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

Abstract

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.

The Locus Preservation Hypothesis: Shared Linguistic Profiles across Developmental Disorders and the Resilient Part of the Human Language Faculty

“…One explanation we contemplated in the present work relates to the possibility of an underlying uniform etiology across the reviewed disorders. This uniformity can be traced back to brain network organization (van den Heuvel and Sporns, 2013 ; Crossley et al, 2014 ; Benítez-Burraco and Murphy, 2016 ). Addressing the parallels that can be observed across different levels of representation (phenome, connectome, dynome, and oscillome) from a phylogenetic perspective, we have established a connection between the hypothesis put forth in the present work and the “syntax-before-phonology” hypothesis of Collier et al ( 2014 ): Syntax is better preserved because it evolved before other domains of language (e.g., morphology and phonology).…”

“…The important question is why syntactic operations are better preserved in a consistent way across disorders with different genetic etiology. One explanation is that the phenotypic overlaps that we identified are in fact surface reflections of more deeply rooted overlaps at the connectome or even the oscillome (Benítez-Burraco and Murphy, 2016 ). Observing that the hierarchy of brain oscillations has remained remarkably preserved during mammalian evolution (Buzsáki et al, 2013 ), Benítez-Burraco and Murphy ( 2016 ) suggest that language deficits in various cognitive disorders can be traced back to a brain syntax network.…”

“…One explanation is that the phenotypic overlaps that we identified are in fact surface reflections of more deeply rooted overlaps at the connectome or even the oscillome (Benítez-Burraco and Murphy, 2016 ). Observing that the hierarchy of brain oscillations has remained remarkably preserved during mammalian evolution (Buzsáki et al, 2013 ), Benítez-Burraco and Murphy ( 2016 ) suggest that language deficits in various cognitive disorders can be traced back to a brain syntax network. In this context, it can be argued that syntax is preserved because it is implemented through a network that is less novel in evolutionary terms, hence more resilient to impairment.…”

Robust candidates for language development and evolution are significantly dysregulated in the blood of people with Williams syndrome

“…The second subset consists on strong candidates for language evolution, as compiled by Boeckx and Benítez-Burraco (2014a;2014b) and Benítez-Burraco and Boeckx (2015). These are genes involved in the globularization of the human skull/brain and the cognitive changes accounting for our species-specific ability to learn and use languages (aka our language-readiness), and fulfil the following criteria: they have changed (and/or interact with genes that have changed) after our split from Neanderthals/Denisovans (including changes in their coding regions and/or their epigenetic profile); they play some known role in brain development, regionalization, wiring, and/or function; and/or they are candidates for language dysfunction in broad cognitive disorders, particularly, ASD and schizophrenia (SZ) (see Benítez-Burraco and Murphy, 2016;Murphy and Benítez-Burraco, 2016; 2017 for details about their role in language processing).…”

Genomics of Speech and Language Disorders

“…MED13L is implicated in neural crest induction and is highly expressed in the cerebellum after birth [175] . MED13L relates functionally to EP300 and CREBBP products, link proteins between the FOXP2 and ROBO1 pathway [176] . In a case-report described by Jimenez-Romero et al [177] a SNP was identified in MED13L (chr12: 116675396A> G, G, GRCh37), which associates with a profound language disturbance in the expressive domain, cognitive retardation, behavioral disturbances and an autism-like phenotype.…”