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，但有些人比其他人衰老得更优雅。为什么？我们假设，一个重要因素是神经区别性的个体差异。在之前的工作中，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明显。此外，我们还发现，拥有更独特神经表征的老年人在一系列流体处理任务中的表现明显好于其他人。动物研究证实了这些与年龄相关的神经特异性降低，并表明神经递质伽马-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，我们建议调查与年龄相关的神经区别性变化的范围、原因和后果。首先，我们将使用功能磁共振来测试听觉皮质、躯体感觉皮质和运动皮质的神经区别性是否会像在视觉皮质一样下降(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Lorazepam来操纵GABA水平，以调查与年龄相关的GABA减少是否导致神经区别性降低(目标2：原因)。第三，我们将收集大量评估同一参与者行为表现的指标，以评估神经区别性和行为之间的关系(目标3：后果)。拟议中的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水平的变化是否是原因之一。这些洞察力可以为新的干预措施提供基础，以减缓或甚至逆转在正常衰老期间出现的行为下降。

 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.