本研究目的，在探討以行為症狀區分的ADHD次分類型，是否也能在認知功能上有其相對映的區辨？本研究以行為症狀量表DBRS，測量受試者在不專心注意與過動/易衝動向度上的行為症狀表現，以神經心理測驗GDS，測量受試者在不專心注意與過動/易衝動向度上的認知功能表現。 本研究假設認為，以行為症狀量表DBRS所區辨出的不同ADHD次分類型，在神經心理測驗GDS上，應具有不同的認知功能表現模式。透過對63名6~9歲的男性學齡受試者，由行為症狀量表DBRS區分ADHD次分類型，並以單因子變異數分析及Pearson積差相關等方式，檢驗不同次分類型間在神經心理測驗GDS上的認知功能差異與關係。 研究結果顯示，以DBRS所區分的次分類型，在GDS各相關認知功能指標上，都無法有效獲得顯著的差異與關係；大部分的測驗指標，皆未能有效支持本研究假設。研究結果顯示，在本研究樣本中，受試者母親在DBRS上填答的行為症狀表現，與受試者在神經心理測驗GDS上的認知功能表現，未能展現出一致及可茲對映的區辨能力。並在討論中針對此結果，提出可能的原因及相關的建議。 / The purpose of this study is to explore that if ADHD subtypes which are discriminated by behavioral symptoms could reflect the same discriminance on cognitive functions. In this study, the performance of inattention and hyperactive/impulsive behavioral symptoms are measured by the behavioral symptom scale, DBRS; and the performance of inattention and hyperactive/impulsive cognitive functions are measured by the neuropsychological testing, GDS. The hypotheses of this study are that the different ADHD subtypes which are measured by behavioral symptom scale, DBRS, should have different performance pattern of cognitive functions in GDS. This study sorts 63 male subjects, aged from 6 to 9 years old, into 4 subtypes and compares the differences by one way ANOVA and explores the relationships by Pearson product-moment correlation, so as to exam the cognitive differences and the relationships between subtypes on neuropsychological test, GDS. The results show that the subtypes which is discriminated by DBRS have no significant differences on most related cognitive-functioning indexes of GDS. Most testing indexes do not support the hypothese in this study. From the samples of this study the results show that the performance of behavioral symptoms on DBRS, based on mother's evaluation of subject's behavior, and subjects’ performance of cognitive functions on GDS do not have consistent or matched patern. The probabilistic explanation and related suggestion will be proposed in discussion.

失憶型輕度認知功能障礙（a-MCI）患者被認為是演變成為阿茲海默症的高危險群，在早期由於海馬迴結構的神經纖維糾結，患者會開始產生記憶障礙。Braak和Braak在1991年將神經纖維糾結分成六個時期，開始會先從海馬迴結構的前內鼻區和側海馬迴產生病變，最後才會順延到海馬迴本體。由於前內鼻區主要處理事件及物件特徵，側海馬迴主要處理空間背景訊息，海馬迴本體主要處理空間位置記憶，所以本研究假設事件及物件特徵與空間背景訊息的配對記憶在a-MCI階段就會產生障礙，而空間位置記憶則在輕度阿茲海默症會開始產生障礙，如果不同階段神經病變的認知功能表現，可以在研究結果中呈現出來，或許可以協助找到早期偵測海馬迴結構病變的神經認知功能指標。 本研究受試者主要包含正常組（NC組）30人，失憶型輕度認知功能障礙組（a-MCI組）30人和輕度阿茲海默症組（AD組）30人，共計90人。每組受試者均接受神經心理測驗衡鑑和本研究自行發展的空間脈絡記憶測驗。空間脈絡記憶測驗總共分為三個部分：（1）空間位置記憶測驗：要求受試者回憶之前在地圖上隨機出現的建築物位置；（2）事件與地點連結測驗：事件和地點配對出現後，要求受試者選擇事件所配對的地點背景為何；（3）地點與物體的連結測驗：物體和地點配對出現後，要求受試者選擇該地點之前出現的物體為何。 研究結果呈現，不同組別在神經心理測驗結果，a-MCI組在延宕提取以及記憶保留的部分相較於其他認知功能顯著較差，而AD組相較於a-MCI組，除了記憶力表現更差外，其他認知功能的缺損也更為嚴重。而不同組別在空間脈絡記憶的結果，空間位置記憶分測驗呈現NC組＞a-MCI組＞AD組的結果，在事件與地點的連結分測驗呈現NC組＞a-MCI組＝AD組的結果，在地點與物體的連結分測驗呈現NC組＞a-MCI組＞AD組的結果。從ROC曲線分析呈現，空間脈絡記憶測驗相較於其他篩檢測驗，在區分NC組和a-MCI組的敏感度及特異度較好，而MMSE則在區分a-MCI組和AD組的敏感度及特異度較好。 研究結果呈現a-MCI受試者在一般認知功能尚未顯著下降的同時，空間脈絡記憶就已經呈現障礙，這可能和早期神經纖維糾結所破壞的區域有關，結果也呈現空間脈絡記憶測驗在a-MCI階段，比其他篩檢測驗能更敏感的區分出正常和異常的患者。