Approaching motor and language deficits in autism from below: a biolinguistic perspective

Benítez‐Burraco, Antonio; Boeckx, Cédric

doi:10.3389/fnint.2015.00025

Cited by 6 publications

(5 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regardless of the potential impact on diagnosis, our findings point to a need for further research on the development of clinical instruments that are better tailored towards autism in females [ 48 ]. Additionally, with the emerging view that RRB through its purported association with language deficits may serve as an endophenotype of ASD, future work should examine the link between the sex differences in RRB and the lack of sex differences in communication impairments reported here, and sex-specific risk genes in ASD [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Sex differences in structural organization of motor systems and their dissociable links with repetitive/restricted behaviors in children with autism

2015

View full text Add to dashboard Cite

BackgroundAutism spectrum disorder (ASD) is diagnosed much less often in females than males. Emerging behavioral accounts suggest that the clinical presentation of autism is different in females and males, yet research examining sex differences in core symptoms of autism in affected children has been limited. Additionally, to date, there have been no systematic attempts to characterize neuroanatomical differences underlying the distinct behavioral profiles observed in girls and boys with ASD. This is in part because extant ASD studies have included a small number of girls.MethodsLeveraging the National Database for Autism Research (NDAR), we first analyzed symptom severity in a large sample consisting of 128 ASD girls and 614 age- and IQ-matched ASD boys. We then examined symptom severity and structural imaging data using novel multivariate pattern analysis in a well-matched group of 25 ASD girls, 25 ASD boys, 19 typically developing (TD) girls, and 19 TD boys, obtained from the Autism Brain Imaging Data Exchange (ABIDE).ResultsIn both the NDAR and ABIDE datasets, girls, compared to boys, with ASD showed less severe repetitive/restricted behaviors (RRBs) and comparable deficits in the social and communication domains. In the ABIDE imaging dataset, gray matter (GM) patterns in the motor cortex, supplementary motor area (SMA), cerebellum, fusiform gyrus, and amygdala accurately discriminated girls and boys with ASD. This sex difference pattern was specific to ASD as the GM in these brain regions did not discriminate TD girls and boys. Moreover, GM in the motor cortex, SMA, and crus 1 subdivision of the cerebellum was correlated with RRB in girls whereas GM in the right putamen—the region that discriminated TD girls and boys—was correlated with RRB in boys.ConclusionsWe found robust evidence for reduced levels of RRB in girls, compared to boys, with ASD, providing the strongest evidence to date for sex differences in a core phenotypic feature of childhood ASD. Sex differences in brain morphometry are prominent in the motor system and in areas that comprise the “social brain.” Notably, RRB severity is associated with sex differences in GM morphometry in distinct motor regions. Our findings provide novel insights into the neurobiology of sex differences in childhood autism.Electronic supplementary materialThe online version of this article (doi:10.1186/s13229-015-0042-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Sex differences in structural organization of motor systems and their dissociable links with repetitive/restricted behaviors in children with autism

2015

View full text Add to dashboard Cite

show abstract

“…Interestingly, changes in some ASD-candidate genes have been selected in AMHs after our split from extinct hominins, paradigmatically, in AUTS2 , a gene that according to Green et al ( 2010 ) displays the strongest signal of positive selection in AMHs compared to Neanderthals. Importantly, some of the candidates for ASD belong to the two set of genes highlighted above, including CTNNB1 , HRAS , DLX1 , DLX5 , PTEN , and SMURF1 (which are part of the set centered on RUNX2), and ROBO2 , FOXP1 , POU3F2 , and CNTNAP2 (which belong to the second set of genes; see Benítez-Burraco and Boeckx, 2015b for details), whereas some other candidates (including AUTS2 , PAX6 and some of its partners, like TBR1 and FEZF2 ) provide additional links between the RUNX2 and the ROBO-FOXP2 interactomes (Figure 3 ; see Benítez-Burraco and Boeckx, 2015a for details). Because the involvement of these three sets of genes in both interfaces of language, this overlapping may account for the observed deficits in ASD regarding language abilities (see Benítez-Burraco and Boeckx, 2015b for discussion).…”

Section: Asd-related Genes and Some Evolutionary Concernsmentioning

confidence: 99%

The Oscillopathic Nature of Language Deficits in Autism: From Genes to Language Evolution

Benítez‐Burraco

Murphy

2016

Front. Hum. Neurosci.

