Several lines of evidence provide support for a model of abnormal connectivity to explain the underlying neuropathology of autism. However, no study has provided converging evidence of both functional and structural connectivity abnormalities in individuals with autism spectrum disorders (ASD). In this proposal, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) will be used to investigate abnormalities in neural connectivity in ASD. We will study two domains of impairment (face perception and response to social information) and determine how neural connectivity relates to symptom severity. Twenty-five individuals with high functioning ASD (FSIQ >80) and 25 typically developing (TD) individuals will participate in the study. The TD group will be matched to the ASD group according to age, gender, and FSIQ. White matter structural abnormalities (reduced fractional anisotropy) are hypothesized to be correlated to abnormal functional connectivity in ASD. The degree of abnormality in measures of structural and functional connectivity is expected to be mediated by clinical severity. A Career Development Award is requested in order to develop the skills necessary to conduct multimodal imaging research. The applicant will obtain training in DTI and develop methods for combining and statistically analyzing imaging data from different imaging modalities. Consultation and training from experts in the fields of neuroimaging and autism spectrum disorders will be augmented by coursework and seminars. The implementation of this training plan will yield a cohesive and thorough assessment of the integrity of white matter connections that underlie specific impairments in ASD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01NS059675-03
Application #
7821266
Study Section
NST-2 Subcommittee (NST)
Program Officer
Hirtz, Deborah G
Project Start
2008-05-01
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2011-04-30
Support Year
3
Fiscal Year
2010
Total Cost
$167,832
Indirect Cost
Name
University of Washington
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Velasquez, Francisco; Qin, Xiaoyan Angela; Reilly, Melissa A et al. (2017) Neural correlates of emotional inhibitory control in autism spectrum disorders. Res Dev Disabil 64:64-77
Kleinhans, Natalia M; Reiter, Maya A; Neuhaus, Emily et al. (2016) Subregional differences in intrinsic amygdala hyperconnectivity and hypoconnectivity in autism spectrum disorder. Autism Res 9:760-72
Kleinhans, Natalia M; Richards, Todd; Greenson, Jessica et al. (2016) Altered Dynamics of the fMRI Response to Faces in Individuals with Autism. J Autism Dev Disord 46:232-241
Prat, Chantel S; Stocco, Andrea; Neuhaus, Emily et al. (2016) Basal ganglia impairments in autism spectrum disorder are related to abnormal signal gating to prefrontal cortex. Neuropsychologia 91:268-281
Schur, Ellen A; Kleinhans, Natalia M; Goldberg, Jack et al. (2012) Acquired differences in brain responses among monozygotic twins discordant for restrained eating. Physiol Behav 105:560-7
Kleinhans, Natalia M; Pauley, Gregory; Richards, Todd et al. (2012) Age-related abnormalities in white matter microstructure in autism spectrum disorders. Brain Res 1479:1-16
Kleinhans, Natalia M; Richards, Todd; Weaver, Kurt E et al. (2009) Brief report: biochemical correlates of clinical impairment in high functioning autism and Asperger's disorder. J Autism Dev Disord 39:1079-86