目前臨床常用的MMSE測驗，因為複合了多項認知功能，反而適合用於篩檢已經為輕度阿茲海默症的患者。 / Background: Amnesic mild cognitive impairment (a-MCI) was identified to have a high risk to become Alzheimer’s disease (AD). In early stage of AD, because of neurofibrillary tangles, patient began complaining progressive memory deficits. The progressive course of neurofibrillary tangles was divided into 6 stages (Braak and Braak, 1991). Initially, the neurofibrillary tangles destroyed perirhinal and parahippocampus neurons, which may correspond to the a-MCI stage and then proceed to hippocampal body that correspond to early AD. According to previous studies, the perirhinal is primarily associated with item features encoding, the parahippocampus associated with scene features encoding, and the hippocampus associated with spatial location memory. Based on these findings, we hypothesized that the item and scene features association memory would show impairments in a-MCI and the spatial location memory would not be impaired in a-MCI but in early AD. If the different stages could be discriminated by the performance on spatial context memory test that we design, it can be utilized in clinical settings to assist the diagnosis of a-MCI. Method: Three groups of subjects were selected from the clinic of the neurological department of Chang Gung Memorial Hospital, including normal subjects (n=30), a-MCI subjects not diagnosed with dementia (n=30), and mild AD subjects (n=30). All of them were administered a package of neuropsychological tests and a self-developed spatial context memory test that include three sub-tests: (1) a spatial location memory test: subjects have to recognize the location of a building that was appeared in a map; (2) an event-place association memory test: subjects need point out which spatial scene that was associated with this event; and (3) a place-object association memory test: subjects need point out which object that was associated with this place shown before. Result: In neuropsychological tests, a-MCI group demonstrated significant impairment in delay retrieval and memory retention in comparison to their performance on tests for other cognitive functions. The AD group showed decline in overall cognitive functions including declarative memory and others. In the spatial context memory test, both the spatial location memory test and the place-object association memory subtest showed a decline in a-MCI group, and a further decline in AD group; the event-place association memory test presented significant decreases in both a-MCI and AD group in comparison to normal control, but no difference between the two clinical groups. Conclusion: The current study shows that the spatial context memory in a-MCI patients has greater impairment than their general cognitive function. Compared with other screening test, the spatial context memory has greater sensitivity and specificity to discriminate a-MCI from NC.

