Brain Glutamate Dynamics Predict Positive Agency in Healthy Women.

Contributions of brain glutamate to conscious emotion are not well understood. Here we evaluate the relationship of experimentally-induced change in neocortical glutamate (△Glu) and subjective states in well individuals. Drug challenge with d -amphetamine (AMP; 20 mg oral), methamphetamine (MA; Desoxyn®, 20 mg oral), and placebo (PBO) was conducted on three separate test days in a within-subjects double blind design. Proton magnetic resonance spectroscopy (MRS) quantified neurometabolites in the right dorsal anterior cingulate cortex (dACC) 140-150 m post-drug and PBO. Subjective states were assessed at half hour intervals over 5.5-hours on each session, yielding 3,792 responses per participant (91,008 responses overall, N =24 participants). Self-reports were reduced by principal components analysis to a single factor score of AMP- and MA-induced Positive Agency (△PA) in each participant. We found drug-induced △Glu related positively with △PA (△Glu MA r =+.44, p <.05, N =21), with large effects in females (△Glu MA r =+.52, p <.05; △Glu AMP r =+.61, p <.05, N =11). States related to △Glu in females included rise in subjective stimulation, vigor, friendliness, elation, positive mood, positive affect ( r 's=+.51 to +.74, p <.05), and alleviation of anxiety ( r =-.61, p <.05, N =11). Self-reports correlated with DGlu to the extent they loaded on △PA ( r =.95 AMP, p =5x10 -10 ; r =.63 MA, p =.0015, N =11), indicating coherence of △Glu effects. Timing data indicated Glu shaped emotion both concurrently and prospectively, with no relationship to pre-MRS emotion (△Glu AMP r =+.59 to +.65, p's <.05; △Glu MA r =+.53, p <.05, N =11). Together these findings indicate substantive, mechanistic contributions of neocortical Glu to positive agentic states in healthy individuals, most readily observed in women.