View full text Add to dashboard Cite

Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders involving a number of deficits to linguistic cognition. The gap between genetics and the pathophysiology of ASD remains open, in particular regarding its distinctive linguistic profile. The goal of this article is to attempt to bridge this gap, focusing on how the autistic brain processes language, particularly through the perspective of brain rhythms. Due to the phenomenon of pleiotropy, which may take some decades to overcome, we believe that studies of brain rhythms, which are not faced with problems of this scale, may constitute a more tractable route to interpreting language deficits in ASD and eventually other neurocognitive disorders. Building on recent attempts to link neural oscillations to certain computational primitives of language, we show that interpreting language deficits in ASD as oscillopathic traits is a potentially fruitful way to construct successful endophenotypes of this condition. Additionally, we will show that candidate genes for ASD are overrepresented among the genes that played a role in the evolution of language. These genes include (and are related to) genes involved in brain rhythmicity. We hope that the type of steps taken here will additionally lead to a better understanding of the comorbidity, heterogeneity, and variability of ASD, and may help achieve a better treatment of the affected populations.

show abstract

“…Likewise, the MDFIC locus is among the top five percent S score regions in modern humans (Green et al 2010, table S37). Finally, both genes are functionally related to RUNX2, which encodes an osteogenic factor that controls the closure of cranial sutures and several aspects of brain growth, and that has been related to the changes that brought about our more globular brain (case) and our species-specific mode of cognition, including language (Boeckx and Benítez-Burraco 2014;Benítez-Burraco and Boeckx 2015). Further confirmation of this hypothesis would need to be supported by the analysis of the enhancers' sequences in extinct hominins and by mimicking the attested changes (if any) in a human cell line.…”

Section: Discussionmentioning

confidence: 99%

Functional genetic characterization by CRISPR-Cas9 of two enhancers ofFOXP2in a child with speech and language impairment

Torres-Ruíz¹,

Benítez‐Burraco

Martínez-Lage³

et al. 2016

Preprint

View full text Add to dashboard Cite

Mutations in the coding region of FOXP2 are known to cause speech and language impairment.Microdeletions involving the region downstream the gene have been also associated to speech and cognitive deficits. We recently described a girl harbouring a complex chromosomal rearrangement with one breakpoint downstream the gene that might affect their speech and cognitive abilities via physical separation of distant regulatory DNA elements. In this study, we have used highly efficient targeted chromosomal deletions induced by the CRISPR/Cas9 genome editing tool to demonstrate the functionality of two enhancers (FOXP2-E proximal and FOXP2-E distal ) located in the intergenic region between FOXP2 and its adjacent MDFIC gene. Deletion of any of these two functional enhancers in the neuroblastomic cell line SK-N-MC downregulates FOXP2 and decreases FOXP2 protein levels, conversely it upregulates MDFIC and increases MDFIC protein levels. This suggests that both regulatory elements may be shared between FOXP2 and MDFIC. We expect these findings contribute to a deeper understanding of how FOXP2 and MDFIC are regulated to pace neuronal development supporting speech and language. KEYWORDSFOXP2, MDFIC, speech and language impairment, Spanish, CRISP-Cas9, functional enhancer

show abstract

Approaching motor and language deficits in autism from below: a biolinguistic perspective

Cited by 6 publications

References 52 publications

Sex differences in structural organization of motor systems and their dissociable links with repetitive/restricted behaviors in children with autism

Sex differences in structural organization of motor systems and their dissociable links with repetitive/restricted behaviors in children with autism

The Oscillopathic Nature of Language Deficits in Autism: From Genes to Language Evolution

Functional genetic characterization by CRISPR-Cas9 of two enhancers ofFOXP2in a child with speech and language impairment

Contact Info

Product

Resources

About