自閉症青少年、未患病手足與一般發展青少年在語意處理歷程之神經機制差異

Abstract

自閉症光譜疾患(Autism spectrum disorder, ASD)為一種高度遺傳的疾病，而異常的語意處理為其常見的症狀。本研究檢驗ASD青少年、未患病手足以及一般發展青少年在語意處理表現上的神經機制差異，藉由探討ASD在語意處理時的內在表現型(endophenotype)以進一步了解基因的影響。其中，內在表現型乃指與ASD相關的遺傳特徵。本研究招募39位ASD青少年(平均年齡為14.8歲，標準差為3.9)、39位未患病ASD手足(平均年齡為15.7歲，標準差為5.2)、40位一般發展青少年(平均年齡為14.6歲，標準差為4.7)，三組在智力分數、年齡、慣用手沒有顯著差異。受試者在磁振造影(Magnetic Resonance Imaging, MRI）儀器中完成語意判斷作業，即判斷前後出現的兩個中文字是否有意義上的關聯。在作業表現上，三組之正確率與反應時間皆未達顯著差異。在進行中文語意處理時，未患病ASD手足與一般發展青少年在左側顳中迴(middle temporal gyrus, MTG)的活化較ASD青少年強。此外，相較於一般發展青少年，未患病ASD手足與ASD青少年在楔狀葉（cuneus）有較多的活化。最後，未患病ASD手足的左側額下迴（inferior frontal gyrus, IFG）活化程度介在一般發展青少年與ASD青少年之間。本研究結果支持在進行語意處理時，其異常的左側額下迴與楔狀葉神經活化為ASD的一種內在表現型。根據本研究，推論未患病ASD手足具備相對完好的語意表徵系統，然而在進行語意處理時會如同ASD青少年，傾向採取以知覺為基礎的策略（perception-based strategies），同時操弄語意表徵的能力亦較不成熟。

Autism spectrum disorder (ASD) is characterized as a highly heritable disorder, and aberrant semantic processing is one of common symptoms in individuals with ASD. Unaffected ASD siblings usually have similar genetic backgrounds and early-life environments with individuals with ASD, with a higher risk of developing the same disorder. However, little is known about genetic contributions to neural mechanisms of semantic processing in unaffected ASD siblings. Therefore, this study aimed to adopt an endophenotype approach to investigate the differences in underlying neural mechanisms of semantic processing in youths with ASD, their unaffected siblings, and typically developing (TD) youths. Endophenotypes for ASD were defined as similarly heritable traits that were correlated with ASD. This study recruited 39 ASD youths (mean age = 14.8 years, standard deviation [SD] = 3.9 years), their unaffected siblings (mean age = 15.7 years, SD= 5.2 years), and 40 TD youths (mean age = 14.6 years, SD= 4.7 years). These three groups of participants were matched with IQ, age, and handedness. Participants were instructed to judge whether two Chinese characters were related in meaning in an MRI scanner. Our behavioral result showed that there were no significant differences on accuracy and reaction time among these three groups. Brain imaging data revealed that unaffected siblings and TD youths showed greater brain activation in the left MTG as compared with ASD youths. Moreover, the unaffected siblings and ASD youths showed greater cuneus activation as compared to TD youths. Furthermore, unaffected siblings showed intermediate left IFG activation between TD and ASD youths, with the strongest activation in TD youths and the weakest in ASD youths. Our findings provided a supportive evidence that abnormal neural activation in the left IFG and the cuneus during semantic processing could serve as an endophenotype of ASD. For our unaffected ASD siblings, they may have intact lexical representation system as TD youths; however, because of shared genetic features with ASD, they adpoted the same perception-based strategies as ASD youths, and may have rather immature ability to manipulate semantic representations.