Forbes Erika E, Rodriguez Eric E, Musselman Samuel, Narendran Rajesh
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2014 May 7;9(5):e94640. doi: 10.1371/journal.pone.0094640. eCollection 2014.
Although altered function in neural reward circuitry is widely proposed in models of addiction, more recent conceptual views have emphasized the role of disrupted response in prefrontal regions. Changes in regions such as the orbitofrontal cortex, medial prefrontal cortex, and dorsolateral prefrontal cortex are postulated to contribute to the compulsivity, impulsivity, and altered executive function that are central to addiction. In addition, few studies have examined function in these regions during young adulthood, when exposure is less chronic than in typical samples of alcohol-dependent adults. To address these issues, we examined neural response and functional connectivity during monetary reward in 24 adults with alcohol dependence and 24 psychiatrically healthy adults. Adults with alcohol dependence exhibited less response to the receipt of monetary reward in a set of prefrontal regions including the medial prefrontal cortex, lateral orbitofrontal cortex, and dorsolateral prefrontal cortex. Adults with alcohol dependence also exhibited greater negative correlation between function in each of these regions and that in the nucleus accumbens. Within the alcohol-dependent group, those with family history of alcohol dependence exhibited lower mPFC response, and those with more frequent drinking exhibited greater negative functional connectivity between the mPFC and the nucleus accumbens. These findings indicate that alcohol dependence is associated with less engagement of prefrontal cortical regions, suggesting weak or disrupted regulation of ventral striatal response. This pattern of prefrontal response and frontostriatal connectivity has consequences for the behavior patterns typical of addiction. Furthermore, brain-behavior findings indicate that the potential mechanisms of disruption in frontostriatal circuitry in alcohol dependence include family liability to alcohol use problems and more frequent use of alcohol. In all, these findings build on the extant literature on reward-circuit function in addiction and suggest mechanisms for disrupted function in alcohol dependence.
尽管成瘾模型中广泛提出神经奖赏回路功能改变，但最近的概念观点强调前额叶区域反应中断的作用。眶额皮质、内侧前额叶皮质和背外侧前额叶皮质等区域的变化被认为导致了成瘾核心的强迫性、冲动性和执行功能改变。此外，很少有研究在成年早期研究这些区域的功能，此时接触酒精的时间不像典型酒精依赖成年样本那样具有长期性。为了解决这些问题，我们研究了24名酒精依赖成年人和24名精神健康成年人在金钱奖励过程中的神经反应和功能连接。酒精依赖成年人在包括内侧前额叶皮质、外侧眶额皮质和背外侧前额叶皮质在内的一组前额叶区域对金钱奖励的反应较弱。酒精依赖成年人在这些区域中的每一个区域与伏隔核之间的功能负相关性也更强。在酒精依赖组中，有酒精依赖家族史的人内侧前额叶皮质反应较低，饮酒更频繁的人内侧前额叶皮质与伏隔核之间的负性功能连接更强。这些发现表明，酒精依赖与前额叶皮质区域参与度降低有关，提示腹侧纹状体反应的调节减弱或中断。这种前额叶反应和额纹状体连接模式对成瘾典型的行为模式有影响。此外，脑-行为研究结果表明，酒精依赖中额纹状体回路中断的潜在机制包括酒精使用问题的家族易感性和更频繁的饮酒。总之，这些发现建立在成瘾奖赏回路功能的现有文献基础上，并提出了酒精依赖功能中断的机制。
