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Cited by 116Autism Spectrum Disorder ResearchNeural and Behavioral Psychology StudiesFunctional Brain Connectivity Studies

Brain Mechanisms Supporting Flexible Cognition and Behavior in Adolescents With Autism Spectrum Disorder

Open access
Uddin, Lucina Q.·2021·Biological Psychiatry
DOI 10.1016/j.biopsych.2020.05.010PMC PMC7677208
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Abstract

Cognitive flexibility enables appropriate responses to a changing environment and is associated with positive life outcomes. Adolescence, with its increased focus on transitioning to independent living, presents particular challenges for youths with autism spectrum disorder (ASD) who often struggle to behave in a flexible way when faced with challenges. This review focuses on brain mechanisms underlying the development of flexible cognition during adolescence and how these neural systems are affected in ASD. Neuroimaging studies of task switching and set-shifting provide evidence for atypical lateral frontoparietal and midcingulo-insular network activation during cognitive flexibility task performance in individuals with ASD. Recent work also examines how intrinsic brain network dynamics support flexible cognition. These dynamic functional connectivity studies provide evidence for alterations in the number of transitions between brain states, as well as hypervariability of functional connections in adolescents with ASD. Future directions for the field include addressing issues related to measurement of cognitive flexibility using a combination of metrics with ecological and construct validity. Heterogeneity of executive function ability in ASD must also be parsed to determine which individuals will benefit most from targeted training to improve flexibility. The influence of pubertal hormones on brain network development and cognitive maturation in adolescents with ASD is another area requiring further exploration. Finally, the intriguing possibility that bilingualism might be associated with preserved cognitive flexibility in ASD should be further examined. Addressing these open questions will be critical for future translational neuroscience investigations of cognitive and behavioral flexibility in adolescents with ASD.

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Crossref · 10.1016/j.biopsych.2020.05.010

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  • Findingcitation

    Links between brain network maturation and flexible behaviors are not yet firmly established.

    “While the development of cognitive flexibility is a topic of considerable interest, links between brain network maturation and flexible behaviors are not yet firmly established.”
    Quote in the paperSubstantial claim
  • Findingreasoning

    Measurement issues still complicate the study of cognitive flexibility in ASD.

    “Measurement issues still complicate the study of cognitive flexibility in ASD.”
    Quote in the paperSubstantial claim
  • Findingown data

    The reviewed dynamic functional connectivity studies have utilized different subsets from the larger ABIDE datasets, with minimal sample overlap across studies.

    “The studies reviewed here have utilized different subsets from the larger ABIDE datasets, with minimal sample overlap across studies (Table 2).”
    Quote in the paperNot a substantial claim
  • Findingnone given

    Few functional neuroimaging studies of cognitive flexibility in ASD have been conducted.

    “Despite the critical role of cognitive flexibility for supporting adaptive functioning in autism, few functional neuroimaging studies of cognitive flexibility in ASD have been conducted (Table 1).”
    Quote in the paperSubstantial claim
  • Findingcitation

    Dynamic functional connectivity approaches are already revealing patterns of brain dynamics that distinguish youth with ASD.

    “While several methodological issues have yet to be resolved (112), dynamic functional connectivity approaches are already revealing interesting patterns of brain dynamics that distinguish youth with ASD (Table 2).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [112] Lurie, 2020, Questions and controversies in the study of time-varying functional connectivity in resting fMRI, Network Neuroscience source

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    Findingcitation

    No studies to date have focused specifically on adolescents with ASD, despite the well-characterized maturation of executive function circuitry in typical development.

    “No studies to date have focused specifically on adolescents with ASD, despite the well-characterized maturation of EF circuitry in typical development (90,91).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [90] Casey, 2015, Beyond simple models of self-control to circuit-based accounts of adolescent behavior, Annu Rev Psychol source

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    • cites [91] Larsen, 2018, Adolescence as a neurobiological critical period for the development of higher-order cognition, Neurosci Biobehav Rev source

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    Findingcitation

    The task-based fMRI literature has not yet converged on the neural circuitry underlying cognitive flexibility in ASD, though atypical lateral frontoparietal and midcingulo-insular activation is generally observed.

