Development and In Vivo Validation of a Theoretical Framework and Practical Methods to Improve Safety and Efficacy of Neuromodulation Electrodes

尽管临床应用广泛，但通过植入电极来理解电刺激安全性的理论框架却令人惊讶地有限。我们目前对刺激安全性的理解大多是在上世纪80年代和90年代用非常有限的电极几何形状、材料、刺激系统和刺激位置从现象上确定的。目前，为支持提交给食品和药物管理局（FDA）的电极安全性的台式测试主要集中在确定驱动电极/电解质界面水水解的外加电荷密度上。在本提案中，我们寻求验证，优化和分发一个更准确地预测慢性体内安全性问题的台式测试框架。该框架可扩展到涂层微电极设计，包括高密度和/或薄膜阵列，以及新的刺激波形，这两者都是下一代微创神经调节疗法的关键。

Despite widespread clinical use, the theoretical framework by which to understand safety of electrical stimulation through implanted electrodes is surprisingly limited. Most of our current understanding of stimulation safety was phenomenologically determined in the 80s and 90s using very limited electrode geometries, materials, stimulation systems, and stimulation locations. Current benchtop testing of electrode safety to support submissions to the Food and Drug Administration (FDA) is predominantly focused on identifying the applied charge density that drives the hydrolysis of water at the electrode/electrolyte interface. In this proposal, we seek to validate, optimize, and distribute a benchtop testing framework that more accurately predicts chronic in-vivo safety issues. This framework is extensible to coated microelectrode designs, including high-density and/or thin-film arrays, as well as to novel stimulation waveforms – both of which are critically enabling for next-generation minimally invasive neuromodulation therapies.