Autism spectrum disorder (ASD) is a complex neurodevelopment disorder of largely unknown etiology affecting 1 in 68 children. While much progress has been made towards understanding the neurobiology of social and communication deficits associated with the disorder, very little is known regarding the neurobiological basis of restricted and repetitive behaviors central to the ASD diagnosis. The goal of the current project is to understand the relationship between cognitive flexibility and brain function during evoked (task) and intrinsic (resting) states in youth with and without ASD. Cognitive flexibility, the capacity to switch between mental processes, is often impaired in children with ASD in ways that can severely impact transitions during day-to- day activities of life. Cognitive inflexibilitymay underlie the emergence of restricted and repetitive behaviors in ASD. Understanding the neural mechanisms underlying cognitive inflexibility in ASD is critical for tailoring therapies to treat tis under-studied yet pervasive symptom. The PI has recently published preliminary evidence of reduced dynamic range of connectivity patterns, or neural inflexibility, in children with ASD. The proposed research will go beyond these preliminary findings and explicitly test whether one aspect of restricted and repetitive behaviors --cognitive inflexibility-- is linked with a corresponding neural inflexibility in ASD. A novel approach to assessing brain function and dysfunction is the quantification of dynamic functional connectivity, or time-varying patterns of functional coupling between brain regions. The goals of the study are to address three aims: 1) to understand the neural bases of cognitive flexibility in children with ASD and TD children during evoked brain states, 2) to understand the neural bases of cognitive flexibility in children with ASD and TD children during intrinsic brain states, and 3) to investigate relationships between activation patterns during evoked brain states, dynamic functional connectivity patterns during intrinsic brain states, and behavioral measures of flexibility in ASD. To address these aims, the project will implement traditional task- based functional MRI, dynamic functional connectivity analyses of resting-state fMRI, and integration of task and resting state fMRI with behavioral measures of cognitive flexibility. This program of research responds to the Interagency Autism Coordinating Committee's strategic plan to understand the neural circuitry that is affected in ASD. As behavioral inflexibility is an important cause of difficulties in carin for autistic individuals, these findings will potentially have a major impact on quality of life for children with ASD and their caregivers.

Public Health Relevance

Autism spectrum disorder (ASD) affects 1:68 individuals, and the incidence continues to rise steadily, making the disorder an urgent public health concern. While much progress has been made towards understanding the neurobiology of social and communication deficits associated with the disorder, very little is known regarding the neurobiological basis of restricted and repetitive behaviors central to the ASD diagnosis. Understanding the neural mechanisms underlying cognitive inflexibility in ASD is critical for tailoring therapies to treat this under- studied yet pervasive symptom.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH107549-03
Application #
9329481
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Gilotty, Lisa
Project Start
2015-09-08
Project End
2020-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Miami Coral Gables
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
625174149
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Vij, Shruti G; Nomi, Jason S; Dajani, Dina R et al. (2018) Evolution of spatial and temporal features of functional brain networks across the lifespan. Neuroimage 173:498-508
Chen, Heng; Wang, Jia; Uddin, Lucina Q et al. (2018) Aberrant functional connectivity of neural circuits associated with social and sensorimotor deficits in young children with autism spectrum disorder. Autism Res 11:1643-1652
Bolt, Taylor; Prince, Emily B; Nomi, Jason S et al. (2018) Combining region- and network-level brain-behavior relationships in a structural equation model. Neuroimage 165:158-169
Uddin, Lucina Q; Nomi, Jason S; H├ębert-Seropian, Benjamin et al. (2017) Structure and Function of the Human Insula. J Clin Neurophysiol 34:300-306
Chen, Heng; Uddin, Lucina Q; Duan, Xujun et al. (2017) Shared atypical default mode and salience network functional connectivity between autism and schizophrenia. Autism Res 10:1776-1786
Uddin, Lucina Q (2017) Mixed Signals: On Separating Brain Signal from Noise. Trends Cogn Sci 21:405-406
Ivanova, Anna; Zaidel, Eran; Salamon, Noriko et al. (2017) Intrinsic functional organization of putative language networks in the brain following left cerebral hemispherectomy. Brain Struct Funct 222:3795-3805
Steimke, Rosa; Nomi, Jason S; Calhoun, Vince D et al. (2017) Salience network dynamics underlying successful resistance of temptation. Soc Cogn Affect Neurosci 12:1928-1939
Uddin, L Q; Dajani, D R; Voorhies, W et al. (2017) Progress and roadblocks in the search for brain-based biomarkers of autism and attention-deficit/hyperactivity disorder. Transl Psychiatry 7:e1218
Nomi, Jason S; Vij, Shruti Gopal; Dajani, Dina R et al. (2017) Chronnectomic patterns and neural flexibility underlie executive function. Neuroimage 147:861-871

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