注意力不足過動症患者之腦部結構的變異及與神經心理功能的關聯性

前言注意力不足過動症 (Attention-Deficit/Hyperactivity Disorder, ADHD) 的患者除了專注力不佳、過動及衝動的臨床症狀外，也常有神經心理功能的障礙，然而這些神經心理功能障礙潛在的神經結構變異目前仍未有定論，故論文中將使用結構性的腦影像分析來探討此問題。擴散頻譜磁振造影 (diffusion spectrum imaging, DSI) 及體積形態學分析 (voxel-based morphometry, VBM) 均可應用於腦部結構的研究，擴散頻譜磁振造影能提供關於神經纖維束的走向及特性 (property) 的資訊，而體積形態學分析可用來量測皮質及白質的區域體積，進行全腦的比較，本研究利用上述二種影像工具結合神經心理功能的評估結果，希望可進一步了解與ADHD患者神經心理功能障礙相關的腦部變異。研究目標釐清ADHD兒童的腦部結構和臨床症狀及神經心理功能 (如：專注力、執行功能、反應時間的個體內差異 [intra-individual variability]) 之相關性。研究方法論文中包括三個研究：(一) 找出和ADHD兒童的注意力功能相關的神經束，並了解神經束特性和專注力表現的相關性。(二) 找出和ADHD兒童的執行功能相關的神經束，並了解神經束特性和執行功能的相關性。(三) 找出和反應時間個體內差異相關的腦區，並比較ADHD兒童及對照組的異同。前二個研究為擴散頻譜磁振造影研究，研究中挑選了多條可能和注意力及執行功能相關的神經束，如雙側的額葉紋狀體神經束 (frontostriatal tract)、上縱束 (superior longitudinal fasciculus)、弓狀束 (arcuate fasciculus) 及扣帶迴 (cingulum bundle)，並計算各神經束的generalized fractional anisotropy (GFA) 值來代表神經束的特性。統計分析中除比較ADHD組與年齡、性別、慣用手、智商配對的典型發展對照組的GFA值的差異外，也用多線性迴歸模式分析所研究的神經束和注意力及執行功能表現的相關性。第三個研究為體積形態學的研究，比較ADHD組與典型發展對照組，在全腦灰質及白質體積與反應時間個體內差異的關聯性。結果【研究一】 50位ADHD兒童及50位對照組的研究結果發現，ADHD患者的左側額葉紋狀體神經束、雙側上縱束及右側扣帶迴的GFA值均較典型發展對照組低。在神經束的GFA值和臨床症狀的關聯性中，右側上縱束和注意力症狀的關聯性最強；而在神經束的GFA值和注意力測驗表現的關聯性中，ADHD患者與典型發展對照組呈現不同的關聯性模式。【研究二】 45位ADHD兒童及45位對照組的研究結果發現，ADHD患者的左側額葉紋狀體神經束、左側上縱束、左側弓狀束及右側扣帶迴的GFA值均較典型發展對照組低。另外，對照組大部分的執行功能和額葉紋狀體神經束及扣帶迴特性的變化相關，而ADHD患者大部分的執行功能和額葉紋狀體神經束、上縱束及弓狀束特性的變化相關。【研究三】 55位ADHD兒童及55位對照組的研究結果發現，大腦灰質的右側顳葉上回 (superior temporal gyrus)、右側後端腦島 (posterior insula) 及雙側小腦，在ADHD患童呈現和個體內差異的相關性；二組的右側額葉下回 (inferior frontal gyrus)、扣帶皮層 (cingulate cortex) 及丘腦 (thalamus) 的體積和個體內差異的相關性，呈現明顯的組間差異。白質體積的分析顯示ADHD患童的左側鉤束 (uncinate fasciculus) 、左側上放射冠 (superior corona radiata) 及雙側下小腦腳 (inferior cerebellar peduncle) 的白質體積和個體內差異相關；二組在右側前放射冠 (anterior corona radiata)、左側胼胝體的壓部 (splenium of corpus callosum)、雙側小腦的白質及胼胝體的膝部 (genu of corpus callosum) 的體積和個體內差異的相關性，呈現明顯的組間差異。討論【研究一】及【研究二】神經束的GFA值和注意力測驗表現/執行功能的關聯性中，ADHD患者與典型發展對照組呈現不同的關聯性模式，推測ADHD患者因為神經束特性的變化，造成不佳的注意力測驗表現/執行功能。研究結果也顯示除了額葉紋狀體神經束之外，上縱束、弓狀束及扣帶迴在神經心理功能的重要性。【研究三】腦部灰質及白質的多個區域的體積變化可解釋ADHD患者的反應時間個體內差異，研究中所發現的灰質區域都是處理及整合資訊的重要區域，而所發現的白質區域都是位在感覺及動作控制有關的重要神經束上，推測ADHD患者的反應時間個體內差異的表現可能與資訊處理及動作控制的功能異常相關。結論這三個研究証實ADHD兒童的腦部結構和臨床症狀、專注力、執行功能及反應時間的個體內差異之相關性。

