Learning disabilities during childhood have adverse long-term consequences for academic and professional success and quality of life. Impaired learning can be particularly detrimental for children with autism spectrum disorder (ASD). Relative to their peers, children with ASD go on to achieve lower levels of post-secondary education, employment, and independent living. Yet, the cognitive, behavioral, and neural mechanisms underlying learning in children with ASD remain poorly understood. ASD is characterized by heterogeneous clinical presentations and cognitive abilities, likely resulting in highly variable learning profiles in affected children. Little is known about the neurobiology of learning in school-age children with ASD in any cognitive domain. In the current project period, we found heterogeneous patterns of math abilities in a large cohort of children with ASD, consistent with epidemiological reports indicating that 17-40% of children with ASD display lower-than-expected math achievement scores. We also found novel evidence that math abilities are associated with restricted and repetitive interests and behaviors (RRIB), a core clinical symptom of ASD. We propose, in this renewal, to leverage our innovative and high-impact line of research to investigate heterogeneity in learning and brain plasticity, and its links to RRIB and cognitive inflexibility, in children with ASD. Using a theoretically motivated cognitive training protocol, state-of-the-art brain imaging, and advanced multivariate computational techniques, we propose to test the hypotheses that (i) children with ASD and low math abilities (LMA-ASD) will show different learning profiles relative to children with ASD and high math abilities (HMA-ASD) and typically developing (TD) children and (ii) compared to the HMA-ASD and TD groups, the LMA-ASD group will demonstrate weaker plasticity in two distinct brain systems important for math learning: the visuospatial number system, anchored in the intra-parietal sulcus and fusiform gyrus, and the declarative memory system, anchored in the medial temporal lobe. We will also investigate whether RRIB and cognitive inflexibility have a negative influence on learning in ASD, and determine the extent to which these effects are mediated by aberrant functioning of the salience network, a prefrontal cognitive control system anchored in the anterior insula and anterior cingulate cortex. The proposed work will provide important new insights into the neurocognitive basis of heterogeneous learning profiles in children with ASD and is highly relevant to the mission of the NIH ?Research on Autism Spectrum Disorders? (PA-16-388). Identifying behavioral and neural sources of heterogeneity in learning and their links to clinical symptoms in a quantitatively rigorous manner will have significant implications for informing the etiology of ASD and more critically, for optimizing learning in affected children.

Public Health Relevance

Autism spectrum disorders (ASD) have an estimated incidence of 1:68, among the most common and pervasive neurodevelopmental disorders. Learning disabilities during childhood have adverse long-term consequences for academic and professional success and quality of life, and impaired learning can be particularly detrimental for children with ASD. The proposed studies will address significant gaps in our knowledge of learning disabilities in affected children and advance our understanding of the neurobiology of learning in ASD using a theoretically motivated cognitive training protocol, multimodal brain imaging, and cutting-edge computational analysis, and thereby generate foundational knowledge necessary for reducing the public health burden of autism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH084164-06A1
Application #
9335078
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Gilotty, Lisa
Project Start
2011-06-01
Project End
2022-01-31
Budget Start
2017-04-01
Budget End
2018-01-31
Support Year
6
Fiscal Year
2017
Total Cost
$770,410
Indirect Cost
$277,888
Name
Stanford University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Padmanabhan, Aarthi; Lynch, Charles J; Schaer, Marie et al. (2017) The Default Mode Network in Autism. Biol Psychiatry Cogn Neurosci Neuroimaging 2:476-486
Hiniker, Alexis; Rosenberg-Lee, Miriam; Menon, Vinod (2016) Distinctive Role of Symbolic Number Sense in Mediating the Mathematical Abilities of Children with Autism. J Autism Dev Disord 46:1268-81
Escovar, Emily; Rosenberg-Lee, Miriam; Uddin, Lucina Q et al. (2016) The Empathizing-Systemizing Theory, Social Abilities, and Mathematical Achievement in Children. Sci Rep 6:23011
Chang, Ting-Ting; Metcalfe, Arron W S; Padmanabhan, Aarthi et al. (2016) Heterogeneous and nonlinear development of human posterior parietal cortex function. Neuroimage 126:184-95
Abrams, Daniel A; Chen, Tianwen; Odriozola, Paola et al. (2016) Neural circuits underlying mother's voice perception predict social communication abilities in children. Proc Natl Acad Sci U S A 113:6295-300
Odriozola, Paola; Uddin, Lucina Q; Lynch, Charles J et al. (2016) Insula response and connectivity during social and non-social attention in children with autism. Soc Cogn Affect Neurosci 11:433-44
Uddin, Lucina Q; Supekar, Kaustubh; Lynch, Charles J et al. (2015) Brain State Differentiation and Behavioral Inflexibility in Autism. Cereb Cortex 25:4740-7
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
Qin, Shaozheng; Young, Christina B; Duan, Xujun et al. (2014) Amygdala subregional structure and intrinsic functional connectivity predicts individual differences in anxiety during early childhood. Biol Psychiatry 75:892-900
Iuculano, Teresa; Rosenberg-Lee, Miriam; Supekar, Kaustubh et al. (2014) Brain organization underlying superior mathematical abilities in children with autism. Biol Psychiatry 75:223-30

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