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研究生:林昰樺
研究生(外文):Shih-Hua Lin
論文名稱:自閉症患者執行功能缺損的神經機制:體素形態計量學分析
論文名稱(外文):Neural Substrates involving Executive Function Impairments in Patients with Autism Spectrum Disorder: a Voxel-Based Morphometry Study
指導教授:高淑芬高淑芬引用關係
指導教授(外文):Shur-Fen Gau
口試委員:商志雍吳恩賜吳文超
口試委員(外文):Chi-Yung ShangJoshua Goh Oon SooWen-Chau Wu
口試日期:2022-01-20
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:腦與心智科學研究所
學門:醫藥衛生學門
學類:其他醫藥衛生學類
論文種類:學術論文
論文出版年:2022
畢業學年度:110
語文別:英文
論文頁數:58
中文關鍵詞:自閉症體素為基礎的形態計量學無閾值團簇增強法執行功能執行功能缺損理論
外文關鍵詞:autism spectrum disordersvoxel-based morphometryThreshold-Free Cluster Enhancement Analysisexecutive functionexecutive dysfunction theory
DOI:10.6342/NTU202200162
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研究背景:
自閉症疾患(autism spectrum disorder, ASD)為具有腦功能異常的神經發展障礙,執行功能的缺損被報告為自閉症患者的重要特徵之一,且被認為能解釋其主要核心症狀。過去關於自閉症執行功能的相關研究,不曾探討該族群能力如類群分佈與能力之異質性,且相關的神經影像學腦結構變異證據不足;真實生活情境執行功能表現分群之腦結構變異,與基礎執行功能及整體症狀間的關聯仍未明。
研究方法:
本研究招募了76位確診為自閉症的6-18歲的男性受試者,與相同性別與年齡範圍之72名正常發展者作為研究對象。透過收集171位相同年齡區段男性典型發展對照組(typically developing control, TDC)的執行功能行為評定量表(Behavior Rating Inventory of Executive Function, BRIEF)之綜合評分來定義執行功能缺損(executive function deficit, EFD)標準,將自閉症受試者分為兩組:ASD+EFD組31名 (平均年齡 ± SD, 13.6±2.3 歲)及ASD-EFD組45名(平均年齡 ± SD, 13.0±2.6 歲)。所有受試者皆接受智力測驗與收集相關問卷資料,透過劍橋自動化神經心理測驗檢驗與執行功能缺損理論相關基礎功能之表現,選取之分測驗為:快速視覺訊息處理作業(Rapid Visual Information Processing, RVP)、劍橋河內塔測驗(Stockings of Cambridge, SOC)、內外向度轉換測驗(intra-dimension/extra-dimensional set-shifting performance, ID/ED)、空間工作記憶測驗(Spatial Working Memory, SWM),並藉由主成分分析之特徵選取方法擷取神經心理學測驗之重要指標商數進行分析。透過以體素為基礎的形態計量學分析(Voxel Based Morphometry, VBM) 磁振造影高解析度的T1結構影像,得到腦統計圖像並以無閾值團簇增強法(Threshold-Free Cluster Enhancement, TFCE)進行處理,獲得腦局部灰質體積變異資訊。續以擷取腦統計圖內對比組合為顯著差異之局部灰質體積,將其與神經心理學測驗、社交反應量表(Social Responsiveness Scale, SRS)進行關聯性的分析與討論。
研究結果:
執行功能基礎能力之表現經過控制年齡、全量表智商後,發現SWM錯誤數在ASD兩組分別統計顯著的大於TDC。
腦影像學分析結果:透過無閾值團簇增強法發現有以下三種對比組合為顯著:ASD+EFD>ASD-EFD、ASD+EFD>TDC、以及ASD-EFD>TDC。ASD+EFD腦灰質局部變異位於社交認知功能、心智理論、及靜息態腦網路之預設模式網路(default mode network, DMN) 與警覺網路(salience network, SN) 的腦區; ASD-EFD與ASD+EFD比較時,其腦部樣態更接近TD;ASD兩組其顳葉與梭狀回灰質體積增加;局部灰質變異與執行功能基礎能力及症狀之關聯性: SWM與自閉症患者的眶額皮質(orbital frontal cortex, OFC)體積有顯著關聯性;自閉症顳中回(Middle temporal gyrus)灰質體積增加則減輕整體症狀嚴重度,卻也與SOC計畫思考時間延長有關。
結論:
自閉症整體執行功能行為表現的異質性源於大腦局部灰質的變異,這些變異與自閉症社交認知功能、心智理論、靜息態腦網路、及整體症狀有關。本研究提供證據支持自閉症具有執行功能的缺損,尤以空間工作記憶與灰質變異相關。
Background:
Deficits in executive functions are among the essential features and theories of autism spectrum disorder (ASD) and may explain some behavioral phenotypes of ASD. Executive function (EF) heterogeneity within ASD has not been investigated yet to depict profiles from real-world performance to fundamental EFs. Moreover, the brain structural alteration contributing to executive dysfunction and clinical symptoms remains unclear.
