Age-related Changes in Neural Distinctiveness: Scope, Causes and Consequences

 描述（由申请人提供）：认知，感觉和运动功能通常都会随着年龄的增长而下降，但有些人的年龄比其他人更优雅。为什么？为什么？我们假设一个重要的因素是神经特异性的个体差异。在以前的工作中，我们反复发现，与年轻人相比，老年人对不同刺激的神经激活模式明显不那么独特。此外，我们发现，具有更独特的神经表征的老年人在一系列流体处理任务中表现得比其他人好得多。动物实验证实了这些与年龄相关的神经特异性下降，并表明神经递质γ-氨基丁酸（GABA）的下降可能是一个重要原因。在这项工作的基础上，我们建议调查的范围，原因和后果的年龄相关的变化，神经的独特性。首先，我们将使用功能性MRI来测试听觉皮层、体感皮层和运动皮层的神经特异性是否会像视觉皮层一样下降（目标1：范围）。其次，我们将使用磁共振光谱来测量GABA水平，并使用GABA激动剂劳拉西泮来操纵GABA水平，以研究年龄相关的GABA减少是否会导致神经特异性降低（目的2：原因）。第三，我们将收集一系列广泛的测量方法，评估相同参与者的行为表现，以评估神经特异性和行为之间的关系（目标3：后果）。这些研究将为大脑如何随年龄变化提供新的见解，这些变化是否可以预测成功的衰老，以及GABA水平的变化是否是一个促成因素。这些见解可以为新的干预措施提供基础，以减缓甚至逆转正常衰老期间出现的行为衰退。

 DESCRIPTION (provided by applicant): Cognitive, sensory, and motor function all usually decline with age, but some people age much more gracefully than others. Why? We hypothesize that one important factor is individual differences in neural distinctiveness. In previous work we've repeatedly found that neural activation patterns in response to different stimuli are significantly less distinctive in older compared with younger adults. Furthermore, we've found that older adults with more distinctive neural representations perform significantly better than others on a range of fluid processing tasks. Animal work confirms these age-related reductions in neural distinctiveness and suggests that declines in the neurotransmitter gamma-aminobutyric acid (GABA) may be an important cause. Building on this work, we propose to investigate the scope, cause, and consequences of age-related changes in neural distinctiveness. First, we will use functional MRI to test whether neural distinctiveness declines in auditory cortex, somatosensory cortex, and motor cortex, like it does in visual cortex (Aim 1: Scope). Second, we will use magnetic resonance spectroscopy to measure GABA levels and use the GABA agonist Lorazepam to manipulate GABA levels in order to investigate whether age-related reductions in GABA cause reductions in neural distinctiveness (Aim 2: Cause). Third, we will collect an extensive battery of measures assessing behavioral performance in the same participants in order to assess the relationship between neural distinctiveness and behavior (Aim 3: Consequences). The proposed studies will provide novel insights into how the brain changes with age, whether those changes can predict successful aging, and whether changes in GABA levels are a contributing cause. Such insights could provide the basis for novel interventions to slow, or conceivably even reverse, the behavioral declines seen during normal aging.