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 #
5R01MH107549-04
Application #
9542380
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Gilotty, Lisa
Project Start
2015-09-08
Project End
2020-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
4
Fiscal Year
2018
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
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
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
Nomi, Jason S; Bolt, Taylor S; Ezie, C E Chiemeka et al. (2017) Moment-to-Moment BOLD Signal Variability Reflects Regional Changes in Neural Flexibility across the Lifespan. J Neurosci 37:5539-5548
Nomi, Jason S; Vij, Shruti Gopal; Dajani, Dina R et al. (2017) Chronnectomic patterns and neural flexibility underlie executive function. Neuroimage 147:861-871
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
Bolt, Taylor; Nomi, Jason S; Yeo, B T Thomas et al. (2017) Data-Driven Extraction of a Nested Model of Human Brain Function. J Neurosci 37:7263-7277
Burrows, Catherine A; Timpano, Kiara R; Uddin, Lucina Q (2017) Putative Brain Networks Underlying Repetitive Negative Thinking and Comorbid Internalizing Problems in Autism. Clin Psychol Sci 5:522-536
Uddin, Lucina Q (2017) Mixed Signals: On Separating Brain Signal from Noise. Trends Cogn Sci 21:405-406
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

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