Micro-magnetic Stimulation of Auditory Neurons: a New Paradigm in Overcoming Hearing Loss

据世界卫生组织估计，超过5%的世界人口(3.6亿人：3200万儿童)患有失聪。无人看管的听力损失会导致孤立感、孤独感和极度沮丧。这在老年人中尤其普遍。听力损失不仅严重损害了沟通，还经常导致儿童口语能力的延迟。可以使用许多不同程度成功的策略来减少听力障碍的有害影响：这些策略包括筛查、保护、字幕、手语，以及助听器和人工耳蜗(CI)等辅助设备。CI设备通过将声波编码为电脉冲来发挥作用。反过来，这些脉冲决定了施加到内耳(耳蜗神经)神经元上的电荷量，从而传递一种丢失或减弱的声音感觉。全世界已经植入了大约324,000个CI，使一些人能够很好地感知语音。然而，结果是高度可变和不可预测的。日常情况，如在嘈杂环境中理解语音和欣赏音乐，给用户带来了巨大的挑战。一个主要的原因是顺式离子不能精确地控制高导电性脑脊液中的电荷路径。这项工作寻求一种有希望的、新颖的直接电刺激的替代方案--通过安装在柔性衬底上并植入耳蜗内的电脉冲线圈进行微磁刺激。耳壳内微线圈阵列可以更具特异性地激活听神经元，同时还可以实现更长期的安全性，因为微线圈完全被包裹起来。微磁线圈的适用范围自然可以扩大，以克服平衡、视力以及改善大脑深部刺激的损失。为了进一步提高这项研究的社会影响，与疾病控制和预防中心以及芬班克科学中心的合作将在弗吉尼亚州亚特兰大启用和促进听力健康意识和教育。拟议的工作是推进对局部感应场如何刺激神经元的理解的必要的第一步。与需要巨大线圈和消耗相当大能量的经颅磁刺激相比，植入目标神经组织近端的微线圈可能会更有效地接触神经系统。为了进行这项研究，将开发在聚合物基板上建立微线圈的直接金属喷墨打印方法。这些设备将用医用级聚合物完全封装，并在溶液中进行测试，以检查阻抗漂移和泄漏电流。体外实验也将通过在2D多通道电极阵列(MEA)上培养的器官型螺旋神经节神经元来完成。2D-MEA和相关软件系统将使非侵入性、闭环式微磁刺激和神经反应记录成为前所未有的可能。由此，将评估神经阈值和特异性，并与传统的基于CI电极的刺激进行比较。以平行和高度协作的方式，将在人类身体耳蜗中进行阵列插入研究，以评估插入创伤、插入深度和标量壁距离。更广泛地说，新型印刷和添加剂制造的应用，与柔性电子技术相结合，有可能将神经接口技术的制造转变为洁净室外的工艺，同时实现与支持驱动电子和包装的无缝集成。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

As estimated by the World Health Organization, over 5% of the world's population (360 million individuals: 32 million children) experience disabling hearing loss. Unattended hearing loss results in feelings of isolation, loneliness, and extreme frustration. This is especially prevalent in older individuals. Not only does hearing loss severely impair communication, it often leads to delays in spoken language abilities in children. A host of strategies, with varying degrees of success, can be used to reduce the detrimental effects of hearing disability: these range from screening, protection, captioning, sign language, to assistive devices such as hearing aids and cochlear implants (CI). CI devices function by coding sound waves as electrical pulses. In turn, these pulses determine the amount of electrical charge applied to neurons in the inner ear (cochlea) thereby conveying a lost or diminished sensation of sound. Approximately 324,000 CI have been implanted worldwide enabling some individuals to perceive speech very well. However, outcomes are highly variable and unpredictable. Everyday situations, such as understanding speech in noisy settings, and appreciating music, present users with significant challenges. A major contributor is the inability of CIs to precisely control the path of electrical charge in the highly conductive intracochlear fluid. This work pursues a promising and novel alternative to direct electrical stimulation - micro-magnetic stimulation via electrically pulsed coils housed on a flexible substrate and implanted in the cochlea. An intracochlear micro-coil array can activate auditory neurons with greater specificity while also enabling longer-term safety since the micro-coils are fully encapsulated. The applicability of micro-magnetic coils can naturally be extended to overcome loss in balance, sight, as well as to improve deep brain stimulation. To further enhance the societal impact of the research, partnerships with the Centers for Disease Control and Prevention, and Fernbank Science Center will enable and promote hearing health awareness and education in Atlanta, GA.The proposed work is a necessary first-step toward advancing an understanding of how locally induced fields may serve to excite neurons. In contrast with transcranial magnetic stimulation requiring a bulky coil and consuming considerable power, micro-coils implanted proximal to target neural tissue may engage the nervous system more effectively. To pursue this research, direct metal inkjet printing methods to build micro-coils on polymeric substrates will be developed. The devices will be fully encapsulated with a medical grade polymer and tested in solution to examine for impedance shifts and leakage current. Ex-vivo testing will also be accomplished with organotypic spiral ganglion neurons cultured on a 2D multichannel electrode array (MEA). The 2D-MEA and associated software system will enable the unprecedented possibility of non-invasive, closed-loop micro-magnetic stimulation and neural response recording. From this, neural threshold and specificity will be assessed and compared with conventional CI electrode-based stimulation. In a parallel and highly collaborative fashion, array insertion studies in human cadaver cochleae to assess insertion trauma, depth of insertion, and scalar wall distances will be pursued. More broadly, the application of novel printing and additive manufacturing, combined with flexible electronics, has the potential to transform fabrication of neural interface technologies to processes outside of the cleanroom, while enabling seamless integration with supporting drive electronics and packaging.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.