中文摘要 厚朴，採用厚朴植物之樹皮，是ㄧ種已知可應用於治療精神疾病的傳統天然藥物，例如：憂鬱症等。厚朴主要的有效多酚環成分已被證實具有抗氧化、抗發炎及抗興奮性毒殺等神經保護作用，因此，推測厚朴可作為一種潛在治療像是帕金森氏症這累神經退化性疾病之藥物。本研究之目的為探討厚朴是否可以預防與治療因百草枯及MPTP所誘導的毒害及學習、記憶和運動功能缺失等行為異常現象。本研究監測Oregon-R品系之果蠅(年齡：1-2, 20天或30天)之壽命在長期暴露於百草枯(5-20 mM)並先給予厚朴(100, 300或600 mg/L)治療之變化。其結果顯示，厚朴無法延長暴露在百草枯環境下之果蠅壽命。另外，我們給予雄性ICR小鼠(30-35 g)，連續五天，每日一劑MPTP(25 mg/kg, i.p.)，誘導神經毒性及行為異常現象。在共同投藥組別，在給予MPTP注射前一小時，先以灌餵方式給予小鼠厚朴(100或300 mg/kg)預防，連續五天後，只單獨給予厚朴治療連續十四天。後投藥組別，在給予最後一劑MPTP後，連續十四天給予厚朴(100或300 mg/kg).治療。在控制組別中，給予生理食鹽水(0.9%, i.p.)及灌餵玉米油。結果顯示，MPTP與厚朴並不影響小鼠之運動協調功能，然而，可利用新位置辨識能力測試及新物體辨識認知行為測試，檢測因MPTP所引起之認知功能障礙現象，由我們結果中顯示，不論是與MPTP共同給予厚朴治療抑或是後處理厚朴皆可恢復因MPTP所造成的認知功能障礙現象，此外，厚朴也可恢復因MPTP所造成多巴胺神經元及多巴胺轉運子受損之情形，另外，我們也初步發現，厚朴可在海馬迴中使Nrf2表現量提升。因此，初步結果表明，厚朴將可成為未來治療帕金森氏症之天然藥物。 / Cortex Magnoliae, the bark of Magnolia officinalis, has been prescribed in the traditional herbal medicine to treat a variety of mental disorders including depression. The main constituents of cortex Magnoliae contain the biphenyl compounds such as honokiol and magnolol. Both biphenyl compounds were shown to have the neuronal protective effect which is related to the anti-oxidation, anti-inflammation, and anti-excitatory toxicity. Thus, it was proposed that cortex Magnoliae may act as the potential therapeutic agent for the treatment of neurodegenerative disorders such as Parkinson’s disease (PD). The aim of the present study was to examine whether cortex Magnoliae exhibits the neuroprotective and therapeutic action against the neuronal toxicity and behavioral deficits in learning, memory, and motor function induced by neurotoxin paraquat and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in PD-like models. The lifespan of flies from Oregon-R strain of Drosophila melanogaster (age: 1-2, 20 or 30 days) chronically exposed to paraquat (5-20 mM) with pre-treatment of Cortex Magnoliae (100, 300 or 600 mg/L) were measured. Results showed that pre-treatment of Cortex Magnoliae could not extend the lifespan of the flies reduced by paraquat. On the other hand, male ICR mice (30-35g) were administered with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days to induce neurotoxicity and behavioral impairment. In co-treatment group, male mice were orally administrated with cortex Magnoliae (100 or 300 mg/kg) 1 hour before MPTP injection for 5 days and then followed by oral administration of cortex Magnoliae alone for consecutive 14 days. Mice in post-treatment group were orally administered with cortex Magnoliae (100 or 300 mg/kg) for consecutive 14 days after the final injection of MPTP. Mice in control group were injected with saline (0.9%, i.p.) and orally administrated with vehicle (corn oil). Our results showed that MPTP and cortex Magnoliae did not affect mouse coordination and balance in beam walking test. However, cortex Magnoliae improved the cognitive impairments determined by novel-location recognition task (NLRT) and novel-object recognition task (NORT) in MPTP-induced PD mouse. Additionally, cortex Magnoliae restored MPTP-induced loss of dopaminergic neurons and recovered MPTP-induced loss of dopamine transporters in striatum. Cortex Magnoliae also activated Nrf2 in hippocampus. Therefore, the preliminary results suggest that cortex Magnoliae may be a novel candidate for the treatment of Parkinson's disease in the future. The pharmacological mechanism of cortex Magnoliae in PD treatment needs further study.

