Involvement of glutamate in rest‐stimulus interaction between perigenual and supragenual anterior cingulate cortex: A combined fMRI‐MRS study

Abstract

The brain shows a high degree of activity at rest. The significance of this activity has come increasingly into focus. At present, however, the interaction between this activity and stimulus-induced activity is not well defined. The interaction between a task-negative (perigenual anterior cingulate cortex, pgACC) and task-positive (supragenual anterior cingulate cortex, sgACC) region during a simple task was thus investigated using a combination of fMRI and MRS. Negative BOLD responses in the pgACC were found to show a unidirectional effective connectivity with task-induced positive BOLD responses in the sgACC. This connectivity was shown to be related specifically with glutamate levels in the pgACC. These results demonstrate an interaction between deactivation from resting-state and resting-state glutamate levels in a task-negative region (pgACC), and task-induced activity in a task-positive region (sgACC). This provides insight into the neuronal and biochemical mechanisms by means of which the resting state activity of the brain potentially impacts upon subsequent stimulus-induced activity.

The relationship between MEG and fMRI

“…Duncan et al (Duncan et al, 2011) found that glutamate levels in the perigenual ACC were positively correlated with BOLD signal change in the supragenual ACC. Falkenberg and colleagues (Falkenberg et al, 2012) measured basal glutamate in the left and right dorsal ACC and BOLD during an auditory cognitive control task.…”

“…Relatively few studies have assessed the role of glutamate in the BOLD response to a stimulus (Duncan et al, 2011, Falkenberg et al, 2012. Duncan et al (Duncan et al, 2011) found that glutamate levels in the perigenual ACC were positively correlated with BOLD signal change in the supragenual ACC.…”

Resting state glutamate predicts elevated pre-stimulus alpha during self-relatedness: A combined EEG-MRS study on “rest-self overlap”

“…Most importantly, this correlation was biochemically, regionally, and neuronally specific: it applied to glutamate but not other metabolites; to the PACC, not other regions; and to pre-stimulus (e.g., prior to presentation or perception of the stimulus), not GLUTAMATE,ALPHA AND SELF 11 postonset (e.g., during stimulus presentation or perception) stimulus-related ERSP differences. Glutamate has been demonstrated to modulate resting state measures like the BOLD amplitude in fMRI (Enzi et al, 2012), and the PACC functional connectivity to cortical and subcortical regions (Duncan et al, 2011Falkenberg et al, 2012). These findings, however, left unresolved how glutamatergic modulation of resting state activity influences stimulus-induced activity, in general, and self-related stimuli, in particular.…”

“…Although inhibitory GABA has recently been shown to mediate EEG taskevoked measures like gamma band oscillations (Lally et al, 2014;Muthukumaraswamy, Edden, Jones, Swettenham, & Singh, 2009), studies on excitatory glutamate modulation of EEG measures have been reported less widely (for exceptions, see Lally et al, 2014; for animal studies, see MoralesVillagrán, Medina-Ceja, & López-Pérez, 2008). Glutamate is an excitatory transmitter that fMRI and magnetic resonance spectroscopy (MRS) analyses have shown to mediate resting state activity, including both intra-regional activity levels and trans-regional functional levels (Duncan, Enzi, Wiebking, & Northoff, 2011;Duncan et al, 2013;Enzi et al, 2012; also see Falkenberg, Westerhausen, Specht, & Hugdahl, 2012;Scheidegger et al, 2012). Such glutamatergic modulation of the resting state suggests that glutamate might mediate the influence of pre-stimulus state activity on stimulus-related activity.…”

“…Based upon the rest-self overlap considerations adumbrated above, we hypothesized that glutamate in the PACC-but not in the other regionswould mediate elevated pre-stimulus alpha power at frontal regions for stimuli that subjects assessed as high self-related. Our group has abundant experience in combining MRS with other imaging modalities (Duncan et al, 2011Enzi et al, 2012;Hayes et al, 2013;Northoff, 2007;Wiebking et al, 2014); this experience enabled us to link prestimulus (e.g., prior to stimulus presentation or perception) activity levels (as measured in EEG) to biochemical modulation by resting state glutamate concentration (as measured in MRS).…”