EFRI-BSBA Integration of Dynamic Sensing and Actuating of Neural Microcircuits

神经微电路动态感知和驱动的集成PI：Arto V.Nurmikko建议的EFRI计划旨在通过开发和融合新一代生物感知(记录)和驱动(神经刺激)技术，在我们理解大脑微电路及其功能的复杂非线性动力学方面开发变革性的范例。这项拟议的研究在动物模型中使用了带有外部光子和微电子接口的大脑电路，特别是为了研究所谓的“工作记忆”--大脑的“随机存取记忆”。在神经工程层面，这项拟议的研究整合了一套新的微观尺度的神经感知和驱动工具，用于参与大脑的特定感知和规划行动--特别是前额叶皮质的信息处理动力学。一个关键的实验驱动因素是开发一种新的微光学/光子设备技术，该技术将通过大脑皮层微电路的感觉通路实现精确的时空靶向，并在特定动物模型中实时成像该电路。传感器/致动器工程中独特的设备技术元素集成了超紧凑的多元素光发射器阵列和微电子芯片规模的传感器，用于实时激发和绘制大脑微电路，并通过细胞级别的遗传和纳米材料敏化来实现刺激响应和记录。开发具有相关脑科学范式的感知/致动微工具的目标是为微设备接口铺平道路，以便跨大脑中的一组神经元进行双向访问。双向性要求神经记录和神经刺激可以在细胞水平上同时实现，对于多个神经元，并最终在空间和时间上实现多个脑部位。开发一类特定的大脑接口探测器，将当代光子学/光电子学的方法协同起来，从大脑的微电路中读取神经信息，并将其写入大脑的微电路，这是这项计划中的EFRI提案的贡献目标。在更广泛的背景下，这项研究旨在促进闭环反馈紧凑型设备技术的实施，该技术有望提供全新类别的神经接口，用于(I)促进对大脑从感知到驱动的理解-具有微电路动力学的细胞级别分辨率，(Ii)旨在将该技术应用于潜在的治疗和假肢应用。例如，对大脑工作记忆功能的研究与精神分裂症、注意力缺陷障碍等神经疾病密切相关，并与癫痫有关。该团队的目标是在哺乳动物动物模型(体外和体内)中利用该项目的研究成果，以便关键的脑科学范式，如根本重要的“工作记忆”，将被转化为人类神经科学和康复目标。通过在团队中加入临床神经学接口，我们拟议的研究旨在为我们揭开神经系统疾病的面纱做出贡献，为阐明和探索类脑系统对其他技术的适用性铺平道路，并通过在物理科学和生命科学交叉的前沿领域开发先进技术来提高美国在全球经济中的竞争力。对这些主题的研究也有望培养出真正接受跨学科教育的一代“神经工程”研究生，以及创新型企业和企业家。

ABSTRACTIntegration of Dynamic Sensing and Actuating of Neural MicrocircuitsPI: Arto V. Nurmikko The proposed EFRI program aims to develop transformative paradigms in our understanding of the complex nonlinear dynamics of brain microcircuits and their function, by developing and fusing a new generation biosensing (recording) and actuation (neurostimulation) techniques to a potent toolbox. The proposed research engages brain circuits with external photonic and microelectronic interfaces in animal models, in particular for the study of the so-called "working memory" - the brain's "random access memory". At the neuroengineering level, the proposed research integrates new set of neural sensing and actuation tools on the microscale that are applied to engage with specific sensing and planning action by the brain - in particular the dynamics of information processing in the prefrontal cortex. A key experimental driver is the development of a new micro-optical/photonic device technology that will enable precise spatio-temporal targeting through sensory pathways of cortical microcircuitry and the imaging of this circuitry in real time in specific animal models. The unique device technology elements in the sensor/actuator engineering integrate ultracompact multi-element arrays of light emitters and microelectronic chip-scale sensors for excitation and mapping of the brain microcircuitry in real-time, which has been rendered both stimulus responsive and recordable by cellular-level genetic and nanomaterial sensitizing. The goal of the development of sensing/actuation microtools with associated brain science paradigms is to pave way for microdevice interfaces for bidirectional access across a population of neurons in the brain. Bidirectionality requires that both neural recording and neural stimulation can be achieved simultaneously at cellular level for multiple neurons, and ultimately multiple brain sites, spatially and temporally. Development of a class of specific brain-interfaces probes which synergize approaches from contemporary photonics/optoelectronics for "reading" and "writing" neural information from/to brain's microcircuits is the contributing aim of this planned EFRI proposal. In a broader context, the research aims to facilitate the implementation of a closed-loop feedback compact device technology that offers the promise of entirely new classes of neural interfaces for (i) advancing the understanding of the brain from sensing to actuation- with cellular level resolution of microcircuit dynamics, (ii) aim the application of the technology to potentially therapeutic and prosthetic applications. For example, the study of the working memory function in the brain is closely associated with neurological diseases such as schizophrenia, attention deficit disorder and has been linked to epilepsy. The team aims to leverage the research outcomes from this program in mammalian animal models (in vitro and in vivo) so that key brain science paradigms such as the fundamentally important "working memory" will find translation to human neuroscience and rehabilitative goals. By including within the team a clinical neurology interface, our proposed research is envisioned to contribute to our unraveling of neurological disease, pave way for elucidating and exploring the applicability the nature of the brain-like systems to other technologies, as well as improve U.S. competitiveness in the global economy through advanced technology development in a frontier area at the intersection of physical and life sciences. The research on these topics is also expected to create a generation of "neuroengineering" graduate students with true interdisciplinary education, as well as innovative businesses and entrepreneurs.