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.

Figure 1.

MRS and fMRI experiments. a, A VOI was placed at the PCC/PCu for ¹H spectroscopy. b, Regional GABA and glutamate concentrations were assessed using MRS techniques. c, An n-back working memory task was administered to probe the default mode network deactivation, with 0-back as the control condition (time scale is 2 s). d, Behavioral performance (dprime) during the working memory task demonstrated a significant memory load effect. e, Individual GABA spectra. A weighting function of Lorentzian–Gaussian transformation (lb = −3 Hz, gb = 8 Hz) was applied, and the displayed peak intensities were normalized to N-acetylaspartic acid.

Figure 2.

Brain activity during the working memory task. a, Brain areas showing main effect of the working memory task revealed by voxelwise ANOVA (corrected p < 0.01). To illustrate task-induced activation and deactivation, brain activities within these areas at the 3-back level are shown. b, Cognitive load modulated deactivation in the PCC/PCu region. (c) The PCC/PCu deactivation was significantly correlated with 3-back working memory task performance.

Figure 3.

Partial regression plots. PCC/PCu deactivation can be predicted by age and regional glutamate and GABA concentrations assessed by MRS at resting state.