This proposal is designed to facilitate career development of Jeffrey Anderson, MD PhD as an independent investigator to conduct longitudinal neuroimaging studies of functional MR connectivity in neurodevelopmental and neuropsychiatric disorders, with particular expertise in functional connectivity abnormalities in autism. Although the applicant has extensive mentored research experience during PhD training in electrophysiology of the brain, and extensive neuroradiological training in functional imaging methods, he has not had experience conducting large clinical imaging investigations, requiring patient recruitment and assessment and multivariate statistical analysis of large imaging datasets. The specific research aims of this proposal develop these skills through a longitudinal study of functional connectivity in autism. There is now extensive evidence that functional connectivity abnormalities between brain regions are present in autism, which continue to develop through childhood and adolescence. These connectivity abnormalities comprise a promising technique for identifying autism subtypes, predicting prognosis, and guiding treatment. Yet the mechanism for connectivity abnormalities remains unknown. This proposal seeks to use a longitudinal investigation of functional connectivity in autism to establish whether connectivity disturbances are generalized, localized to connections of specific path length, or associated with specific functional networks. The longitudinal design will allow assessment of how these connectivity abnormalities develop through late childhood and adolescence, and will leverage the largest imaging dataset of high-functioning autism DTI and volumetric scans from late childhood to early adulthood, allowing cross-modality analysis of brain connectivity. Long term goals of the proposal are to leverage the applicant's combined training in mathematics, neuroscience, and clinical neuroimaging to build a rigorous, broad-based imaging laboratory that can make major contributions to diagnosis and understanding of neurological disorders by probing functional connectivity abnormalities in brain networks using novel imaging methods.

Public Health Relevance

This project seeks to provide mentorship and focused research experience to provide skills necessary for him to lead cutting-edge longitudinal imaging investigations of functional connectivity in neurodevelopmental and neuropsychiatric disorders. As a primary application, a longitudinal study will be performed characterizing the mechanism and distribution of functional connectivity abnormalities in autism, yielding immense public health benefits.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZRG1-BDCN-Q (02))
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Gilotty, Lisa
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University of Utah
Schools of Medicine
Salt Lake City
United States
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Lange, Nicholas; Travers, Brittany G; Bigler, Erin D et al. (2015) Longitudinal volumetric brain changes in autism spectrum disorder ages 6-35 years. Autism Res 8:82-93
Shprecher, David R; Gannon, Keenan; Agarwal, Nivedita et al. (2014) Elucidating the nature and mechanism of tic improvement in tourette syndrome: a pilot study. Tremor Other Hyperkinet Mov (N Y) 4:217
Di Martino, A; Yan, C-G; Li, Q et al. (2014) The autism brain imaging data exchange: towards a large-scale evaluation of the intrinsic brain architecture in autism. Mol Psychiatry 19:659-67
Zielinski, Brandon A; Prigge, Molly B D; Nielsen, Jared A et al. (2014) Longitudinal changes in cortical thickness in autism and typical development. Brain 137:1799-812
Anderson, Jeffrey S; Zielinski, Brandon A; Nielsen, Jared A et al. (2014) Complexity of low-frequency blood oxygen level-dependent fluctuations covaries with local connectivity. Hum Brain Mapp 35:1273-83
Ferguson, Michael A; Nielsen, Jared A; Anderson, Jeffrey S (2014) Altered resting functional connectivity of expressive language regions after speed reading training. J Clin Exp Neuropsychol 36:482-93
Liu, Wei; Awate, Suyash P; Anderson, Jeffrey S et al. (2014) A functional network estimation method of resting-state fMRI using a hierarchical Markov random field. Neuroimage 100:520-34
Nielsen, Jared A; Zielinski, Brandon A; Fletcher, P Thomas et al. (2014) Abnormal lateralization of functional connectivity between language and default mode regions in autism. Mol Autism 5:8
Alaerts, Kaat; Woolley, Daniel G; Steyaert, Jean et al. (2014) Underconnectivity of the superior temporal sulcus predicts emotion recognition deficits in autism. Soc Cogn Affect Neurosci 9:1589-600
Duffield, Tyler C; Trontel, Haley G; Bigler, Erin D et al. (2013) Neuropsychological investigation of motor impairments in autism. J Clin Exp Neuropsychol 35:867-81

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