Optical stimulation of neural tissue

描述(由申请人提供)：神经刺激是基础神经生理学研究和一些临床应用中的一种基本方法。虽然自早期的神经电刺激以来，电极设计和刺激方法已经取得了重大进展，但这种方法从根本上讲是不变的，而且是有限的。这一建议提出了一种基于脉冲红外光的体内神经激活的新范式。光刺激提供了一种无接触、空间选择性、无伪影的方法，而不会引起组织损伤，这在许多诊断和治疗临床应用中可能具有明显的优势。这项针对PA-04-006(神经技术研究、开发和增强)的技术开发建议旨在优化这一用于外周和皮质神经激活的新方法。该提案旨在确定这项新的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体，从而产生无伪影的空间特定的动作电位；2)光刺激可以在不损害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来激活神经细胞膜的离子通道。这项建议的具体目标是以系统的方式设计的，以评估和评估光刺激的安全性、有效性和机制，并将其与周围和中枢神经系统(运动皮质)的电刺激进行直接比较。为了实现这些目标，具体目标是：具体目标(1)：评估激光对周围神经的有效和安全刺激参数。具体目的(2)：确定视神经刺激的生理和物理机制。具体目标(3)：评估和确定有效和安全刺激皮质神经组织的激光参数。具体目的(4)：比较视觉刺激和电学方法在运动皮质功能定位中的空间特异性和有效性。具体目的(5)：证明视觉神经刺激在人类的临床安全性和有效性。到拟议的拨款申请期结束时，我们将就光学神经刺激的基础达成普遍共识，优化用于光学神经刺激的激光参数，确定空间分辨率的极限，并展示该方法在动物周围神经和皮质刺激以及早期人类临床前试验中的安全性和有效性。

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.