Functional Connectivity Disruption in Neonates with Prenatal Marijuana Exposure.
Functional Connectivity Disruption in Neonates with Prenatal Marijuana Exposure.
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DOI：
10.3389/fnhum.2015.00601
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发表时间：
2015
影响因子：
2.9
通讯作者：
Gao W
中科院分区：
文献类型：
--
作者：
Grewen K;Salzwedel AP;Gao W
产前大麻暴露(PME)与神经行为和认知障碍有关；然而，儿童和青春期的研究结果并不一致。1型大麻素受体(CB1R)调节胎儿神经发育，介导PME对对学术和社会成功至关重要的功能回路次级行为的发育的影响。这项研究的目的是调查在出生后环境长期影响之前，产前大麻对早期大脑功能回路发育的影响。我们测量了2-6 周婴儿在未镇静睡眠期间的静息功能连接性(+MJ：20联合使用PME和尼古丁、酒精、阿片类药物和/或选择性5-羟色胺再摄取抑制剂；−MJ：23暴露于相同的其他药物而不吸食大麻，CTR：20非药物对照组)。检测胎儿CB1R高表达的皮质下种子区的连通性。在岛和三个纹状体连接：岛前-小脑、右侧尾状-小脑、右侧尾状-右侧梭形回/枕下部、左侧尾状-小脑，观察到大麻特异性差异。与−、MJ和CTR组相比，+MJ新生儿在所有簇中的连接性都较低。纹状体与涉及视觉空间和运动学习、注意力以及运动和语言产生的运动输出微调的区域的连接改变，可能会导致这一高危人群报告的神经行为缺陷。岛前连接中断可能导致感觉间信号与突显估计、动机、决策和后来的药物使用的整合发生变化。与CTR相比，+MJ和−MJ组均显示左侧杏仁核种子与额叶皮质高度连接，丘脑后部种子与海马区连接不足，提示这些环路易受多种药物的影响。
Prenatal marijuana exposure (PME) is linked to neurobehavioral and cognitive impairments; however, findings in childhood and adolescence are inconsistent. Type-1 cannabinoid receptors (CB1R) modulate fetal neurodevelopment, mediating PME effects on growth of functional circuitry sub-serving behaviors critical for academic and social success. The purpose of this study was to investigate the effects of prenatal marijuana on development of early brain functional circuitry prior to prolonged postnatal environmental influences. We measured resting state functional connectivity during unsedated sleep in infants at 2–6 weeks (+MJ: 20 with PME in combination with nicotine, alcohol, opiates, and/or selective serotonin reuptake inhibitors; −MJ: 23 exposed to the same other drugs without marijuana, CTR: 20 drug-free controls). Connectivity of subcortical seed regions with high fetal CB1R expression was examined. Marijuana-specific differences were observed in insula and three striatal connections: anterior insula–cerebellum, right caudate–cerebellum, right caudate–right fusiform gyrus/inferior occipital, left caudate–cerebellum. +MJ neonates had hypo-connectivity in all clusters compared with −MJ and CTR groups. Altered striatal connectivity to areas involved in visual spatial and motor learning, attention, and in fine-tuning of motor outputs involved in movement and language production may contribute to neurobehavioral deficits reported in this at-risk group. Disrupted anterior insula connectivity may contribute to altered integration of interoceptive signals with salience estimates, motivation, decision-making, and later drug use. Compared with CTRs, both +MJ and −MJ groups demonstrated hyper-connectivity of left amygdala seed with orbital frontal cortex and hypo-connectivity of posterior thalamus seed with hippocampus, suggesting vulnerability to multiple drugs in these circuits.