Causes and consequences of functional reorganisation in the ageing brain

随着年龄的增长，人们在完成复杂的认知任务时往往会变得更糟。这种影响因人而异，有些人的能力大幅下降，而另一些人则保持高水平的功能。神经科学家试图通过调查年轻人与老年人的大脑活动模式来理解这些变化。当他们执行复杂的任务时，老年人通常在年轻人参与的大脑区域中表现出较少的活动，这可能表明神经处理效率较低。他们也经常比年轻人在其他大脑区域表现出更多的激活，通常是在相反的大脑半球。其原因是有争议的：活动增加可能表明老年人使用额外的大脑区域来弥补核心网络功能的减少。或者，活动的增加可能代表了未能“关闭”对任务表现没有贡献的大脑区域（称为去分化）。这些研究通常使用老年人比年轻人更难的任务。对于老年人可以做得和年轻人一样好甚至比年轻人更好的任务，大脑活动是如何变化的，人们知之甚少。这一点至关重要，因为大脑变化的补偿理论和去分化理论在这种情况下预测了不同的结果。为了解决这个问题，我们将使用脑成像（fMRI）来研究当人们对单词的含义做出“语义”决定时，大脑活动的年龄相关变化。语义处理为当前的理论提供了一个关键的测试，因为老年人在某些方面做得不太好，但在其他方面胜过年轻人。具体来说，老年人比年轻人拥有更发达的语义知识（即，他们知道更多的话），由于他们更大的生活经验。然而，他们在控制如何使用这些知识方面不太熟练。通过直接对比基于控制的任务与基于知识的任务，我们将首次确定与年龄相关的性能增强以及减少相关的活动变化。在以前的研究中，年轻人在语义处理过程中只激活了左半球，而老年人在更大程度上激活了右半球。补偿理论预测，当老年人的表现水平高于年轻人时，这些模式将被逆转。我们将改变每项任务的难度，以研究大脑功能在要求更高或更低的条件下如何变化。根据补偿观点，难度越大，两个年龄组的右脑激活越多。重要的是，我们将使用一种新的多回波神经成像技术，这将提高我们对前颞叶成像的能力。这个大脑区域在储存单词知识方面至关重要，但人们对它知之甚少，因为传统的神经成像技术在这个区域提供的数据很少。我们预测，老年人会比年轻人更多地参与这一区域，这与他们更丰富的知识相一致。最后，我们将使用脑刺激暂时扰乱年轻人的左右额叶功能，并观察其对语义处理的影响。这将为补偿账户提供强有力的检验。如果右脑起着补偿作用，那么干扰右脑会损害语义判断的能力，尤其是当任务非常困难时，尤其是对于在扫描过程中表现出强烈右脑激活的个体，这些研究将推进晚年大脑变化的理论。在以前工作的重大进展中，我们将更好地了解老年人如何利用保留的能力和大脑区域，以及补偿损失。因此，该项目将有助于BBSRC的优先领域“终生健康老龄化”。

As people get older, they tend to get worse at completing complex cognitive tasks. This effect varies considerably across individuals, with some people showing large declines in ability while others maintain a high level of functioning. Neuroscientists have tried to understand these changes by investigating patterns of brain activity in young vs. older people. When they perform complex tasks, older people typically show less activity in the brain regions engaged by young people, which may indicate less efficient neural processing. They also frequently show more activation than young people in other brain areas, often those in the opposite brain hemisphere. The reason for this is disputed: increased activity may indicate that older people engage extra brain areas to compensate for reduced function in the core network. Alternatively, the increased activity may represent a failure to "switch off" brain regions that do not contribute to task performance (known as dedifferentiation).These investigations have typically used tasks which older people find more difficult than young people. Little is known about how brain activity changes for tasks that older people can do as well as, or even better than, young people. This is critical because the compensatory and dedifferentiation theories of brain change predict different results in this situation.To address this, we will use brain imaging (fMRI) to investigate age-related changes in brain activity when people make "semantic" decisions about the meanings of words. Semantic processing provides a critical test of current theories because older people do less well in some aspects but outperform young people in others. Specifically, older people have more developed semantic knowledge than young people (i.e., they know more words), due to their greater life experience. However, they are less skilled at controlling how they use this knowledge. By directly contrasting a control-based task with a knowledge-based task, we will identify activity changes associated with age-related performance enhancements as well as reductions for the first time. In previous studies, young people have activated only left-hemisphere regions during semantic processing while older people activated the right hemisphere to a greater extent. The compensation theory predicts that these patterns will be reversed when older people perform at a higher level than young people.We will vary the difficulty of each task to investigate how brain function varies under more or less demanding conditions. According to the compensation view, greater difficulty should result in more right-hemisphere activation in both age groups. Importantly, we will use a novel multi-echo neuroimaging technique that will improve our ability to image the anterior temporal lobes. This brain region is critically involved in storing word knowledge but little is known about it because conventional neuroimaging techniques provide poor data on this region. We predict that older people will engage this region more than young people, consistent with their greater knowledge.Finally, we will use brain stimulation to temporarily disrupt the function of left and right frontal lobes in young people and observe the effects on their semantic processing. This will provide a strong test of the compensatory account. If the right hemisphere plays a compensatory role, disrupting it should impair ability to make semantic judgements, particularly when the task is very difficult and particularly for individuals who showed strong right-hemisphere activation during scanning.These studies will advance theories of brain change in later life. In a major advance on previous work, we will develop a better understanding of how older people capitalise on preserved abilities and brain regions, as well as compensating for losses. Thus, the project will contribute to the BBSRC priority area of "Healthy ageing across the lifecourse".