Subjective Valuation of Physical Effort in Health and Disease

项目摘要 康复治疗依从性的一个主要障碍是患者的努力不足， 疲劳和无法克服的努力的感觉。如果一项体育锻炼感觉很费力， 如果你觉得一项运动不那么费力，你可能更有可能坚持下去。 尽管基于努力的判断无处不在，而且在各种神经系统疾病中会受到干扰， 对身体努力的主观评价机制的研究有限。的 这一建议的中心假设是，个人对努力的主观评价反映在她的内在 运动皮层的兴奋性，并且该度量对疾病状态敏感。我们将进行实验， 健康人参与者;和一组患有多发性硬化症（MS）的参与者。我们已经开发出一种 一种新的基于努力的选择范式，使我们能够获得一个精确的客观衡量个人的 对努力的主观评价我们将使用这种方法，结合计算建模，功能 磁共振成像（fMRI）和非侵入性脑刺激，以研究其机制 负责主观评价努力。在目标1中，我们将研究运动生理学如何影响 健康参与者的主观努力评估。我们将使用经颅磁刺激（TMS）， 侵入性地探测参与者运动皮层的生理特性;我们将有同样的 参与者在接受功能磁共振成像扫描时做出关于努力的决定，并使用这些数据进行计算。 模拟他们对努力和相关大脑活动的主观评价。这些实验将使我们能够测试 个体对努力价值的表征与运动生理学之间的关系。在目标2中， 确定MS患者主观努力评估的机制。我们将使用TMS和fMRI， 研究MS中努力价值的神经和行为表征。这些实验将揭示 对MS患者的神经回路产生影响，他们会感到疲劳。我们的研究 将有一个广泛的影响领域的决策和电机控制解剖的基本 负责评估体力劳动的机制。这项工作将提供一个理解的神经 MS中努力感被破坏的潜在机制，并可能最终揭示神经行为标记物 以及神经调节干预以帮助预测和治疗康复不依从性。

PROJECT SUMMARY A major hurdle to compliance with rehabilitation therapies is poor effort on the part of patients, caused by fatigue and feelings of insurmountable effort. If a physical exercise feels very effortful one may be unwilling to exert the effort required, whereas if an exercise feels less effortful one may be more likely to persevere. Despite the ubiquity of effort-based judgments, and their disruption in a variety of neurological conditions, the mechanisms responsible for the subjective valuation of physical effort have received limited investigation. The central hypothesis of this proposal is that an individual's subjective valuation of effort is reflected in her inherent excitability of motor cortex, and that this metric is sensitive to disease state. We will perform experiments in healthy human participants; and a group of participants with multiple sclerosis (MS). We have developed a novel effort-based choice paradigm that allows us to obtain a precise objective measure of an individual's subjective valuation of effort. We will use this approach, in combination with computational modeling, functional magnetic resonance imaging (fMRI), and noninvasive brain stimulation, to investigate the mechanisms responsible for the subjective valuation of effort. In Aim 1 we will study how motor physiology influences subjective effort valuation in healthy participants. We will use transcranial magnetic stimulation (TMS) to non invasively probe the physiological properties of participants' motor cortex; and we will have the same participants make decisions about effort while they are scanned with fMRI, and use this data to computationally model their subjective valuation of effort and associated brain activity. These experiments will allow us to test the relationships between an individual's representations of effort value and motor physiology. In Aim 2 we will identify the mechanisms of subjective effort valuation in patients with MS. We will use TMS and fMRI to investigate the neural and behavioral representations of effort value in MS. These experiments will shed light on the neural circuits that are disrupted in individuals with MS, suffering from feelings of fatigue. Our studies will have a broad impact on the fields of decision-making and motor control by dissecting the fundamental mechanisms responsible for physical effort valuation. This work will provide an understanding of the neural mechanisms underlying disrupted feelings of effort in MS, and may eventually reveal neurobehavioral markers and neuromodulatory interventions to aid in the prediction and treatment of rehabilitation non-compliance.