Glutamate modulates resting state activity in the perigenual anterior cingulate cortex - a combined fMRI-MRS study

The perigenual anterior cingulate cortex (PACC) shows high resting state activity and is considered part of the default-mode network (DMN). However, the biochemical underpinnings of the PACC's high resting state activity remain unclear. While animal-based evidence points toward a role for the glutamatergic system, the modulation of the resting state activity level by itself as distinguished from stimulus-induced activity remains to be shown in humans. Using combined fMRI-MRS in healthy subjects, we here demonstrate that the PACC resting state concentration of glutamate is directly related to the level of resting state activity in the same region. In contrast, no such relationship could be detected during the anticipation of reward and punishment, nor in an independent control region (the left anterior insula). Taken together, our findings demonstrate for the first time the modulation of the PACC resting state activity level by the concentration of glutamate in the same regions. This contributes to a better understanding of the biochemical basis for the brain's resting state activity as well as providing some clues regarding its apparent pathological upregulation in psychiatric disorders like the major depressive disorder.