Exploring the role of cortical inhibition in neural distinctiveness and behavior

不同类别的刺激所诱发的神经激活模式明显不同。诱发模式不同的程度被称为神经特异性。我们的研究小组和其他人发现，神经的独特性往往会随着年龄的增长而下降，并且那些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，以前的动物研究发现，GABA的药理学操作会导致神经特异性的变化。基于这些发现，我们假设抑制的个体差异与神经特异性的个体差异有关，而神经特异性又与认知表现有关。我们打算在人类身上测试这个模型。 目前在F99阶段，候选人正在招募大量的年轻人样本，并使用经颅磁刺激来测量皮质抑制，磁共振光谱来测量GABA水平，功能性MRI来测量神经特异性，以及一系列经过验证的任务来测量认知和行为表现。然后，候选人将测试神经特异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特异性，GABA和皮质抑制的个体差异是否与认知和行为的个体差异有关。 在K 00阶段，候选人将把重点转移到研究老年人的这些因素。衰老与活动能力的大幅下降有关，即使没有重大疾病。然而，一些老年人经历严重的衰退，而其他人则没有。我们假设神经特异性和GABA水平的个体差异将预测各种步行任务的运动表现。因此，在两项拟议研究的过程中，候选人将评估和实验性地操纵老年人的GABA水平，并将测量对神经特异性和各种步行指标的影响。候选人将使用MRS测量GABA水平，功能性MRI评估神经特异性，步行任务评估移动性，以及高清经颅直流电刺激（HD-tDCS）和连续theta脉冲TMS（cTBS）分别降低或增加GABA水平。 拟议的研究提供了机会，阐明与年龄相关的认知和行为障碍的根本原因。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预防与健康老龄化相关的认知和运动障碍。

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.