While significant advances have been made in identifying brain functional and structural difference between individuals with autism spectrum disorders (ASD) and typically developing (TD) individuals, little is known regarding differences in large-scale brain network interactions that underlie the social deficits in ASD. The purpose o this investigation is to examine the connectivity patterns of brain areas that participate in neura networks for social cognition and imitation in children with ASD, given the key role that imitation plays in successful social interactions and in social cognition in general. We theorize that abnormalities in connections among these neural systems can interfere with, and disrupt the normative social cognitive development in ASD. Within this theoretical framework, we are making three key predictions regarding the nature of social impairment in ASD: (1) functional and structural connectivity patterns within and between imitation and social cognition networks will be atypical in ASD~ (2) the atypical organization of these networks will be linked to impairments in social and overall functioning in ASD~ (3) altered maturation of these networks in ASD will be evidenced by diminished age-effects on the connectivity indices in these networks. These predictions will be tested with a multimodal approach, utilizing two complementary neuroimaging techniques (fMRI and DTI) to assess both functional and structural connectivity in imitation and social brain networks in a sample of 80 ASD and 80 TD children and adolescents ages 7-18 years (comprised of a dataset from children aged 7-11 years to be collected under the proposed study and a dataset from older children aged 12-18 years currently being acquired under the mentor's grant~ R01 MH081023~ PI: M?ller). The comprehensive, multimodal imaging scope, the relatively large sample size, the developmental perspective allowed by a broad age range, as well as novel, fast-developing approaches to measuring network connectivity, all constitute particular strengths of this career development proposal. Successful completion of this research is contingent upon the applicant's proposed training in two imaging modalities (fMRI and DTI), which is critical to her overall research goals of investigating widespread abnormalities throughout the brain in relation to social cognition and behavior. This career development award focuses on assisting the applicant in establishing new expertise while building on prior sound training in clinical neuropsychology, cognitive and affective neuroscience and, particularly, application of cognitive neuroscience methods (EEG/ERPs) to investigating social cognition. These skills will contribute to the design and implementation of the proposed research plan, and position the applicant well in her effort to effectively carry on and expand this independent line of research. The environment at San Diego State University and University of California, San Diego, along with the mentorship team the applicant has selected, form a uniquely suited setting to further her training in pursuit of hr long-term career goal of becoming a successful independent social neuroscience researcher.

Public Health Relevance

The proposed career award aims to examine the neural bases of social impairments in autism, specifically focusing on the integrity of connections among distributed brain regions in autism. The proposed research program emphasizes obtaining training in two neuroimaging modalities, which would outfit a new investigator with expertise necessary for investigating neural mechanisms underlying social cognition in typical and atypical development. Given the dramatic rise in the numbers of children diagnosed with autism, a disorder that severely compromises the ability to participate productively in society, findings from the proposed studies may have significant implications for an early detection, diagnosis and intervention programs for autism spectrum disorders.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Scientist Development Award - Research & Training (K01)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Anderson, Kathleen C
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San Diego State University
Schools of Arts and Sciences
San Diego
United States
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Linke, Annika C; Jao Keehn, R Joanne; Pueschel, Ellyn B et al. (2018) Children with ASD show links between aberrant sound processing, social symptoms, and atypical auditory interhemispheric and thalamocortical functional connectivity. Dev Cogn Neurosci 29:117-126
Abbott, Angela E; Linke, Annika C; Nair, Aarti et al. (2018) Repetitive behaviors in autism are linked to imbalance of corticostriatal connectivity: a functional connectivity MRI study. Soc Cogn Affect Neurosci 13:32-42
Fishman, Inna; Linke, Annika C; Hau, Janice et al. (2018) Atypical Functional Connectivity of Amygdala Related to Reduced Symptom Severity in Children With Autism. J Am Acad Child Adolesc Psychiatry 57:764-774.e3
Nair, Sangeeta; Jao Keehn, R Joanne; Berkebile, Michael M et al. (2018) Local resting state functional connectivity in autism: site and cohort variability and the effect of eye status. Brain Imaging Behav 12:168-179
Di Martino, Adriana; O'Connor, David; Chen, Bosi et al. (2017) Enhancing studies of the connectome in autism using the autism brain imaging data exchange II. Sci Data 4:170010
Jahedi, Afrooz; Nasamran, Chanond A; Faires, Brian et al. (2017) Distributed Intrinsic Functional Connectivity Patterns Predict Diagnostic Status in Large Autism Cohort. Brain Connect 7:515-525
Solders, Seraphina K; Carper, Ruth A; Müller, Ralph-Axel (2017) White matter compromise in autism? Differentiating motion confounds from true differences in diffusion tensor imaging. Autism Res 10:1606-1620
Linke, Annika C; Olson, Lindsay; Gao, Yangfeifei et al. (2017) Psychotropic medication use in autism spectrum disorders may affect functional brain connectivity. Biol Psychiatry Cogn Neurosci Neuroimaging 2:518-527
Carper, Ruth A; Treiber, Jeffrey M; DeJesus, Shannon Yandall et al. (2016) Reduced Hemispheric Asymmetry of White Matter Microstructure in Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry 55:1073-1080
Abbott, Angela E; Nair, Aarti; Keown, Christopher L et al. (2016) Patterns of Atypical Functional Connectivity and Behavioral Links in Autism Differ Between Default, Salience, and Executive Networks. Cereb Cortex 26:4034-45

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