Executive Function in Autism Spectrum Disorder: History, Theoretical Models, Empirical Findings, and Potential as an Endophenotype

Demetriou, Eleni; DeMayo, Marilena M.; Guastella, Adam J.

doi:10.3389/fpsyt.2019.00753

“…Further, the parahippocampal gyrus, isthmus cingulate cortex, and entorhinal cortex, are all part of the limbic system, which has been associated with impaired socioemotional and face processing in ASD (48)(49)(50)(51). In addition, the DLPFC is primarily associated with executive functioning, an aspect of impairment in ASD (52), and the insula has been linked to abnormalities of emotional/affective sensory functions in ASD (53). We also examined the effect of ASD in a subsample of non-carriers of the microdeletion, i.e.…”

Section: Discussionmentioning

confidence: 99%

Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

Gudbrandsen¹,

Bletsch

²

,

Mann

³

et al. 2020

Preprint

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Background: A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 Deletion Syndrome (22q11.2DS), are similar to those in idiopathic illness. This study aimed to examine if ASD symptomatology in 22q11.2DS is underpinned by the same – or distinct – neural systems that mediate these symptoms in non-deletion carriers. Methods: We examined vertex-wise estimates of cortical volume (CV), surface area (SA), and cortical thickness across 131 individuals between 6 and 25 years of age including (1) 50 individuals with 22q11.2DS, out of which n=25 had a diagnosis of ASD, (2) 40 non-carriers of the microdeletion with a diagnosis of ASD (i.e. idiopathic ASD), and (3) 41 typically developing (TD) controls. We employed a 2-by-2 factorial design to identify neuroanatomical variability associated with the main effects of 22q11.2DS and ASD, as well as their interaction. Further, using canonical correlation analysis (CCA), we compared neuroanatomical variability associated with the complex (i.e. multivariate) clinical phenotype of ASD between 22q11.2 deletion carriers and non-carriers. Results: The set of brain regions associated with the main effect of 22q11.2DS was distinct from the neuroanatomical underpinnings of the main effect of ASD. Moreover, significant 22q11.2DS-by-ASD interactions were observed for CV and SA in the dorsolateral prefrontal cortex, precentral gyrus, and posterior cingulate cortex, suggesting that the neuroanatomy of ASD is significantly modulated by 22q11.2DS ( p <0.01). We further established that the multivariate patterns of neuroanatomical variability associated with differences in symptom profiles significantly differed between 22q11.2 deletion carriers and non-carriers. Limitations: We employed a multicenter design to overcome single-site recruitment limitations, however, FreeSurfer derived measures of surface anatomy have been shown to be highly reliable across scanner platforms and field-strengths’. Further, we controlled for gender to address the differing distribution between idiopathic ASD individuals and the other groups. Nonetheless, the gender distribution in our sample reflects that of the respective populations, adding to the generalizability of our results. Last, we included individuals with a relatively wide age range (i.e. 6-25 years). Conclusions: Our findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD.

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“…Further, the parahippocampal gyrus, isthmus cingulate cortex, and entorhinal cortex, are all part of the limbic system, which has been associated with impaired socioemotional and face processing in ASD [48][49][50][51]. In addition, the DLPFC is primarily associated with executive functioning, an aspect of impairment in ASD [52], and the insula has been linked to abnormalities of emotional/affective sensory functions in ASD [53]. We also examined the effect of ASD in a subsample of non-carriers of the microdeletion, i.e., in idiopathic ASD individuals relative to TD controls, with similar results.…”