Method:
We recruited 76 boys with ASD and 72 typically developing control (TDC) boys aged 6 -18 years old. According to the Behavior Rating Inventory of Executive Function (BRIEF) data of TDC, we defined executive function deficit (EFD) criteria. ASD youths were divided into 31 in ASD+ EFD and 45 in ASD- EFD. The Cambridge neuropsychological test automated battery (CANTAB) examined fundamental EFs. Voxel-based morphometry (VBM) with the Threshold-Free Cluster Enhancement Analysis (TFCE) algorithm was applied to structural magnetic resonance imaging (MRI) data to find gray matter volume (GMV) alteration.
Results:
The TFCE results revealed that ASD+EFD showed gray matter alteration in regions related to social cognition, theory of mind (ToM), default mode network (DMN), and salience network (SN) as compared to others. The ASD-EFD group demonstrated a brain pattern more like TDC when compared with ASD+EFD. Increased GMV in the fusiform gyrus and temporal lobes was noted in both ASD+EFD and ASD-EFD. In addition, increased GMV of the orbital frontal cortex (OFC) was related to more SWM errors in ASD. The increased GMV of the middle temporal gyrus could alleviate symptom severity but was associated with prolonged thinking time in SOC.
Conclusion:
ASD youths have heterogeneous EF and are related to GM alterations located in regions of social cognition, ToM, resting-state networks. This study provides evidence to support the EF deficits, particularly spatial working memory, in ASD.
口試委員審定書 i
謝辭 ii
中文摘要 iii
英文摘要 vi
目錄 viii
圖目錄 xi
表目錄 xii
1 Introduction 1
1.1 Executive Function in ASD 2
1.2 Neuroanatomical Alteration in ASD 3
1.3 Neural substrates for Executive Function in ASD 6
1.4 The rationale for this study 7
2 Methods 9
2.1 Participants and procedures 9
2.2 Measures 10
2.2.1 Instruments assessing ASD diagnosis and other psychiatric disorders 10
2.2.2 Behavior Rating Inventory of Executive Function (BRIEF) 11
2.2.3 Social Responsiveness Scale (SRS) 12
2.2.4 Cambridge neuropsychological test automated battery (CANTAB) 13
2.3 Feature Selection of Neuropsychological Tests by Principal Components Analysis (PCA) 15
2.4 Structural MRI acquisition and processing 17
2.4.1 Magnetic Resonance Imaging (MRI) 17
2.4.2 Voxel-Based Morphometry (VBM) 17
2.5 Statistical analysis 18
2.5.1 Voxel-Based Morphometry (VBM) 19
2.5.2 Threshold-Free Cluster Enhancement (TFCE) 20
2.5.3 The association analysis among regional gray matter volumes, Neuropsychological tests, and clinical measures 20
3 Results 22
3.1 Demographic and clinical characteristics 22
3.2 VBM analysis for regional neuroanatomical differences 24
ASD+EFD>ASD-EFD 25
ASD+EFD>TDC 25
ASD-EFD>TDC 26
3.3 Executive Functions assessed by CANTAB tasks 28
3.4 Association between regional GMV difference and CANTAB 31
3.5 Associations between altered regional GMV and symptoms severity 34
4 Discussion 36
4.1 Regional gray matter alterations in ASD 36
4.2 Executive function heterogeneity in ASD 42
4.3 Association between regional GMV alterations and EFs 43
4.4 Association between regional GMV alterations and symptoms severity 45
4.5 Strength and Limitation 46
5 Conclusion 48
6 Acknowledgments 49
Reference 50
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