Subjective Valuation of Physical Effort in Health and Disease

项目总结 遵守康复治疗的一个主要障碍是患者方面的努力不佳，原因是 疲惫和难以克服的努力的感觉。如果一项体育锻炼感觉非常费力，一个人可能不愿意 付出所需的努力，而如果一项运动感觉不那么费力，你可能更有可能坚持下去。 尽管基于努力的判断无处不在，而且它们在各种神经状况下都受到了破坏，但 负责对体力的主观评估的机制得到的调查有限。这个 这一建议的中心假设是，一个人对努力的主观评价反映在他的内在 运动皮质的兴奋性，这一指标对疾病状态很敏感。我们将在 健康的人类参与者；以及一组患有多发性硬化症(MS)的参与者。我们已经开发出一种 新的基于努力的选择范式，允许我们获得一个人的准确的客观衡量 对努力的主观评价。我们将使用这种方法，结合计算建模、泛函 磁共振成像(FMRI)和非侵入性脑刺激，以探讨其机制 对努力的主观评价负责。在目标1中，我们将研究运动生理学如何影响 健康受试者主观努力评价。我们将使用经颅磁刺激(TMS)来治疗非 侵入性地探测参与者运动皮质的生理特性，我们就会有同样的结果 参与者在接受fMRI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估。这些实验将使我们能够测试 个体对努力价值的表现与运动生理学之间的关系。在《目标2》中我们将 多发性硬化症患者主观努力评估的机制我们将使用TMS和fMRI 研究努力价值在多发性硬化症中的神经和行为表征。这些实验将揭示 多发性硬化症患者的神经回路被破坏，感到疲倦。我们的研究 将对决策和电机控制领域产生广泛的影响 负责体力工作评估的机制。这项工作将提供对神经的理解 多发性硬化症患者努力感觉紊乱的潜在机制，并最终可能揭示神经行为标志物 和神经调节干预，以帮助预测和治疗康复不依从。

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.