| Autor: |
White TL; Carney Institute for Brain Science, Brown University, Providence, Rhode Island 02912. United States.; Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island 02912. United States.; Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island 02912. United States.; Center for Human Rights and Humanitarian Studies, Watson Institute, Brown University, Providence, Rhode Island 02912. United States.; University of Cambridge, Clare Hall, Cambridge CB3 9AL England. U.K., Gonsalves MA; Neuroscience Graduate Program, Brown University, Providence, Rhode Island 02912. United States., Harris AD; Department of Radiology, CAIR Program, Alberta Children's Hospital Research Institute, and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta T2N 1N4, Canada., Walsh EG; Carney Institute for Brain Science, Brown University, Providence, Rhode Island 02912. United States., Joyce HE; Undergraduate Program in Cognitive Neuroscience, Brown University, Providence, Rhode Island 02912. United States. |
| Jazyk: |
angličtina |
| Zdroj: |
ACS chemical neuroscience [ACS Chem Neurosci] 2024 Feb 07; Vol. 15 (3), pp. 491-502. Date of Electronic Publication: 2024 Jan 18. |
| DOI: |
10.1021/acschemneuro.3c00521 |
| Abstrakt: |
Contributions of brain glutamate (Glu) to conscious emotion are not well understood. Here, we evaluate the relationship of experimentally induced change in neocortical Glu (ΔGlu) and subjective states in well individuals, using combined application of pharmacological challenge, magnetic resonance spectroscopy (MRS), and comprehensive affective assessment. 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 MRS quantified neurometabolites in the right dorsal anterior cingulate cortex 140-150 min post-drug and PBO. Subjective states were assessed at half hour intervals over 5.5 h on each session, yielding 3792 responses per participant (91,008 responses overall, N = 24 participants), with self-reports reduced by principal components analysis (PCA). PCA produced a primary factor score of AMP- and MA-induced positive agency (ΔPA). MRS indicated drug-induced ΔGlu related positively to ΔPA (ΔGlu MA r = +0.44, p < 0.05, N = 21), with large effects in females (ΔGlu MA r = +0.52, p < 0.05; ΔGlu AMP r = +0.61, p < 0.05, N = 11). Subjective states related to ΔGlu included rise in subjective stimulation, vigor, friendliness, elation, positive mood, positive affect ( r 's = +0.51 to +0.74, p < 0.05), and alleviation of anxiety in females ( r = -0.61, p < 0.05, N = 11). These self-reports correlated with ΔGlu to the extent they loaded on ΔPA ( r = 0.95 AMP, p = 5 × 10 -10 ; r = 0.63 MA, p = 0.0015, N = 11), indicating the coherence of ΔGlu effects on emotional states. Timing data indicated Glu shaped positive emotion both concurrently and prospectively, with no relationship with pre-MRS emotion (ΔGlu AMP r = +0.59 to +0.65, p 's < 0.05; ΔGlu MA r = +0.53, p < 0.05, N = 11). Together these findings indicate substantive, mechanistic contributions of neocortical Glu to positive agentic states in healthy individuals, which are most readily observed in women. The findings illustrate the promise of combined application of pharmacological challenge, comprehensive affective assessment, and MRS neuroimaging techniques in basic and clinical studies. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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