A biological framework for understanding and modulating apathy in healthy people

随着年龄的增长，我们完成脑力和体力要求高的任务的能力会下降。然而，研究表明，由于衰老的影响，我们也会失去完成脑力和体力要求高的任务的动力。冷漠——参与和执行对身心都有要求的任务的意愿降低——在年轻人中以轻微的形式普遍存在，但至关重要的是，随着年龄的增长，它会显著增加，阻碍老年人的日常生活。年轻人的冷漠也可能产生相当大的长期影响，成本高昂，影响教育、就业和公民参与。尽管保持动力对于健康老龄化很重要，但我们对导致年轻人或老年人冷漠的生物学过程知之甚少。在这项研究中，我的目的是建立一个冷漠的生物学模型。我将测试从导致动机降低的大脑过程的动物模型中发展出来的具体想法。以这个模型为基础，我将测试大脑中导致动物停止做脑力和体力要求高的任务的关键通路是否也导致了人们在动力方面的个体差异。利用新的数学方法结合健康年轻人的脑成像技术，我将建立一个基于生物学的年轻人和老年人冷漠模型。然后，我将利用现代的非侵入性脑刺激技术，探索是否可以通过刺激我们基于动物模型预测的与动机有关的大脑部分来增加动机。本研究将解决三个关键问题：(1)老年人的积极性下降到何种程度？大多数关于衰老动机的研究都采用了问卷调查的方式，询问人们感觉自己有多有动力。不幸的是，这些并没有为我们提供一个可以解释冷漠背后的生物学模型。使用两个新的任务，它们的设计是基于用于探索动物决策的任务，我将研究老年人与年轻人相比，在完成脑力和体力要求高的任务时的动机是如何的，以及他们克服疲劳的动机是如何的。对老鼠、鸟类和猴子的动机基础过程的研究为我们提供了大脑中对保持动物动力至关重要的通路的模型。然而，目前还不清楚这些“动机回路”的工作方式、人类的冷漠以及随着年龄的增长动机的变化之间有什么联系。使用功能性磁共振成像（可以告诉我们某个区域是否通过执行任务而被“激活”）和弥散张量成像（可以告诉我们大脑各区域之间的联系有多紧密），我将测试大脑中负责激励动物的相同路径是否也负责激励人类。然后，我将测试老年人这些通路的变化是否会导致他们缺乏动力。(3)我们能通过刺激大脑来提高老年人和缺乏活力的年轻人的积极性吗？一旦我提出的冷漠模型得到验证，我就会确定我就会确定大脑刺激技术可以针对的区域。通过以一种特殊的方式刺激这些区域，我预测我们可以增加人们克服认知和身体需求的意愿，并使人们较少受到疲劳的影响。也就是说，我的目标是努力提高人们的积极性，从而开发出改善冷漠的潜在技术。这项工作将提供冷漠的第一个生物学模型，以及大脑的变化如何导致老年人更严重的冷漠。该模型将为研究人员、临床医生和行业提供一个框架，在此基础上建立旨在提高动机的治疗技术和技术。

As we get older our ability to do mentally and physically demanding tasks declines. However, research shows that we also lose motivation to complete mentally and physically demanding tasks through the effects of aging. Apathy - a reduction in the willingness to engage and perform mentally and physically demanding tasks - is widespread in mild forms in young adults, but crucially, it significantly increases as we age, hampering the daily lives of the elderly. Apathy in young adults may also have considerable long-term effects with significant costs, affecting education, employment and civic engagement. Despite the importance of keeping motivated for healthy aging, very little is known about the biological processes that lead to apathy in the young or the elderly. In this research I aim to establish a biological model of apathy. I will test specific ideas developed from animal models of the processes in the brain that lead to reduced motivation. Using this models as a basis, I will test whether key pathways in the brain that lead animals to stop doing mentally and physically demanding tasks are also responsible for causing individual differences in how motivated people are . Using new mathematical approaches in conjunction with brain imaging techniques in healthy young adults I will build a biologically based model of apathy in the young and the elderly. Using modern non-invasive brain stimulation techniques I will then explore whether motivation can be increased by stimulating parts of the brain we predict are involved in motivation based on our animal model.There are three key questions this research will address: (1) To what extent is motivation reduced in the elderly? Most research that has looked at motivation in aging, has used questionnaires, asking people about how motivated they feel. Unfortunately, these do not provide us with a model that can explain the biology behind apathy. Using two new tasks, the designs of which are based on tasks used to explore animal decision-making, I will examine how motivated the elderly are compared to young adults to do mentally and physically demanding tasks and how motivated they are to overcome fatigue. (2) What is the biology of apathy Research into the processes that underpin motivation in rats, birds and monkeys has provided us with a models of the pathwys in the brain that are crucial for keeping animals motivated. However, it is unknown what the links are between how these 'motivational circuits' work, apathy in humans, and changes in motivation through aging. Using functional Magnetic Resonance Imaging (which can tell us about whether an area is 'activated' by doing a task) and Diffusion Tensor Imaging (which can tell us about how strongly connected to each other brain areas are) I will test whether the same pathways in the brain that are responsible for motivating animals are also responsible for motivating humans. I will then test whether changes in these pathways in older people leads to them being less motivated.(3) Can we increase motivation in the elderly and the apathetic young by stimulating the brain? Once my proposed model of apathy has been tested, I will have identified I will have identified regions that can targeted by brain stimulation techniques. By stimulating these areas in a particular way, I predict that we can increase people's willingness to overcome cognitive and physical demands, and make people less influenced by fatigue. That is, I aim to try and increase how motivated people are, in order to develop potential techniques for ameliorating apathy.This work will provide the first biological model of apathy and how changes in the brain can lead to greater levels of apathy in the elderly. This model will provide researchers, clinicians and industry with a framework on which to base therapeutic techniques and technologies aimed at increasing motivation.