近年來，功能性磁振造影技術發展迅速，使得大腦神經活動關聯性在腦神經科學中逐漸發展成熟。同時，網路理論的發展在近代也引起關注，在生物物理中，小世界網路(Small-World Network)被廣泛運用在大腦神經網路，其群聚性高、特徵路徑短之性質與大腦各個腦區間反應及高效率傳遞資訊的特性相似。有鑑於此，本論文藉由小世界網路的特性探討大腦的老化現象。 本研究以靜息態功能性磁振造影(Resting-state fMRI)量測年輕人及老年人大腦資料，並以右側腦島(Ins.R)作為核心，建構以腦島為核心的正及負相關網路。隨後，我們觀察在小世界特性明顯下的全域網路參數(Global Network Parameters)及區域網路參數(Regional Network Parameters)之老化現象。最後，我們利用多重攻擊策略模擬網路多點受損之情況，以了解網路之脆弱性。 我們研究結果指出，以腦島建立之負相關網路的常規化特徵路徑(Normalized Characteristic Path Length)會隨年紀而減短。並在區域網路參數所選出之重要網路樞紐中發現以腦島所建構之相關網路與認知功能(Cognitive Function)及中樞自主神經系統(Central Autonomic System)具有相關，且正相關網路中左側前扣帶和旁扣帶腦回(ACIN.L)及左側緣上回(SMG.L)隨著老化有顯著差異。期望可幫助醫學上了解中樞自主系統與認知功能在老化下之狀況。

本論文之目的在於探討「在」各種構式的概念、句式的意義以及語意上的各種分布，從語料中觀察母語人士和非母語人士「在」使用上的差異，並將研究結果應用於華語教材的設計中。研究者將先前關於「在」的詞類討論、構式的內容、句式義、相關變式的文獻做一整裡，發現過去「在」的研究多集中於語言現象的討論，在教學上的應用較少，於是運用認知功能學派的理論釐清「在」的概念、構式意義和功能後，調查語料庫「在」的語意和構式的分布，發現「在+處所」的構式無論是臺灣母語人士的語料庫還是中介語語料庫都顯示極高的頻率，占學習者書面語語料中的76.6％，口語語料也占了63.5％，其他語意範疇所占的比例不高，和母語人士相較下，調查結果顯示非母語人士在書面語上對「在」的使用掌握度不夠全面，仍停留在原型的語意，而口語的掌握度較高。因此，本文以構式語法和認知語言學的理論為基礎，一方面使用語料庫研究法考察語意範疇的分布，另一方面採用對比法研究檢視華語學習者的中介語句，並使用變換分析法討論句式變化的合理性，更進一步將構式、隱現、相關變式的考察成果結合認知功能教學法與任務式教學法，設計出符合認知功能主張的教材內容與練習，以幫助學生徹底掌握「在」構式的深刻內涵。 / The purpose of this study is to investigate concepts associated with zài constructions, focusing on their different meanings and semantic distributions. Having observed native speakers’ and non-native speakers’ different performances in corpora, the researcher applies the study results to the design of Taiwan Mandarin teaching materials. After reviewing literature on discussions about part of speeches of zài, zài constructions, meanings of sentences and related transformations, the researcher discovers that previous studies have made more efforts to discuss linguistic phenomena rather than pedagogic applications. As a result, by utilizing the theories of cognitive-functional approaches to clarify the concepts, constructional meanings, and functions of zài, the researcher investigates the semantic and construction distributions of zài and finds out that “zài+ location” displays the highest frequency in both corpora of native and non-native speakers: 76.6％ in interlanguage corpora in form of written language and 63.5％ in interlanguage corpora in form of spoken language. Other semantic categories, however, have lower frequency. In addition, the result of investigation indicates that non-native speakers hardly master all dimensions of zài, and they still remain at the prototypical level in written language, but know spoken language better. Therefore, based on construction grammar and cognitive linguistics, this study on the one hand uses corpus study to inspect the distribution of semantic categories, and on the other hand, adopts contrastive study to inspect Mandarin learners’ interlanguage and employs transformation analysis to debate the rationality of transformation. Furthermore, the researcher, based on the results of studies on constructions, appearance and disappearance of zài , transformations with cognition-functional teaching methods and the task-based approach, designs contents and exercises conforming to cognition-functional approaches in order to help Mandarin learners know zài constructions thoroughly.

