Multichannel Microstimulation of Primary Afferent Neurons to Restore Propriocepti

描述（由申请人提供）：NIH神经假体项目在皮质控制神经假体领域取得了如此多的成功，以至于FDA已经批准了多项人体试验，以测试脑机接口（BMI）皮质植入物的安全性和有效性。 BMI技术的一个重要应用是假肢的直接皮层控制。 这一领域的最新进展导致了迄今为止最有能力的假肢的诞生，包括DEKA的“卢克臂”和约翰霍普金斯APL的“模块化假肢”。 然而，在这方面的努力的一个关键差距是缺乏体感反馈，这是需要支持propriception和触觉的假肢。 如果没有这些感觉，用户将永远无法从这些先进的肢体中获得最大的益处，因为如果没有感觉反馈，这些设备将仍然是麻木的体外“工具”，而不是集成的功能齐全的肢体。 我们的目标是双重的：为了更好地理解感觉反馈的性质以及外周感觉活动传递到初级躯体感觉皮层（S1）的方式，并开发躯体感觉神经接口（SSNI），其将为用户的神经假肢提供本体感觉反馈。 我们以前提出，初级传入微刺激（PAMS）在背根神经节（DRG）可以用来提供替代体感反馈到中枢神经系统。 我们已经证明，在猫中，PAMS可以从各种感觉方式中招募小群体的传入神经（Gaunt et al. 2009），并且这种刺激可以将有意义的活动传递到S1（Weber et al. 2011）。 在开发这种动物模型的过程中取得的成功产生了许多新的问题和假设，并提出了一系列新的实验。 具体地，这些实验集中于表征PAMS的以下能力：1）当PAMS模式基于运动期间在DRG中记录的神经活动时，将感觉信息传输到麻醉猫中的S1，2）当PAMS模式基于制造的静态和动态输入时，将可辨别的感觉信息传输到麻醉猫中的S1，3）在清醒站立的猫中，将可辨别的感觉信息传递到S1，这对于改变对地面支撑扰动的姿势反应是有用的。 这些实验的范围从进一步研究PAMS的能力到测试PAMS可预测地改变运动行为的能力。 这项工作将进一步发展SSNI，对未来基于BMI的假肢至关重要，并解决有关感觉反馈在控制正常运动行为中的作用的基本问题。

DESCRIPTION (provided by applicant): The NIH neuroprosthesis program has fostered so much success in the area of cortically controlled neuroprostheses that the FDA has approved multiple human trials to test the safety and efficacy of cortical implants for brain machine interfaces (BMI). One important application of BMI technologies is the direct cortical control of prosthetic limbs. Recent advances in this field have led to the creation of the most capable prosthetic arms yet developed, including the DEKA 'Luke arm' and Johns Hopkins APL 'Modular Prosthetic Limb'. However, a critical gap in this effort is the lack of somatosensory feedback which is needed to support propriception and tactile sensations for the artificial limb. Without these sensations, users will never achieve maximum benefit from these advanced limbs, because without sensory feedback, these devices will remain as numb, extracorporeal 'tools', rather than integrated fully functional limbs. Our goals are twofold: to better understand the nature of sensory feedback and the way in which peripheral sensory activity is conveyed to primary somatosensory cortex (S1), and to develop a somatosensory neural interface (SSNI) that will provide the user with proprioceptive feedback for their neuroprosthesics limb. We have previously proposed that primary afferent microstimulation (PAMS) in the dorsal root ganglia (DRG) can be used to deliver surrogate somatosensory feedback to the central nervous system. We have demonstrated that in cats, PAMS can recruit small populations of afferents from a variety of sensory modalities (Gaunt et al. 2009) and that this stimulation can transmit meaningful activity to S1 (Weber et al. 2011). The success achieved during the development of this animal model generated a number of new questions and hypothesis upon which a series of new experiments are proposed. Specifically, these experiments focus on characterizing the ability of PAMS to 1) transmit sensory information to S1 in anesthetized cats when the PAMS patterns are based on neural activity recorded in the DRG during movement, 2) transmit discriminable sensory information to S1 in anesthetized cats when the PAMS patterns are based on fabricated static and dynamic inputs, and 3) transmit discriminable sensory information to S1 in awake standing cats, useful for modifying postural responses to ground support perturbations. These experiments range from further investigations of the capabilities of PAMS to testing the ability of PAMS to predictably modify motor behaviors. This work will further the development of a SSNI, critical for the future of BMI based prosthetic limbs, as well as address fundamental questions regarding the role of sensory feedback in the control of normal motor behaviors.