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

In the paper

“No studies to date have focused specifically on adolescents with ASD, despite the well-characterized maturation of EF circuitry in typical development (90,91).”

What the sources say

• Not checked yetcites [90] Casey, 2015, Beyond simple models of self-control to circuit-based accounts of adolescent behavior, Annu Rev Psychol source
• Not checked yetcites [91] Larsen, 2018, Adolescence as a neurobiological critical period for the development of higher-order cognition, Neurosci Biobehav Rev source

In the paper

“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.”

What the sources say

• Not checked yetcites [89] Zhang, 2020, Executive function in high-functioning autism spectrum disorder: A meta-analysis of fMRI studies, J Autism Dev Disord source

In the paper

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

In the paper

“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.”

In the paper

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

In the paper

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

In the paper

“Different aspects of EF such as updating, shifting, and inhibition are thought to be correlated, yet separable (4).”

What the sources say

• Not checked yetcites [4] Miyake, 2012, The nature and organization of individual differences in executive functions: Four general conclusions, Curr Dir Psychol Sci source

In the paper

“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).”

What the sources say

• Not checked yetcites [6] Gioia, 2000, Behavior rating inventory of executive function, Child Neuropsychol source

In the paper

“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.”

In the paper

“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).”

What the sources say

• Not checked yetcites [5] Dang, 2020, Why are self-report and behavioral measures weakly correlated?, Trends Cogn Sci source

In the paper

“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).”

What the sources say

• Not checked yetcites [55] Engelhardt, 2019, The neural architecture of executive functions is established by middle childhood, Neuroimage source

In the paper

“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).”

What the sources say

• Not checked yetcites [15] Toplak, 2013, Practitioner review: do performance-based measures and ratings of executive function assess the same construct?, J Child Psychol Psychiatry source

In the paper

“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).”

What the sources say

• Not checked yetcites [69] Anderson, 2014, Prevalence and correlates of postsecondary residential status among young adults with an autism spectrum disorder, Autism source

In the paper

“Flexibility supports the transition to adulthood, which is associated with increased demands including navigation of new social relationships and independent living (37–39).”

What the sources say

• Not checked yetcites [37] Bailey, 2007, Cognitive accuracy and intelligent executive function in the brain and in business, Ann N Y Acad Sci source
• Not checked yetcites [38] Burt, 2012, Resilience in the transition to adulthood, Dev Psychopathol source
• Not checked yetcites [39] Kapp, 2011, Transition to adulthood for high-functioning individuals with autism spectrum disorders

In the paper

“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).”

What the sources say

• Not checked yetcites [30] Nee, 2018
• Not checked yetcites [31] Hoffstaedter, 2014, The role of anterior midcingulate cortex in cognitive motor control: Evidence from functional connectivity analyses, Hum Brain Mapp source
• Not checked yetcites [32] Margulies, 2019, Network convergence zones in the anterior midcingulate cortex, Handb Clin Neurol source
• Not checked yetcites [33] Wager, 2004, Neuroimaging studies of shifting attention: a meta-analysis, Neuroimage source

In the paper

“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).”

What the sources say

• Not checked yetcites [60] Dajani, 2016, Heterogeneity of executive functions among comorbid neurodevelopmental disorders, Sci Rep source
• Not checked yetcites [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 yetcites [62] Brunsdon, 2014, Exploring the “fractionation” of autism at the cognitive level, Autism source
• Not checked yetcites [63] Happe, 2006, Executive function deficits in autism spectrum disorders and attention-deficit/hyperactivity disorder: Examining profiles across domains and ages, Brain Cogn source

In the paper

“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).”

What the sources say

• Not checked yetcites [40] Anderson, 2002, Assessment and development of executive function (EF) during childhood, Child Neuropsychol source
• Not checked yetcites [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
• Not checked yetcites [42] Hunter, 2012
• Not checked yetcites [43] Cepeda, 2001, Changes in executive control across the life span: Examination of task-switching performance, Dev Psychol source

In the paper

“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).”

What the sources say

• Not checked yetcites [70] Yerys, 2012, Brief report: Impaired Flexible Item Selection Task (FIST) in school-age children with autism spectrum disorders, J Autism Dev Disord source
• Not checked yetcites [71] Yeung, 2016, Abnormal frontal theta oscillations underlie the cognitive flexibility deficits in children with high-functioning autism spectrum disorders, Neuropsychology source
• Not checked yetcites [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
• Not checked yetcites [73] Russo, 2007, Deconstructing executive deficits among persons with autism: implications for cognitive neuroscience, Brain Cogn source
• Not checked yetcites [74] Geurts, 2009, The paradox of cognitive flexibility in autism, Trends Cogn Sci source

In the paper

“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).”

What the sources say

• Not checked yetcites [49] Jacobs, 2011, Are executive skills primarily mediated by the prefrontal cortex in childhood? Examination of focal brain lesions in childhood, Cortex source

In the paper

“Reduced frontal lobe contributions are thought to underlie immature control processes in children, who activate posterior but not prefrontal regions during EF tasks (48).”

What the sources say

• Not checked yetcites [48] Bunge, 2002, Immature frontal lobe contributions to cognitive control in children: evidence from fMRI, Neuron source

In the paper

“the dorsal anterior insula (dAI), which detects behaviorally-relevant stimuli and coordinates dynamic switches between brain networks (29).”

What the sources say

• Not checked yetcites [29] Uddin, 2015, Salience processing and insular cortical function and dysfunction, Nat Rev Neurosci source

In the paper

“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).”

