FUNCTIONAL MRI OF ATTENTION REGULATION IN PEOPLE WITH AND WITHOUT AUTISM

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。明确正常和病理注意过程的神经基础是基础科学和临床科学的一个重要目标，只有先进的生物医学成像技术才能完成。相对而言，我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），以及在一定程度上使用脑电图的脑地形图绘制，已经获得了关于人脑中注意力功能组织的解剖学信息。然而，PET有一些局限性。例如，PET(1)要求受试者暴露于放射性物质中；(2)时间和空间分辨率较差；(3)需要对受试者进行平均，因此无法获得有关个体的可靠信息；(4)需要使用回旋加速器，因此只能在几个中心使用。脑电映射提供了很好的时间信息，大约几十毫秒，但受到它所能提供的空间信息程度的严重限制。磁共振成像（MRI）的最新进展首次允许开发功能性磁共振成像（fMRI）来绘制大脑活动图（MRI用于脑解剖成像已有一段时间了）。使用fMRI的研究具有广泛研究和临床应用的巨大潜力，因为fMRI(1)不需要暴露于放射性物质中，(2)时间分辨率仅受脑血流动力学限制，空间分辨率可与传统MRI相媲美，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的核磁共振扫描仪上实施(5)，并已成功地用于健康和紊乱的儿童。这一突破的发生是因为现在已经开发出了高效的梯度回忆序列，可以检测T2*区域的增加，这反映了神经元激活后皮层顺磁脱氧血红蛋白水平的降低。本研究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对目标导向行为的注意力进行适当的调节。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，随着任务需求的变化而解除和转移注意，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。在行为和神经方面，这些手术在正常和障碍发育中都有很好的特征（Bunge等人，2002；Casey等人，1997；Luna等人，2001；Vaidya等人，1998）。本研究探讨了高功能自闭症（HFA，即IQ 85）与健康儿童和成人在社会和非社会两个领域的注意调节的神经基础。对社会线索给予注意的神经系统不同于对非社会线索给予注意的神经系统。自闭症患者存在社会和非社会注意缺陷。然而，很少有研究直接比较社会和非社会领域的注意调节。因此，自闭症患者的社会注意力或非社会注意力是否不成比例地受损尚不清楚。从拟议的研究中获得的知识将在临床上具有重要意义，有助于明确自闭症与其他涉及注意力失调的发育障碍之间的特异性神经认知诊断标准。此外，这些知识将增加对发展注意力系统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.