Repeated Traumatic Brain Injuries and Problematic Cannabis Use: An Electrophysiological Investigation of Potential Mechanisms.

项目概要/摘要。每年有350万例创伤性脑损伤（TBI）1，其中 个人头部受伤，导致暂时性意识丧失（LoC）或改变 到25岁时，近三分之一的年轻人将经历反复TBI（rTBI;即，2或 更多的损伤导致LoC或AoC），3从而加剧了持续性认知和 情绪功能障碍与各种精神病理学状况有关，4，5包括有问题的 6 -8考虑到大麻合法性最近的变化以及大麻使用的相关增加， 关键是要了解rTBI和大麻问题之间的明显联系，定义为社会损害 (e.g.,难以维持关系），职业（例如，工作或学习表现下降），或 财务（例如，由于使用大麻而无法支付账单）域。虽然 几项流行病学调查表明，那些有TBI病史的人， 相对于非TBI对照，有问题的物质使用的潜在机制知之甚少 解释这种联系是由于几乎所有前瞻性研究都系统性排除了有rTBI病史的个体， 对大麻使用的调查，以及几乎所有rTBI前瞻性研究都排除大麻使用者 (see Bjork和Grant，2009年进行了审查）。10这一疏忽对两个有关的问题留下了不充分的答案。 问题：rTBI史是否预示着更大的大麻相关问题，如果是，解释是什么？ 这种脆弱性的机制？ 与NIDA的中心重点一致，即确定高风险国家脆弱性的解释过程， 人群，本研究提出了一种新的前瞻性研究，测试是否rTBI相关 与大麻有关的问题然后，我们将测试rTBI可能增加的假定间接途径 通过使用事件相关电位（ERP）方法，特别是晚期阳性电位， (LPP)在观看和下调对情绪图像和N2/P3成分的反应时， 反应抑制任务期间的振幅。拟议研究的第一个具体目标是测试rTBI是否具有 与大麻问题有直接关系。这将通过两个横截面（即， 基线）和预期的大麻问题，通过自我报告和临床访谈进行评估。第二 具体的目的是通过提高情绪反应来测试rTBI对大麻问题的间接影响 (i.e.,更大的LPP，同时观看大麻线索和威胁图像）。第三个具体目标是测试 rTBI通过情绪调节困难对大麻问题的间接影响（即，更高的LPP， 意志调节大麻渴望，更大的LPP，同时认知地重新评估威胁图像）。 最后，第四个具体目标是测试RTBI对大麻问题的间接影响， 抑制控制（即，在反应抑制期间，N2和P3分量振幅变钝）。

Project Summary/Abstract. There are 3.5 million annual cases of Traumatic Brain Injury (TBI)1 in which an individual receives an injury to the head that results in a temporary loss of consciousness (LoC) or alteration of consciousness (AoC).2 By age 25, nearly one-third of young adults will experience repeated TBI (rTBI; i.e., 2 or more injuries resulting in LoC or AoC),3 thereby exacerbating the potential for persistent cognitive and emotional dysfunction that is linked to a variety of psychopathological conditions,4,5 including problematic cannabis use.6-8 Given recent changes to cannabis legality, and associated increases in cannabis use,9 it is critical to understand the apparent link between rTBI and cannabis problems, defined as impairment in social (e.g., difficulty maintaining relationships), occupational (e.g., decreased performance at work or school), or financial (e.g., being unable to pay bills due to substance use) domains as a result of cannabis use. Although several epidemiological surveys have demonstrated that those with a TBI history have increased rates of problematic substance use relative to non-TBI controls little is known about the potential mechanisms explaining this link due to the systematic exclusion of individuals with a rTBI history from nearly all prospective investigations of cannabis use and the exclusion of cannabis users from nearly all prospective studies of rTBI (see Bjork and Grant, 2009 for a review).10 This oversight has left inadequate answers to two concerning questions: Does rTBI history predict greater cannabis-related problems and, if so, what are the explanatory mechanisms of this vulnerability? Consistent with a central focus of NIDA on identifying explanatory processes of vulnerability in high-risk populations, the present study proposes a novel prospective investigation that tests whether rTBI is associated with cannabis-related problems. We will then test putative indirect pathways via which rTBI may increase cannabis problems by utilizing event-related potential (ERP) methodology, notably the Late Positive Potential (LPP) amplitude while viewing and down-regulating responses to emotional images and the N2/P3 component amplitudes during a response inhibition task. The first specific aim of the proposed study is to test if rTBI has a direct relationship with cannabis problems. This will be accomplished through both cross-sectional (i.e., baseline) and prospective cannabis problems, as assessed via self-report and clinical interview. The second specific aim is to test the indirect effect of rTBI on cannabis problems through heightened emotion reactivity (i.e., greater LPP while viewing cannabis cues and threatening images). The third specific aim is to test the indirect effect of rTBI on cannabis problems through emotion regulation difficulties (i.e., greater LPP while volitionally regulating cannabis craving, greater LPP while cognitively re-appraising threatening images). Lastly, the fourth specific aim is to test the indirect effect of rTBI on cannabis problems through deficits in inhibitory control (i.e., blunted N2 and P3 component amplitudes during response inhibition).