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γ-氨基丁酸能抑制在双眼竞争期间控制知觉意识。

GABAergic Inhibition Gates Perceptual Awareness During Binocular Rivalry.

机构信息

Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire 03755.

McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.

出版信息

J Neurosci. 2019 Oct 16;39(42):8398-8407. doi: 10.1523/JNEUROSCI.0836-19.2019. Epub 2019 Aug 26.

Abstract

Binocular rivalry is a classic experimental tool to probe the neural machinery of perceptual awareness. During rivalry, perception alternates between the two eyes, and the ebb and flow of perception is modeled to rely on the strength of inhibitory interactions between competitive neuronal populations in visual cortex. As a result, rivalry has been suggested as a noninvasive perceptual marker of inhibitory signaling in visual cortex, and its putative disturbance in psychiatric conditions, including autism. Yet, direct evidence causally implicating inhibitory signaling in the dynamics of binocular rivalry is currently lacking. We previously found that people with higher GABA levels in visual cortex, measured using magnetic resonance spectroscopy, have stronger perceptual suppression during rivalry. Here, we present direct causal tests of the impact of GABAergic inhibition on rivalry dynamics, and the contribution of specific GABA receptors to these dynamics. In a crossover pharmacological design with male and female adult participants, we found that drugs that modulate the two dominant GABA receptor types in the brain, GABA (clobazam) and GABA (arbaclofen), increase perceptual suppression during rivalry relative to a placebo. Crucially, these results could not be explained by changes in reaction times or response criteria, as determined through rivalry simulation trials, suggesting a direct and specific influence of GABA on perceptual suppression. A full replication study of the GABA modulator reinforces these findings. These results provide causal evidence for a link between the strength of inhibition in the brain and perceptual suppression during rivalry and have implications for psychiatric conditions including autism. How does the brain accomplish perceptual gating? Here we use a direct and causal pharmacological manipulation to present insight into the neural machinery of a classic illusion of perceptual awareness: binocular rivalry. We show that drugs that increase GABAergic inhibition in the brain, clobazam (GABA modulator) and arbaclofen (GABA modulator), increase perceptual suppression during rivalry relative to a placebo. These results present the first causal link between GABAergic inhibition and binocular rivalry in humans, complementing classic models of binocular rivalry, and have implications for our understanding of psychiatric conditions, such as autism, where binocular rivalry is posited as a behavioral marker of disruptions in inhibitory signaling in the brain.

摘要

双眼竞争是一种经典的实验工具,可用于探测感知意识的神经机制。在竞争中,感知在两只眼睛之间交替,感知的涨落被建模为依赖于视觉皮层中竞争神经元群体之间抑制相互作用的强度。因此,竞争被认为是视觉皮层中抑制信号的非侵入性感知标记,其在包括自闭症在内的精神疾病中的潜在干扰。然而,目前缺乏直接证据表明抑制信号在双眼竞争的动力学中起因果作用。我们之前发现,使用磁共振波谱测量的视觉皮层中 GABA 水平较高的人在竞争中具有更强的感知抑制。在这里,我们提出了直接的因果测试,以检验 GABA 能抑制对竞争动力学的影响,以及特定 GABA 受体对这些动力学的贡献。在一项有男性和女性成年参与者参与的交叉药理学设计中,我们发现,调节大脑中两种主要 GABA 受体类型的药物,GABA(氯巴占)和 GABA(阿巴氯芬),相对于安慰剂增加了竞争中的感知抑制。至关重要的是,这些结果不能通过竞争模拟试验确定的反应时间或反应标准的变化来解释,这表明 GABA 对感知抑制有直接和特定的影响。对 GABA 调节剂的全复制研究强化了这些发现。这些结果为大脑中抑制强度与竞争期间感知抑制之间的联系提供了因果证据,并对包括自闭症在内的精神疾病产生了影响。大脑如何实现感知门控?在这里,我们使用直接和因果药理学操作来深入了解经典感知意识错觉的神经机制:双眼竞争。我们表明,增加大脑中 GABA 能抑制的药物,氯巴占(GABA 调节剂)和阿巴氯芬(GABA 调节剂),相对于安慰剂增加了竞争期间的感知抑制。这些结果在人类中首次提供了 GABA 能抑制与双眼竞争之间的因果联系,补充了经典的双眼竞争模型,并对我们理解自闭症等精神疾病产生了影响,在这些疾病中,双眼竞争被认为是大脑中抑制信号中断的行为标记。

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本文引用的文献

1
Slower Binocular Rivalry in the Autistic Brain.自闭症大脑中双眼竞争更慢。
Curr Biol. 2019 Sep 9;29(17):2948-2953.e3. doi: 10.1016/j.cub.2019.07.026. Epub 2019 Aug 15.
6
Attention model of binocular rivalry.双眼竞争的注意模型。
Proc Natl Acad Sci U S A. 2017 Jul 25;114(30):E6192-E6201. doi: 10.1073/pnas.1620475114. Epub 2017 Jul 10.
7
Arbaclofen in fragile X syndrome: results of phase 3 trials.阿巴氯芬治疗脆性X综合征:3期试验结果
J Neurodev Disord. 2017 Jun 12;9:3. doi: 10.1186/s11689-016-9181-6. eCollection 2017.

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