出生前暴露於多氯聯苯年輕男性的神經認知功能：行為與功能性核磁共振之研究

Abstract

多氯聯苯(Polychlorinated biphenyls;PCBs)為食物鏈中重要的有機汙染物，由於它的廣泛性，生物放大性以及毒性，多氯聯苯的污染一直是一個重要的環境課題。在動物實驗當中，早期多氯聯苯的暴露會引起認知彈性的疲乏，工作記憶的缺損，衝動控制的喪失以及視覺空間能力的低下。而在人類流行病學研究上，證據顯示出生前多氯聯苯的暴露對兒童的工作記憶，語言能力與注意力都有不好的影響。然而，由於矛盾的動物實驗結果以及過去對認知功能影響研究的追蹤時間都不夠長，無法確定出生前多氯聯苯暴露對成人認知功能的影響。 1978到1979年在台灣中部發生了著名的”油症事件”，許多居民因食用了遭汙染的米糠油而遭受大量多氯聯苯的毒害。過去研究發現這些中毒母親的小孩在發展里程碑上較為遲緩，在智力測驗上的表現也較差。在6至16歲間，油症母親的男性子代在操作智商的分項測驗與母親體內的多氯聯苯濃度呈負相關。為了瞭解出生前多氯聯苯暴露對男性子代成年後認知功能的影響，本研究利用魏氏智力測驗(Wechsler Adult Intelligence Scale, 3rd edition; WAIS-III)追蹤成年的男性油症子代；此外，本研究利用兩種不同認知作業：工作記憶(Working memory)相關的二回推測驗以及視覺空間能力(Visuospatial function)相關的圖型旋轉測驗，進行功能性核磁共振造影，來了解認知功能改變的神經基礎。 本研究共募集了22位男性成年受試者(10位油症子代以及12位社區控制組，平均年齡：29.2歲)。在魏氏智力測驗中，無論是全量表智商，語文智商，操作智商及其所有的分項測驗上，兩組表現均無統計上顯著之差異。在認知作業方面，無論是二回推作業或是圖型旋轉作業中，在正確率與反應時間的表現上均無差異。在功能性核磁共振的結果方面，二回推作業以及圖型旋轉作業所活化的大腦區域，兩組的血氧濃度相依對比(Blood Oxygen-Level dependent;BOLD)訊號並未有差別。但相對於社區對照組，油症子代在兩側內額葉(Medial frontal cortex)與後扣帶迴(Posterior cingulated gyrus)在二回推測驗中的訊號較強，但在圖型旋轉測驗的訊號較弱。這樣的結果顯示油症子代有工作誘發去活化(Task Induced Deactivation; TID)的改變。另外，在圖型旋轉測驗中，油症子代在右側顳葉的訊號也較社區對照組弱。 受限於受試者人數，本研究並無法證實出生前多氯聯苯暴露對認知功能的長期影響。但功能性核磁共振的結果可為多氯聯苯對認知功能影響的神經機轉，提供線索。

Polychlorinated biphenyls(PCBs) are persistent organic pollutants present in food chain and a major environmental concern due to their ubiquity, bioamplification and toxicity. In animal studies, early exposure of PCBs was associated with impairment of cognitive flexibility, working memory, inhibitory control and visuospatial learning. In epidemiological studies, prenatal PCBs exposure has been shown to have negative effect on children’s cognitive functions, including working memory, language function and attention. However, the long term effect of prenatal PCBs exposure was not ascertained due to controversial data in animal studies and short follow-up time in epidemiological studies. An incident of mass PCBs exposure occurred in central Taiwan due to ingestion of contaminated cooking oil in 1978-1979. Previous studies had shown delayed developmental milestones and lower intelligence in children born to exposed mothers(Yucheng cohort). At ages of 6 to 16 years old, boys in this cohort had their subscales of performance IQ correlate negatively with the PCBs level of their mothers. To study the long term effect of prenatal PCBs exposure, we followed the cognitive functions with WAIS-III (Wechsler Adult Intelligence Scale, 3rd edition) in this cohort in their adult ages and also investigated neural basis of cognitive function changes with functional magnetic resonance image(fMRI) with two paradigms: a two-back task and a picture rotation task, which were related to working memory and visuospatial function, respectively. Twenty-two young male adults (12 health control and 10 Yucheng cohort. mean age:29.2 years old) joined this study. There were no statistically significant differences in full IQ, verbal IQ, performance IQ and all of their subscales between these two groups. In the behavioral results of the two-back task and picture rotation task, no statistical significant difference was noted in the accuracy and reaction time in both of the tasks. In fMRI studies of both paradigms, the BOLD signal showed no statistical difference in the task-activating cortical area between the two groups. Comparing to the control, boys in the Yucheng cohort showed increased BOLD signal in bilateral medial frontal cortex and posterior cingulated gyrus in the two-back task but reduced signal in the similar area in the picture rotation task, indicating alteration in the task induced deactivation(TID). Reduced BOLD signal was also seen over right medial temporal lobe in the paradigm of picture rotation in the Yucheng group. Due to the small case number, this study was not empowered to fully support the notion that prenatal PCBs exposure had long term effect on cognitive function. The findings in task related fMRI may shed light on the possible neural mechanism of the PCBs effects.