Divergence and Variability of Language Maps in Autism

描述（由申请人提供）：尽管普遍认为自闭症 有生物学原因，大脑异常位点之间的特定联系， 认知行为障碍仍然未知。功能性神经成像 研究没有提供一个清晰的画面，可能是由于病因 自闭症样本的异质性。我们将探讨潜在的异常， 自闭症的脑功能组织，特别关注个体 变异性，使用功能性MRI（fMRI）-一种成像技术， 有足够的能力进行个别分析。30个口头人， 孤独症，24例患有Alzheimer综合征（AS）的受试者，以及年龄，性别和 将研究偏手性匹配的对照。我们的项目将侧重于语言 --这个领域不仅在延迟方面区分自闭症和AS， 缺陷，但也具有广泛的能力， 成人自闭症人群将在听觉和 语音辨别和词汇语义联想。几 补充数据分析路径（分组和个体内; 规范化和原生空间）将使我们能够：（i）识别一致的 自闭症和AS组的功能图异常;（ii）量化 每个受试者的激活灶与正常的空间差异， 患者组内的个体变异性;（iii）将不同的模式 异常功能图与语言技能的措施;及（iv） 区分功能图的病理性紊乱的影响 补偿性可塑性。我们将测试假设，根据这些假设， 孤独症（以及在较小程度上的AS）神经系统的病理性障碍 分化和贫困的互动语言经验， 关键的发育期导致异常的神经功能图， 异常明显的个体差异。自闭症的语言延迟 进一步假设与非典型半球优势相关， 语言最后，我们预计，个别变量模式的异常 功能图将与语言结果的水平相关。识别 大脑图谱和成年人的功能水平之间的这种联系， 阐明自闭症个体差异的意义， 病因学和异常发展的不同途径。

DESCRIPTION (provided by applicant): Despite a general consensus that autism has biological causes, the specific links between brain loci of abnormality and cognitive-behavioral impairments remain unknown. Functional neuroimaging studies do not provide a clear picture, possibly due to etiological heterogeneity of autism samples. We will explore potential abnormalities of functional brain organization in autism with specific focus on individual variability, using functional MRI (fMRI) -- an imaging technique with sufficient power for individual analyses. Thirty verbal individuals with autism, 24 subjects with Asperger syndrome (AS), and age, gender, and handedness-matched controls will be studied. Our project will focus on language -- a domain which not only differentiates autism and AS in terms of delay and deficit, but is also characterized by a wide spectrum of abilities within the adult autistic population. FMRI will be performed during auditory and phonological discrimination, and lexical semantic association. Several complementary data analysis paths (groupwise and intraindividually; in normalized and native space) will enable us: (i) to identify consistent abnormalities of functional maps for autism and AS groups; (ii) to quantify activation foci in each subject in terms of spatial divergence from normal and individual variability within patient groups; (iii) to relate varying patterns of abnormal functional maps with measures of language skill; and (iv) to distinguish effects of pathological disturbance of functional maps from those of compensatory plasticity. We will test hypotheses, according to which in autism (and to a lesser extent in AS) pathological disturbance of neural differentiation and impoverished interactive language experience during critical developmental periods result in aberrant neurofunctional maps and abnormally pronounced individual variability. Language delay in autism is further hypothesized to be associated with atypical hemispheric dominance for language. Finally, we expect that individually variable patterns of abnormal functional maps will be correlated with level of language outcome. Identifying such links between brain maps and level of functioning achieved in adults will elucidate the significance of individual variation in autism in terms of different pathways of etiology and abnormal development.