Neuroimaging Research Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224.
J Neurosci. 2013 Nov 20;33(47):18566-73. doi: 10.1523/JNEUROSCI.1973-13.2013.
Deactivation of the human brain's default mode network (DMN) is regarded as suppression of endogenous activity to support exogenous task-related processes. This phenomenon has important functional relevance and insufficient DMN deactivation has been implicated in several neuropsychiatric disorders. However, the neurochemical mechanism of the DMN's deactivation remains largely unknown. In the present study, we test the hypothesis that the major excitatory and inhibitory neurotransmitters, glutamate and GABA, respectively, are associated with DMN deactivation. We used magnetic resonance spectroscopy to measure neurotransmitter concentrations in the posterior cingulate cortex/precuneus (PCC/PCu), a key component of the DMN, and functional magnetic resonance imaging to evaluate DMN deactivation induced by an n-back working memory task. Our results demonstrate significant associations of glutamate and GABA with DMN deactivation. Specifically, high regional GABA concentration in the PCC/PCu area is associated with enhanced deactivation induced by the task in the same region, whereas high glutamate concentration is associated with reduced deactivation. Furthermore, the association between GABA and DMN deactivation increases with the cognitive loads. These neurochemical characteristics of DMN deactivation may provide novel insights toward better understanding of the DMN's functions under normal physiological conditions and dysfunctions in neuropsychiatric disorders.
大脑默认模式网络(DMN)的去激活被认为是对内源性活动的抑制,以支持外源性与任务相关的过程。这一现象具有重要的功能相关性,并且 DMN 去激活不足与几种神经精神障碍有关。然而,DMN 去激活的神经化学机制在很大程度上仍然未知。在本研究中,我们检验了以下假设,即主要的兴奋性和抑制性神经递质谷氨酸和 GABA 分别与 DMN 的去激活有关。我们使用磁共振波谱测量了后扣带回皮层/楔前叶(PCC/PCu)——DMN 的一个关键组成部分——中的神经递质浓度,并使用功能磁共振成像评估了 n-back 工作记忆任务引起的 DMN 去激活。我们的结果表明,谷氨酸和 GABA 与 DMN 去激活有显著关联。具体来说,PCC/PCu 区域的局部 GABA 浓度较高与该区域任务诱导的去激活增强有关,而谷氨酸浓度较高则与去激活减少有关。此外,GABA 与 DMN 去激活之间的关联随着认知负荷的增加而增加。DMN 去激活的这些神经化学特征可能为更好地理解正常生理条件下 DMN 的功能和神经精神障碍中的功能障碍提供新的见解。