This finding indicates that the relationship between dACC glutamate concentrations and impulsive decision making can, at least partly, be attributed to connectivity of the left dACC with the midbrain. Preclinical literature has indicated a role for glutamate in impulsivity (for a review see Pattij and Vanderschuren 2008). For instance, selective and nonselective NMDA receptor antagonists have been shown to increase impulsive behavior in animal models (Higgins et al. 2003; Mirjana et al. 2004). Systemic pretreatment with an mGlu2/3 receptor agonist attenuates impulsive
behavior seen after serotonin receptor stimulation Inhibitors,research,lifescience,medical (Wischhof et al. 2011). In humans, a recent study of Hoerst et al. (2010) examined glutamate levels in the dACC in patients with borderline personality disorder and healthy controls. Irrespective of diagnosis, higher Glu/Cr was associated with higher self-reported (trait) impulsivity (Hoerst et al. 2010). Anterior cingulate Glu/Cr was also found Inhibitors,research,lifescience,medical to be increased in untreated children with ADHD, a disorder characterized by impaired impulse control (Hammerness et al. 2012). In keeping with these findings, Inhibitors,research,lifescience,medical the current study revealed that glutamate concentrations
in the dACC were associated with impulsive decision making. Interestingly, the current study revealed associations between dACC glutamate concentrations and resting state connectivity of the dACC with other brain regions (the midbrain and the left and right PCC). This is consistent with a previously described correlation between ¹H MRS glutamate concentrations and resting Inhibitors,research,lifescience,medical state functional connectivity (Horn et al. 2010), suggesting that the amount of glutamate, which is present in neuronal and glial metabolic and neurotransmitter pools as measured by ¹H MRS, underlies the observed synchronization Inhibitors,research,lifescience,medical among these brain regions as assessed with resting state functional connectivity measures. This is not very surprising, as it is thought that the intrinsic energy product info demands of neuron populations in different brain regions with a common functional purpose have wired together
through synaptic Cilengitide plasticity, and thereby form so-called resting state networks (e.g., Lewis et al. 2009). It is well known that glutamate plays a critical role in synaptic plasticity. Unfortunately, ¹H MRS does not allow distinguishing the specific contribution of different components of the glutamatergic system to spontaneous coherence of BOLD sellectchem signal fluctuations between brain regions. ¹H MRS glutamate measurements reflect primarily intracellular glutamate and does not directly measure synaptic glutamate transmission (Gruetter et al. 1998). Furthermore, quantification and separation of glutamate by use of ¹H MRS is technically difficult because glutamate overlaps in its chemical shift range with glutamine and γ-amino butyric acid (GABA).