Neurobiological consequences of binge alcohol consumption in young adults

描述（由申请人提供）：我们提出的研究目的是利用磁共振波谱（MRS）和神经心理学评估来检查酗酒对18-24岁年轻人脑代谢物和认知功能的影响。在这一“初显成年”时期，额叶和联合皮层的微调的最后阶段使额叶介导的决策和反应抑制能力得到显著改善，同时减少冲动行为。先前的研究已经确定，大量饮酒与大脑结构和功能异常以及大脑代谢物的改变有关。这些改变在前额叶皮层特别突出，可能导致酒精相关的执行功能缺陷，支持了酒精使用障碍的额叶功能障碍假说。本研究将使用专用质子（1H） MRS技术来量化和比较18-24岁男性和女性酗酒者（BD）和轻度饮酒者（LD）的前扣带皮层（ACC）和顶枕皮质（POC）中的质子代谢物。这项提议的一个新组成部分是使用MEGAPRESS和2D-JPRESS可靠地检测和量化前额叶皮层中GABA和谷氨酸（酒精作用的中心靶点）的能力。据报道，n -乙酰-天冬氨酸（NAA）、胆碱和肌醇（myo-I）在重度酒精使用者中显示出变化，本提案也将对此进行研究。光谱数据将与认知表现相关，重点关注执行功能，这是一个被广泛报道的认知额叶介导区域，显示出酒精使用障碍的缺陷。这项研究的结果将对公共卫生问题有重大意义，因为确定“初成年期”与酗酒有关的神经生物学相关性，将有助于填补现有文献中关于大脑酒精影响的空白，该人群不仅酗酒率最高，而且酒精滥用和依赖率最高。

DESCRIPTION (provided by applicant): The aim of our proposed study is to examine the effects of binge alcohol consumption on brain metabolites and cognitive function in 18-24 year olds using magnetic resonance spectroscopy (MRS) and neuropsychological assessment. The final stages of fine-tuning in frontal and association cortices that occur during this period of "emerging adulthood" permit notable improvements in frontally mediated decision-making and response inhibition abilities, while decreasing impulsive behavior. Previous work has identified that heavy alcohol consumption is associated with structural and functional brain abnormalities, and altered cerebral metabolites. These alterations, which are particularly prominent in the prefrontal cortex, likely contribute to alcohol-related executive function deficits, supporting a frontal dysfunction hypothesis in alcohol use disorders. This proposal will use specialized proton (1H) MRS techniques to quantify and compare proton metabolites in the anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) of 18-24 year old male and female binge (BD) and light alcohol drinkers (LD). A novel component of this proposal is the ability to reliably detect and quantify GABA and glutamate, central targets of alcohol action, in the prefrontal cortex using MEGAPRESS and 2D-JPRESS. N-acetyl-aspartate (NAA), choline, and myo-inositol (myo-I), reported to show alterations in heavy alcohol users, will also be examined in this proposal. Spectroscopic data will be examined relative to cognitive performance, with a focus on executive functioning, a frontally mediated area of cognition most widely reported to show deficits in alcohol use disorders. The results of this study will have significant relevance for public health concern, as identification of neurobiological correlates associated with binge alcohol consumption during "emerging adulthood" will help fill a gap in the existing literature on brain alcohol effects in a population that demonstrates not only the highest rate of binge drinking, but also the highest rate of alcohol abuse and dependence. PUBLIC HEALTH RELEVANCE: The overall aim of our proposed study is to examine the effects of binge alcohol consumption on brain metabolites in 18-24 year subjects by applying magnetic resonance spectroscopy (MRS) single voxel methods to reliably detect and quantify GABA, glutamate, and other proton metabolites, in the anterior cingulate region of the prefrontal cortex at 4 Tesla. Spectroscopic data will be examined relative to cognitive performance, with a focus on executive functioning, a frontally mediated area of cognition most widely reported to show deficits in alcohol use disorders. The results of this study will have significant relevance for public health concern, as identification of neurobiological correlates associated with binge alcohol consumption during "emerging adulthood" will help fill a gap in the existing literature on brain alcohol effects in a population that demonstrates not only the highest rate of binge drinking, but also the highest rate of alcohol abuse and dependence.