http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/143 2026-03-12T07:25:05Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76822 標題: 高階重複侷限行為於自閉症患者之灰質變化分析; Alterations of Gray Matter Volume of Higher-Order Restricted and Repetitive Behaviors in Autism Spectrum Disorder 作者: Guan-Jye Seng; 諶冠潔 摘要: 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. 2020-01-01T00:00:00Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/19919 標題: 飲食操弄對於小鼠記憶的影響; Effects of nutritional manipulations on memory in mice 作者: Ya-Yun Cheng; 鄭雅云 摘要: 卡路里節制(Calorie Restriction, CR)在許多不同物種上已被發現能有效降低與老化相關疾病發生的風險，以及增進認知功能的效果。然而，飲食成分中，哪一種營養成分扮演了主要的角色，藉由卡路里的節制調控了認知功能的可塑性。在本篇論文中，在不同營養成分下，本實驗利用物體辨認測驗(Novel Object Recognition, NOR)評估小鼠的記憶功能以及利用廣場測驗(Open Field Test)檢視小鼠自發性活動能力。發現飲食成分中的蛋白質(Protein)，其中的必需胺基酸-色胺酸(Tryptophan) 在卡路里節制的情況下扮演了主要的角色促使記憶的增強。本研究結果更進一步顯示: 卡路里節制能調控認知記憶功能，且需要藉由海馬迴(Hippocampus)裡的腺苷單磷酸活化蛋白激酶(AMP-activated protein kinase, AMPK)活化的參與。另外，實驗結果發現AMPK的促進劑，Metformin，可以有效地增強小鼠的記憶表現；然而，AMPK的抑制劑，Compound C(CC)，能有效地反轉因卡路里節制而增強記憶的好處。綜合以上所有結果顯示: 本篇論文鑑定出小鼠在卡路里節制的情況下，飲食成分中的色胺酸，為最主要能調控並促進記憶增強的營養成分，且其過程必須透過海馬迴內AMPK的活化。該研究結果強烈顯示，其結果在臨床治療與老化相關的腦功能障礙上具有重要意義。; Calorie restriction (CR) has been shown to reduce the incidence of age-related diseases and improve cognitive functions in a variety of species. However, it remains unknown as to whether specific nutrient primarily works to mediate CR-induced cognitive plasticity. In this study, I evaluated the memory functions of mice under different dietary conditions by novel object recognition (NOR) tasks and the spontaneous motor activity by open field test. I found that protein derived essential amino acid-tryptophan played a major role in CR-induced memory enhancement. My results further revealed that hippocampal AMPK activation is essential for CR-mediated cognitive memory regulation since AMPK activation. I found that metformin, an AMPK activator, could significantly enhance the memory performance of mice, while CR-induced memory enhancement was attenuated by Compound C (CC), an AMPK inhibitor. Taken together, this study identified tryptophan as a critical nutrient that could mediate improved recognition memory essentially through AMPK activation under CR condition in mice. This study may have a critical implication in treating age-related brain dysfunctions in a clinical setting. 2015-01-01T00:00:00Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/54878 標題: 飲食中的巨量營養素組成與腦中灰質在健康年輕成人與老年人的不同關係; Dietary macronutrient composition is differentially associated with gray matter volume in healthy young and older adults 作者: Shu-Yun Yuan; 袁淑韵 摘要: 在生命發展的過程中，來自飲食攝取的能量及其營養素是對神經結構發展與功能極其重要的因子。但對於飲食中的巨量營養素與腦部結構與功能在非肥胖或非飲食失功能的人類身上，其間的關聯，目前的資訊是有限的。我們假設隨著人類攝取的巨量營養素的不同程度，會使腦中灰質體積大小與認知功能表現有差異。更重要地，飲食與腦的關係會隨著年齡的不同，而有需求上的不同。在本研究中，我們徵求了在台灣本地32位年輕成人(年齡在20~30歲之間)與21位年長成人(年齡在60歲以上)，讓他們參與(a)至少三天的系統性飲食紀錄(b)受測關於認知功能表現的神經心理學測驗，以及(c)結構性腦部核磁共振照影，以得知參與者腦中灰質體積大小。參與者必須無臨床上的身心疾病，且無飲食失調狀況。研究方法(a)我們依照台灣地區衛福部食品藥物管理署的資料庫，算出每位受試者其飲食內容中的碳水化合物含量、蛋白質含量，及脂質含量(b)我們使用的神經心理學測驗有簡短智能測驗(MMSE)、魏氏智力測驗III(WAIS III)、魏氏記憶測驗III (WMS III)、早期失智症篩檢量表(AD-8) (c)計算腦中灰質體積大小則是用版本5.2.0的Freesurfer 軟體，以得知全腦不同腦區的灰質體積。我們的研究結果發現在健康年輕成人當中，飲食中攝取較多比例的碳水化合物者，腦中易有較小的灰質體積;而在健康老年人當中，飲食中攝取較多比例的碳水化合物者，腦中卻易有較大的灰質體積。而在攝取蛋白質含量的多寡，對健康年輕成人來說其腦中灰質體積較不易受影響;但對老年人來說，攝取蛋白質含量越高，其腦中灰質體積就越小。在巨量營養素與腦中灰質在健康年輕成人與健康老年人的關係，年紀不同對於營養攝取的需求不同占了一個關鍵性的角色。