孤独症儿童动作发展障碍的神经机制

动作发展障碍(Developmental motor disorders)是孤独症谱系障碍的常见特征。通过系统回顾孤独症儿童动作发展障碍的神经科学研究, 发现γ-氨基丁酸和5-羟色胺浓度的改变及γ-氨基丁酸相关蛋白和Shank蛋白的表达异常不仅会损害中枢神经系统的发育, 而且还能导致突触兴奋性与抑制性失衡, 进而改变孤独症儿童小脑和大脑皮层运动区的功能连接。孤独症儿童小脑、基底神经节和胼胝体结构的改变对全脑的连通性产生了负面影响。神经生化机制和脑结构的异常共同导致了脑功能的异常, 最终造成孤独症儿童的动作发展障碍。此外, 动作发展障碍与孤独症核心症状共同的神经基础主要包括镜像神经元系统紊乱, 丘脑、基底神经节和小脑异常以及SLC7A5和PTEN 基因突变。未来研究需要关注与运动密切相关的其他神经递质, 如乙酰胆碱和多巴胺; 探索动作发展障碍神经网络的动态机制及其形成; 剖析该障碍的神经机制和自闭症核心症状神经机制的相互作用。     

孤独症与镜像神经元

孤独症是起始于婴幼儿时期的由脑功能障碍引起的长期发展性障碍,有3种典型的症状:社会交往与言语沟通障碍及出现刻板僵化行为.孤独症的病因复杂,镜像神经元的发现和研究,使得研究者有望揭开孤独症症状背后的神经机制,并为孤独症的诊断和治疗予以新的启发.     

孤独症:大脑极端男性化的表现形态?

2002年,英国剑桥大学Baron-Cohen等研究者正式提出了广受关注的孤独症"极端男性脑理论"(Extreme Male Brain Theory),核心观点是认为孤独症是男性认知风格的极端变体,其在以"共情"为特征的女性心理特质上存在缺陷,而在以"系统化"为特征的男性心理特质上获得扩展。极端男性脑理论以"共情-系统化理论"为基础,又拓展到之后的"高度系统化理论",理论体系不断完善。尽管也面临一些挑战,但该理论业已得到心理学、神经科学乃至生物学等多学科大量研究的汇聚式支持,尤其是有关孤独症早期宫内过高雄性激素的发现更为其提供了最为有力的证据。在这一框架下,孤独症群体中的男性居多、指长比、利手、玩耍行为、父母职业以及孤岛能力等相关特质都能得到较合理解释,这为我们认识孤独症现象提供了崭新的视角。     

孤独症谱系障碍者视觉定向与视觉搜索的特点及神经机制

定向网络是注意网络的重要组成部分, 主要包括视觉定向与视觉搜索两大任务。对于这两大注意任务, 正常个体在神经机制上存在较大的重叠, 然而, 孤独症个体却表现出截然相反的行为证据。研究者从非社会信息的注意视角发现, 一般而言, 在视觉定向上, 孤独症个体注意转移不存在缺陷, 而注意脱离存在困难, 但该结论仍有争议; 在视觉搜索上, 孤独症个体存在视觉搜索优势, 但该优势发生的阶段及原因仍需进一步探究。未来研究应进一步考察孤独症个体在视觉定向任务中左右视野的不对称性、视觉搜索优势的内在机制及两大注意任务之间的相互关系。     

高功能孤独症者非字面语义理解缺陷：隐喻视角的ERP研究

研究采用事件相关电位技术从隐喻语义理解角度考察了高功能孤独症成人非字面语义理解中的行为特点及脑半球参与模式。行为结果显示：高功能孤独症成人对新异隐喻句的反应时最长,两类隐喻句的反应时均长于普通成人,但错误率上两组被试间无差异。脑电结果显示：高功能孤独症组对新异隐喻句的N400波幅最大,未出现半球偏侧化现象,传统隐喻句在左半球的N400波幅大于右半球,两类隐喻句的N400波幅均大于正常被试。结论：高功能孤独症成人具备隐喻理解能力,并对新异隐喻的理解做出更多努力,但右脑功能异常仍旧存在,左右半球在总体功能或神经联通性上仍旧弱于常人。     

孤独症者面孔加工中眼部注视不足,是回避还是忽视?

