Department of Psychology, University of Michigan, Ann Arbor, Michigan 48109-1043.
Max Planck Institute for Human Development, 14195 Berlin, Germany.
J Neurosci. 2021 Nov 10;41(45):9350-9360. doi: 10.1523/JNEUROSCI.0335-21.2021. Epub 2021 Nov 3.
Aging is associated with cognitive impairment, but there are large individual differences in these declines. One neural measure that is lower in older adults and predicts these individual differences is moment-to-moment brain signal variability. Testing the assumption that GABA should heighten neural variability, we examined whether reduced brain signal variability in older, poorer performing adults could be boosted by increasing GABA pharmacologically. Brain signal variability was estimated using fMRI in 20 young and 24 older healthy human adults during placebo and GABA agonist sessions. As expected, older adults exhibited lower signal variability at placebo, and, crucially, GABA agonism boosted older adults' variability to the levels of young adults. Furthermore, poorer performing older adults experienced a greater increase in variability on drug, suggesting that those with more to gain benefit the most from GABA system potentiation. GABA may thus serve as a core neurochemical target in future work on aging- and cognition-related human brain dynamics. Prior research indicates that moment-to-moment brain signal variability is lower in older, poorer performing adults. We found that this reduced brain signal variability could be boosted through GABA agonism in older adults to the levels of young adults and that this boost was largest in the poorer performing older adults. These results provide the first evidence that brain signal variability can be restored by increasing GABAergic activity and suggest the promise of developing interventions targeting inhibitory systems to help slow cognitive declines in healthy aging.
衰老是与认知障碍相关的，但这些衰退在个体之间存在很大差异。一种在老年人中较低且预测这些个体差异的神经测量指标是大脑信号的即时波动。为了检验 GABA 应该提高神经可变性的假设，我们研究了是否可以通过增加 GABA 来增强老年人中较低的大脑信号可变性。在安慰剂和 GABA 激动剂治疗期间，使用 fMRI 估计了 20 名年轻和 24 名年长健康成年人的大脑信号可变性。正如预期的那样，老年人在安慰剂下表现出较低的信号可变性，而且，至关重要的是，GABA 激动剂将老年人的可变性提高到了年轻人的水平。此外，表现较差的老年人在药物治疗中经历了更大的可变性增加，这表明那些受益最大的人从 GABA 系统增强中获益最多。因此，GABA 可能是未来与衰老和认知相关的人类大脑动力学研究的核心神经化学靶点。先前的研究表明，老年人和表现较差的成年人的大脑信号可变性较低。我们发现，通过 GABA 激动剂可以提高老年人的大脑信号可变性，使其达到年轻人的水平，而表现较差的老年人的这种提高幅度最大。这些结果首次提供了证据，表明可以通过增加 GABA 能活动来恢复大脑信号可变性，并表明开发针对抑制系统的干预措施以帮助减缓健康衰老中的认知衰退的前景。
