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方面往往会变得更差。这种影响因人而异，有些人表现出能力的大幅下降，而另一些人则保持着高水平的功能。神经学家试图通过研究年轻人和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，老年人在年轻人参与的大脑区域通常表现出较少的活动，这可能表明神经处理效率较低。他们还经常在其他大脑区域表现出比年轻人更活跃的表现，通常是在相反的大脑半球。这其中的原因是有争议的：活动增加可能表明老年人会利用额外的大脑区域来补偿核心网络中功能的下降。另一种可能是，活动增加可能表明未能关闭与任务表现无关的大脑区域(称为去分化)。这些研究通常使用的是老年人认为比年轻人更难完成的任务。对于老年人能做得和年轻人一样好、甚至更好的任务，我们几乎不知道大脑活动会发生什么变化。这一点很关键，因为大脑变化的补偿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，我们将使用大脑成像(FMRI)来研究当人们对单词的含义做出“语义”决定时，大脑活动与年龄相关的变化。语义加工对当前的理论提出了关键的考验，因为老年人在某些方面做得不好，但在其他方面却优于年轻人。具体地说，由于老年人的生活经验较多，他们的语义知识比年轻人更发达(即他们知道更多的词)。然而，他们不太擅长控制自己如何使用这些知识。通过直接对比基于控制的任务和基于知识的任务，我们将第一次确定与年龄相关的绩效增强和减少相关的活动变化。在之前的研究中，年轻人在语义加工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，当老年人的表现高于年轻人时，这些模式将发生逆转。我们将根据每项任务的难度来研究大脑功能在要求较高或较低条件下的变化。根据补偿论的观点，难度越大，两个年龄段的右脑激活程度都会越高。重要的是，我们将使用一种新的多回波神经成像技术，这将提高我们成像前颞叶的能力。这一大脑区域主要负责存储单词知识，但人们对此知之甚少，因为传统的神经成像技术在这一区域提供的数据很差。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是一致的。最后，我们将使用脑刺激暂时扰乱年轻人的左右额叶功能，并观察其对语义加工的影响。这将是对补偿性账户的有力考验。如果右脑起到了补偿作用，那么干扰右脑应该会削弱做出语义判断的能力，特别是在任务非常困难的情况下，尤其是对那些在扫描过程中表现出强烈右脑激活的人来说。这些研究将推动晚年大脑变化的理论。在以前工作的基础上，我们将更好地理解老年人如何利用保留下来的能力和大脑区域，以及如何补偿损失。因此，该项目将有助于BBSRC的优先领域“整个生命过程中的健康老龄化”。

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".