Medical Neuroscience Graduate Program, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Indiana Alcohol Research Center, Indiana University School of Medicine, Indianapolis, IN, USA.
Neuropsychopharmacology. 2024 Jan;49(2):396-404. doi: 10.1038/s41386-023-01684-3. Epub 2023 Aug 7.
High-intensity sweet-liking has been linked to alcohol use disorder (AUD) risk. However, the neural underpinning of this association is poorly understood. To find a biomarker predictive of AUD, 140 participants (social and heavy drinkers, ages 21-26) underwent functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task and stimulation with high (Sucrose)- and low-concentration sucrose, as well as viscosity-matched water. On another day after imaging, and just before free-access intravenous alcohol self-administration, participants experienced a 30 mg% alcohol prime (10 min ascent) using the Computerized Alcohol Infusion System. Principal component analysis (PCA) of subjective responses (SR) to the prime's ascending limb generated enjoyable (SR) and sedative (SR) intoxication components. Another PCA created one component reflective of self-administered alcohol exposure (AE) over 90 min. Component loadings were entered as regressors in a voxel-wise general linear fMRI model, with reward type as a fixed factor. By design, peak prime breath alcohol concentration was similar across participants (29 ± 3.4 mg%). SR on the prime's ascending limb correlated positively with [Sucrose> Water] in the supplementary motor area and right dorsal anterior insula, implicating the salience network. Neither SR component correlated with the brain's response to MID. AE was unrelated to brain reward activation. While these findings do not support a relationship between alcohol self-administration and (1) subjective liking of or (2) regional brain response to an intensely sweet taste, they show that alcohol's enjoyable intoxicating effects on the rising limb correspond with anterior insular and supplementary motor area responses to high-concentration sucrose taste. No such associations were observed with MID despite robust activation in those regions. Insula and supplementary motor area responses to intense sensations relate to a known risk factor for AUD in a way that is not apparent with a secondary (monetary) reward.
高强度甜味偏好与酒精使用障碍（AUD）风险有关。然而，这种关联的神经基础理解甚少。为了找到预测 AUD 的生物标志物，140 名参与者（社交和重度饮酒者，年龄 21-26 岁）在货币激励延迟（MID）任务期间接受功能磁共振成像（fMRI），并接受高（蔗糖）和低浓度蔗糖以及粘度匹配水的刺激。在成像后的另一天，即在自由静脉内酒精自我给药之前，参与者使用计算机化酒精输注系统经历了 30mg%酒精引发（10 分钟上升）。对引发剂上升支的主观反应（SR）进行主成分分析（PCA），产生愉快（SR）和镇静（SR）中毒成分。另一个 PCA 创建了一个反映 90 分钟内自我管理的酒精暴露（AE）的组件。组件负荷作为回归量输入到体素级别的一般线性 fMRI 模型中，奖励类型作为固定因素。通过设计，参与者之间的峰值引发呼吸酒精浓度相似（29±3.4mg%）。在上升支上的 SR 与补充运动区和右侧背侧前岛叶中的[蔗糖>水]呈正相关，表明突出网络。这两个 SR 成分都与大脑对 MID 的反应无关。AE 与大脑奖励激活无关。虽然这些发现不支持酒精自我给药与（1）对强烈甜味的主观喜好或（2）对区域大脑对强烈甜味的反应之间的关系，但它们表明，酒精在上升支上对愉快的陶醉作用与对高浓度蔗糖味道的前岛叶和补充运动区反应相对应。尽管在这些区域有强烈的激活，但没有观察到与 MID 的这种关联。强烈感觉的岛叶和补充运动区反应与 AUD 的一个已知风险因素有关，而与次要（货币）奖励无关。
