The objective of our proposed research is to help establish the neurophysiological mechanisms that underlie core cognitive dysfunctions in autism. Based on clinical, psychiatric research evidence and evidence from this laboratory, we hypothesize that pervasive abnormalities in attention mechanisms may underlie core areas of cognitive and social dysfunction in people with autism. This hypothesis will be investigated by obtaining direct evidence of neurophysiological abnormalities in autism in three key areas of attention: the capturing, maintaining and shifting of attention. Event-related potentials (ERP) will be recorded from nonretarded young adults with autism (age: 18 - 33 years) and from matched normal controls. The visual and auditory ERP components which are known to be associated with attention will be recorded concomitantly with behavioral performance in selective attention tasks. The ERP and performance data will be compared between the subject groups, and the relationship between behavioral performance deficits and ERP abnormalities in autism will be examined. The proposed experiments will study: 1. Capturing attention: The auditory mismatch negativity (MMN) known to be elicited by stimulus changes when subjects' attention is focused elsewhere, is absent in people with autism. The experiments will determine stimulus and modality factors which hinder or facilitate the detection of stimulus changes in an unattended channel in autism. 2. Maintaining a focus of selective attention: Early sensory gating mechanisms and facilitation processes for selective attention in autism will be studied. The experiments will determine the earliest neurophysiological stages at which control of selective attention begins to fragment in people with autism. 3. Shifting attention: These experiments will study the P700 which is elicited by stimuli which signal subjects to shift attention from a current to a new focus; and other ERP components which are elicited by stimuli from the new focus. The experiments will determine modality and response factors which affect the capacity to shift attention in people with autism. Information learned from these experiments will contribute to the understanding of deficits in selective attention mechanisms in people with autism, and will impact future remedial approaches to help autistic individuals improve their performance in cognitive and social areas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH036840-08
Application #
3375946
Study Section
Psychopathology and Clinical Biology Research Review Committee (PCB)
Project Start
1990-08-01
Project End
1994-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Rady Children's Hospital-San Diego
Department
Type
DUNS #
City
San Diego
State
CA
Country
United States
Zip Code
92123
Courchesne, Eric; Pramparo, Tiziano; Gazestani, Vahid H et al. (2018) The ASD Living Biology: from cell proliferation to clinical phenotype. Mol Psychiatry :
Fingher, Noa; Dinstein, Ilan; Ben-Shachar, Michal et al. (2017) Toddlers later diagnosed with autism exhibit multiple structural abnormalities in temporal corpus callosum fibers. Cortex 97:291-305
Solso, Stephanie; Xu, Ronghui; Proudfoot, James et al. (2016) Diffusion Tensor Imaging Provides Evidence of Possible Axonal Overconnectivity in Frontal Lobes in Autism Spectrum Disorder Toddlers. Biol Psychiatry 79:676-84
Pramparo, Tiziano; Lombardo, Michael V; Campbell, Kathleen et al. (2015) Cell cycle networks link gene expression dysregulation, mutation, and brain maldevelopment in autistic toddlers. Mol Syst Biol 11:841
Pramparo, Tiziano; Pierce, Karen; Lombardo, Michael V et al. (2015) Prediction of autism by translation and immune/inflammation coexpressed genes in toddlers from pediatric community practices. JAMA Psychiatry 72:386-94
Lombardo, Michael V; Pierce, Karen; Eyler, Lisa T et al. (2015) Different functional neural substrates for good and poor language outcome in autism. Neuron 86:567-77
Manning, Janessa H; Courchesne, Eric; Fox, Peter T (2013) Intrinsic connectivity network mapping in young children during natural sleep. Neuroimage 83:288-93
Eyler, Lisa T; Pierce, Karen; Courchesne, Eric (2012) A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism. Brain 135:949-60
Courchesne, Eric; Mouton, Peter R; Calhoun, Michael E et al. (2011) Neuron number and size in prefrontal cortex of children with autism. JAMA 306:2001-10
Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie (2011) Brain growth across the life span in autism: age-specific changes in anatomical pathology. Brain Res 1380:138-45

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