临床行为观察发现,孤独症谱系障碍(Autism Spectrum Disorder,简称ASD)个体在社会交往中较少注视他人眼部。近年的眼动研究发现,ASD个体面孔加工中的眼部注视不足随年龄增长而逐渐显现,与脑电技术相结合的眼动研究进一步发现ASD个体的面孔认知加工障碍与眼部注视不足存在关联。该障碍的潜在认知神经机制可能既源于原生性的杏仁核激活异常,也源于次生性的社会脑发展异常。然而,ASD个体的杏仁核是过度激活主动回避眼部还是激活不足被动忽视眼部尚无定论。今后研究者应横跨不同年龄阶段和不同研究层次,同时搜集眼动与神经生理数据,开展横向比较与纵向追踪相结合的相关研究。     

孤独症谱系障碍者的情绪韵律识别

情绪韵律识别是从声学线索变化中提取情绪信息,进而推断他人情绪状态的过程。情绪韵律识别缺陷是孤独症谱系障碍者的一种常见表现,此缺陷会受到情绪韵律强度、字面语义、情景语境、心理声学能力和共患疾病的影响。目前,该人群情绪韵律识别缺陷的原因探析集中于心智化能力不足、社会动机缺失和经验匮乏假说等。孤独症谱系障碍者情绪韵律识别的神经机制研究主要集中于与健康人群的比较,相关发现包括情绪韵律识别的右半球优势效应、局部脑区激活增多、大脑网络连接不足和早期注意模式异常。未来,应该进一步提高实验范式的生态效度,注重孤独症个体差异因素,整合相关理论解释,并开发有效的测评工具和干预策略。     

孤独症碎镜理论述评

孤独症是泛指一大类在社会交往、沟通方面存在功能缺陷的疾病, 至今病因尚未阐明。“碎镜理论”作为孤独症研究领域的新兴理论, 在神经—认知层面较先前理论更为全面地解释了孤独症的各种临床行为表现, 并为这些异常行为间的相互关系提供了一种统一性的研究视角。文章首先对镜像神经元的发现进行了简介, 在此基础上对碎镜理论的由来及其与孤独症相关功能(包括动作识别与模仿、心理理论、共情以及语言理解)缺陷的关系进行了综述, 最后通过区分主动模仿和自动模仿, 就镜像神经元系统及其调控系统与孤独症关系中存在的问题进行了反思与展望。     

共情的认知神经研究回顾

共情是指个体对他人情绪和想法的感受及理解,它在人类个体和社会的发展中起到了重要作用。近年来,脑成像技术为研究共情的神经基础提供了有力的技术支持,发现了共情的关键功能脑区。基础与临床的实验证据表明,更好地理解共情的神经机制对于孤独症、反社会人格等精神障碍有重要的意义。该文对相关的研究进行了综述并对未来可能的研究方向提出了展望     

孤独症儿童共同注意的神经基础及早期干预

共同注意是指两个人共同对某一事物加以注意, 分享对该事物的兴趣, 它是儿童社会认知发展的奠基性能力。首先, 孤独症儿童共同注意发展主要体现在注视转换、主动展示、分享等能力发展滞后及缺陷; 孤独症儿童共同注意的神经基础：应答性共同注意主要涉及后部皮层注意网络(如颞上沟后部、顶内沟等), 自发性共同注意涉及前部皮层注意网络(如前扣带皮层、背内侧额叶等); 最后, 以回合式教法和关键反应训练为基本方法, 论述了共同注意干预的新近模式和效果评估。未来研究应在孤独症儿童的共同注意发展的年龄特征及机制、共同注意的脑区可塑性及脑网络的发展以及开发更有效的干预方法等方面展开大量研究。     

The study of autism as a distributed disorder

Past autism research has often been dedicated to tracing the causes of the disorder to a localized neurological abnormality, a single functional network, or a single cognitive-behavioral domain. In this review, I argue that autism is a "distributed disorder" on various levels of study (genetic, neuroanatomical, neurofunctional, behavioral). "Localizing" models are therefore not promising. The large array of potential genetic risk factors suggests that multiple (or all) emerging functional brain networks are affected during early development. This is supported by widespread growth abnormalities throughout the brain. Interactions during development between affected functional networks and atypical experiential effects (associated with atypical behavior) in children with autism further complicate the neurological bases of the disorder, resulting in an "exponentially distributed" profile. Promising approaches to a better characterization of neural endophenotypes in autism are provided by techniques investigating white matter and connectivity, such as MR spectroscopy, diffusion-tensor imaging (DTI), and functional connectivity MRI. According to a recent hypothesis, the autistic brain is generally characterized by "underconnectivity." However, not all findings are consistent with this view. The concepts and methodology of functional connectivity need to be refined and results need to be corroborated by anatomical studies (such as DTI tractography) before definitive conclusions can be drawn.     

