fMRI of Hippocampal Function in Cannabis Users

描述（由申请人提供）：R03申请的最终修订将使用功能性磁共振成像（fMRI）检查大麻对视觉空间记忆和海马功能的影响。许多动物研究表明，暴露于大麻素后海马会出现异常，这表明与大麻使用相关的认知加工中的关键缺陷可能与海马功能有关。研究表明，大麻会影响记忆、额叶和执行功能、决策和运动技能。然而，以前的研究并没有系统地评估海马体的空间处理。由于人类海马体中高浓度的大麻素，大麻对这一大脑区域的影响是非常有趣的。此外，大多数研究主要招收男性受试者，因此很难审查性别与大麻使用之间的相互影响。本研究的具体目的是：1a)评估大麻在评估空间记忆和联想视觉记忆任务时海马介导的挑战范式中对fMRI BOLD信号变化的影响；1b)评估大麻对视觉空间任务表现的影响及其与fMRI BOLD活动的关系；2)并检查使用大麻和不使用大麻的受试者在这些反应中的性别差异。这项拟议中的研究将比较10名男性和10名女性重度大麻吸烟者和10名男性和10名女性健康非吸烟者。我们的主要假设是，在完成海马体依赖性记忆挑战任务时，与不吸烟的对照组相比，当前吸食大麻的人的BOLD反应显着降低。此外，我们假设在认知挑战范式中，男性和女性（无论是否吸烟）的神经激活模式存在差异，以及他们在这些任务中的表现存在性别差异。最后，我们预测了吸烟状况和性别之间的相互作用，即与男性对照、男性大麻吸烟者和女性对照相比，女性大麻吸烟者会表现出更低的海马BOLD反应和更低的视觉空间表现。这项研究的新颖之处在于，它包括fMRI挑战范式和对海马处理敏感的神经心理学测量，以评估与大麻使用相关的颞叶变化。鉴于大麻使用者视觉空间记忆功能的数据缺乏以及与性别的相互作用，我们相信这些研究将进一步加深我们对大麻使用背后的神经变化的理解，并为理解药物滥用人群中的性别影响提供新的见解。目前关注吸食大麻影响的研究报告称，吸食大麻会改变大脑功能和完成日常活动的能力，然而，迄今为止，很少有人研究大麻对视觉空间记忆的潜在影响。该项目旨在研究大麻对空间记忆和海马功能的影响，使用定制挑战范式结合功能磁共振成像（fMRI）技术。这项研究的数据将阐明大麻使用对学习和记忆的影响，并可能为干预和治疗的发展提供新的见解。

DESCRIPTION (provided by applicant): This final revision of an R03 application will examine the effects of marijuana on visuospatial memory on hippocampal function using functional magnetic resonance imaging (fMRI). A number of animal studies have demonstrated hippocampal abnormalities after exposure to cannabinoids, suggesting that key deficits in cognitive processing associated with cannabis use may be related to hippocampal function. It has been shown that cannabis affects memory, frontal and executive function, decision-making and motor skills. However, previous studies have not systematically assessed hippocampal spatial processing. Due to the high concentrations of cannabinoids in the human hippocampus, the effects of cannabis in this brain region are of significant interest. Furthermore, most studies have enrolled predominantly male subjects making it difficult to examine the interactive effects between gender and cannabis use. The specific aims of the current proposal are 1a) to evaluate the effects of marijuana on fMRI BOLD signal changes during hippocampus-mediated challenge paradigms assessing both spatial memory and associative visual memory tasks; 1b) to evaluate the effects of marijuana on performance of visuospatial tasks and the relationship with fMRI BOLD activity; 2) and to examine sex differences in these responses for both marijuana using and non-using subjects. The proposed study will compare 10 male and 10 female current heavy marijuana smokers and 10 male and 10 female healthy non-smoking controls. Our primary hypothesis is that significant decreases in BOLD response will be found for current marijuana smokers compared with non-smoking controls during completion of hippocampal-dependent memory challenge tasks. Further, we hypothesize differential pattern of neural activation between men and women (regardless of smoking condition) during the cognitive challenge paradigms, as well as a sex differences in their performance of these tasks. Lastly, we predict an interaction between smoking condition and sex, whereby female marijuana smokers will exhibit reduced hippocampal BOLD response and reduced visuospatial performance compared to male controls, male marijuana smokers, and female controls. This investigation is novel in that it includes fMRI challenge paradigms and neuropsychological measures sensitive to hippocampal processing to evaluate temporal lobe changes associated with cannabis use. Given the paucity of data on visuospatial memory function in marijuana users and the interaction with gender, we believe these studies will further our understanding of the neural changes underlying cannabis use and provide new insight into understanding gender effects in substance abusing populations. Current research investigations focusing on the effects of smoking marijuana have reported alterations in brain function and in the ability to complete daily activities, however, few thus far have examined the potential impact on visuospatial memory. The proposed project is designed to examine the effects of marijuana on spatial memory and hippocampal function using customized challenge paradigms in conjunction with functional magnetic resonance imaging (fMRI) techniques. Data from this study will clarify the impact of marijuana use on learning and memory, and may provide new insights for the development of intervention and treatment.