Exploring the role of cortical inhibition in neural distinctiveness and behavior

探索皮质抑制在神经独特性和行为中的作用

• 批准号: 10255512
• 负责人: Dalia Khammash
• 金额: $ 3.27万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10255512
• 关键词: Age; Age-associated memory impairment; Aging; Agonist; Animals; Auditory area; Behavior; Behavioral; Categories; Cognition; Cognitive; Data; Disease; Elderly; Equilibrium; Face; Foundations; Functional Magnetic Resonance Imaging; GABA Agonists; Gait; Human; Impaired cognition; Individual; Individual Differences; Intervention; Knowledge; Lead; Light; Liquid substance; Macaca; Magnetic Resonance Spectroscopy; Measures; Mediating; Methods; Modeling; Motor; Motor Cortex; Music; Neuropsychological Tests; Neurotransmitters; Participant; Pattern; Performance; Pharmacology; Phase; Physiologic pulse; Play; Predictive Factor; Primates; Reporting; Research; Research Project Grants; Role; Sampling; Speech; Stimulus; Task Performances; Testing; Transcranial magnetic stimulation; Visual Cortex; Walking; Work; age related; base; behavioral impairment; cognitive performance; cognitive task; experience; gamma-Aminobutyric Acid; healthy aging; improved; insight; motor behavior; motor impairment; normal aging; novel; prevent; recruit; relating to nervous system; therapy development; visual motor; visual processing; young adult

Neural activation patterns evoked by separate categories of stimuli are clearly different. The extent to which the evoked patterns are different is referred to as neural distinctiveness. Our research group and others have found that neural distinctiveness tends to decline with age, and that older adults who maintain more distinctive neural representations perform better on a range of cognitive tasks. Additionally, previous animal work has found that pharmacological manipulations of GABA cause changes in neural distinctiveness. Based on those findings, we hypothesize that individual differences in inhibition are associated with individual differences in neural distinctiveness, which in turn are related to cognitive performance. We propose to test this model in humans. Currently in the F99 phase, the candidate is recruiting a large sample of young adults and using transcranial magnetic stimulation to measure cortical inhibition, magnetic resonance spectroscopy to measure GABA levels, functional MRI to measure neural distinctiveness, and a battery of validated tasks to measure cognitive and behavioral performance. The candidate will then test whether individual differences in neural distinctiveness are associated with individual differences in cortical inhibition/GABA concentration. The candidate will also test whether individual differences in neural distinctiveness, in GABA, and in cortical inhibition are associated with individual differences in cognition and behavior. In the K00 phase, the candidate will shift her focus to studying these factors in older adults. Aging is associated with substantial declines in mobility, even in the absence of significant disease. However, some older people experience serious declines while others do not. We hypothesize that individual differences in neural distinctiveness and GABA levels will predict motor performance on various walking tasks. Over the course of two proposed studies the candidate will therefore assess and experimentally manipulate GABA levels in older adults and will measure the effects on both neural distinctiveness and on various walking metrics. The candidate will use MRS to measure GABA levels, functional MRI to assess neural distinctiveness, walking tasks to assess mobility, and high-definition transcranial direct current stimulation (HD-tDCS) and continuous theta burst TMS (cTBS) to respectively decrease or increase GABA levels. The proposed studies afford the opportunity to shed light on the underlying causes of age-related cognitive and behavioral impairments. Such an understanding is the first step in developing interventions that could slow, or conceivably even prevent, the cognitive and motor impairments associated with healthy aging.

不同类别的刺激所引起的神经激活模式明显不同。诱发模式的不同程度被称为神经区别性。我们的研究小组和其他人发现，神经的区别性往往会随着年龄的增长而下降，保持更独特的神经表征的老年人在一系列认知任务中表现得更好。此外，以前的动物工作已经发现，GABA的药理操作会导致神经区别性的变化。基于这些发现，我们假设抑制的个体差异与神经区别性的个体差异有关，而神经区别性的个体差异又与认知表现有关。我们建议在人体上测试这一模型。目前处于F99阶段，候选人正在招募大量年轻人样本，并使用经颅磁刺激来测量皮质抑制，磁共振波谱来测量GABA水平，功能磁共振成像来测量神经区别性，以及一系列经过验证的任务来测量认知和行为表现。然后，候选人将测试神经区别性的个体差异是否与皮质抑制/GABA浓度的个体差异相关。候选人还将测试神经区别性、GABA和皮质抑制方面的个体差异是否与认知和行为的个体差异有关。在K00阶段，候选人将把重点转移到研究老年人的这些因素上。即使在没有重大疾病的情况下，衰老也与活动能力的大幅下降有关。然而，一些老年人经历了严重的衰退，而另一些人则没有。我们假设，神经区别性和GABA水平的个体差异将预测各种行走任务中的运动表现。因此，在两个拟议的研究过程中，候选人将评估和实验操纵老年人的GABA水平，并将测量对神经区别性和各种行走指标的影响。候选人将使用MRS来测量GABA水平，使用功能磁共振来评估神经区别性，使用步行任务来评估移动性，并使用高清晰度经颅直流电刺激(HD-tDC)和连续电刺激(CTBS)来分别降低或提高GABA水平。拟议的研究为阐明与年龄相关的认知和行为障碍的根本原因提供了机会。这样的理解是开发干预措施的第一步，这些干预措施可以减缓甚至可以预防与健康老龄化相关的认知和运动障碍。