However, as ¹H MRS does not directly measure synaptic glutamate transmission, but rather reflects metabolic and neurotransmitter pools of glutamate within a ROI (Gruetter et al. 1998), and resting state functional connectivity does not represent glutamatergic projections from one brain region to another, animal research is needed to further investigate this interpretation of the

current findings. It is important to stress that our results Inhibitors,research,lifescience,medical should be viewed in light of some methodological limitations. First, the sample size was modest, which might limit the Enzalutamide mw generalizability of the current results. Second, because of the exploratory nature of our study, Inhibitors,research,lifescience,medical we applied a statistical threshold for significance that did not fully account for the issue of multiple comparisons. However, the observed correlation between delay discounting (AUC values) and glutamate concentrations and between delay discounting and functional connectivity of the dACC with the midbrain remained significant when correcting for multiple comparisons. Instead, there

was a trend toward a significant correlation between glutamate concentrations Inhibitors,research,lifescience,medical and dACC functional connectivity with the midbrain when fully correcting for multiple comparisons. Although the current study was set up as a pilot study and gives a first indication of the interaction between glutamate concentrations and functional connectivity between brain regions under rest in predicting impulsive behavior, future Inhibitors,research,lifescience,medical studies are required using larger sample sizes (and thereby increasing statistical power) to replicate the current findings. In conclusion, the current findings suggest

that individual differences in impulsive Inhibitors,research,lifescience,medical decision making depend on intrinsic properties of the dACC and not merely on task-related cognitive processes, supporting the idea that altered basic conditions of brain functioning lead to abnormal functional responses. This is important to acknowledge, because spontaneous intrinsic brain processes have been proposed to be a potential promising biomarker of disease (Greicius 2008) and impulsive decision making is a common feature in several psychiatric disorders. Recent findings have indicated that there is a genetic influence on individual differences Parvulin in delay discounting (Boettiger et al. 2007; Eisenberg et al. 2007; Anokhin et al. 2011). Assuming there is a long road between genes and higher-order cognitive functions, intrinsic properties of brain functioning in the form of resting state glutamate concentrations or functional connectivity, may provide an intermediate step between genes and abnormalities in higher-order cognitive functions, such as excessive delay discounting.