Glutamate in Salience Network Predicts BOLD Response in Default Mode Network During Salience Processing

Abstract

BackgroundBrain investigations identified salience network (SN) comprising the dorsal Anterior Cingulate Cortex (dACC) and the Anterior Insula (AI). Magnetic resonance spectroscopy (MRS) studies revealed the link between the glutamate concentration in the ACC and alterations in attentional scope. Hence, we investigated whether glutamate concentration in the dACC modulates brain response during salience processing.MethodsTwenty-seven healthy subjects (12♀, 15♁) provided both STEAM MRS at 7T measuring glutamate concentrations in the dACC as well as a functional magnetic resonance imaging (fMRI) task to study the influence on content-related salience processing and expectedness. Salience was modulated for both sexual and non-sexual emotional photos in either expected or unexpected situations. Correlation between MRS and task fMRI was investigated by performing regression analyses controlling for age, gender, and gray matter partial volume.Results/ConclusionDuring picture processing, the extent of deactivation in the Posterior Cingulate Cortex (PCC) was attenuated by two different salience attributions: sexual content and unexpectedness of emotional content. Our results indicate that stimulus inherent salience induces an attenuation of the deactivation in PCC, which is in turn balanced by higher level of glutamate in the dACC.

GABA, Glutamate and Neural Activity: A Systematic Review With Meta-Analysis of Multimodal 1H-MRS-fMRI Studies

“…Overbeek et al ( 34 ) observed ACC glutamate levels were positively associated with NBR in a cluster spanning from the PCC and precuneus to the occipital cortex and cerebellum. Von During et al ( 45 ) also found that ACC glutamate levels were positively associated with NBR in the PCC, with higher glutamate predicting higher deactivation of this area in response to a variety of stimuli. Neural activity in a variety of other regions were also negatively correlated with ACC glutamate levels in this study (see Table 4 ).…”

“…supragenual ACC Glx levels, however, were not associated with pgACC activation during the empathy task. ACC glutamate levels were also studied in conjunction to neural activity during a salience processing task using emotional and erotic pictures ( 45 ). Activation in the sgACC related to unexpectedness of emotional pictures displayed a negative correlation with glutamate.…”

“…For the meta-analysis investigating the relationship between ACC glutamate levels and local activation during emotion processing, seven studies were included ( 29 , 31 , 32 , 35 , 44 , 45 , 49 ). As with the previous meta-analysis on cognitive control, studies utilised a mixture of correlation and regression analyses.…”

“…These findings add to the simplified positive relationship with inter-regional neural activity reported in Duncan et al ( 4 ). A negative relationship between BOLD activity in DMN regions, such as the PCC/PCu, were speculated to be due to higher ACC glutamate levels supporting facilitation of salience processing, thus resulting in stronger deactivation of DMN regions ( 39 , 45 ). However, this relationship seems to be region-dependant as glutamate levels measured within the DMN, specifically the PCC, were positively related with DMN neural activation, where higher glutamate levels predicted lower local deactivation ( 60 ).…”

Neurochemistry of Visual Attention

“…Several studies have found that subanesthetic doses of the NMDA receptor antagonist ketamine induce psychoses-like symptoms in healthy volunteers ( Krystal et al, 1994 ; Malhotra et al, 1996 ). Ketamine influences memory ( Malhotra et al, 1996 ; Morgan and Curran, 2006 ) and modulates attentional processes ( Oranje et al, 2000 ; Watson et al, 2009 ; Gunduz-Bruce et al, 2012 ; Fuchs et al, 2015 ; von Düring et al, 2019 ; but see Morgan et al, 2004 ; van Wageningen et al, 2010 ). For example, Fuchs et al (2015) investigated the influence of ketamine on top-down attentional control using a visual cueing paradigm.…”