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.
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