title: Basal ganglia impairments in autism spectrum disorder are related to abnormal signal gating to prefrontal cortex.
abstract: Research on the biological basis of autism spectrum disorder has yielded a list of brain abnormalities that are arguably as diverse as the set of behavioral symptoms that characterize the disorder. Among these are patterns of abnormal cortical connectivity and abnormal basal ganglia development. In attempts to integrate the existing literature, the current paper tests the hypothesis that impairments in the basal ganglia's function to flexibly select and route task-relevant neural signals to the prefrontal cortex underpins patterns of abnormal synchronization between the prefrontal cortex and other cortical processing centers observed in individuals with autism spectrum disorder (ASD). We tested this hypothesis using a Dynamic Causal Modeling analysis of neuroimaging data collected from 16 individuals with ASD (mean age=25.3 years; 6 female) and 17 age- and IQ-matched neurotypical controls (mean age=25.6, 6 female), who performed a Go/No-Go test of executive functioning. Consistent with the hypothesis tested, a random-effects Bayesian model selection procedure determined that a model of network connectivity in which basal ganglia activation modulated connectivity between the prefrontal cortex and other key cortical processing centers best fit the data of both neurotypicals and individuals with ASD. Follow-up analyses suggested that the largest group differences were observed for modulation of connectivity between prefrontal cortex and the sensory input region in the occipital lobe [t(31)=2.03, p=0.025]. Specifically, basal ganglia activation was associated with a small decrease in synchronization between the occipital region and prefrontal cortical regions in controls; however, in individuals with ASD, basal ganglia activation resulted in increased synchronization between the occipital region and the prefrontal cortex. We propose that this increased synchronization may reflect a failure in basal ganglia signal gating mechanisms, resulting in a non-selective copying of signals to prefrontal cortex. Such a failure to prioritize and filter signals to the prefrontal cortex could result in the pervasive impairments in cognitive flexibility and executive functioning that characterize autism spectrum disorder, and may offer a mechanistic explanation of some of the observed abnormalities in patterns of cortical synchronization in ASD.
authors.affiliation: Department of Psychology, University of Washington, United States; Institute for Learning and Brain Sciences, University of Washington, United States. Electronic address: csprat@uw.edu.
authors.forename: Chantel S
authors.initials: CS
authors.lastname: Prat
authors.affiliation: Department of Psychology, University of Washington, United States; Institute for Learning and Brain Sciences, University of Washington, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Stocco
authors.affiliation: Seattle Children's Research Institute, United States; University of Washington Autism Center, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Neuhaus
authors.affiliation: Department of Radiology, University of Washington, United States; University of Washington Autism Center, United States.
authors.forename: Natalia M
authors.initials: NM
authors.lastname: Kleinhans
mesh_terms: D000328:Adult; D000067877:Autism Spectrum Disorder / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology*; D001480:Basal Ganglia Diseases / Q000150:complications* / Q000000981:diagnostic imaging; D001931:Brain Mapping; D016022:Case-Control Studies; D003344:Cortical Synchronization / Q000502:physiology*; D056344:Executive Function / Q000502:physiology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D008959:Models, Neurological; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011569:Psychiatric Status Rating Scales; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: Autism spectrum disorder; Basal ganglia; Cortical synchronization; Dynamic causal modeling; Executive functioning; fMRI