Neurobiological consequences of binge alcohol consumption in young adults

描述(申请人提供)：我们建议的研究目的是利用磁共振波谱(MRS)和神经心理学评估来研究酗酒对18-24岁青少年大脑代谢物和认知功能的影响。额叶和联想皮质微调的最后阶段发生在这一“初露头角的成年期”期间，这允许额叶调节的决策和反应抑制能力的显著改善，同时减少冲动行为。以前的研究已经发现，大量饮酒与大脑结构和功能异常以及大脑代谢物改变有关。这些变化，尤其是在前额叶皮质，可能导致与酒精相关的执行功能缺陷，支持酒精使用障碍的额叶功能障碍假说。这项建议将使用专门的质子(1H)MRS技术来量化和比较18-24岁的酗酒(BD)和轻度饮酒者(LD)前扣带回(ACC)和顶枕叶(POC)中的质子代谢物。这项建议的一个新组成部分是能够使用MEGAPRESS和2D-JPRESS可靠地检测和定量酒精作用的前额叶皮质中的GABA和谷氨酸。N-乙酰天冬氨酸(NAA)、胆碱和肌醇(Myo-I)，据报道显示重度酒精使用者的变化，也将在这项提案中进行检查。光谱数据将与认知表现相关，重点是执行功能，这是一个正面调节的认知领域，最广泛的报道显示酒精使用障碍中的缺陷。这项研究的结果将与公共卫生问题具有重要的相关性，因为确定与“成年初期”酗酒有关的神经生物学关联将有助于填补现有文献中关于酒精对大脑影响的空白，该文献不仅显示出酗酒的最高比率，而且还表明酗酒和依赖的比率最高。 公共卫生相关性： 我们建议的研究的总体目标是通过应用磁共振波谱(MRS)单体素方法可靠地检测和定量4特斯拉时前额叶皮质前扣带区的GABA、谷氨酸和其他质子代谢物，来检验酗酒对18-24岁受试者大脑代谢物的影响。光谱数据将与认知表现相关，重点是执行功能，这是一个正面调节的认知领域，最广泛的报道显示酒精使用障碍中的缺陷。这项研究的结果将与公共卫生问题具有重要的相关性，因为确定与“成年初期”酗酒有关的神经生物学关联将有助于填补现有文献中关于酒精对大脑影响的空白，该文献不仅显示出酗酒的最高比率，而且还表明酗酒和依赖的比率最高。

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.