關鍵字

注意力不足過動症；擴散頻譜造影；體積形態學分析；注意力；執行功能；個體內差異

並列摘要

Introduction Individuals with Attention deficit/hyperactivity disorder (ADHD) has core symptoms of inattention and hyperactivity/impulsivity, and show a broad range of deficits in neuropsychological domains. Although neuroimaging studies have highlighted the brain structural abnormality in ADHD, its association with neuropsychological performance has rarely been studied. Hence, this thesis is concerned with these questions. We used diffusion spectrum imaging (DSI) to reconstruct white matter tracts and to measure the microstructural property of selected fiber tracts, and adopted voxel-based morphometry (VBM) approach to identify the variation of regional gray matter (GM) or white matter (WM) volume. We aimed to investigate the different neural substrates underpinning neuropsychological performance in children with ADHD, in terms of attentional performance, executive functions and intra-individual variability (IIV) in reaction time. Method We try to answer our study question with three studies with specific aims: (1) To find altered white matter tract property in children with ADHD, and to examine how them are associated with impaired attentional performance; (2) To explore whether there are different white matter tracts involving in executive functions in youths with ADHD; (3) To investigate how regional volumes would be related to IIV based on the ex-Gaussian parameters in ADHD. The first two studies used DSI method. We focused on several white matter tracts which may related with attentional performance and executive functions, which included frontostriatal (FS) tract (including striatum to dorsolateral prefrontal cortex, ventrolateral prefrontal cortex and orbitofrontal cortex), superior longitudinal fasciculus (SLF), arcuate fasciculus (AF) and cingulum bundle (CB). We compared the generalized fractional anisotropy (GFA) values of the white matter tracts between the ADHD and individually-matched controls. We also used backward elimination procedure to identify the fitted model containing the variables from these tracts which maintained significant effects on measures of neuropsychological tasks. The third study used VBM method to conduct an whole-brain analysis about the correlations between IIV and regional brain volume in ADHD and individually-matched controls. Results 【Study 1】 In 50 youths with ADHD and 50 matched controls, youths with ADHD had lower GFA in left frontostriatal tracts, bilateral SLF and right CB. Our study highlights that alteration of the right SLF in GFA values was most significantly associated with the clinical symptom of inattention in ADHD youths. Besides FS tracts, the GFA value of the SLF, CB were also associated with attention performance in youths with ADHD and controls. 【Study 2】 In 45 youths with ADHD and 45 matched controls, youths with ADHD had lower GFA in the left FS tract, left SLF, left AF and right CB. The ADHD and control groups demonstrated different association patterns between executive functions and fiber tract microstructural property. Most of the executive functions were associated with microstructural property of the FS tract and CB in controls, while with that of the FS tract, SLF and AF in youths with ADHD. 【Study 3】 Using 55 ADHD youths and individually-matched controls, we identified several neural substrates underpinning IIV in ADHD youths. For GM, IIV was associated with regional volume in right superior temporal gyrus, right posterior insula and bilateral cerebellum in ADHD youths. There was significant IIV-by-group interaction in cingulate cortex, thalamus and right inferior frontal gyrus. For WM, IIV was associated with regional volume in the left uncinate fasciculus, the bilateral inferior cerebellar peduncle and the left superior corona radiata. There was significant IIV-by-group interaction in the genu of corpus callosum, right anterior corona radiata, left splenium of corpus callosum, and the arbor vitae of bilateral cerebellum. Discussion The involvement of different fiber tracts or alternation of regional brain volume in neuropsychological performance in ADHD may imply neuropathological underpinnings of ADHD or the possibility of a compensatory mechanism. Conclusions Our studies highlight that structural neural substrates underpinning the neuropsychological functions are atypical in youths with ADHD.

並列關鍵字

Attention deficit hyperactivity disorder ； attention ； diffusion spectrum imaging ； executive function ； intra-individual variability ； voxel-based morphometry

參考文獻

Adler, L. A., B. Dirks, P. Deas, A. Raychaudhuri, M. Dauphin, K. Saylor and R. Weisler (2013). "Self-Reported quality of life in adults with attention-deficit/hyperactivity disorder and executive function impairment treated with lisdexamfetamine dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel-group study." BMC Psychiatry 13: 253.

American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition Arlington, VA, American Psychiatric Association

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國際替代計量

注意力不足過動症患者之腦部結構的變異及與神經心理功能的關聯性

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