FUNCTIONAL MRI OF ATTENTION REGULATION IN PEOPLE WITH AND WITHOUT AUTISM

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。明确正常和病理注意过程的神经基础是基础和临床科学的一个重要目标，只有通过先进的生物医学成像技术才能实现这一目标。人们对人类注意力的功能解剖学知之甚少。直到最近，只有正电子发射断层扫描(PET)，以及在某种程度上使用脑电的脑地形图，才产生了关于人脑注意功能组织的解剖信息。然而，宠物有几个局限性。例如，PET(1)要求受试者接触放射性物质，(2)时间和空间分辨率差，(3)要求对受试者进行平均，因此无法获得关于个人的可靠信息，(4)需要使用回旋加速器，因此仅限于几个中心使用。EEG映射提供了良好的时间信息，大约是几十毫秒，但它可以提供的空间信息的程度严重限制了它。磁共振成像(MRI)的最新进展首次使功能磁共振(FMRI)的发展成为可能，以绘制大脑活动图(MRI用于成像大脑解剖结构已有一段时间)。使用功能磁共振成像的研究具有广泛研究和临床应用的巨大潜力，因为功能磁共振成像(1)不需要暴露于放射性物质，(2)具有仅受脑血流动力学限制的时间分辨率，以及与传统MRI相当的空间分辨率，从而允许大脑解剖和人类认知之间的细粒度联系，(3)可以为个人提供有用的信息，(4)可以在许多医疗机构(5)现有的MRI扫描仪上实施，并已成功用于健康和障碍儿童。这一突破的出现是因为现在已经开发出有效的梯度回忆序列，可以检测到T2*区域的增加，反映了神经元激活导致的皮质顺磁性脱氧血红蛋白水平的降低。目前的建议采用认知神经科学的分析方法来研究自闭症。自闭症是一种常见的发育障碍，严重损害认知、情感和社会功能。正常的认知功能需要在目标导向的行为服务中适当地调节注意力。注意调节的操作包括选择、吸引和维持对任务相关刺激的注意，随着任务要求的改变而分离和转移注意，以及抑制或抑制对任务无关刺激的注意。这些操作是拟议研究的重点。这些手术在正常和紊乱的发育、行为和神经方面都有很好的特征(Bunge等人，2002年；Casey等人，1997年；露娜等人，2001年；Vaidya等人，1998年)。本研究从社会性和非社会性两个领域考察了高功能自闭症患者(智商85)和健康儿童和成人注意调节的神经基础。为社交线索提供注意力的神经系统与为非社交线索提供注意力的神经系统不同。自闭症患者存在社会性和非社会性注意力缺陷。然而，很少有研究直接比较社会领域和非社会领域的注意调节。因此，目前尚不清楚自闭症患者的社会注意力或非社会注意力是否受到不成比例的损害。这项拟议研究的知识将对明确神经认知诊断标准具有临床意义，这些标准针对自闭症和其他涉及注意力失调的发育障碍。此外，这些知识将增加对注意系统发育的神经生理学的理解。

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. Specifying the neural basis of normal and pathological attentional processes is an important goal for basic and clinical sciences that will only be accomplished with advanced biomedical imaging techniques. Relatively little is known about the functional anatomy of human attention. Until recently, only positron emission tomography (PET), and to some extent brain topographic mapping using EEGs, have yielded such anatomical information about the functional organization of attention in the human brain. PET, however, has several limitations. For example, PET (1) requires that subjects be exposed to radioactive substances, (2) has poor temporal and spatial resolution, (3) requires averaging over subjects, so that one cannot obtain reliable information about individuals, and (4) requires access to a cyclotron and thus is limited in use to a few centers. EEG mapping provides good temporal information, on the order of tens of milliseconds, but is severely limited by the degree of spatial information it can provide. Recent advances in magnetic resonance imaging (MRI) have allowed, for the first time, the development of functional MRI (fMRI) to map brain activity (MRI has been used to image brain anatomy for some time). Studies using fMRI have great potential for widespread research and clinical use because fMRI (1) does not require exposure to a radioactive substance, (2) has temporal resolution limited only by brain hemodynamics, and spatial resolution comparable to conventional MRI, thereby allowing fine-grained links between brain anatomy and human cognition, (3) can yield useful information for an individual (4) can be implemented on MRI scanners present at many medical facilities (5) and has been successfully used in healthy and disordered children. This breakthrough occurred because efficient gradient-recalled sequences have now been developed that can detect T2* regional increases reflecting reduced paramagnetic deoxyhemoglobin levels in cortex consequent to neuronal activation. The present proposal takes a cognitive neuroscience analytic approach to investigating Autism. Autism is a common developmental disorder that significantly impairs cognitive, emotional, and social functioning. Normal cognitive functioning requires appropriate regulation of attention in the service of goal directed behavior. Operations of attention regulation include selecting, engaging, and sustaining attention to task-relevant stimuli, disengaging and shifting attention as task demands change, and inhibiting or suppressing attention to task-irrelevant stimuli. These operations are the focus of the proposed study. These operations have been well characterized in normal and disordered development, behaviorally and neurally (Bunge et al., 2002; Casey et al., 1997; Luna et al., 2001; Vaidya et al., 1998). The proposed study examines the neural basis of attention regulation in high functioning autistic (HFA, i.e., IQ 85) and healthy children and adults, in two domains, social and non-social. Neural systems subserving attention to social cues differ from those subserving attention to non-social cues. Both social and non-social attention deficits are observed in Autism. Few studies, however, have directly compared attentional regulation in social and non-social domains. Therefore, it is unknown whether social or non-social attention is disproportionately impaired in Autism. Knowledge from the proposed study will be clinically significant for specifying neurocognitive diagnostic criteria that are specific to Autism relative to other developmental disorders involving attentional dysregulation. Further, this knowledge will increase understanding about the neurophysiology of developing attentional systems.