Young children with autism show atypical brain responses to fearful versus neutral facial expressions of emotion

Evidence suggests that autism is associated with impaired emotion perception, but it is unknown how early such impairments are evident. Furthermore, most studies that have assessed emotion perception in children with autism have required verbal responses, making results difficult to interpret. This study utilized high-density event-related potentials (ERPs) to investigate whether 3-4-year-old children with autism spectrum disorder (ASD) show differential brain activity to fear versus neutral facial expressions. It has been shown that normal infants as young as 7 months of age show differential brain responses to faces expressing different emotions. ERPs were recorded while children passively viewed photos of an unfamiliar woman posing a neutral and a prototypic fear expression. The sample consisted of 29 3-4-year-old children with ASD and 22 chronological age-matched children with typical development. Typically developing children exhibited a larger early negative component (N300) to the fear than to the neutral face. In contrast, children with ASD did not show the difference in amplitude of this early ERP component to the fear versus neutral face. For a later component, typically developing children exhibited a larger negative slow wave (NSW) to the fear than to the neutral face, whereas children with autism did not show a differential NSW to the two stimuli. In children with ASD, faster speed of early processing (i. e. N300 latency) of the fear face was associated with better performance on tasks assessing social attention (social orienting, joint attention and attention to distress). These data suggest that children with ASD, as young as 3 years of age, show a disordered pattern of neural responses to emotional stimuli.     

Brain development in autism: early overgrowth followed by premature arrest of growth

Due to the relatively late age of clinical diagnosis of autism, the early brain pathology of children with autism has remained largely unstudied. The increased use of retrospective measures such as head circumference, along with a surge of MRI studies of toddlers with autism, have opened a whole new area of research and discovery. Recent studies have now shown that abnormal brain overgrowth occurs during the first 2 years of life in children with autism. By 2-4 years of age, the most deviant overgrowth is in cerebral, cerebellar, and limbic structures that underlie higher-order cognitive, social, emotional, and language functions. Excessive growth is followed by abnormally slow or arrested growth. Deviant brain growth in autism occurs at the very time when the formation of cerebral circuitry is at its most exuberant and vulnerable stage, and it may signal disruption of this process of circuit formation. The resulting aberrant connectivity and dysfunction may lead to the development of autistic behaviors. To discover the causes, neural substrates, early-warning signs and effective treatments of autism, future research should focus on elucidating the neurobiological defects that underlie brain growth abnormalities in autism that appear during these critical first years of life.     

Atypical shape bias and categorization in autism: Evidence from children and computational simulations

The shape bias, a preference for mapping new word labels onto the shape rather than the color or texture of referents, has been postulated as a word‐learning mechanism. Previous research has shown deficits in the shape bias in children with autism even though they acquire sizeable lexicons. While previous explanations have suggested the atypical use of color for label extension in individuals with autism, we hypothesize an atypical mapping of novel labels to novel objects, regardless of the physical properties of the objects. In Experiment 1, we demonstrate this phenomenon in some individuals with autism, but the novelty of objects only partially explains their lack of shape bias. In a second experiment, we present a computational model that provides a developmental account of the shape bias in typically developing children and in those with autism. This model is based on theories of neurological dysfunctions in autism, and it integrates theoretical and empirical findings in the literature of categorization, word learning, and the shape bias. The model replicates the pattern of results of our first experiment and shows how individuals with autism are more likely to categorize experimental objects together on the basis of their novelty. It also provides insights into possible mechanisms by which children with autism learn new words, and why their word referents may be idiosyncratic. Our model highlights a developmental approach to autism that emphasizes deficient representations of categories underlying an impaired shape bias.     

Why we need cognitive explanations of autism

In the 70 years since autism was described and named there have been huge changes in the conceptualization of this enigmatic condition. This review takes a personal perspective on the history of autism research. The origins of the first cognitive theories of autism, theory of mind and weak central coherence, are discussed and updated to inform future developments. Selected experimental findings are interpreted in the historical context of changes that have been brought about by advances in methodology. A three-level framework graphically illustrates a causal chain between brain, mind, and behaviour to facilitate the identification of phenotypes in neurodevelopmental disorders. Cognition is placed at the centre of the diagram to reveal that it can link together brain and behaviour, when there are complex multiple mappings between the different levels.     

