密歇根神经独特性（MiND）研究方案：探究与年龄相关的神经去分化的范围、成因及后果。
Michigan Neural Distinctiveness (MiND) study protocol: investigating the scope, causes, and consequences of age-related neural dedifferentiation.
作者信息
Gagnon Holly, Simmonite Molly, Cassady Kaitlin, Chamberlain Jordan, Freiburger Erin, Lalwani Poortata, Kelley Shannon, Foerster Bradley, Park Denise C, Petrou Myria, Seidler Rachael D, Taylor Stephan F, Weissman Daniel H, Polk Thad A
机构信息
Department of Psychology, University of Michigan, 530 Church Street, Ann Arbor, MI, 48109, USA.
Department of Psychology, University of Utah, 380 S 1530 E, Salt Lake City, UT, 84112, USA.
出版信息
BMC Neurol. 2019 Apr 12;19(1):61. doi: 10.1186/s12883-019-1294-6.
BACKGROUND
Aging is often associated with behavioral impairments, but some people age more gracefully than others. Why? One factor that may play a role is individual differences in the distinctiveness of neural representations. Previous research has found that neural activation patterns in visual cortex in response to different visual stimuli are often more similar (i.e., less distinctive) in older vs. young participants, a phenomenon referred to as age-related neural dedifferentiation. Furthermore, older people whose neural representations are less distinctive tend to perform worse on a wide range of behavioral tasks. The Michigan Neural Distinctiveness (MiND) project aims to investigate the scope of neural dedifferentiation (e.g., does it also occur in auditory, motor, and somatosensory cortex?), one potential cause (age-related reductions in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA)), and the behavioral consequences of neural dedifferentiation. This protocol paper describes the study rationale and methods being used in complete detail, but not the results (data collection is currently underway).
METHODS
The MiND project consists of two studies: the main study and a drug study. In the main study, we are recruiting 60 young and 100 older adults to perform behavioral tasks that measure sensory and cognitive function. They also participate in functional MRI (fMRI), MR spectroscopy, and diffusion weighted imaging sessions, providing data on neural distinctiveness and GABA concentrations. In the drug study, we are recruiting 25 young and 25 older adults to compare neural distinctiveness, measured with fMRI, after participants take a placebo or a benzodiazepine (lorazepam) that should increase GABA activity.
DISCUSSION
By collecting multimodal imaging measures along with extensive behavioral measures from the same subjects, we are linking individual differences in neurochemistry, neural representation, and behavioral performance, rather than focusing solely on group differences between young and old participants. Our findings have the potential to inform new interventions for age-related declines.
TRIAL REGISTRATION
This study was retrospectively registered with the ISRCTN registry on March 4, 2019. The registration number is ISRCTN17266136 .
背景
衰老常与行为障碍相关，但有些人比其他人衰老得更优雅。原因何在？一个可能起作用的因素是神经表征独特性的个体差异。先前的研究发现，与年轻参与者相比，老年参与者视觉皮层中对不同视觉刺激的神经激活模式往往更相似（即独特性更低），这一现象被称为与年龄相关的神经去分化。此外，神经表征独特性较低的老年人在各种行为任务上的表现往往更差。密歇根神经独特性（MiND）项目旨在研究神经去分化的范围（例如，它是否也发生在听觉、运动和体感皮层？）、一个潜在原因（与年龄相关的抑制性神经递质γ-氨基丁酸（GABA）减少）以及神经去分化的行为后果。本方案文件详细描述了所使用的研究原理和方法，但未提及结果（目前正在进行数据收集）。
方法
MiND项目包括两项研究：主要研究和药物研究。在主要研究中，我们招募了60名年轻人和100名老年人来执行测量感觉和认知功能的行为任务。他们还参与功能磁共振成像（fMRI）、磁共振波谱和扩散加权成像检查，提供有关神经独特性和GABA浓度的数据。在药物研究中，我们招募了25名年轻人和25名老年人，在参与者服用安慰剂或应能增加GABA活性的苯二氮䓬类药物（劳拉西泮）后，比较通过fMRI测量的神经独特性。
讨论
通过从同一受试者收集多模态成像测量以及广泛的行为测量，我们正在将神经化学、神经表征和行为表现的个体差异联系起来，而不是仅仅关注年轻和老年参与者之间的群体差异。我们的研究结果有可能为与年龄相关的衰退提供新的干预措施。
试验注册
本研究于2019年3月4日在ISRCTN注册中心进行了回顾性注册。注册号为ISRCTN17266136 。
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