    “The task-based fMRI literature has not yet converged on the neural circuitry underlying cognitive flexibility in ASD (89), though atypical L-FPN and M-CIN activation is generally observed.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [89] Zhang, 2020, Executive function in high-functioning autism spectrum disorder: A meta-analysis of fMRI studies, J Autism Dev Disord source

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    Findingnone given

    To date, no studies have explicitly explored the link between atypical brain dynamics and cognitive flexibility in ASD.

    “To date, no studies have explicitly explored the link between atypical brain dynamics and cognitive flexibility in ASD.”
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    Findingnone given

    The data thus far provide evidence for both alterations in the number of transitions between brain states and hyper-variability of functional connections in adolescents with ASD.

    “The data thus far provides evidence for both alterations in the number of transitions between brain states, and hyper-variability of functional connections in adolescents with ASD.”
    Quote in the paperSubstantial claim

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    Findingnone given

    The neural mechanisms associated with successful implementation of the Unstuck and On Target intervention are yet unknown.

    “The neural mechanisms associated with successful implementation of this intervention are yet unknown.”
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    Findingnone given

    It is completely unknown how puberty, which marks the beginning of adolescence, influences the development of brain systems underlying cognitive flexibility in autism.

    “Additionally, it is completely unknown how puberty, which marks the beginning of adolescence, influences the development of brain systems underlying cognitive flexibility in autism.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Different aspects of executive function such as updating, shifting, and inhibition are thought to be correlated yet separable.

    “Different aspects of EF such as updating, shifting, and inhibition are thought to be correlated, yet separable (4).”
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    • cites [4] Miyake, 2012, The nature and organization of individual differences in executive functions: Four general conclusions, Curr Dir Psychol Sci source

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    Premisecitation

    The Behavior Rating Inventory of Executive Function is an informant-report measure developed for parents and teachers to assess executive function in children aged 5 to 18 years.

    “One such measure, the Behavior Rating Inventory of Executive Function (BRIEF), is an informant-report measure developed for parents and teachers to assess EF in 5–18 year-old children (6).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Gioia, 2000, Behavior rating inventory of executive function, Child Neuropsychol source

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    Premisenone given

    Dynamic functional connectivity studies provide evidence for alterations in the number of transitions between brain states and hyper-variability of functional connections in adolescents with ASD.

    “These dynamic functional connectivity studies provide evidence for alterations in the number of transitions between brain states, as well as hyper-variability of functional connections in adolescents with ASD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Informant-report questionnaires typically have greater ecological validity, while laboratory-based measures can provide greater construct validity for assessing executive function and cognitive flexibility.

    “EF ability and cognitive flexibility can be assessed using informant-report questionnaires, which typically have greater ecological validity, or laboratory-based measures, which can provide greater construct validity(5).”
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    • cites [5] Dang, 2020, Why are self-report and behavioral measures weakly correlated?, Trends Cogn Sci source

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    Premisecitation

    Task-based fMRI findings show that brain networks involved in executive function are in place in children aged 8 to 14, with the dorsal anterior cingulate cortex and right anterior insula showing greater activation across more demanding task periods.

    “Findings from the task-based fMRI literature demonstrate that brain networks involved in EF are in place in children aged 8–14, with the dACC and rAI showing greater activation across more demanding task periods (55).”
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    • cites [55] Engelhardt, 2019, The neural architecture of executive functions is established by middle childhood, Neuroimage source

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    Premisecitation

    Informant and self-report measures of real-world executive function and laboratory performance-based neuropsychological measures do not always converge; the BRIEF correlates with other questionnaire measures but not with laboratory-based executive function measures.

