Causes and consequences of functional reorganisation in the ageing brain

衰老大脑功能重组的原因和后果

• 批准号: BB/T004444/1
• 负责人: Paul Hoffman
• 金额: $ 58.01万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT004444%2F1
• 关键词: Causes; consequences; functional; reorganisation; ageing

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".

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越来越差。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。神经科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，老年人通常在年轻人参与的大脑区域表现出较少的活动，这可能表明神经处理效率较低。他们也经常比年轻人在大脑的其他区域表现出更多的活跃，通常是在相反的大脑半球。其原因有争议：活动增加可能表明老年人使用额外的大脑区域来补偿核心网络功能的减少。另一种解释是，大脑活动的增加可能代表着无法“关闭”与任务表现无关的大脑区域（称为去分化）。这些调查通常使用老年人认为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，甚至比年轻人做得更好的任务，大脑活动是如何变化的，我们知之甚少。这是至关重要的，因为大脑变化的代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，我们将使用脑成像（fMRI）来研究当人们对单词的意思做出“语义”决定时，大脑活动与年龄相关的变化。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，但在其他方面却比年轻人做得好。具体来说，老年人比年轻人有更发达的语义知识（即，他们知道更多的单词），因为他们有更多的生活经验。然而，他们不太擅长控制如何使用这些知识。通过直接对比基于控制的任务和基于知识的任务，我们将首次确定与年龄相关的性能增强和降低相关的活动变化。在之前的研究中，年轻人在语义处理过程中只激活了左半球区域，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，这些模式将被逆转。我们将改变每个任务的难度，以研究大脑功能在更高或更低要求的条件下是如何变化的。根据补偿理论，难度越大，两个年龄组的右半球活动就越活跃。重要的是，我们将使用一种新的多回声神经成像技术，这将提高我们对前颞叶成像的能力。这一大脑区域在存储单词知识方面起着至关重要的作用，但由于传统的神经成像技术提供的这一区域的数据很差，因此人们对它知之甚少。我们预测，老年人将比年轻人更多地参与这一领域，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破坏年轻人左右额叶的功能，并观察其对语义加工的影响。这将为补偿性解释提供强有力的检验。如果右半球起着补偿性作用，那么干扰右半球应该会损害做出语义判断的能力，特别是当任务非常困难时，特别是对于在扫描过程中表现出强烈右半球激活的个体。这些研究将推进晚年大脑变化的理论。在先前工作的基础上，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，以及如何补偿损失。因此，该项目将有助于《健康老龄化公约》的优先领域，即“整个生命过程中的健康老龄化”。

项目成果

Perceptual and Semantic Representations at Encoding Contribute to True and False Recognition of Objects.

编码时的感知和语义表示有助于物体的真假识别。

• DOI: 10.1523/jneurosci.0677-21.2021
• 发表时间: 2021
• 期刊: the official journal of the Society for Neuroscience
• 作者: Naspi L

Discourse coherence modulates use of predictive processing during sentence comprehension

话语连贯性调节句子理解过程中预测处理的使用

• DOI: 10.1016/j.cognition.2023.105637
• 发表时间: 2024
• 期刊: Cognition
• 影响因子: 3.4
• 作者: Carter G

Similar neural networks respond to coherence during comprehension and production of discourse

类似的神经网络在理解和产生话语过程中对连贯性做出反应

• DOI: 10.1101/2021.06.24.449717
• 发表时间: 2021
• 作者: Morales M

Stimulus-independent neural coding of event semantics: Evidence from cross-sentence fMRI decoding

事件语义的刺激独立神经编码：来自跨句功能磁共振成像解码的证据

• DOI: 10.1101/2020.10.06.327817
• 发表时间: 2020
• 作者: Asyraff A

Stimulus-independent neural coding of event semantics: Evidence from cross-sentence fMRI decoding.

• DOI: 10.1016/j.neuroimage.2021.118073
• 发表时间: 2021-08-01
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Asyraff A;Lemarchand R;Tamm A;Hoffman P
• 通讯作者: Hoffman P