Investigating the Mechanisms and Functional Consequences of Age-Related Neural Dedifferentiation

摘要： 许多认知能力，包括情景记忆，流体智力和执行功能。即使是健康人在70岁和80岁时典型的较轻微的认知障碍也会对生活质量产生负面影响。此外，与痴呆相关的神经病理学在出现显著临床症状之前数年就开始了。这一漫长的前驱期使得早期发现“不成功”的大脑衰老轨迹成为一种优势。因此，了解年龄对认知能力影响的神经基础是很重要的。本研究的目的是阐明与年龄相关的差异，在精度与知觉，可能是概念，信息在大脑中表示的因素。有人提出，年龄相关的神经去分化-随着年龄的减少，在神经表征的选择性和精确性-在认知老化中起着关键作用。我们提出了一系列的研究，以确定这种现象的潜在神经机制和功能意义。 这项研究的一部分将研究个体刺激引起的神经元活动模式的精度和方差是否会随着年龄的变化而变化，正如一个有影响力的理论框架所预测的那样。我们还将确定是否个别刺激的去分化与不同刺激类别的神经选择性相关的减少。第二条线索建立在动物和人类研究的基础上，表明神经对感知刺激的选择性受到任务需求的调节。第三条链将决定是否与年龄相关的神经去分化观察简单的知觉刺激扩展到复杂的认知任务，即不同的语义判断。在研究的第四部分，我们将确定神经去分化的措施是否与大脑结构和认知表现的个体差异有关。最后一个链将使用头皮脑电图检查与年龄相关的神经去分化的时间动态。在这条链中，我们的目标是确定神经分化是否出现在老年人相对于年轻人的时间较晚，以及是否与年龄相关的“神经噪声”增加有助于与年龄相关的神经去分化。

ABSTRACT: Numerous cognitive abilities, including episodic memory, fluid intelligence and executive function. Even the more modest cognitive impairment typical of healthy people as they reach their 70’sand 80’s can negatively impact quality of life. Moreover, the neuropathology associated with dementia onsets years before the emergence of significant clinical symptoms. This long prodromal period places a premium on early detection of trajectories of ‘unsuccessful’ brain aging. For these reasons, it is important to understand the neural bases of the effects of age on cognitive abilities. The present research aims to elucidate factors contributing to age-related differences in the precision with which perceptual and, possibly conceptual, information is represented in the brain. It has been proposed that age-related neural dedifferentiation – a reduction with age in the selectivity and precision of neural representations – plays a critical role in cognitive aging. We propose a series of studies to identify the potential neural mechanisms and functional significance of this phenomenon. One strand of the research will examine whether the precision and variance of the patterns of neuronal activity elicited by individual stimuli differs with age, as is predicted in an influential theoretical framework. We will also determine whether dedifferentiation for individual stimuli is associated with related reductions in neural selectivity for different stimulus categories. A second strand builds on animal and human research showing that neural selectivity for perceptual stimuli is modulated by task demands. A third strand will determine whether the age-related neural dedifferentiation observed for simple perceptual stimuli extends to complex cognitive tasks, namely, different semantic judgments. In a fourth strand of the research, we will identify whether measures of neural dedifferentiation are associated with individual differences in brain structure and cognitive performance. A final strand will use scalp EEG to examine the temporal dynamics of age-related neural dedifferentiation. Within this strand, we aim to determine if neural differentiation emerges later in time in older relative to younger adults, and if age-related increases in ‘neural noise’ contribute to age-related neural dedifferentiation.