    “It is important to note that informant and self-report measures of real-world EF and laboratory performance-based neuropsychological measures do not always converge. The BRIEF correlates with other questionnaire measures, but not with laboratory-based measures of EF, suggesting that subjective and objective measures may not assess the same underlying constructs (15).”
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    • cites [15] Toplak, 2013, Practitioner review: do performance-based measures and ratings of executive function assess the same construct?, J Child Psychol Psychiatry source

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    Premisecitation

    Cognitive flexibility deficits in early life can manifest as difficulties in transitioning to independent living and maintaining employment, and may contribute to the outcome that less than 20% of adults with ASD live independently and are fully employed.

    “Cognitive flexibility deficits in early life can manifest as difficulties in transitioning to independent living and maintaining employment, and may contribute to the grim outcome that less than 20% of adults with ASD live independently and are fully employed (69).”
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    • cites [69] Anderson, 2014, Prevalence and correlates of postsecondary residential status among young adults with an autism spectrum disorder, Autism source

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    Premisecitation

    Flexibility supports the transition to adulthood, which is associated with increased demands including navigation of new social relationships and independent living.

    “Flexibility supports the transition to adulthood, which is associated with increased demands including navigation of new social relationships and independent living (37–39).”
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    • cites [37] Bailey, 2007, Cognitive accuracy and intelligent executive function in the brain and in business, Ann N Y Acad Sci source

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    • cites [38] Burt, 2012, Resilience in the transition to adulthood, Dev Psychopathol source

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    • cites [39] Kapp, 2011, Transition to adulthood for high-functioning individuals with autism spectrum disorders

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    Premisecitation

    Broader executive function networks include nodes in the dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, and superior parietal lobule, which contribute to working memory, motor control, and attention, respectively.

    “These regions work in the context of broader EF networks with nodes in the dorsolateral prefrontal cortex (dlPFC), dorsal anterior cingulate cortex (dACC), and superior parietal lobule (SPL) which contribute to working memory (30), motor control (31,32), and attention (33), respectively (see (25) for review) (Figure 1).”
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    • cites [30] Nee, 2018

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    • cites [31] Hoffstaedter, 2014, The role of anterior midcingulate cortex in cognitive motor control: Evidence from functional connectivity analyses, Hum Brain Mapp source

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    • cites [33] Wager, 2004, Neuroimaging studies of shifting attention: a meta-analysis, Neuroimage source

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    Premisecitation

    A majority of those diagnosed with ASD experience difficulties with executive function, but individual levels of impairment vary greatly, and executive function deficits can improve with age.

    “While a majority of those diagnosed with ASD experience difficulties with EF, a great deal of heterogeneity exists with respect to individual levels of impairment (60–62), and EF deficits can improve with age (63).”
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    • cites [60] Dajani, 2016, Heterogeneity of executive functions among comorbid neurodevelopmental disorders, Sci Rep source

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    • cites [61] Baez, 2020, Parsing heterogeneity of executive function in typically and atypically developing children: A conceptual replication and exploration of social function, J Autism Dev Dis source

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    Premisecitation

    Cognitive flexibility emerges in early life, increases sharply between 7 and 9 years of age, develops protractedly, becomes largely mature by age 20, continues to improve through adolescence and adulthood, peaks between 21 and 30 years, and then declines in later life.

    “Cognitive flexibility emerges in early life, showing sharp increases between 7–9 years of age, then follows a protracted development throughout young adulthood, becoming largely mature by age 20 (40,41). However, this skill continues to improve throughout adolescence and adulthood, peaking between 21–30 years of age before declining in later life (40,42,43).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [40] Anderson, 2002, Assessment and development of executive function (EF) during childhood, Child Neuropsychol source

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    • cites [41] Dick, 2014, The development of cognitive flexibility beyond the preschool period: an investigation using a modified Flexible Item Selection Task, J Exp Child Psychol source

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    • cites [43] Cepeda, 2001, Changes in executive control across the life span: Examination of task-switching performance, Dev Psychol source

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    Premisecitation

    Despite reports of cognitive flexibility deficits in ASD, particularly in younger children, there are conflicting notions regarding the extent, nature, etiology, and neurobiology of these deficits.