研究目的：本研究的目的，是以縱貫研究的方式探討自閉症類疾患兒童自學齡前期至學齡期的臨床診斷穩定度、自閉症狀嚴重度變化、適應行為型態與其變化、內外化行為。 研究方法：本研究納入28名自閉症類疾患與18位非自閉症類疾患，於三個時間點進行評估：時間點一平均生理年齡為2歲半、時間點二為4歲、時間點三為9歲半。本研究分析三個時間點之臨床診斷穩定度以及後兩個時間點之評估資料。症狀嚴重度方面，以自閉症診斷會談問卷修訂版之晤談評估；適應行為方面，以文蘭適應行為量表第二版評估；認知功能方面，時間點二時以穆林發展量表評估，時間點三時使用魏氏兒童智力量表第四版評估；內外化行為方面，時間點三時以阿肯巴克實證衡鑑系統中的兒童行為檢核表評估。 研究結果：本研究結果顯示，自閉症類疾患從學齡前期至學齡期的臨床診斷穩定度高，若分亞型來看，自閉性疾患的診斷穩定度比其他未註明之廣泛性發展疾患高。症狀嚴重度方面，學齡期時自閉症類疾患兒童的溝通、侷限及重複刻板行為有顯著改善，社交行為亦有改善趨勢。適應行為方面，學齡前期及學齡期皆未發現自閉症類疾患與非自閉症類疾患之表現型態有差異，兩組在社會化領域的表現皆較其他領域來得差。自閉症類疾患的適應行為於學齡期時，年齡當量顯著增加，但社會化適應行為標準分數反而退步；進一步以認知功能分組檢視，則發現高功能自閉症類疾患在日常生活技巧與社會化領域的進步幅度顯著較多。內外化行為方面，學齡期時自閉症類疾患個案的退縮/憂鬱分量尺與社會問題分量尺之分數高於非自閉症類疾患，且自閉症類疾患在退縮/憂鬱、社會問題、注意力問題等三個分量尺上，皆有超過一半的個案達到邊緣範圍以上之分數；未發現內外化行為與自閉症狀嚴重度之間的相關。 結論：自閉症類疾患兒童到了學齡期大部分仍維持臨床診斷，顯示其自閉特徵仍然穩定存在，不過症狀嚴重度的整體趨勢會隨著年紀改善；但若以個體差異來看，每位個案進步的程度呈現高異質性，每位個案症狀改變的程度可能不同。自閉症類兒童的社會化適應行為從學齡前期至學齡期皆為其弱項，雖適應行為會隨著年齡進步，但社會化適應行為仍追不上同儕程度；高功能自閉症類疾患兒童的適應行為在日常生活技巧與社會化領域的進步幅度顯著較多，可能與認知功能有關。內外化行為方面，自閉症類疾患兒童的退縮/憂鬱問題、社會問題、注意力問題較多，但與症狀嚴重度無關。 / Purposes: The purpose of this longitudinal study was to examine the stability of clinical diagnosis, symptom severity, adaptive function and enternal/external behavior from toddler to school age in children with autism spectrum disorders (ASDs). Methods: Twenty eight children diagnosed with ASDs and eighteen children with Non-ASDs participated at time 1 (mean chronological age was 2.5 years old), and then followed at time 2 (mean chronological age was 4 years old) and at time 3 (mean chronological age was 9.5 years old). This study examines the stability of clinical diagnosis from time 1 to time 3, and analyze the measurement data between time 2 and time 3. Autism Diagnostic Interview-Revised (ADI-R) was used to measure autistic symptom severity at time 2 and time 3; Vineland Adaptive Behavior Scales-II (VABS-II) was used to measure daily adaptive behavior at time 2 and time 3; Mullen Scale of Early Learning (MSEL) or Wechsler intelligence scale for children-Fourth Edition (WISC-IV) was used to measure cognitive function at two time points; Child Behavior Checklist for Ages 6-18 (CBCL/6-18) was used to measure enternal and external behavior at time 3. Results: The stability of clinical diagnosis was high from toddler age to school age, and the stability of Autistic Disorder was higher than Pervasive Developmental Disorder Not Otherwise Specified. The ADI-R scores of communication domain, repetitive and stereotyped behavior domain were decreased at school age, while reciprocal social interaction domain was also declined but no significant difference. All domains of VABS-II standard score were no significant difference between ASDs and Non-ASDs at two time point, and the score of social domain was worst in both two groups. The VABS-II standard score of social