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Personality traits have been linked with both brain structure and function. However, the exact relationship between personality traits and other behavioural measures with neurometabolites, measured with proton magnetic resonance spectroscopy, is not clear. Here we investigated the association between behavioural measures (i.e., personality traits, resilience, perceived stress, self-esteem, hopelessness, psychological distress) and metabolite ratios (i.e., of choline-containing compounds [Cho], creatine and phosphocreatine [Cr], and N-acetyl-aspartate [NAA]) in the posterior cingulate cortex (pCC) and the dorsal anterior cingulate cortex (dACC) and surrounding white matter (WM) regions in healthy emerging adults (N = 57, 26 women, mean age=23.40 years, SD=2.50). The pCC and the dACC were selected for their known involvement as important brain network hubs and their association to five factor personality dimensions and other psychological measures. Spectral analysis as well as statistics for demographic, clinical, and imaging data were performed. Correlation and multiple regression analyses were used to test the relationship between metabolite ratios and behavioural scores in the entire sample as well as in female and male participants separately. The entire sample showed significant (p

Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive imaging technique that measures the concentration of metabolites in defined areas of the human brain in vivo. The underlying structure of natural metabolism-emotion relationships is unknown. Further, there is a wide range of between-person differences in metabolite concentration in healthy individuals, but the significance of this variation for understanding emotion in healthy humans is unclear. Here we investigated the relationship of two emotional constructs, agency and flexibility, with the metabolites glutamate and glutamine (Glx), N-acetylaspartate (tNAA), choline (Cho), creatine (tCr), and myo-inositol (Ins) in the right dorsal anterior cingulate cortex (dACC) in medically and psychiatrically healthy volunteers (N = 20, 9 female; mean age = 22.8 years, SD = 3.40). The dACC was selected because this region is an integrative hub involved in multiple brain networks of emotion, cognition and behavior. Emotional traits were assessed using the Multidimensional Personality Questionnaire Brief Form (MPQ-BF), an empirically derived self-report instrument with an orthogonal factor structure. Phenotypes evaluated were positive and negative agency (MPQ-BF Social Potency, Aggression), emotional and behavioral flexibility (MPQ-BF Absorption, Control-reversed), and positive and negative affect (MPQ-BF Social Closeness; Stress Reaction, Alienation). The resting concentration of tNAA in the dACC was robustly positively correlated with Absorption (r = +0.56, unadjusted p = .005), moderately positively correlated with Social Potency (r = +0.42, unadjusted p = .03), and robustly negatively correlated with Aggression (r = -0.59, unadjusted p = .003). Absorption and Aggression accounted for substantial variance in tNAA (R2 = 0.31, 0.35; combined R2 = 0.50), and survived correction for multiple comparisons (Holm-Bonferroni adjusted p = .032, 0.021, respectively). dACC Glx and Cho had modest relationships with behavioral flexibility and social affiliation that did not survive this multiple correction, providing effect sizes for future work. Principal Component Analysis (PCA) revealed a three-factor orthogonal solution indicating specific relationships between: 1) Glx and behavioral engagement; 2) Cho and affiliative bonding; and 3) tNAA and a novel dimension that we term neuroaffective reserves. Our results inform the neurobiology of agency and flexibility and lay the groundwork for understanding mechanisms of natural emotion using 1H-MRS.

Background: Salience network (SN) connectivity is altered in schizophrenia, but the pathophysiological origin remains poorly understood. The goal of this multimodal neuroimaging study was to investigate the role of glutamatergic metabolism as putative mechanism underlying SN dysconnectivity in first episode psychosis (FEP) subjects. Methods: We measured glutamate + glutamine (Glx) in the dorsal anterior cingulate cortex (dACC) from 70 antipsychotic-naïve FEP subjects and 52 healthy controls (HC). The dACC was then used as seed to define positive and negative resting state functional connectivity (FC) of the SN. We used multiple regression analyses to test main effects and group interactions of Glx and FC associations. Results: dACC Glx levels did not differ between groups. Positive FC was significantly reduced in FEP compared to HC, and no group differences were found in negative FC. Group interactions of Glx-FC associations were found within the SN for positive FC, and in parietal cortices for negative FC. In HC, higher Glx levels predicted greater positive FC in the dACC and insula, and greater negative FC of the lateral parietal cortex. These relationships were weaker or absent in FEP. Conclusions: Here, we found that positive FC in the SN is already altered in medication-naïve FEP, underscoring the importance of considering both correlations and anticorrelations for characterization of pathology. Our data demonstrate that Glx and functional connectivity work differently in FEP than in HC, pointing to a possible mechanism underlying dysconnectivity in psychosis.