高階重複侷限行為於自閉症患者之灰質變化分析

Abstract

背景 重複侷限行為是自閉症類群障礙主要的症狀之一，並且導致功能上的缺損。重複侷限行為可分為低階行為（重複性感覺動作行為）以及高階行為（固執行為）。過去研究發現高階重複侷限行為是自閉症類群障礙獨立於年齡、性別、智力及其他症狀的特定特徵，且可作為亞型分組的變項。認知彈性及視覺記憶可能與這些行為相關，然而，固執行為的結構性神經基礎及其相關的認知功能目前仍不清楚。 方法 本研究招募140位自閉症青年及124位一般發展之控制組（平均年齡15.8歲），自閉症青年組依照三題ADI-R中的固執行為項目總分，分別以3分及中位數分為高固執行為（HIS）組及低固執行為（LIS）組。本研究使用劍橋神經心理測驗作為認知彈性及視覺記憶之測驗。在結構核磁掃瞄後，使用體素的形態分析法，以全腦無假設之設計，找出三組之灰質體積差異，之後將提取出有差異之區域灰質體積與認知功能分數進行相關性分析。 結果 以3分為切分點分組，94位自閉症青年屬於高固執行為組，46位自閉症青年屬於低固執行為組。以中位數為切分點，66位自閉症青年屬於高固執行為組，74位為自閉症青年屬於低固執行為組。自閉症青年相較於控制組表現出較差的認知彈性和視覺記憶，不論切分點，高固執行為組相較控制組表現出較差的視覺記憶。以3分的切分點分組，高固執行為組相較於低固執行為組，有較小的左側緣上回（supramarginal gyrus）及左側顳上極（superior temporal pole），以及較大的左側小腦第八小葉（cerebellar lobule VIII），與控制組相比則有較大的右側顳中回（middle temporal gyrus）及雙側的小腦第八小葉（cerebellar lobule VIII），低固執行為組相較於控制組，則有較大的左側顳上極（superior temporal pole）。高固執行為組中之左側顳上極（ superior temporal pole）及左側小腦第八小葉（cerebellar lobule VIII）及低固執行為組中之左側緣上回（supramarginal gyrus）、左側顳上極（superior temporal pole）及左側小腦第八小葉（cerebellar lobule VIII）與認知彈性錯誤呈負相關，高固執行為組中之雙側小腦第八小葉（cerebellar lobule VIII） 與較佳的視覺記憶呈正相關。以中位數為切點，高固執行為組相較於低固執行為組有較小的右側顳上極（superior temporal pole），相較於控制組則有較大的右側枕下回（inferior occipital gyrus）、小腦蚓部第九小葉（vermis IX）以及左側小腦小葉crus II (cerebellar crus II)。其中，高固執行為組的右側顳上極（superior temporal pole）及左側小腦小葉crus II （cerebellar crus II）與認知彈性錯誤呈負相關。 結論 擁有較嚴重固執行為的自閉症青年在頂葉、顳葉以及小腦有灰質體積之變化，其中顳葉及後側小腦區域的變化特別與認知彈性，並且可能是一種代償性的體積增大。結果支持，固執行為可能為自閉症類群障礙之重複侷限行為中的一特殊特徵，並具有潛力能夠作為自閉症亞型分組的變項。

Background. Restricted and repetitive behaviors (RRBs) as a hallmark symptom in autism spectrum disorder (ASD) leading to functional impairments had been conceptually classified as lower-order (repetitive sensory-motor behaviors, RSMB) and higher-order behaviors (insistence on sameness, IS). Previous studies had suggested that higher-order RRBs may be a more specific characteristic in ASD and a promising grouping variable as it may be an independent dimension from age, sex, IQ, and other symptom domains. Cognitive flexibility and visual memory may serve as the cognitive underpinnings of these behaviors. However, the neuroanatomical correlates of IS and the related underlying cognitive functions remain unclear. Methods. We recruited 140 youth with ASD and 124 typically developing (TD) controls (mean age=15.8 yrs). Youth with ASD were stratified into two groups- the higher score of insistence on sameness (HIS) and the lower score of insistence on sameness (LIS) by 3 IS items in the Autism Diagnostic Interview-Revised. Two cutting points were used: sum score of IS of 3 and the median. The differences in cognitive flexibility and visual memory among the three groups were assessed by the Cambridge Neuropsychological Test Automated Battery (CANTAB). T1-weighted images were acquired and analyzed using Statistical Parametric Mapping version 12 and voxel-based morphometry (VBM) methods to identify differences in gray matter (GM) volume among three groups with a whole-brain hypothesis-free approach. The correlation analyses were performed between the identified regions and the cognitive functions. Results. There were 94 or 74 participants in the HIS group and 46 or 66 participants in the LIS group stratified by the sum score of IS of 3 or by the median, respectively. The ASD group showed poorer cognitive flexibility and visual memory compared to TD controls, especially consistent poorer visual memory in the HIS group across different stratifications. Stratified by the sum score of IS of 3, the HIS group showed decreased GM volumes in the left supramarginal gyrus and left superior temporal pole and increased GM volumes in the left cerebellar lobule VIII compared to the LIS group. Compared to TD controls, the HIS group showed increased GM volumes in the right middle temporal gyrus, and bilateral cerebellar lobule VIII and the LIS group showed increased GM volumes in the left superior temporal pole. Left superior temporal pole and left cerebellar lobule VIII in the HIS group and left supramarginal gyrus, left superior temporal pole and left cerebellar VIII in the LIS were negatively correlated with errors in cognitive flexibility. Bilateral cerebellar lobule VIII volumes were positively correlated with better visual memory in the HIS group. Stratified by the median, the HIS group showed decreased GM volumes in the right superior temporal pole compared to the LIS group and increased GM volumes in right inferior occipital gyrus, vermis IX and left cerebellar crus II compared to TD controls. The right superior temporal pole and left cerebellar crus II were negatively correlated with errors in cognitive flexibility in the HIS group. Conclusions. Our findings demonstrated altered GM volumes in the parietal, temporal, and posterior regions of the cerebellum in youth with ASD with more severe IS. The alterations, especially in the superior temporal pole and posterior regions of the cerebellum, were correlated with cognitive flexibility, implying a compensatory enlargement. This work provides evidence to suggest that the IS may be a unique feature from the RRBs domain in ASD and would be a potential stratification variable.