domain was reduced although the age equivalent was increased at school age, and the standard score of other domains were no significant difference between the two time points but all age equivalents were improved at school age. Dividing ASDs to high-function ASDs and low-function ASDs to analyze the growth rate of adaption behaviors, the results indicated that the growth rate of adaption behaviors were higher in high-function ASDs at daily skill domain and social domain. Children with ASDs had significant higher scores on Withdrawn/Depressed scale and Social Problem scale than Non-ASDs in CBCL, and over 50 percent of ASDs scored above the borderline range at Withdrawn/Depressed scale, Social Problem scale and Attention Problem scale. In addition, there were no significant correlations between CBCL and ADI-R. Conclusions: In summary, the study showed that most of ASDs sustained the clinical diagnosis from preschool age to school age, however, the autistic symptom severity was declined. Additionally, the improvement of symptom severity of individual ASDs was high variability. The social adaptive behavior was worst in both toddler age and school age in ASDs. Although these children with ASD developed some of adaptive behaviors in the school age, the magnitude of improvement couldn’t equal to the change of their chronological age, especially in socialization domain. The growth rate of daily skill domain and social domain were higher in high-function ASDs than low-function ASDs, might associated with cognitive function. More Children with ASDs had withdrawn/depressed problem, social problem and attention problem, but there were not related to autistic symptom severity.

雙酚化合物在文獻報導中發現具有抗發炎和抗氧化的能力，因為其親脂性的特性，雙酚化合物可以輕易穿透血腦屏障到中樞神經系統發揮其藥理活性。因此，雙酚化合物被評估可做為潛在預防及治療神經退化性疾病如帕金森氏症的神經保護藥物。本研究目的為探討新合成的雙酚化合物MH101及MH102是否具有神經保護和治療效用，而對抗神經毒素(包含巴拉圭、過氧化氫及MPTP)引起的神經毒害及其誘發的動物行為異常(如: 學習、記憶及運動協調)。研究中應用Oregon-R的果蠅(年齡: 1-2, 7, 20 和 30天)做為檢測模式，果蠅暴露在巴拉圭 (5-20 mM)或過氧化氫(0.3 %-3 %)環境下，並且給予MH101 (0.1-3 μM)。結果顯示MH101未能有效地減緩巴拉圭及過氧化氫所引起果蠅壽命的下降。此外，給予雄性ICR小鼠 (25-30 g) 腹腔注射MPTP (25mg/kg)每天一次連續五天，觀察神經毒素誘發的行為異常和神經毒害。在觀察保護效果的研究中，雄性小鼠在給予MPTP前一小時腹腔注射MH101 (1-3 mg/kg) 或MH102 (0.1-3 mg/kg) 每天一次連續五天，之後單獨給予MH101或MH102治療連續九天。後處理的組別，雄性小鼠在給予MPTP每天一次連續五天後，每天腹腔注射MH101 (1-3 mg/kg) 或MH102 (0.1-3 mg/kg)連續九天。控制組組別，小鼠則給予生理食鹽水(0.9%)及玉米油的混合液。結果顯示，MH101、MH102及MPTP皆不影響小鼠橫桿行走試驗的運動平衡和協調能力。然而，在前處理和後處理MH101或MH102後用新位置辨識能力測試和新物體辨識能力測試觀察MPTP引起的認知缺失，實驗結果顯示MH101及MH102皆恢復短期記憶和長期記憶的認知辨識指標。另外，前處理和後處理MH101或MH102雖有些微恢復紋狀體內MPTP引起多巴胺神經損傷及多巴胺轉運子減少的趨勢，但不顯著。由此推論，雙酚化合物MH101及MH102具有預防及改善神經毒素所引發的認知與學習缺陷，未來可能發展成為神經退化性疾病如帕金森氏症之潛力治療藥物，另針對MH101及MH102在神經損傷及動物行為障礙的恢復和保護藥理機制則需進一步實驗探討。 / Biphenols which are the main constituents of the traditional herbs have been found to possess the antiinflammatory and antioxidative properties. Due to the lipophilic activity, biphenols can readily cross the blood brain barrier to exert their pharmacological effects in the central nervous system. Thus, biphenols are proposed to act as the novel neuroprotective agents for treatment of neurodegenerative disorders such as Parkinson’s disease (PD). The aim of the present study was to examine whether the new synthetic biphenolic compounds MH101 and MH102 have the neuroprotective and therapeutic actions against the neurotoxicity and the behavioral impairments (e.g. learning, memory, and motor coordination) induced by neurotoxins including paraquat, hydrogen peroxide, and MPTP in PD-like animal models. The following experiments examined the lifespan of flies from Oregon-R strain of Drosophoila melanogaster (age: 1-2, 7, 20 and 30 days) chronically exposed to paraquat (5-20 mM) or hydrogen peroxide (0.3 %-3 %) under MH101 (0.1-3 μM) treatment. Our results showed that MH101 could not effectively influence the reduced lifespan of the flies induced by paraquat and hydrogen peroxide. Furthermore, male ICR mice (25-30 g) were administrated with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days to induce neuronal damage and cognitive deficits. For the protective study, male mice were administrated with MH101 (1-3 mg/kg, i.p.) or MH102 (0.1-3 mg/kg, i.p.) 1 hour prior to MPTP injection once daily for 5 days, and followed daily treatment with MH101 or MH102 alone for consecutive 9 days after the final injection of MPTP. For the post-treatment study, male mice were administrated with MPTP (25 mg/kg, i.p.) once daily for 5 consecutive days, and followed by daily treatment of MH101 or MH102 for 9 days. Mice in control group were injected with vehicle (0.9% saline + corn oil). The results showed that MH101, MH102, and MPTP alone did not alter the motor functions of coordination and balance in beam walking test. On the other hand, both pre-treatment and post-treatment of MH101 and MH102 reversed the cognitive dysfunction induced by MPTP detected by novel location recognition test (NLRT) and novel object recognition test (NORT). Data demonstrated that MH101 and MH102 reversed the reduction in recognition index (RI) of short term memory and long term memory in MPTP-induced PD model. However, pre-treatment and post-treatment of MH101 or MH102 slightly recovered MPTP-induced loss of dopamine neurons and dopamine transporter in striatum. Therefore, the results suggest that biphenols including MH101 and MH102 may be the candidates for treatment of neurodegenerative diseases such as PD. In the future, it will need further study to determine the pharmacological mechanism of MH101 and MH102 in protection and restoration of neuronal injury and cognitive impairment.