Section: Discussionmentioning

confidence: 99%

Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

Gudbrandsen

¹

,

Bletsch

²

,

Mann

³

et al. 2020

View full text Add to dashboard Cite

Background: A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 deletion syndrome (22q11.2DS), are similar to those in idiopathic illness. This study aimed to examine if ASD symptomatology in 22q11.2DS is underpinned by the same-or distinct-neural systems that mediate these symptoms in non-deletion carriers. Methods: We examined vertex-wise estimates of cortical volume (CV), surface area (SA), and cortical thickness across 131 individuals between 6 and 25 years of age including (1) 50 individuals with 22q11.2DS, out of which n = 25 had a diagnosis of ASD, (2) 40 non-carriers of the microdeletion with a diagnosis of ASD (i.e., idiopathic ASD), and (3) 41 typically developing (TD) controls. We employed a 2-by-2 factorial design to identify neuroanatomical variability associated with the main effects of 22q11.2DS and ASD, as well as their interaction. Further, using canonical correlation analysis (CCA), we compared neuroanatomical variability associated with the complex (i.e., multivariate) clinical phenotype of ASD between 22q11.2 deletion carriers and non-carriers. Results: The set of brain regions associated with the main effect of 22q11.2DS was distinct from the neuroanatomical underpinnings of the main effect of ASD. Moreover, significant 22q11.2DS-by-ASD interactions were observed for CV and SA in the dorsolateral prefrontal cortex, precentral gyrus, and posterior cingulate cortex, suggesting that the neuroanatomy of ASD is significantly modulated by 22q11.2DS (p < 0.01). We further established that the multivariate patterns of neuroanatomical variability associated with differences in symptom profiles significantly differed between 22q11.2 deletion carriers and non-carriers.

show abstract

“…Further, the parahippocampal gyrus, isthmus cingulate cortex, and entorhinal cortex, are all part of the limbic system, which has been associated with impaired socioemotional and face processing in ASD (43)(44)(45)(46). In addition, the DLPFC is primarily associated with executive functioning, an aspect of impairment in ASD (47), and the insula has been linked to abnormalities of emotional/affective sensory functions in ASD (48). We also examined the effect of ASD in a subsample of non-carriers of the microdeletion, i.e.…”

Section: Discussionmentioning

confidence: 99%

Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

Gudbrandsen¹,

Bletsch

²

,

Mann

³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Background: A crucial step to understanding the mechanistic underpinnings of autism spectrum disorder (ASD), is to examine if the biological underpinnings of ASD in genetic high-risk conditions, like 22q11.2 Deletion Syndrome (22q11.2DS), are similar to those in idiopathic illness. This study aimed to examine if ASD symptomatology in 22q11.2DS is underpinned by the same – or distinct – neural systems that mediate these symptoms in non-deletion carriers. Methods: We examined vertex-wise estimates of regional cortical volume (rCV), surface area (SA), and cortical thickness across 131 individuals between (6-25 years) including (1) 50 individuals with 22q11.2DS, out of which n=25 had a diagnosis of ASD, (2) 40 non-carriers of the microdeletion with a diagnosis of ASD (i.e. idiopathic ASD), and (3) 41 typically developing (TD) controls. We employed a 2-by-2 factorial design to identify neuroanatomical variability associated with the main effects of 22q11.2DS and ASD, as well as their interaction. Further, using canonical correlation analysis (CCA), we compared neuroanatomical variability associated with the complex (i.e. multivariate) clinical phenotype of ASD between 22q11.2 deletion carriers and non-carriers. Results: The set of brain regions associated with the main effect of 22q11.2DS was distinct from the neuroanatomical underpinnings of the main effect of ASD. Moreover, significant 22q11.2DS-by-ASD interactions were observed for rCV and SA in the dorsolateral prefrontal cortex, precentral gyrus, and posterior cingulate cortex, suggesting that neuroanatomy of ASD is significantly modulated by 22q11.2DS ( p <0.01). We further established that the multivariate patterns of neuroanatomical variability associated with differences in symptom profiles significantly differed between 22q11.2 deletion carriers and non-carriers (RV coef =0.06, p <0.7 vs. RV coef =0.196, p <0.0001). Limitations: We employed a multicenter design to overcome single-site recruitment limitations, however, FreeSurfer derived measures of surface anatomy have been shown to be highly reliable across scanner platforms and field-strengths’. Further, we controlled for gender to address the differing distribution between idiopathic ASD individuals and the other groups. Nonetheless, the gender distribution in our sample reflects that of the respective populations, adding to the generalizability of our results. Last, we included individuals with a relatively wide age range (i.e. 6-25 years). Conclusions: Our findings indicate that neuroanatomical correlates of ASD symptomatology in carriers of the 22q11.2 microdeletion diverge from those in idiopathic ASD.

show abstract

Executive Function in Autism Spectrum Disorder: History, Theoretical Models, Empirical Findings, and Potential as an Endophenotype

Cited by 145 publications

References 179 publications

Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

Neuroanatomical underpinnings of autism symptomatology in carriers and non-carriers of the 22q11.2 microdeletion

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