Brain-controlled Functional Electric Stimulation after SCI

严重脊髓损伤(SCI)后的功能恢复尚未实现，给患者及其家庭和整个社会带来了不必要的负担。这项工作的长期目标是为那些遭受严重神经损伤或疾病的人开发恢复功能的干预措施。这个项目的目标是开发新的机器学习方法，能够控制进入脊髓的功能性电刺激(FES)以恢复功能。电刺激将与理疗相结合，以优化康复。研究人员假设，传统的物理疗法可以改善严重脊髓损伤后的功能恢复，与建议的FES相结合，将显著改善结果。了解这种相互作用很重要，因为对于FES来说，通过物理治疗保持肌肉质量、骨密度和整体心血管健康是必要的。对于那些截瘫(失去双腿功能)的人来说尤其如此，他们希望用自己的腿走路。这项工作的智力价值在于，目前正在进行的人类研究表明，在严重的神经损伤或疾病后，使用脑源性信号来加强物理治疗。计划中的研究预计将提供对支持改善结果的机制的洞察，以便为如何最好地利用这些脑源性信号提供指导。到目前为止，这些信号几乎只应用于上肢功能的恢复。这项计划中的工作意义重大，因为它将把这些功能扩展到腿部功能。脊髓损伤后恢复肢体功能与恢复上肢功能有明显的不同，因为大部分肢体运动是有节奏的运动，而大脑对肢体的控制更多地与对这些有节奏运动的调整(如避障)有关，而不是与上肢的调节有关。此外，这项工作将通过研讨会、本科生研究机会和毕业论文工作，吸引新一代女孩和年轻妇女参与神经科学和工程学。这将通过与女性工程师协会的成员进行一对一的指导来实现，将女性工程学学生与她们感兴趣的研究项目联系起来。本项目的目标是开发脑机接口(BMI)控制的功能性电刺激(BMI-FES)，以解释物理治疗对大脑中运动控制编码的影响。驱动假说是，传统物理疗法和BMI-FES的结合将显著改善预后。传统物理疗法可改善严重脊髓损伤(SCI)后的功能恢复。为了验证这一假设，研究计划被组织在三个目标下。第一个目标是确定物理治疗对学习BMI的影响。脊髓损伤动物模型的BMI任务是学习控制向右或向左倾斜的平台，这涉及到姿势控制和两侧大脑皮质接触。初始记录将用于根据PI开发的基于无刺激时间直方图(PSTH)的分类器对解码器进行参数化。BMI的表现(功能恢复和肢体运动)将在12周的时间范围内进行比较，包括没有和有物理治疗(机动自行车和跑步机运动)。预期的结果是，接受治疗的BMI将改善BMI的表现，因为治疗将创建一个新的大脑皮层回路，可以更好地编码倾斜平台的运动，而不是在没有治疗的情况下SCI后形成的大脑皮层回路。第二个目标是建立BMI-FES的动力系统模型。利用系统辨识分析，建立运动皮质的动态模型，以辨识线性模型所能满足的状态空间。从OBJ 1记录的数据将用于开发模型系统的第一个通道。在第二个过程中，将记录神经数据，同时通过刺激神经系统的硬膜外刺激器(EES)提供广泛的刺激。记录的跨电极响应将被用来提取关于刺激下系统结构的信息，这使得线性时不变(LTI)系统能够完全规范。预期的结果是，一个单一的线性模型可以解释在给定记录会话中测试的所有倾斜和相关的EES刺激。模型参数预计会随着时间的推移而变化，但随着治疗反应的可塑性和BMI在任务中的表现稳定下来，单一模型将会出现。第三个目标是设计一种BMI-FES的闭环控制系统，它从三个来源适应可塑性：1)物理治疗，2)学习BMI控制，3)从大鼠感觉运动系统对FES的反应中获得体感反馈。实验将确定BMI控制的FES是否可以改善动物在倾斜任务、跑步机上和开阔空间中的功能恢复，并将评估治疗对这种功能恢复的影响。预期的结果是，与没有刺激或紧张性刺激相比，受控的FES将更好地促进功能恢复，而且BMI-FES在接受治疗的动物中将比没有接受治疗的动物更有效。这一点很重要，因为它表明动力系统框架是产生刺激模式的有效方法，治疗诱导的可塑性与通过学习体重指数控制而诱导的可塑性是协同的。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Recovery of function after severe spinal cord injury (SCI) has not yet been achieved, producing undue burden on patients, their families and society as a whole. The long-term goal of this work is to develop interventions for those subjected to severe neurological injury or disease that restore function. The goal of this project is to develop novel machine learning approaches that are able to control functional electrical stimulation (FES) into the spinal cord to restore function. Electrical stimulation will be combined with physical therapy to work to optimize recovery. The investigator hypothesizes that combinations of traditional physical therapy, known to improve functional recovery after severe SCI, and the proposed FES will significantly improve outcome over either alone. It is important to understand this interaction because, in the case of FES, maintaining muscle mass, bone density and overall cardiovascular health through physical therapy is necessary. This is especially true for the case of those with paraplegia (loss of use of both legs) who desire to walk using their own legs. The Intellectual Merit of this work is that there are currently on-going studies in humans that use brain-derived signals to augment physical therapy after severe neurological injury or disease. The studies planned are expected to provide insight into the mechanisms that support improved outcome in order to provide guidance into how best to use these brain-derived signals. To date, these signals have been almost exclusively applied to restoration of upper limb function. The planned work is significant because it will expand these capabilities to lower limb functions. Restoring lower limb function after SCI is distinctly different from restoring upper limb function because much of the lower limb movements are rhythmic locomotion and brain control of lower limbs is more often associated with adjustments to these rhythmic movements (e.g. avoiding obstacles) than that of upper limbs. Moreover, this work will engage a new generation of girls and young