Resting-State Glutamate and GABA Concentrations Predict Task-Induced Deactivation in the Default Mode Network

Abstract

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.