    “Despite reports of cognitive flexibility deficits in ASD (70,71), particularly in younger children (72,73), there are conflicting notions regarding the extent, nature, etiology, and neurobiology of these deficits (74).”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [70] Yerys, 2012, Brief report: Impaired Flexible Item Selection Task (FIST) in school-age children with autism spectrum disorders, J Autism Dev Disord source

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    • cites [71] Yeung, 2016, Abnormal frontal theta oscillations underlie the cognitive flexibility deficits in children with high-functioning autism spectrum disorders, Neuropsychology source

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    • cites [72] van den Bergh, 2014, Age related differences of executive functioning problems in everyday life of children and adolescents in the autism spectrum, J Autism Dev Disord source

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    Premisecitation

    Adolescents with frontal lesions and those with extra-frontal lesions show little differentiation on a range of executive functions, suggesting that adolescents use more distributed brain networks for executive skills than adults.

    “On a range of EFs including attentional control, goal setting, and cognitive flexibility, little differentiation was observed between adolescents (age 7–16) with frontal lesions and those with extra-frontal lesions, suggesting that adolescents utilize more distributed brain networks for executive skills than adults (49).”
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    • cites [49] Jacobs, 2011, Are executive skills primarily mediated by the prefrontal cortex in childhood? Examination of focal brain lesions in childhood, Cortex source

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    Premisecitation

    Reduced frontal lobe contributions are thought to underlie immature control processes in children, who activate posterior but not prefrontal regions during executive function tasks.

    “Reduced frontal lobe contributions are thought to underlie immature control processes in children, who activate posterior but not prefrontal regions during EF tasks (48).”
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    • cites [48] Bunge, 2002, Immature frontal lobe contributions to cognitive control in children: evidence from fMRI, Neuron source

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    Premisecitation

    The dorsal anterior insula detects behaviorally relevant stimuli and coordinates dynamic switches between brain networks.

    “the dorsal anterior insula (dAI), which detects behaviorally-relevant stimuli and coordinates dynamic switches between brain networks (29).”
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    • cites [29] Uddin, 2015, Salience processing and insular cortical function and dysfunction, Nat Rev Neurosci source

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    Premisecitation

    Diffusion imaging studies in 8- to 22-year-olds support the network segregation-with-age account and link this neurodevelopmental process with enhanced executive function with age.

    “Diffusion imaging studies examining structural connectivity in 8–22 year-olds support the network segregation-with-age story, and further link this neurodevelopmental process with enhanced EF with age (52).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Baum, 2017, Modular segregation of structural brain networks supports the development of executive function in youth, Curr Biol source

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    Premisecitation

    In over 2000 9- to 10-year-olds from the ABCD dataset, individual differences in general cognitive ability could be predicted from functional connectivity patterns, but whole-brain connectomes could not reliably predict individual differences in flexibility.

    “A recent study of over 2000 9–10 year olds from the ABCD dataset found that while individual differences in general cognitive ability could be predicted from functional connectivity patterns, whole brain connectomes could not reliably predict individual differences in flexibility (58).”
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    • cites [58] Sripada, 2019, Prediction of neurocognition in youth from resting state fMRI [published online ahead of print Aug 19], Mol Psychiatry

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    Premisecitation

    A meta-analysis found broad impairments across multiple executive function domains in children and adolescents with ASD assessed using neuropsychological measures; deficits in cognitive flexibility decreased with age and were observed in those with and without comorbid ADHD.

    “In a meta-analysis, broad impairments across multiple EF domains were observed in children and adolescents with ASD assessed using neuropsychological measures. Deficits in cognitive flexibility decreased with age, and were observed in those with and without comorbid attention-deficit/hyperactivity disorder (ADHD) (64).”
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    • cites [64] Lai, 2017, Meta-analysis of neuropsychological measures of executive functioning in children and adolescents with high-functioning autism spectrum disorder, Autism Res source

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    Premisecitation

    Another meta-analysis including psychometric, experimental, and questionnaire-based measures of executive function and a wider age range reported broad dysfunction in ASD that is relatively stable across development, with the largest effect sizes for studies using the BRIEF questionnaire.