women in neuroscience and engineering through workshops, undergraduate research opportunities and graduate thesis work. This will be accomplished by performing one-on-one mentorships with members of the Society for Women Engineers to connect female engineering students with research projects of interest to them. The goal of this project is to develop Brain Machine Interface (BMI) controlled functional electrical stimulation (BMI-FES) that can account for the impact of physical therapy on the encoding of motor control in the brain using a rat model of complete mid-thoracic spinal transection. The driving hypothesis is that combinations of traditional physical therapy, known to improve functional recovery after severe spinal cord injury (SCI), and BMI-FES will significantly improve outcome over either alone. To test this hypothesis, the research plan is organized under three objectives. The FIRST Objective is to identify the impact of physical therapy on learning BMI. The BMI task for the SCI animal model is to learn to control a platform that is being tilted to the right or the left, which involves postural control and bilaterally engages the cortex. Initial recordings will be used to parameterize the decoder based on a peristimulus time histogram (PSTH)-based classifier developed by the PI. BMI Performance (functional recovery and limb kinetics) will be compared without and with physical therapy (motorized bike and treadmill locomotion) over a 12 week time frame. The expected outcome is that BMI with therapy will improve BMI Performance because therapy will create a new cortical circuit that can encode for movements of the tilt platform better than the cortical circuit that develops after SCI in the absence of therapy. The SECOND Objective is to develop a dynamical systems model of BMI-FES. Using systems identification analysis, a dynamic model of motor cortex will be developed to identify the state-space within which a linear model is sufficient. Data recorded from OBJ 1 will be used to develop a first pass of the model system. In the second pass, neural data will be recorded while a broad range of stimulations are delivered via the epidural stimulator (EES) that excite the neural system. The recorded responses across electrodes will be used to extract information about the structure of the system under stimulation, which allows complete specification of a linear time-invariant (LTI) system. The expected outcome is that a single linear model can account for all of the tilts and relevant EES stimulations tested within a given recording session. Model parameters are expected to change over time, but as plasticity in response to therapy and BMI performance in the task stabilize, that a single model will emerge. The THIRD Objective is to design a closed-loop control system for BMI-FES that accommodates plasticity from three sources: 1) physical therapy, 2) learning BMI control and 3) somatosensory feedback from the response of the rat's sensorimotor system to FES. Experiments will determine if BMI controlled FES can improve functional recovery of the animal in the tilt task, on the treadmill and in the open space, and will assess the impact of therapy on this functional recovery. The expected outcome is that controlled FES will improve functional recovery more than no stimulation or tonic stimulation and that BMI-FES will be more effective in animals that receive therapy compared to those that do not. This is important because it would suggest that the dynamical system framework is an effective method to generate stimulation patterns and that plasticity induced by therapy is synergistic with plasticity induced by learning the BMI control.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.