Bariselli Sebastiano, Lovinger David M
National Institute on Alcohol Abuse and Alcoholism, Intramural Research Program, National Institutes of Health, Bethesda, Maryland; Center on Compulsive Behaviors, Intramural Research Program, National Institutes of Health, Bethesda, Maryland.
National Institute on Alcohol Abuse and Alcoholism, Intramural Research Program, National Institutes of Health, Bethesda, Maryland.
Biol Psychiatry. 2021 Oct 15;90(8):516-528. doi: 10.1016/j.biopsych.2021.05.014. Epub 2021 May 21.
The term fetal alcohol spectrum disorder includes a group of diseases caused by fetal alcohol exposure (FAE). Patients with fetal alcohol spectrum disorder display heterogeneous socioemotional and cognitive deficits, particularly in the domain of executive function, that share symptoms with other neuropsychiatric disorders. Despite the availability of several preclinical models, the developmental brain defects causally linked to behavioral deficits induced by FAE remain poorly understood. Here, we first review the effects of FAE on corticostriatal development and its impact on both corticostriatal pathway function and cognitive abilities. We propose three non-mutually exclusive circuit models of corticostriatal dysfunctions to account for some of the FAE-induced cognitive deficits. One model posits that associative-sensorimotor imbalance causes hyper goal-directed behavior, and a second model implies that alteration of prefrontal-striatal behavioral suppression circuits results in loss of behavioral inhibition. A third model suggests that local striatal circuit deficits affect striatal neuronal ensemble function to impair action selection and performance. Finally, we discuss how preclinical approaches applied to these circuit models could offer potential rescue strategies for executive function deficits in patients with fetal alcohol spectrum disorder.
术语“胎儿酒精谱系障碍”包括一组由胎儿酒精暴露(FAE)引起的疾病。胎儿酒精谱系障碍患者表现出异质性的社会情感和认知缺陷,尤其是在执行功能领域,这些缺陷与其他神经精神疾病有共同症状。尽管有几种临床前模型,但与FAE诱导的行为缺陷有因果关系的发育性脑缺陷仍知之甚少。在这里,我们首先回顾FAE对皮质纹状体发育的影响及其对皮质纹状体通路功能和认知能力的影响。我们提出了三种并非相互排斥的皮质纹状体功能障碍回路模型,以解释一些FAE诱导的认知缺陷。一种模型假定联合感觉运动失衡会导致过度的目标导向行为,第二种模型意味着前额叶-纹状体行为抑制回路的改变会导致行为抑制丧失。第三种模型表明局部纹状体回路缺陷会影响纹状体神经元集合功能,从而损害动作选择和表现。最后,我们讨论应用于这些回路模型的临床前方法如何能够为胎儿酒精谱系障碍患者的执行功能缺陷提供潜在的挽救策略。