NEURAL MECHANISMS OF ATTENTIONAL NETWORKS IN AUTISM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 自闭症是一种脑功能发育障碍，以社会交往和沟通障碍、重复行为和对环境的兴趣受限为特征。它至少影响一千个儿童和成人中的一个。虽然研究已经表明自闭症患者存在显著的认知异常，但这些缺陷的发展过程中的相对首要因素仍不清楚。尽管注意力参与了所有认知功能，作为我们自愿控制思想、感觉和行为的基础，但很少有研究提出，自闭症的认知缺陷可能会发展为基本注意力异常或此类异常的补偿策略的次要后果。这项研究的长期目标是充分描述自闭症患者的注意机制。这一关键步骤将使我们能够将我们对自闭症注意力缺陷的了解与治疗联系起来；因此，将促进自闭症有效治疗的发展。 我们的理论将注意力概念化，认为注意力由三个功能和解剖学定义的大脑网络组成，分别是警示、定向和执行控制。告警网络涉及以音调维持告警状态并对告警信号进行阶段性响应的功能。它涉及到脑干蓝斑中的去甲肾上腺素系统的皮质投射。定向网络包括从众多感官输入中选择信息的功能。颞顶交界区、顶上叶和额叶眼野是这一网络的关键脑区。基底前脑中的胆碱能系统在定向中也起着重要作用。在涉及计划或决策、错误检测、新的或没有好好学习的反应、被判断为困难或危险的情况下，以及在克服习惯性行为的情况下，最需要执行控制。前扣带回皮质(ACC)和外侧前额叶皮质区域参与了这一网络。这些区域是腹侧被盖多巴胺系统的靶点，受多巴胺的调节。对这些网络或其化学神经调节器的任何破坏都可能导致特定的神经和精神缺陷。 注意力功能障碍是自闭症中最常被报道的认知缺陷之一。自闭症患者在注意力的警觉、定向和执行控制方面表现出异常。虽然行为研究一直表明注意力缺陷与自闭症有关，但大脑区域的异常还没有明确地描述为整合的网络，这些网络辅助了注意力的警示、定向和执行控制功能。描述自闭症患者的注意网络特征对于理解自闭症的障碍和治疗的发展具有深远的意义。本研究的主要目的是使用注意网络测试(ANT)来测试自闭症的注意网络模型，该测试是我们之前在健康对照和患者群体中开发和验证的，并使用结构和功能神经成像来探索注意的警告、定向、执行控制的功能，这些注意功能之间的相互作用，以及在自闭症中辅助这些功能的网络的功能性脑活动和连接性。 假设： 据推测，与正常对照组相比： (A)自闭症患者的警报网络存在严重缺陷。丘脑中与警报信号相关的激活会减少和延迟。将有效率较低的主音警报功能，以更长的总反应时间(RT)为索引，并从警报提示中获得更大的好处。 (B)自闭症患者的定向网络存在严重缺陷。顶叶和小脑的激活会减少，这些区域内以及与其他大脑区域的功能连接会出现异常。脱离和转移注意力将会付出更大的代价。 (C)自闭症患者的执行网络将出现核心缺陷。ACC的激活将减弱，ACC和额叶外侧皮质之间的功能连接将中断。当对执行控制的需求较高时，就会表现出较低的执行功能效率。 (D)在自闭症患者中，警报、定向和执行控制网络之间的相互作用将显示出不正常的模式。当对执行功能的需求增加时，警报网络的激活被减少，以避免使效率较低的执行控制网络负担过重。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Autism is a developmental disorder of brain function characterized by deficits of social interaction and communication as well as repetitive behaviors and restricted interest in environment. It affects at least one in a thousand children and adults. While studies have shown significant cognitive abnormalities in autism, the relative primacy in the development of these deficits remains unclear. Although attention is involved in all cognitive functions as the basis for our voluntary control of thoughts, feelings, and actions, few studies have proposed that the cognitive deficits in autism may develop as secondary consequences of fundamental abnormalities of attention or compensatory strategies for such abnormalities. The long-term goal of this research is to fully characterize the attentional mechanisms in autism. This crucial step will enable us to link our knowledge of attentional deficits in autism to treatment; therefore will facilitate the development of effective treatments of autism. Our theory has conceptualized attention as comprised of three functional and anatomically defined brain networks of alerting, orienting, and executive control. The alerting network is related to the function of tonically maintaining the alert state and phasically responding to a warning signal. It involves the cortical projection of the norepinephrine system arising in the locus coeruleus of the brainstem. The orienting network involves the function of selecting information from among numerous sensory inputs. The temporal parietal junction, superior parietal lobe and frontal eye fields are the key brain areas for this network. Cholinergic systems arising in the basal forebrain also play an important role in orienting. Executive control is most needed in situations that involve planning or decision-making, error detection, novel or not well-learned responses, conditions judged difficult or dangerous, and in overcoming habitual actions. The anterior cingulate cortex (ACC) and lateral prefrontal cortical regions are involved in this network. These areas are the targets of the ventral tegmental dopamine system and are modulated by dopamine. Damage to any of these networks or their chemical neuromodulators can produce specific neurological and psychiatric deficits. Impairments of attentional functions are among the most consistently reported cognitive deficits in autism. Individuals with autism demonstrate abnormalities across alerting, orienting, and executive control of attention. Although behavioral studies have consistently shown that the deficits in attention are linked to autism, the abnormalities of the brain areas have not been clearly characterized in terms of the integrated networks subserving the functions of alerting, orienting, and executive control of attention. Characterizing the attentional networks in autism has profound implications for understanding this disorder and development of treatment. The primary aims of this study are to test the attentional network model of autism using the Attention Network Test (ANT), which we previously developed and validated in healthy controls and patient populations, and to use structural and functional neuroimaging to explore the functions of alerting, orienting, executive control of attention, interactions among these attentional functions, and the functional brain activity and connectivity of the networks subserving these functions in autism. Hypotheses: It is hypothesized that comparing to normal controls: (a) There is a significant deficit in the alerting network in individuals with autism. There will be reduced and delayed activation in the thalamus related to an alerting cue. There will be a less efficient tonic alerting function indexed by longer overall reaction time (RT) with greater benefit from an alerting cue. (b) There is a significant deficit in the orienting network in individuals with autism. There will be reduced parietal and cerebellar activation and abnormal functional connectivity within these regions and with other brain areas. There will be greater cost in disengaging and moving of attention. (c) There will be a core deficit in the executive network in individuals with autism. There will be diminished ACC activation and disrupted functional connectivity between ACC and lateral frontal cortex. When there is high demand for executive control, they will show less efficient executive function. (d) The interaction between alerting, orienting, and executive control networks will show an abnormal pattern in individuals with autism. When there is an increased demand on executive functions, activation of the alerting network is reduced in order to avoid over burdening the less efficient executive control networks.