Brain Glutamate Dynamics Predict Positive Agency in Healthy Women: Insights from Combined Application of Pharmacological Challenge, Comprehensive Affective Assessment, and Magnetic Resonance Spectroscopy
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".