    “Another meta-analysis including psychometric, experimental, and questionnaire-based measures of EF and a wider age range of participants also reported broad dysfunction in ASD that is relatively stable across development. Here, effect sizes were found to be largest for studies using the BRIEF questionnaire (65).”
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    • cites [65] Demetriou, 2018, Autism spectrum disorders: A meta-analysis of executive function, Mol Psychiatry source

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    Premisecitation

    Self-report and behavioral measures of the same construct are only weakly correlated, possibly because behavioral measures tap responses during highly structured situations and index maximal performance, whereas self-report assesses behavior across unstructured real-life situations.

    “More generally, self-report and behavioral measures of the same construct are only weakly correlated, possibly due to the fact that behavioral measures tap responses during highly structured situations and typically index maximal performance, whereas self-report assesses how individuals behave across unstructured real-life situations (5).”
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    • cites [5] Dang, 2020, Why are self-report and behavioral measures weakly correlated?, Trends Cogn Sci source

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    Premisecitation

    Although individuals with ASD appear behaviorally rigid in daily activities, neuropsychological and laboratory-based measures of cognitive flexibility provide mixed results with respect to patterns of executive function deficits.

    “Although individuals with ASD appear behaviorally rigid in daily activities, neuropsychological and laboratory-based measures of cognitive flexibility provide mixed results with respect to patterns of EF deficits (74).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [74] Geurts, 2009, The paradox of cognitive flexibility in autism, Trends Cogn Sci source

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    Premisecitation

    Performance-based measures such as the Wisconsin Card Sort Task can hone in on specific cognitive constructs, whereas more ecologically valid measures such as the BRIEF are sensitive indices of real-world behaviors but may be subject to reporter bias.

    “Performance-based measures such as the WCST can hone in on specific cognitive constructs (132), whereas more ecologically-valid measures such as the BRIEF are sensitive indices of real-world behaviors (6) but may be subject to reporter bias.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [132] Hill, 2004, Executive dysfunction in autism, Trends Cogn Sci source

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    • cites [6] Gioia, 2000, Behavior rating inventory of executive function, Child Neuropsychol source

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    Premisecitation

    The right anterior insula has been posited as a locus of dysfunction in ASD, and functional and effective connectivity of this region and the broader midcingulo-insular network is associated with symptom severity in the domain of restricted and repetitive behaviors.

    “The rAI has been posited to be a locus of dysfunction in ASD (86), and functional and effective connectivity of this region and the broader M-CIN is associated with symptom severity in the domain of RRBs (87,88).”
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    • cites [86] Uddin, 2009, The anterior insula in autism: under-connected and under-examined, Neurosci Biobehav Rev source

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    • cites [87] Uddin, 2015, Brain state differentiation and behavioral inflexibility in autism, Cereb Cortex source

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    • cites [88] Uddin, 2013, Salience network–based classification and prediction of symptom severity in children with autism, JAMA Psychiatry source

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    Premisenone given

    Adolescence is a time of dramatic physical, emotional, and social change and represents a particularly vulnerable developmental period for individuals with ASD.

    “Adolescence is a time of dramatic physical, emotional, and social change, and represents a particularly vulnerable developmental period for individuals with ASD.”
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    Premisecitation

    In 6- to 36-year-olds within ABIDE, greater variance of widespread long-range dynamic functional connections in ASD was reported and linked with symptom severity indexed by the Autism Diagnostic Observation Schedule.