; Energy and molecular substrates from dietary intake are important factors for neuronal structural development and function over the lifespan. There is limited information, however, on how human dietary macronutrient levels are associated with brain structure and function, particularly for those not affected by obesity or other dietary dysfunctions. We hypothesized that macronutrient intake levels in humans should have measurable associations with gray matter volume and cognitive ability even in individuals maintaining healthy dietary habits. Importantly, diet-brain associations may differ across age due to differential nutritional requirements. In this study, 32 young (age20-30) and 21 older (age above 60) Taiwanese adults participated in (a) systematic dietary monitoring at least 3 days, (b) neuropsychological tests of cognitive abilities, and (c) T1-weighted magnetic resonance imaging (MRI) of gray matter volumes (256*256 mm in-plane field of view, 1*1*1 mm3 voxels, TR = 2 s, inversion time = 0.9 s, flip angle = 9°). Participants were physically healthy at time of testing with no dietary dysfunction or neurocognitive counter-indications. Individual intake levels of calorie, carbohydrates, lipids, and proteins were scored based on the local food and drug administration database. The neuropsychological test battery included: the mini-mental State Examination (MMSE), the Wechsler Adult Intelligence Scale III (WAIS III), the Wechsler Memory Scale III (WMS III), and the Alzheimer Disease-8 (AD-8) questionnaire.T1 images were analyzed using Freesurfer software ver. 5.2.0 to parcellate regional gray matter volumes across the whole brain. We found in healthy adults, higher proportion of dietary carbohydrates decreased brain volumes in young adults, but increased brain volumes in older adults. Proportion of dietary proteins had minimal effects on young adult brain volumes, but decreased brain volumes in older adults. Age requirements play a critical role in the effect of macronutrients on brain volume in young and older adults. 2015-01-01T00:00:00Z http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/66920 標題: 預期疼痛下的神經機轉; Neural substrates underlying the anticipation of pain 作者: Yao-Wei Shih; 石燿維 摘要: 疼痛是一種容易受到許多認知功能而影響的負面經驗。其中，對於將要接受的疼痛刺激的不同程度的預期也大大的影響我們對於痛覺的主觀感受。雖然已有先前研究對於預期疼痛的神經機轉，然而在增加疼痛的預期以及減少疼痛的預期的關係仍然不清楚，並且目前仍然沒有研究顯示不確定性對於疼痛預期所扮演的角色。為了釐清這些議題，我們招募健康成年人在不同預期的情況下接受功能性磁振造影掃描。首先我們假設增加疼痛的預期和減少疼痛的預期涉及不同的腦區，另外我們也推測不確定疼痛強度的預期和確定疼痛強度的預期由相異的腦區參與。行為結果顯示不確定的預期會增加疼痛評分。功能性磁振造影的分析更進一步顯示說在仍未接受刺激的預期階段，不確定預期和預期強烈疼痛刺激的全腦活動模式相似。另外當受試者在接受疼痛刺激時，我們發現不論何種預期的種類，都有喙部的前扣帶迴皮質和前腦島皮質作為共同的活化區域。這些結果證明了在行為和神經層級上預期對於疼痛的影響，也提供了在不同種類的疼痛預期影響下的相異和共享之神經機制的證據。; Human experiences of pain are robustly shaped by the anticipation of incoming noxious stimuli. Although prior research has explored the neural substrates underlying the anticipation of pain, whether anticipation of increased pain engages similar brain activity as the anticipation of decreased pain remains elusive, and no study so far has examined the role of uncertainty in pain anticipation. To address these issues, we recruited healthy adults to receive fMRI scanning under different anticipation conditions. We hypothesized that anticipation of increased and decreased pain engaged distinct brain regions. We also speculated that anticipation of uncertain pain intensity involved dissimilar brain areas from those related to the anticipation of certain pain intensity. Behavioral results showed that uncertain anticipation enhanced pain ratings. Our fMRI analyses further revealed that, during the anticipation phase, the whole-brain activation patterns in uncertain anticipation and the anticipation of an incoming high pain stimulus were similar. When participants received painful stimuli, we found that, irrespective of the type of anticipation, the rostral portion of the anterior cingulate cortex and the anterior insular cortex were commonly activated regions. These results demonstrate how anticipation affects pain at behavioral and neural levels and provide evidence that distinct and shared neural mechanisms underlie the influence of different types of anticipation on pain experiences. 2017-01-01T00:00:00Z