What the sources say

• Not checked yetcites [52] Baum, 2017, Modular segregation of structural brain networks supports the development of executive function in youth, Curr Biol source

In the paper

“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).”

What the sources say

• Not checked yetcites [58] Sripada, 2019, Prediction of neurocognition in youth from resting state fMRI [published online ahead of print Aug 19], Mol Psychiatry

In the paper

“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).”

What the sources say

• Not checked yetcites [64] Lai, 2017, Meta-analysis of neuropsychological measures of executive functioning in children and adolescents with high-functioning autism spectrum disorder, Autism Res source

In the paper

“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).”

What the sources say

• Not checked yetcites [65] Demetriou, 2018, Autism spectrum disorders: A meta-analysis of executive function, Mol Psychiatry source

In the paper

“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).”

What the sources say

• Not checked yetcites [5] Dang, 2020, Why are self-report and behavioral measures weakly correlated?, Trends Cogn Sci source

In the paper

“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).”

What the sources say

• Not checked yetcites [74] Geurts, 2009, The paradox of cognitive flexibility in autism, Trends Cogn Sci source

In the paper

“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.”

What the sources say

• Not checked yetcites [132] Hill, 2004, Executive dysfunction in autism, Trends Cogn Sci source
• Not checked yetcites [6] Gioia, 2000, Behavior rating inventory of executive function, Child Neuropsychol source

In the paper

“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).”

What the sources say

• Not checked yetcites [86] Uddin, 2009, The anterior insula in autism: under-connected and under-examined, Neurosci Biobehav Rev source
• Not checked yetcites [87] Uddin, 2015, Brain state differentiation and behavioral inflexibility in autism, Cereb Cortex source
• Not checked yetcites [88] Uddin, 2013, Salience network–based classification and prediction of symptom severity in children with autism, JAMA Psychiatry source

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [118] Chen, 2017, Intrinsic functional connectivity variance and state-specific under-connectivity in autism, Hum Brain Mapp source

In the paper

“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.”

What the sources say

• Not checked yetcites [109] Chen, 2016, Distinct global brain dynamics and spatiotemporal organization of the salience network, PLoS Biol source
• Not checked yetcites [110] Douw, 2016, State-dependent variability of dynamic functional connectivity between frontoparietal and default networks relates to cognitive flexibility, Neuroscience source

In the paper

“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).”

What the sources say

• Not checked yetcites [108] Cabral, 2017, Cognitive performance in healthy older adults relates to spontaneous switching between states of functional connectivity during rest, Sci Rep source

In the paper

“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).”

What the sources say

• Not checked yetcites [83] Shafritz, 2008, The neural circuitry mediating shifts in behavioral response and cognitive set in autism, Biol Psychiatry source

In the paper

“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).”

What the sources say

• Not checked yetcites [116] Lacy N de, 2017, Disruption to control network function correlates with altered dynamic connectivity in the wider autism spectrum, Neuroimage Clin source
• Not checked yetcites [117] Watanabe, 2017, Brain network dynamics in high-functioning individuals with autism, Nat Commun source

In the paper

“Young adults with ASD are at increased risk for poor health outcomes, social isolation, financial adversity, and institutionalization (77).”

What the sources say

• Not checked yetcites [77] Bennett, 2018, Autism spectrum disorder and transition-aged youth, Curr Psychiatry Rep source

In the paper

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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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).”

What the sources say

• Not checked yetcites [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

In the paper

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

In the paper

“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).”

What the sources say

• Not checked yetcites [5] Dang, 2020, Why are self-report and behavioral measures weakly correlated?, Trends Cogn Sci source

In the paper

“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).”

What the sources say

• Not checked yetcites [78] Picci, 2015, A two-hit model of autism: Adolescence as the second hit, Clin Psychol Sci source

In the paper

“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).”

What the sources say

• Not checked yetcites [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

In the paper

“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).”

What the sources say

• Not checked yetcites [60] Dajani, 2016, Heterogeneity of executive functions among comorbid neurodevelopmental disorders, Sci Rep source
• Not checked yetcites [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 yetcites [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

In the paper

“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).”

What the sources say

• Not checked yetcites [142] Bialystok, 2012, Bilingualism: Consequences for mind and brain, Trends Cogn Sci source
• Not checked yetcites [143] Dick, 2019, No evidence for a bilingual executive function advantage in the ABCD study, Nat Hum Behav source

In the paper

“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).”

What the sources say

• Not checked yetcites [144] Drysdale, 2015, Children with autism spectrum disorder from bilingual families: A systematic review, Rev J Autism Dev Disord source
• Not checked yetcites [145] Moore, 2006, Working with linguistically diverse families in early intervention: Misconceptions and missed opportunities, Semin Speech Lang source

In the paper

“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).”

What the sources say

• Not checked yetcites [140] Galvan, 2012, Considerations for imaging the adolescent brain, Dev Cogn Neurosci source

In the paper

“and has been shown to be effective for improving classroom behavior, flexibility and problem-solving in children with ASD (135).”

What the sources say

• Not checked yetcites [135] Kenworthy, 2014, Randomized controlled effectiveness trial of executive function intervention for children on the autism spectrum, J Child Psychol Psychiatry source

In the paper

“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).”

What the sources say

• Not checked yetcites [60] Dajani, 2016, Heterogeneity of executive functions among comorbid neurodevelopmental disorders, Sci Rep source