    “Focusing on functional connectivity variance in 6–36 year-olds within ABIDE, greater variance of widespread long-range dynamic functional connections in ASD was reported, and linked with symptom severity indexed by the Autism Diagnostic Observation Schedule (ADOS) (118).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] Chen, 2017, Intrinsic functional connectivity variance and state-specific under-connectivity in autism, Hum Brain Mapp source

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    Premisecitation

    Time-varying but not static functional connectivity of the midcingulo-insular network, as well as dynamics between the default mode/medial frontoparietal network and lateral frontoparietal network, has been shown to predict individual differences in cognitive flexibility.

    “Time-varying (but not static) functional connectivity of the M-CIN (109), as well as dynamics between the default mode/medial frontoparietal network (M-FPN) and L-FPN (110), has been shown to predict individual differences in cognitive flexibility.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [109] Chen, 2016, Distinct global brain dynamics and spatiotemporal organization of the salience network, PLoS Biol source

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    • cites [110] Douw, 2016, State-dependent variability of dynamic functional connectivity between frontoparietal and default networks relates to cognitive flexibility, Neuroscience source

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    Premisecitation

    Older adults who performed more poorly on a battery of cognitive tests exhibited greater frequency of switching between dynamic brain states, whereas high performers exhibited a tendency to be in a state characterized by global coherence.

    “Older adults who performed more poorly on a battery of cognitive tests exhibited greater frequency of switching between dynamic brain states, whereas high performers exhibited a tendency to be in a state characterized by global coherence (108).”
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    • cites [108] Cabral, 2017, Cognitive performance in healthy older adults relates to spontaneous switching between states of functional connectivity during rest, Sci Rep source

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    Premisecitation

    Shafritz and colleagues found reduced activation in frontal, striatal, and parietal regions during shifting trials in young adults with ASD, and a negative correlation between severity of restricted and repetitive behaviors and anterior cingulate and posterior parietal activation.

    “Shafritz and colleagues found reduced activation in frontal, striatal, and parietal regions during shifting trials in young adults with ASD. They also reported a negative correlation between severity of RRBs and anterior cingulate and posterior parietal activation (83).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [83] Shafritz, 2008, The neural circuitry mediating shifts in behavioral response and cognitive set in autism, Biol Psychiatry source

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    Premisecitation

    Using the entire available ABIDE sample aged 6 to 58, decreased state transitions in ASD were found, and this finding of reduced transitions between brain states has been replicated in adults with autism.

    “Another study using the entire available ABIDE sample (ages 6–58) found evidence for decreased state transitions in ASD (116). This finding of reduced transitions between brain states has been replicated in adults with autism (117).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [116] Lacy N de, 2017, Disruption to control network function correlates with altered dynamic connectivity in the wider autism spectrum, Neuroimage Clin source

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    • cites [117] Watanabe, 2017, Brain network dynamics in high-functioning individuals with autism, Nat Commun source

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    Premisecitation

    Young adults with ASD are at increased risk for poor health outcomes, social isolation, financial adversity, and institutionalization.

    “Young adults with ASD are at increased risk for poor health outcomes, social isolation, financial adversity, and institutionalization (77).”
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    • cites [77] Bennett, 2018, Autism spectrum disorder and transition-aged youth, Curr Psychiatry Rep source

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    Interpretationreasoning

    Increased sample inhomogeneity due to data pooling across sites can introduce biases that must be considered.

    “Increased sample inhomogeneity due to data pooling across sites can introduce biases that must be considered.”
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    Premisecitation

    The Flexibility Scale, based on data from 300 6- to 17-year-olds, is an informant report that densely samples cognitive aspects of flexibility in everyday settings and has been shown to discriminate participants with ASD from controls.

    “The Flexibility Scale, based on data collected from 300 6–17 year olds, is an informant report that densely samples cognitive aspects of flexibility in everyday settings and has been shown to discriminate participants with ASD and controls.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [133] Strang, 2017, The flexibility scale: Development and preliminary validation of a cognitive flexibility measure in children with autism spectrum disorders, J Autism Dev Disord source

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    Premisecitation

    During the transition to adulthood, youth with ASD often desire independent living, employment, and social relationships, all of which can be challenging for them to achieve when dealing with persistent social, behavioral, and language deficits.