The Implications of Brain Connectivity in the Neuropsychology of Autism

Autism is a neurodevelopmental disorder that has been associated with atypical brain functioning. Functional connectivity MRI (fcMRI) studies examining neural networks in autism have seen an exponential rise over the last decade. Such investigations have led to the characterization of autism as a distributed neural systems disorder. Studies have found widespread cortical underconnectivity, local overconnectivity, and mixed results suggesting disrupted brain connectivity as a potential neural signature of autism. In this review, we summarize the findings of previous fcMRI studies in autism with a detailed examination of their methodology, in order to better understand its potential and to delineate the pitfalls. We also address how a multimodal neuroimaging approach (incorporating different measures of brain connectivity) may help characterize the complex neurobiology of autism at a global level. Finally, we also address the potential of neuroimaging-based markers in assisting neuropsychological assessment of autism. The quest for a neural marker for autism is still ongoing, yet new findings suggest that aberrant brain connectivity may be a promising candidate.     

人工智能辅助的自闭症早期患者的筛查与诊断

自闭症谱系障碍(Autistic Spectrum Disorders, ASD)的症状早在婴幼儿期就会显现, 越早发现, 越早干预, 治疗效果越好。传统自闭症早期筛查与诊断在评估方法、流程上存在局限, 无法满足大规模筛查和诊断需求。随着人工智能技术的快速发展, 使用智能化方法进行自闭症早期大规模无感筛查与诊断逐渐成为可能。近10年间, 国内外对自闭症智能化识别方法的探索在经典任务行为、面部表情和情绪、眼动、脑影像、运动控制和运动模式、多模态6个领域积累了丰富的研究成果。未来研究应围绕构建国内自闭症早期智能医学筛查与诊断体系, 开发针对婴幼儿患者的筛查工具, 构建融合多模态数据的自闭症婴幼儿智能化识别模型, 建立结合脑影像技术的自闭症精细化诊断方法等方面来开展。     

自闭症谱系障碍的生物基础

自闭症谱系障碍是一组发病于生命早期, 由一系列生理、心理因素引起的神经发育障碍。遗传、脑神经结构、营养素等是自闭症谱系障碍的生物基础的重要来源。个体在孕育早期形成的大脑和机体异常可能是导致自闭症谱系障碍的关键。这种异常在出生后的发育中具体作用于神经活动、脑发育、免疫系统等生理途径。研究者们今后可以尝试横跨不同自闭症谱系障碍亚型、年龄和发育阶段, 开展横向与纵向相结合的大范围研究, 以进一步明确自闭症谱系障碍的生物基础。     

Plasticity of nonneuronal brain tissue: roles in developmental disorders

Neuronal and nonneuronal plasticity are both affected by environmental and experiential factors. Remodeling of existing neurons induced by such factors has been observed throughout the brain, and includes alterations in dendritic field dimensions, synaptogenesis, and synaptic morphology. The brain loci affected by these plastic neuronal changes are dependent on the type of experience and learning. Increased neurogenesis in the hippocampal dentate gyrus is a well-documented response to environmental complexity ("enrichment") and learning. Exposure to challenging experiences and learning opportunities also alters existing glial cells (i.e., astrocytes and oligodendrocytes), and up-regulates gliogenesis, in the cerebral cortex and cerebellum. Such glial plasticity often parallels neuronal remodeling in both time and place, and this enhanced morphological synergism may be important for optimizing the functional interaction between glial cells and neurons. Aberrant structural plasticity of nonneuronal elements is a contributing factor, as is aberrant neuron plasticity, to neurological and developmental disorders such as epilepsy, autism, and mental retardation (i.e., fragile X syndrome). Some of these nonneuronal pathologies include abnormal cerebral and cerebellar white matter and myelin-related proteins in autism; abnormal myelin basic protein in fragile X syndrome (FXS); and abnormal astrocytes in autism, FXS, and epilepsy. A number of recent studies demonstrate the possibility of using environmental and experiential intervention to reduce or ameliorate some of the neuronal and nonneuronal abnormalities, as well as behavioral deficits, present in these neurological and developmental disorders.     

The extreme male brain theory of autism

The key mental domains in which sex differences have traditionally been studied are verbal and spatial abilities. In this article I suggest that two neglected dimensions for understanding human sex differences are 'empathising' and 'systemising'. The male brain is a defined psychometrically as those individuals in whom systemising is significantly better than empathising, and the female brain is defined as the opposite cognitive profile. Using these definitions, autism can be considered as an extreme of the normal male profile. There is increasing psychological evidence for the extreme male brain theory of autism.