Anterior insula glutamate/glutamine is associated with psychopathology scores through overestimating errors

Abstract

Despite having more direct information with functional magnetic resonance spectroscopy (fMRS), little is known about how the brain’s neurochemical mechanisms influence mental health and decision-making. In this study, we examined whether baseline glutamate/glutamine (Glx) and lactate concentrations were related to general anxiety and depression and how they changed according to gains and losses with fMRS scanning during reward learning and computational modeling. The Glx concentration in the anterior insular cortex (AIC), not the medial prefrontal cortex, was positively associated with the general psychopathological factor of anxiety and depression through the mediation of error sensitivity. The AIC Glx level decreased mainly after learning from gains and as the entire task was performed. Conversely, lactate reduction in AIC occurred only during learning from losses and was associated with higher general psychopathology scores. We demonstrated for the first time that both glutamate-related error sensitivity and loss-specific lactate reduction in the AIC are associated with general psychopathology. This study’s results suggest that the AIC is a potential target brain region for glutamate and/or lactate-mediated therapeutics for anxiety and depression.