    “During this period of transition to adulthood, youth with ASD often desire independent living, employment, and social relationships, all of which can be challenging for them to achieve when dealing with persistent social, behavioral, and language deficits (75).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] Ballaban-Gil, 1996, Longitudinal examination of the behavioral, language, and social changes in a population of adolescents and young adults with autistic disorder, Pediatr Neurol source

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    Interpretationreasoning

    Cognitive flexibility deficits can exacerbate the difficult transition period of adolescence, whereas relative sparing of flexibility may ameliorate some of the challenges typically encountered during adolescence.

    “Cognitive flexibility deficits can exacerbate this difficult transition period, whereas relative sparing of flexibility may ameliorate some of the challenges typically encountered during adolescence.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Measures with high reliability such as informant or self-report may better predict individual differences in real-life outcomes, whereas behavioral measures sensitive to within-person experimental manipulations may be important for studying processes that underlie task performance.

    “Measures with high reliability such as informant- or self-report may better predict individual differences in real-life outcomes, whereas behavioral measures that are sensitive to within-person experimental manipulations may be important for studying processes that underlie task performance (5).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Dang, 2020, Why are self-report and behavioral measures weakly correlated?, Trends Cogn Sci source

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  • Classified as probably not a substantial claim.

    Premisecitation

    The two-hit conceptual model of autism posits that early alterations in neurodevelopment lead to a first hit, while pubertal hormones, neural reorganization, and increasing social demands function as a second hit during adolescence that affects adaptive functioning and transitioning to adult roles.

    “The “two-hit” conceptual model of autism posits that early alterations in neurodevelopment lead to a “first hit”, while pubertal hormones, neural reorganization, and increasing social demands function as a “second hit” during adolescence that affects adaptive functioning and transitioning to adult roles (78).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [78] Picci, 2015, A two-hit model of autism: Adolescence as the second hit, Clin Psychol Sci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Exploratory factor analysis of the Flexibility Scale revealed five factors related to Routines/Rituals, Transitions/Change, Special Interests, Social Flexibility, and Generativity, and the scale demonstrated convergent and divergent validity with comparative domains in other measures including the shift subscale of the BRIEF and D-KEFS performance.

    “Exploratory factor analysis revealed evidence for five factors related to Routines/Rituals, Transitions/Change, Special Interests, Social Flexibility, and Generativity, and the scale demonstrated convergent and divergent validity with comparative domains in other measures including the ‘shift’ subscale of the BRIEF and D-KEFS performance (133).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [133] Strang, 2017, The flexibility scale: Development and preliminary validation of a cognitive flexibility measure in children with autism spectrum disorders, J Autism Dev Disord source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Not all children with ASD exhibit the same level and profile of executive function deficits; some studies provide evidence of uniform patterns of abilities across executive function domains, while others suggest that distinct executive function subtypes exist.

    “Importantly, not all children with ASD exhibit the same level and profile of EF deficits. While some studies provide evidence of uniform patterns of abilities across EF domains (60,61), others suggest that distinct EF subtypes exist (136).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [60] Dajani, 2016, Heterogeneity of executive functions among comorbid neurodevelopmental disorders, Sci Rep source

      Not checked in the free run.

    • cites [61] Baez, 2020, Parsing heterogeneity of executive function in typically and atypically developing children: A conceptual replication and exploration of social function, J Autism Dev Dis source

      Not checked in the free run.

    • cites [136] Vaidya, 2020, Data-driven identification of subtypes of executive function across typical development, attention deficit hyperactivity disorder, and autism spectrum disorders, J Child Psychol Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The bilingual advantage refers to the phenomenon that individuals who speak two languages fluently often perform better on tasks of executive function than monolingual individuals.

    “The bilingual advantage refers to the phenomenon that individuals who speak two languages fluently often perform better on tasks of EF than monolingual individuals (142, but see 143).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [142] Bialystok, 2012, Bilingualism: Consequences for mind and brain, Trends Cogn Sci source

      Not checked in the free run.

