的假设。该假设的基本原理是，在新霉素处理的动物中，在具有低神经密度的耳中，存活的神经元也可能具有受损的神经功能，例如延长的神经不应性和对刺激的更大适应。这两个因素都可能导致高速率刺激的低于预期的神经采样，表现为对脉搏率变化不敏感（即，浅MPI斜率）。预测是，如果MPI斜率依赖于神经功能，浅MPI功能应预测较慢的神经恢复不应期和适应刺激。目标3提出了两种基于神经密度和功能度量的自定义映射策略。策略一通过使刺激部位随着神经兴奋的扩散而失活，将刺激目标对准估计具有高神经密度的耳蜗区域。策略二降低了对脉率变化整体敏感性低的受试者的刺激率。使用这些新策略的语音识别性能将与使用受试者的临床地图进行比较。所提出的神经健康的心理物理措施和定制映射策略是简单和时间效率高的，因此具有很大的临床应用潜力。1

 DESCRIPTION (provided by applicant): The condition of the auditory nerve is thought to be one of the most important factors that predict the outcome of a cochlear implant (CI). The neural condition varies across the implanted ears and across cochlear regions within an ear. Speech recognition can potentially be improved if the auditory periphery is stimulated in a way that is th most optimal for each individual based on an assessment of the neural condition of the implanted ear across the electrode array. Assessing neural conditions in living human CI users has been possible by the establishment of non-invasive measures that correlate with the density of the spiral ganglion cells in the animal models. The objective of the current proposal is to assess these clinically-applicable measures of neural health for their applications in human CI users and design customized stimulation strategies based on these measures. In implanted guinea pigs, the count of the spiral ganglion cells near tested electrodes correlate with detection thresholds at low pulse rate, as well as the rate of threshold decrease with the increase of pulse rate, known as multipulse integration (MPI). Guinea pigs with lower thresholds and steeper MPI slopes tended to have higher spiral ganglion cell density. Aim 1 evaluates the two psychophysical measures to determine if they can be used to estimate neural density in human CI users. The prediction is that if the slope of the MPI functions, or the low- rate threshold, is dependent on neural density, the measure should predict place specificity of neural excitation (tuning) in humans. Aim 2 tests the hypothesis that the function of the surviving neurons is the underlying mechanism for the steepness of the MPI functions. The rationale for the hypothesis is that, in neomycin- deafened animals, in ears with low neural density, the surviving neurons are likely to also have impaired neural function, such as prolonged neural refractoriness and greater adaptation to stimulation. Both factors could result in a lower-than-expected neural sampling of the high-rate stimulus manifested as insensitivity to pulse rate change (i.e., shallow MPI slopes). The prediction is that if MPI slope is dependent on neural function, shallow MPI functions should predict slower neural recovery from refractoriness and adaptation to stimulation. Aim 3 proposes two customizing mapping strategies based on the proposed neural density and function measures. Strategy one targets stimulation at cochlear regions estimated to have high neural density by deactivating stimulation sites with spread of neural excitation. Strategy two lowers stimulation rate for subjects who show overall low sensitivity to pulse rate change. Speech recognition performance using these new strategies will be compared to that using the subjects' clinical maps. The proposed psychophysical measures for neural health and the customizing mapping strategies are simple and time-efficient and, thus have great potential for clinical use. 1