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

神经微电路动态传感和驱动的集成EFRI计划旨在通过开发和融合新一代生物传感（记录）和驱动（神经刺激）技术到一个强大的工具箱中，在我们对大脑微电路复杂非线性动力学及其功能的理解中发展变革性范式。拟议中的研究涉及动物模型中带有外部光子和微电子接口的脑回路，特别是研究所谓的“工作记忆”——大脑的“随机存取记忆”。在神经工程层面，本研究在微观尺度上集成了一套新的神经传感和驱动工具，用于参与大脑的特定传感和计划行动，特别是前额叶皮层的信息处理动态。一个关键的实验驱动因素是一种新的微光学/光子器件技术的发展，该技术将通过皮层微电路的感觉通路和该电路在特定动物模型中的实时成像实现精确的时空靶向。传感器/执行器工程中独特的器件技术元素集成了超紧凑的多元件光源阵列和微电子芯片级传感器，用于实时激发和绘制大脑微电路，这已经通过细胞水平的遗传和纳米材料敏化实现了刺激响应和可记录。开发具有相关脑科学范式的传感/驱动微工具的目标是为跨大脑神经元群体双向访问的微设备接口铺平道路。双向性要求在细胞水平上对多个神经元同时进行神经记录和神经刺激，并最终在空间和时间上对多个大脑部位进行神经刺激。开发一类特定的脑接口探针，协同当代光子学/光电子学的方法，从大脑的微电路中“读取”和“写入”神经信息，这是计划中的EFRI提案的贡献目标。在更广泛的背景下，该研究旨在促进闭环反馈紧密型设备技术的实施，该技术提供了全新类型的神经接口的承诺，用于(i)推进对大脑从感知到驱动的理解-具有微电路动力学的细胞水平分辨率，（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系统疾病密切相关，并与癫痫有关。该团队的目标是利用该项目在哺乳动物模型（体外和体内）中的研究成果，以便关键的脑科学范式，如至关重要的“工作记忆”，将找到人类神经科学和康复目标的翻译。通过在团队中加入临床神经病学接口，我们提出的研究设想有助于我们解开神经系统疾病，为阐明和探索类脑系统的本质对其他技术的适用性铺平道路，以及通过在物理和生命科学交叉的前沿领域的先进技术开发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一代具有真正跨学科教育的“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.