Causes and consequences of functional reorganisation in the ageing brain

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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".