研究目的：欲瞭解自閉症類疾患兒童，橫跨幼兒期、學齡前期至學齡期的自閉症狀發展軌跡，探究當中是否存有不同的發展軌跡，並檢視不同發展軌跡的群體在認知功能與適應行為隨時間的變化型態是否有差異，以及不同群體在早期的社會溝通能力或療育經驗上是否有差異。 方法：本研究有37名自閉症類與24位非自閉症類受試者納入分析，共測量三次：時間點一平均生理年齡為2歲半、時間點二為4歲、時間點三為8歲半。於三個時間點皆以自閉症診斷觀察量表評估自閉症狀嚴重度、以及穆林發展量表或魏氏兒童智力量表第四版評估認知功能，在時間點二與時間點三以文蘭適應行為量表第二版評估適應行為；另外，在時間點一以台灣版兩歲期自閉症篩檢工具評估社會溝通能力，以及在時間點一至時間點二之間，以電話訪問的方式紀錄兒童每週參與療育的時數。 結果：由階層式集群分析結果顯示，社交情感嚴重度校正分數可將自閉症類與非自閉症類兒童分群，並於自閉症類兒童中可再分為維持高嚴重度組與退步組。兩組自閉症類兒童於學齡時期在社交情感症狀皆呈現嚴重度明顯上升的趨勢，在認知功能與適應行為隨時間的變化型態相似，不過維持高嚴重度組在認知功能與適應行為有較低的分數（但未達統計顯著）。此外，兩組自閉症類兒童於時間點一的意圖溝通能力即有差異，不過僅共享式注意力可預測日後社交情感症狀發展軌跡之分群。 總結：由結果可見自閉症狀維持高嚴重度組，於認知功能與適應行為有較明顯缺損，推論自閉症類兒童的自閉症狀嚴重度與認知功能及適應行為並非完全獨立的變項。兩組自閉症類兒童於學齡期症狀嚴重度上升，而此趨勢在退步組兒童更為明顯。雖然本研究並未發現早期療育經驗對於社交情感症狀發展的影響，不過共享式注意力對於日後社交情感症狀有預測力。進一步討論此結果在理論與臨床實務上的應用。 / Purposes: the purpose of the study was to plot longitudinal developmental trajectories of autism symptom severity in the children with autism spectrum disorders (ASDs) from toddler age to school age. And to examine whether these different trajectories are associated with the cognitive function, adaptive behavior, early social communication skill, and early intervention experience. Methods: Thirty-seven children with ASDs and 24 children with developmental delay participated at time 1 (mean chronological age was 2.5 years old), and then followed at time 2 (mean chronological age was 4 years old) and time 3 (mean chronological age was 8.5 years old). The study assessed the autism symptom severity by ADOS and cognitive function by MSEL or WISC-Ⅳ at three time points; adaptive behavior by VABS-II at time 2 and time 3; and early social communication skills by T-STAT at time 1 and also used telephone interviews to record participants’ weekly intervention hours during time 1 to time 2. Results: In hierarchical cluster analysis, social affect calibrated severity score (CSS) could discriminate ASDs and Non-ASDs groups, also could divided ASDs into two groups, called persistent high and worsening groups. The social affect symptom severity increased at school age in both groups. On the other hand, the change of cognitive function and adaptive behavior with time showed similar pattern in the two groups. However, participants in the persistent high group have relatively lower scores of cognitive function and adaptive behavior, although did not rearch statistically significant. Furthermore, two ASDs groups at toddler showed difference in intention communication skills; however, only joint attention could predict social affect trajectory subgrouping. Conclusions: In summery, the study showed that persistent high group has more cognitive and adaptive function impairments than the worsening group in the children with ASDs. It seemed that the autistic symptom are not entirely independent with cognitive function and adaptive behavior. Moreover, the symptom severity increased at school age in both the persistent high and the worsening groups, and this trend was more significant in the worsening group. Additionally, the experience of early intervention showed no significant effects on developmental trajectories of social affect symptom; however, the joint attention was found to be an index to predict the development of social affect symptom in ASDs groups. The theoretical and clinical implications were discussed.