Optical stimulation of neural tissue

描述（由申请人提供）：神经刺激在基础神经生理学研究和许多临床应用中都是必不可少的方法。虽然自早期电神经刺激以来，电极设计和刺激方法取得了重大进展，但这种方法基本上没有改变，而且受到限制。提出了一种基于脉冲红外光的体内神经激活新模式。光学刺激提供了一种无接触、空间选择性、无伪影的方法，不会造成组织损伤，在许多诊断和治疗临床应用中可能比电方法具有显著的优势。根据PA-04-006（神经技术研究、开发和增强）的要求，这项技术开发提案旨在优化这种用于外周和皮层神经激活的新方法。该提案旨在确定这种新型神经技术的物理和生理基础，并评估其在体内应用的潜力。为此，我们假设1)脉冲激光可以用来刺激离散的神经细胞群，产生无伪影的、空间特异性的动作电位；2)光刺激可以在不损伤神经组织的情况下完成；3)这种效应的机制是通过释放细胞内钙离子激活神经细胞膜离子通道的热机械过程。本提案的具体目的是以系统的方式来评估和评估光刺激与电刺激在外周和中枢神经系统（运动皮层）的安全性、有效性和机制。具体目的(1)：评估有效、安全刺激周围神经的激光参数。具体目的(2)：确定光神经刺激的生理和物理机制。具体目的(3)：评估和确定有效和安全刺激皮质神经组织的激光参数。特定目的(4)：比较光刺激与电刺激的空间特异性和有效性，以绘制运动皮层的功能图。具体目标(5)：证明人体光神经刺激的临床安全性和有效性。在拨款申请期结束时，我们将对光神经刺激的基础达成普遍共识，优化光神经刺激的激光参数，确定空间分辨率的限制，并在动物和早期人体临床前试验中显示该方法用于外周神经和皮层刺激的安全性和有效性。

DESCRIPTION (provided by applicant): Neural stimulation is an essential method both in fundamental neurophysiological studies as well as in a number of clinical applications. While significant advances have been made in electrode design and stimulation approaches since the early days of electrical neural stimulation, the method is fundamentally unchanged and limited. This proposal presents a new paradigm to in vivo neural activation based on pulsed infrared light. Optical stimulation provides a contact-free, spatially selective, artifact-free method without incurring tissue damage that may have significant advantages over electrical methods for many diagnostic and therapeutic clinical applications. This technology development proposal in response to PA-04-006 (Neurotechnology research, development, and enhancement) is directed towards the optimization of this novel approach for peripheral as well as cortical neural activation. The proposal is designed to determine the physical and physiological basis for this novel neurotechnology as well as assess its potential for in vivo application. Towards this, we hypothesize that 1) pulsed laser light can be used to stimulate discrete populations of neural cells resulting in artifact free, spatially specific action potentials; 2) optical stimulation can be accomplished without causing damage to the neural tissue; and 3) the mechanism of this effect is a thermo-mechanical process resulting in activation of ion channels of neural cell membranes by releasing intracellular calcium. The specific aims of this proposal have been designed in a systematic manner to evaluate and assess safety, efficacy and mechanism of optical stimulation in direct comparison with electrical stimulation in peripheral as well as the central nervous system (motor cortex). To accomplish these goals, the specific aims are: Specific Aim (1): Evaluate laser parameters for effective and safe stimulation of peripheral nerves. Specific Aim (2): Determine the physiological and physical mechanisms of optical neural stimulation. Specific Aim (3): Assess and identify the laser parameters for effective and safe stimulation of cortical neural tissue. Specific Aim (4): Compare spatial specificity and efficacy of optical stimulation to electrical methods for the functional mapping of the motor cortex. Specific Aim (5): Demonstrate clinical safety and efficacy of optical neural stimulation in humans. By the end of the proposed period of the grant application, we will have arrived at a general consensus for the basis of optical neural stimulation, optimized laser parameters for optical nerve stimulation, determined limits of spatial resolution and shown the safety and efficacy of this method for peripheral nerve as well as cortical stimulation in animals as well as in early human preclinical trials.