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以及许多临床应用中的基本方法。虽然自电神经刺激的早期以来，在电极设计和刺激方法方面已经取得了重大进展，但该方法基本上没有改变并且受到限制。这一建议提出了一种新的范例，在体内神经激活的基础上脉冲红外光。光学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，这对于许多诊断和治疗临床应用来说可能具有优于电方法的显著优势。响应PA-04-006（神经技术研究、开发和增强）的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）脉冲激光可用于刺激离散的神经细胞群，产生无伪影的空间特异性动作电位; 2）光学刺激可在不对神经组织造成损伤的情况下完成; 3）这种效应的机制是热机械过程，通过释放细胞内钙激活神经细胞膜的离子通道。本提案的具体目的旨在系统地评价和评估光刺激与外周和中枢神经系统（运动皮层）电刺激直接比较的安全性、有效性和机制。为实现这些目标，具体目标为：具体目标（1）：评价周围神经有效和安全刺激的激光参数。具体目标（2）：确定光学神经刺激的生理和物理机制。特定目的（3）：评估和确定有效和安全刺激皮质神经组织的激光参数。具体目标（四）：比较空间特异性和有效性的光学刺激的电方法的功能映射的运动皮层。特定目的（5）：证明光学神经刺激在人体中的临床安全性和有效性。到拨款申请的建议期限结束时，我们将对光学神经刺激的基础达成普遍共识，优化光学神经刺激的激光参数，确定空间分辨率的限制，并显示该方法用于周围神经的安全性和有效性以及动物和早期人类临床前试验中的皮层刺激。

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.