    • cites [143] Dick, 2019, No evidence for a bilingual executive function advantage in the ABCD study, Nat Hum Behav source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Clinical practitioners commonly advise against providing children with developmental disabilities a bilingual environment, believing that concentrating on one language will better support language development.

    “Despite the potential advantages that bilingualism may confer for EF, clinical practitioners commonly advise against providing children with developmental disabilities a bilingual environment (144), believing that concentrating on one language will better support language development (145).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [144] Drysdale, 2015, Children with autism spectrum disorder from bilingual families: A systematic review, Rev J Autism Dev Disord source

      Not checked in the free run.

    • cites [145] Moore, 2006, Working with linguistically diverse families in early intervention: Misconceptions and missed opportunities, Semin Speech Lang source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dissociable effects of pubertal hormones and age on the adolescent brain have been documented, suggesting that pubertal stage may be a better predictor of cognitive and behavioral maturity than chronological age.

    “Dissociable effects of pubertal hormones and age on the adolescent brain have been documented, suggesting that pubertal stage may be a better predictor of cognitive and behavioral maturity than chronological age (140).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [140] Galvan, 2012, Considerations for imaging the adolescent brain, Dev Cogn Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Unstuck and On Target has been shown to be effective for improving classroom behavior, flexibility, and problem-solving in children with ASD.

    “and has been shown to be effective for improving classroom behavior, flexibility and problem-solving in children with ASD (135).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [135] Kenworthy, 2014, Randomized controlled effectiveness trial of executive function intervention for children on the autism spectrum, J Child Psychol Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Co-occurring conditions associated with cognitive inflexibility have not been adequately considered, despite initial evidence that executive function impairment is more severe in children with comorbid ASD and ADHD.

    “Co-occurring conditions that are associated with cognitive inflexibility have also not been adequately considered, despite initial evidence that EF impairment is more severe in children with comorbid ASD and ADHD (60).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Dajani, 2016, Heterogeneity of executive functions among comorbid neurodevelopmental disorders, Sci Rep source

      Not checked in the free run.

49 of 49

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • A recent review points to atypical L-FPN and M-CIN activation during task switching and set-shifting in autism.

    “A recent review of neural mechanisms underlying cognitive and behavioural flexibility in autism additionally points to atypical patterns of L-FPN and M-CIN activation in response to task switching and set-shifting72.”

    From Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations (2021) · cites this paper as [72]

  • Measurement issues complicate assessment of flexibility deficits and their neural bases in ASD and ADHD because different combinations of laboratory measures, neuropsychological tests, and informant-report questionnaires have been used across studies.

    “Measurement issues complicate the assessment of flexibility deficits and their neural bases in ASD and ADHD, as different combinations of laboratory-based measures, neuropsychological tests and informant-report questionnaires have been used across studies72.”

    From Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations (2021) · cites this paper as [72]

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Authors
Uddin, L. Q.
Affiliations
University of Miami (US)
Corresponding author
Uddin, Lucina Q.
ORCID
Uddin, Lucina Q.
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2021-01
Volume
89
Issue
2
Pages
172-183
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2020.05.010
PMC
PMC7677208
OpenAlex
W3028447440
Cited by
116
References
150
Citations by year
2026: 16 · 2025: 25 · 2024: 16 · 2023: 23 · 2022: 17 · 2021: 14 · 2020: 5
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Canadian Institute for Advanced Research
  • University of Miami
  • National Institute of Mental Health
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Keywords
autism spectrum disorder, cognitive flexibility, adolescents, task switching, set-shifting, frontoparietal network, dynamic functional connectivity, executive function, pubertal hormones, bilingualism, behavioral flexibility
MeSH terms
Autism Spectrum Disorder, Adolescent, Brain, Brain Mapping, Cognition, Humans, Magnetic Resonance Imaging, Executive Function

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