Brain imaging of appetitive decision making in alcohol dependent young women

描述(由申请人提供)：大量饮酒的妇女也更有可能从事危险的生殖行为，增加她们意外怀孕、人际传播感染(Leigh，1999；O‘Hare，1998)和胎儿接触酒精(Streissguth等人，1994)的可能性。国家酒精滥用和酒精中毒研究所最近报告说，大学生中大量饮酒的间歇性增加(Hingson等人，2009年)。了解育龄年轻女性的食欲决策可以为这一日益危险的群体提供适当的干预措施。特别是，需要关于酒精和大脑过程之间的相互作用的更具体的知识，这些过程是动机决策的基础，可能使酒精依赖的女性倾向于危险的行为。青壮年是一个关键时期，在此期间，不仅经常发生生殖，而且酒精依赖和作为决策基础的额叶神经系统也会发展，这表明这两个发育过程之间可能存在相互作用。目前的研究调查了一种假设，即前额叶-边缘系统的功能神经解剖学改变是酗酒和危险生殖行为之间的重要联系。此外，女性的荷尔蒙状态很可能是调节酒精和大脑相互作用的相关因素，可能会给年轻女性及其潜在的后代带来严重的脆弱性。最近的证据表明，在女性食欲决策的整个月经周期，前额-边缘奖赏系统在功能上是不同的(Rupp等人，2009)。具体地说，与黄体期相比，在排卵期进行测试时，评估新男性面孔的女性在眼眶前额皮质中表现出更多的神经激活。我们假设，酒精依赖的年轻女性总体上有一个更敏感的奖赏大脑电路，接近排卵的激素状态进一步增强了冒险的脆弱性。使用功能磁共振成像(FMRI)，我们将检测20名酒精依赖和20名非酒精依赖年轻女性对奖励刺激的神经激活模式，包括酒精、男性面孔和食物的图片。为了测试荷尔蒙状态的影响，我们将在月经周期的两个阶段对骑自行车的女性进行自然测试，包括女性最有可能怀孕的卵泡期。我们预测，酒精依赖女性将在与奖励相关的大脑区域表现出更多的神经激活，而在与行为抑制相关的大脑区域表现出较少的激活，而且这种差异在排卵前后会特别明显。为了年轻女性及其潜在后代的安全，有能力在潜在的欲望状况和伴侣的风险和回报之间取得平衡是至关重要的。了解酒精依赖和非依赖女性的月经周期与神经激活和生殖决策的相互作用，可以增强我们的干预能力，以促进高危年轻女性更安全的食欲行为。 与公共健康相关：年轻的酒精依赖女性表现出大脑功能的变化，这可能会使她们倾向于高风险的生殖决策。大量饮酒的妇女意外怀孕会对产前接触酒精的婴儿产生长期的负面影响。了解酒精依赖引起的功能性神经内分泌变化，如与风险和回报评估相关的神经系统的敏感化，对于促进育龄年轻女性做出最佳的食欲决策，以保护她们及其后代免受酒精暴露的不利影响至关重要。

DESCRIPTION (provided by applicant): Women who consume large amounts of alcohol are also more likely to engage in risky reproductive behavior, increasing their likelihood of unplanned pregnancies, interpersonally transmitted infections (Leigh, 1999; O'Hare, 1998), and fetal alcohol exposure (Streissguth et al., 1994). The National Institute on Alcohol Abuse and Alcoholism recently reported an increase in heavy episodic drinking in college students (Hingson et al., 2009). Understanding appetitive decision-making in young women of reproductive age could inform appropriate intervention for this increasingly at-risk group. In particular, more specific knowledge is needed regarding the interaction between alcohol and the brain processes underlying motivated decision making that may bias alcohol-dependent women towards risky behavior. Young adulthood is a critical time during which not only reproduction most often occurs, but alcohol dependence and frontal neural systems underlying decision making develop, suggesting a possible interaction between the two developmental processes. The current study investigates the hypothesis that altered functional neuroanatomy of the prefrontal-limbic system is an important link between alcohol abuse and risky reproductive behavior. Furthermore, a woman's hormonal state is likely to be a relevant factor mediating alcohol and brain interactions, possibly creating windows of acute vulnerability for young women and their potential offspring. Recent evidence suggests that the prefrontal-limbic reward system differs functionally across a woman's menstrual cycle during appetitive decision-making (Rupp et al., 2009). Specifically, women evaluating novel male faces exhibited more neural activation in the orbitofrontal cortex when tested during ovulation as compared to the luteal phase of the cycle. We hypothesize that alcohol-dependent young women have a more sensitized reward brain circuitry in general, and that the hormonal state close to ovulation further enhances vulnerability to risk taking. Using functional magnetic resonance imaging (fMRI) we will examine the neural activation patterns of 20 alcohol-dependent and 20 nondependent young women in response to rewarding stimuli, including pictures of alcohol, male faces, and food. In order to test for effects of hormonal status, we will test naturally cycling women at two phases across their menstrual cycles, including during the follicular phase when a woman is most likely to conceive. We predict that alcohol-dependent women will demonstrate greater neural activation in brain regions associated with reward and less activation in brain regions related to behavioral inhibition, and that the difference will be especially pronounced around ovulation. The ability to balance between the risk and reward of potential appetitive situations and partners is imperative for the safety of young women and their potential offspring. An understanding of menstrual cycle interactions with neural activation and reproductive decision making in alcohol-dependent and non dependent women can enhance our ability to intervene to promote safer appetitive behavior in at-risk young women. PUBLIC HEALTH RELEVANCE: Young alcohol-dependent women demonstrate changes in brain function that may bias them towards risky reproductive decision-making. Unplanned pregnancies in women who consume large amounts of alcohol have long-term negative consequences for infants prenatally exposed to alcohol. An understanding of the functional neuroendocrinological changes that occur with alcohol-dependence, such as sensitization of neural systems associated with the appraisal of risk and reward, are critical to promote optimal appetitive decision-making in young women of reproductive age to protect them and their offspring from the adverse effects of alcohol exposure.