Using real-time fMRI neurofeedback and motor imagery to enhance motor timing and precision in cerebellar ataxia

7.项目总结 运动想象，尤其是作为物理练习的辅助治疗，有望成为一种强有力的治疗手段。 用于改善运动障碍患者功能的工具。然而，由于其本身的性质，运动意象 不能直接观察到。这使得帮助和评估患者的运动想象努力变得困难。脑区 然而，与运动想象相关的活动是可以通过神经成像观察到的。此外，随着最近的 实时功能磁共振成像神经反馈(rtfMRI-NF)等技术的发展， 运动想象的“行为”可以同时显示给病人和临床医生。我们假设如果病人 可以学习直接“锻炼”他们自己的运动大脑网络，他们可以优化他们的 康复。在这项建议中，我们试图研究将rtfMRI-NF成像训练应用于 患有小脑性共济失调(CA)的个人，这是一种由进行性小脑引起的运动障碍 退化。目前的治疗方法可以通过物理治疗和治疗等方法减缓运动丧失的速度 核心强化，但它们侧重于物理表现，而不是针对潜在的神经 涉及的机制，从而遗漏了根本原因。除了评估运动想象的可行性 RtfMRI-NF在CA中，我们将在rtfMRI会议之后检查额外的家庭治疗的效用。 最后，我们将使用rtfMRI-NF数据进行离线分析，以进行脑图、机器学习和模拟 其他rtfMRI方法，以开发rtfMRI-NF方案的未来迭代。因此，今后的工作目标是 通过确定运动的神经基础(核因子靶点)建立精细化的实验医学框架 精确度，并测试是否通过核磁共振接触这些目标，提高电机性能。如中所述 该提案，AIM 1将在运动想象过程中使用rtfMRI-NF来训练CA参与者，以提高运动准确性。 在一项我们假设CA的实验中，30名CA参与者将在运动想象过程中接受神经营养因子 参与者将能够控制一个核因子接口；2)成像技能将与 外显敲击准确率；3)外显敲击准确率与神经体征相关，而运动 表象技能将与评估的运动表象能力相关。AIM 2将把rtfMRI-NF学习转化为AT- 三周持续训练的家庭治疗策略，其中我们假设1)继续练习 使用成像策略将进一步提高运动计时和精度，以及2)性能 在rtfMRI中，核因子训练与家庭运动表象成绩呈正相关。在探索性的 目的3，我们将检查三个主要问题，以建立未来的实验药物设计。具体来说， 这些问题是：1)尖锐湿疣患者与健康对照组的fMRI活性是否存在组级差异；2)是 对于CA NF可行的健康运动想象模型；以及3)是否可以简化NF会议以提供更多 在较短的疗程中准确的核因子？这项建议是治疗尖锐湿疣的第一个此类建议， 极大地改善运动康复效果的潜力。

7. PROJECT SUMMARY Motor imagery, especially when used as an adjuvant treatment with physical practice, promises to be a powerful tool for improving function in individuals with movement disorders. Yet, due to its very nature, motor imagery cannot be directly observed. This makes it difficult to assist and evaluate a patient's motor imagery efforts. Brain activity associated with motor imagery is, however, observable through neuroimaging. Moreover, with the recent development of technologies like real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF), motor imagery “behavior” can be displayed to both the patient and the clinician. We hypothesize that if patients could learn to “exercise” their own motor brain networks directly, they could optimize their rehabilitation. In this proposal, we seek to examine the feasibility of applying rtfMRI-NF imagery training to individuals with cerebellar ataxia (CA), a movement disorder that results from progressive cerebellar degeneration. Current treatments can slow the rate of motor loss through methods such as physical therapy and core strengthening, but they focus on physical manifestations and do not target the underlying neural mechanisms involved, thereby missing the root cause. In addition to evaluating the feasibility of motor imagery rtfMRI-NF in CA, we will examine the utility of additional at-home therapy, subsequent to the rtfMRI session. Finally, we will use the rtfMRI-NF data for offline analyses for brain mapping, machine learning, and simulating additional rtfMRI approaches to develop future iterations of rtfMRI-NF protocols. Thus, future work aims to establish refined experimental medicine frameworks by identifying neural underpinnings (NF targets) of motor accuracy, and testing whether engaging these targets, through NF, improves motor performance. As outlined in the proposal, Aim 1 will use rtfMRI-NF during motor imagery to train CA participants to improve motor accuracy. Thirty CA participants will receive NF during motor imagery in an experiment in which we hypothesize that 1) CA participants will be able to control a NF interface; 2) imagery skill will be positively correlated to improvements in overt tapping accuracy; and 3) overt tapping accuracy will correlate with neurological signs, whereas motor imagery skill will correlate with assessed motor imagery ability. Aim 2 will translate rtfMRI-NF learning into at- home therapy strategies for three weeks of continued training in which we hypothesize that 1) continued practice with imagery strategies will lead to additional improvements in motor timing and precision, and 2) performance during rtfMRI-NF training will positively correlate with at-home motor imagery performance. In an exploratory Aim 3, we will examine three primary questions to establish future experimental medicine designs. Specifically, these question are 1) Are there group-level differences in fMRI activity in CA versus healthy controls?; 2) Are healthy models of motor imagery viable for CA NF?; and 3) Can the NF session be streamlined to deliver more accurate NF in shorter sessions? This proposal represents the first of its kind in the treatment of CA, with the potential to dramatically improve motor rehabilitation outcomes.