背景與目的: 在1979年台灣發生食用米糠油造成多氯聯苯 (PCBs)中毒事件，受害者稱為「油症」；經胎盤而暴露多氯聯苯的油症第二代從嬰兒時期到青少年時期在神經心理測驗都存在認知功能障礙 。本研究追蹤油症第二代的智力量表，並藉功能性磁振造影(fMRI)觀察中樞系統功能連接和任務時活化的腦網絡，並探討腦網絡活動與認知功能的關聯性。

方法: 對10位油症第二代和12位健康控制組，進行魏氏成人智力量表(WAIS-III)測驗與功能磁振造影，分別利用後扣帶回、左中顳區、左或右前下頂小葉與左下額葉溝為種子點區域，進行靜息態腦功能連接分析；並且觀察「空間工作記憶」任務時皮質的去活化與「視覺空間注意」任務時空間注意力相關腦區的功能偶合。

結果: 油症第二代成年後的魏氏智力分數與控制組沒有差異。油症第二代相較於控制組，工作記憶任務下默認網路的重要節點—內側前額葉(mPFC)—的去活化降低；執行空間注意任務時，左中顳葉運動敏感區域、楔前葉與左前腦島這些負責空間注意力腦區間的功能連接降低。靜息狀態腦功能連接分析顯示油症第二代執行注意網絡和右下頂小葉的功能連接增強；右額頂葉控制網絡與左側顳頂交界、左腦島、右側緣上迴的功能連接減弱；左額頂葉控制網絡與左中額迴功能連接減弱。語言網絡與默認網絡內的功能連接與控制組沒有差異。

結論: 本研究顯示成年油症第二代在臨床上認知功能已正常化，但以功能磁振造影觀察其在任務執行時，默認網絡中內側前額葉(mPFC)的去活化不足，空間注意力相關腦區間功能連接下降，並且靜息狀態表現出的多套腦功能連接網絡異常，可能與多氯聯苯(PCBs)暴露影響神發育有密切的相關性。

Background and aim: In 1979, there were people poisoned by polychlorinated biphenyls (PCBs) due to ingestion of contaminated cooking oil in Taiwan. The victims were called “Yucheng, oil disease”. Yucheng offspring with indirect transplacenta exposure to PCBs were noticed to have cognitive dysfunction by neuropsychological test since childhood to adolescence in previous studies. This study follows up IQ test in Yucheng offspring, analyses the cerebral functional connectivity and task activated brain networks in functional magnetic resonance image (fMRI). We discuss the relationship of brain functional network and neurocognitive function.

Method: 10 Yucheng offspring and 12 health controls undergo Wechsler Adult Intelligence Scale (WAIS) test and brain magnetic resonance image study. We get various brain networks by seed region with posterior cingulate cortex (PCC), left middle temporal motion-sensitive area (MT+), right or left anterior inferior parietal lobule and left inferior frontal sulcus, to analyze the temporal coherence of BOLD signal fluctuation in resting state. Cortical deactivation during working memory task in comparison to control task and functional coupling of spatial attentive areas during spatial attention task are also analyzed.

Results: Comparing adult of Yucheng offspring with health controls, no difference in the WAIS score is observed. In working memory task, there is reduced deactivation of medial prefrontal cortex (mPFC) which is an important node in default mode network (DMN). During spatial attention task, there is reduced functional connectivity between regions associated with processing of spatial attention, such as left anterior insula, left middle temporal area and precuneus. As for functional coupling of brain networks in resting state, Yucheng offspring reveal increased connectivity to right inferior parietal lobule (RIPL) in executive attention network, reduced connectivity to left temporoparietal junction (TPJ), left insula, and right supramarginal gyrus in right frontoparietal control network (FPCN) ,as well as reduced connectivity to left middle frontal gyrus in left FPCN. There is no difference in functional connectivity within DMN and language network among two groups.

Conclusion: We describe normalization of clinical cognitive function in Yucheng offspring in adulthood, while there is failure to deactivate the mPFC within DMN during executive task and aberrant functional connectivity within various brain networks subclinically. These findings may contribute to the understanding of prenatal PCBs exposure and consequence of neural network change in Yucheng offspring.

第一章、緒論 (Introduction) 8
1.1 研究背景 8
1.1.1 油症事件 8
1.1.2 多氯聯苯(PCBs)及同源物對油症二代的神經認知功能與行為影響 9
1.1.3 台灣油症第二代的神經認知與行為功能文獻回顧 9
1.2 靜息態功能性核磁造影功能連接網絡 10
1.2.1 靜息態腦功能連接網絡在認知、精神疾病研究 10
1.2.2 靜息態各種腦功能連接網絡 11
1.2.3 默認網絡 (Default mode network) 12
1.2.4 額頂葉控制網絡(FPCN)、默認網絡(DMN)與執行注意網絡(EAN)之間的關係 14
1.2.5 默認網絡(DMN)去活化(deactivation)在認知與疾病的角色 14
1.2.6 靜息態網路功能連接的分析方法 15
1.3 研究動機與研究問題 16
1.4 研究假說與目標 (1): 油症第二代成人的認知功能追蹤與腦功能連接網絡分析 17
1.5 研究假說與目標 (2): 油症第二代默認網絡(DMN)及工作記憶任務腦區去活化 17
第二章、研究方法與步驟 18
2.1 受試者 (Subjects) 18
2.2 研究方法 18
I. 任務態狀功能磁共振成像— 空間工作記憶測驗 19
II. 靜息態核磁共振檢查方法 20
III. 靜息狀態功能磁共振成像掃描序列 20
IV. 任務態功能磁共振成像掃描序列 20
V. 功能磁振影像(fMRI) 數據分析 21
VI. 靜型態fMRI數據分析 21
2.3 統計分析 22
第三章、 結果 23
3.1 油症第二代成人的認知功能追蹤與腦功能性網絡分析 23
3.1.1 油症第二代成人與控制組的認知功能WAIS-III中文版分數比較 23
3.1.2 油症第二代成人與控制組腦功能網絡分析及比較 23
3.2 油症第二代成人空間工作記憶任務時默認網絡的去活化 26
3.2.1 油症第二代成人工作記憶任務時去活化的腦區 26
3.2.2 靜息態與執行任務時默認網絡(DMN)連接與差異 26
3.2.3油症第二代相較控制組於空間注意任務時默認網絡連接差異 27
3.2.4 靜息態相較於執行空間注意任務時執行注意網絡(EAN)連接與差異 27
3.2.5 油症第二代相較控制組空間注意任務時執行注意網絡(EAN)連接差異 28
第四章、 討論 29
4.1 油症第二代成人的魏氏智力表現 29
4.2 默認網路的功能連接 30
4.3 油症第二代工作記憶任務下默認網路的去活化 30
4.4 任務狀態與靜息狀態的默認網路連接性與差異 31
4.5 執行注意網絡(EAN) 31
4.6 額頂葉控制網絡與語言網絡 33
第五章、結論與展望 33
第六章、參考文獻 34

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