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 (ΔGluMA r = +0.44, p < 0.05, N = 21), with large effects in females (ΔGluMA r = +0.52, p < 0.05; ΔGluAMP 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 (ΔGluAMP r = +0.59 to +0.65, p\'s < 0.05; ΔGluMA 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.
摘要：
大脑谷氨酸（Glu）对意识情绪的贡献尚不清楚。这里,我们评估了实验诱导的新皮质Glu（ΔGlu）变化与健康个体主观状态的关系，使用联合应用药理学挑战，磁共振波谱（MRS），和全面的情感评估。D-苯丙胺（AMP）（20mg口服）的药物攻击，甲基苯丙胺（MA）（Desoxyn，口服20毫克），和安慰剂（PBO）在受试者内部双盲设计中在三个单独的测试日进行。质子MRS定量了药物和PBO后140-150分钟右背前扣带皮质中的神经代谢产物。在每个疗程5.5小时内，以半小时为间隔评估主观状态，每位参与者产生3792个响应(总共91,008个响应，N=24名参与者)，主成分分析(PCA)减少了自我报告。PCA产生了AMP和MA诱导的阳性因子（ΔPA）的主要因子得分。MRS显示药物诱导的ΔGlu与ΔPA呈正相关（ΔGluMAr=0.44，p<0.05，N=21）。对女性的影响很大（ΔGluMAr=0.52，p<0.05；ΔGluAMPr=0.61，p<0.05，N=11）。与ΔGlu相关的主观状态包括主观刺激的增加，活力,友善,elation,积极的情绪,积极影响(r\s=+0.51至+0.74，p<0.05)，和缓解女性焦虑（r=-0.61，p<0.05，N=11）。Theseself-reportedwithΔGlutotheextenttheyloadedonΔPA(r=0.95AMP,p=5×10-10；r=0.63MA，p=0.0015,N=11),表明ΔGlu效应对情绪状态的相干性。时间数据表明Glu同时和前瞻性地塑造了积极情绪，与MRS前情绪无关（ΔGluAMPr=0.59至0.65，p\s<0.05；ΔGluMAr=0.53，p<0.05，N=11）。这些发现一起表明了实质性的，新皮质Glu对健康个体积极状态的机制贡献，这在女性中最容易观察到。这些发现说明了联合应用药理学挑战的前景，综合情感评估，基础和临床研究中的MRS神经成像技术。
