GCR: Reprogramming Biological Neural Networks with Field-Based Engineered Systems

尽管近年来在开发神经假体绕过中枢神经系统(CNS)受损区域方面取得了巨大进展，但这些设备未能阻止潜在退行性疾病的进展，这些疾病是为它们设计的。此外，许多影响眼睛或大脑的神经退行性疾病没有有效的治疗方法，致盲疾病和痴呆症造成的人道主义和经济影响是巨大的，代表不足的群体尤其受到这些疾病的影响。该项目的目标是通过促进受损神经元和神经网络的修复和再生而不是绕过受损区域的疗法来恢复中枢神经系统的功能。为了实现通过设备延缓痴呆症患者视力丧失和神经退化的目标，该团队汇集了工程师、外科医生、神经科学家和大数据/成像科学家。该研究小组将通过实验和计算设计和优化重写受损神经网络形态所需的电刺激波形特征；创建暴露在电场和场梯度中的全球神经网络的“首个”完整中尺度连通性图集；开发健康、变性和电刺激神经网络中神经活动的预测性多尺度计算模型；以及设计和设计用于急性神经刺激神经组织的可编程植入式电子系统。通过最终用户提供设计意见，从而促进开发下一代治疗机会所需的完全集成、互惠、持续的融合合作，在拟议的工作中开发的工具的效用将得到提高。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。

Despite enormous advances in recent years to develop neuroprosthetics to bypass damaged areas of the Central Nervous System (CNS), these devices fail to halt the progression of the underlying degenerative diseases for which they were designed. Moreover, there are no effective therapies for many of the neurodegenerative conditions that affect, for example, the eye or the brain, and the humanitarian and economic impact of blinding diseases and dementia are enormous, with underrepresented groups particularly impacted by these conditions. The goal of this project is to enable restoration of function to the CNS by therapies that promote the repair and regeneration of damaged neurons and neural networks instead of bypassing damaged areas. To achieve this goal of delaying vision loss and neural degeneration in dementia through devices this team brings together engineers, surgeons, neuroscientists and big data/imaging scientists. This research team will devise and optimize, experimentally and computationally, the electrical stimulation waveform characteristics needed to reprogram damaged neural network morphologies; create, “first of its kind” complete mesoscale connectivity atlases of the global neural networks exposed to electric fields and field gradients; develop predictive multiscale computational models of neural activity in healthy, degenerated and electrically stimulated neural networks; and design and engineer programmable implantable electronic systems for the acute neurostimulation of the neural tissue. The utility of the tools developed in the proposed effort will be enhanced by end-users providing design input, thus facilitating fully integrated, mutually beneficial, sustained convergent collaborations that are needed to develop the therapeutic opportunities of the next generation.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.