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大的成功，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质控制。该领域的最新进展导致了最强大的假肢手臂的创造，包括DEKA的“卢克手臂”和约翰霍普金斯APL的“模块化假肢”。然而，这一努力的一个关键缺陷是缺乏支持假肢本体感觉和触觉所需的体感反馈。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好处，因为没有感觉反馈，这些设备将仍然是麻木的、体外的“工具”，而不是集成的全功能肢体。我们的目标有两个：更好地理解感觉反馈的本质，以及外周感觉活动传递到初级体感皮层（S1）的方式，并开发一个体感神经接口（SSNI），为用户的神经假肢提供本体感受反馈。我们之前提出，背根神经节（DRG）的初级传入微刺激（PAMS）可用于向中枢神经系统传递替代体感反馈。我们已经证明，在猫中，PAMS可以从各种感觉模式中招募少量传入事件（Gaunt et al. 2009），并且这种刺激可以将有意义的活动传递给S1 （Weber et al. 2011）。在动物模型的开发过程中取得的成功产生了许多新的问题和假设，在此基础上提出了一系列新的实验。具体来说，这些实验的重点是表征PAMS的能力：1)当PAMS模式基于运动时DRG记录的神经活动时，PAMS向麻醉猫的S1传递感觉信息；2)当PAMS模式基于虚构的静态和动态输入时，PAMS向麻醉猫的S1传递可辨别的感觉信息；3)向清醒站立猫的S1传递可辨别的感觉信息。用于修改对地面支持扰动的姿态响应。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，这对未来基于BMI的假肢至关重要，同时也解决了关于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.