Neurogenetics and auditory processing in developmental dyslexia

doi:10.1016/j.conb.2012.09.003

Current Opinion in Neurobiology

Volume 23, Issue 1, February 2013, Pages 37-42

https://doi.org/10.1016/j.conb.2012.09.003 Get rights and content

Dyslexia is a polygenic developmental reading disorder characterized by an auditory/phonological deficit. Based on the latest genetic and neurophysiological studies, we propose a tentative model in which phonological deficits could arise from genetic anomalies of the cortical micro-architecture in the temporal lobe.

Highlights

► Developmental dyslexia is a specific reading disability with a genetic component. ► Genetic variations associated with dyslexia disrupt neuronal migration and auditory processing. ► Anomalies of cortical micro-circuitry translate in abnormal cortical oscillations. ► Neural oscillations in auditory cortex facilitate processing of phonological units. ► Disrupted auditory cortical oscillations alter access to phonological representations.

Introduction

Dyslexia is a reading disorder of polygenic origin affecting 3–7% of school children, defined by marked difficulties in the acquisition of reading despite normal intelligence, perception and educational opportunities [1]. In most cases, dyslexia is accompanied with a phonological deficit, for example, difficulties in tasks involving speech sounds and dysfunctions of the left perisylvian language network [2] and/or subcortical auditory relays [3, 4]. Understanding how diverse genetic variations can cause a cognitive disorder as specific as dyslexia is the challenge we are currently facing. Animals in which dyslexia genes have been knocked out exhibit both disturbed neuronal migration in auditory cortex and impaired auditory processing. We review the current literature and describe a putative mechanistic model linking neuronal micro-architecture of the auditory cortex to specific alterations of phonological processing.

Section snippets

Molecular genetics of dyslexia and related cognitive and brain phenotypes

Between 2003 and 2006, a first series of genes (DYX1C1, ROBO1, KIAA0319 and DCDC2) were found to be associated with dyslexia [5]. Since then, additional candidate genes have been proposed, raising the number to about 15 [6, 7].

Several of the identified susceptibility alleles have recently been associated not only with the diagnosis of dyslexia but also with reading or spelling phenotypic variability within the general population. A few studies showed KIAA0319, DYX1C1, DCDC2 and CMIP to be

Dyslexia candidate genes influence cortical neuronal migration and microcircuits

The neural effects of the genetic markers identified in humans are now being explored in non-human animals. Candidate genes can be artificially inactivated and the neural consequences followed up from microscopic to functional levels. RNA interference experiments in rodent models suggest that all four primarily identified genes (DYX1C1, ROBO1, DCDC2, KIAA0319) appear to regulate neocortical development, in particular neuronal migration [7, 35, 36, 37], which provides a nice connection with

A mechanistic hypothesis for linking genetic cortical anomalies and the phonological impairment in dyslexia

Further exploring the specific functional consequence of cortical microcircuitry anomalies could represent a promising research avenue. Migration anomalies likely disrupt the physiology of neuronal interactions within and across cortical layers and columns [44], and subsequently impair synchronous neuronal activity emerging from specific interactions across neurons and interneurons [45, 46••] (Figure 3a). In auditory cortices, synchronous bursts of neural activity occur at specific frequencies

Conclusion

Despite new trails in pinpointing the determinants of dyslexia, no direct causal relationship between genetic markers and auditory oscillations is definitely established. The next step should target experiments in animals involving genetic manipulations and dedicated neurophysiological recordings targeting neural oscillations. Finally, the neural oscillation hypothesis is not incompatible with other hypotheses, and the emergence of symptoms during reading acquisition naturally also point to the

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

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Neurodynamics of selected language processes involved in word reading: An EEG study with French dyslexic adults
2024, Journal of Neurolinguistics
This event-related potential (ERP) study aimed to examine at which point in the stream of four cognitive processes of word reading impairment occurs in dyslexic adults. Fourteen French native dyslexic speakers and eighteen matched controls performed a delayed phonological lexical decision task that consisted in deciding whether visual stimuli sounded like French words. Three hundred stimuli equally distributed among five experimental conditions (60 concrete French words, 60 pseudo-homophones, 60 pseudowords, 60 consonant and 60 symbol strings) were presented. Critically, two language processes involving phonological information, namely grapheme-to-phoneme conversion (N320) and memory retrieval of phonological information (Late Positive Complex) were impaired in dyslexics compared to controls. Moreover, lexical access (N400) was significantly modulated by six predictive variables assumed to be reliable markers of dyslexia. In contrast, and unexpectedly, the early processes of visual expertise for print (N170) appeared to operate in the same way in the two groups of participants. The locus of dyslexia is probably to be found primarily in some aspects of phonological processing during word reading. These findings support a clinical neurophysiology model postulating that at least two phonological processes during reading might be impaired in dyslexics, namely grapheme-to-phoneme conversion, and memory retrieval of phonological information.
Phonological deficits in dyslexia impede lexical processing of spoken words: Linking behavioural and MEG data
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Phonological difficulties have been identified as a core deficit in developmental dyslexia, yet everyday speech comprehension, which relies on phonological processing, is seemingly unaffected. This raises the question as to how dyslexic readers process spoken words to achieve normal word comprehension. Here we establish a link between neural correlates of lexical and sublexical processing in auditory words and behaviourally measured phonological deficits using magnetoencephalography (MEG). Spatiotemporally resolved cortical responses to phonological and lexico-semantic information were computed with the event-related regression technique (Hauk et al., 2009) and correlated with dyslexic and non-dyslexic subjects’ phonological skills. We found that phonological deficits reduced cortical responses to both phonological and lexico-semantic information (phonological neighbours and word frequency). Individuals with lower phonological skills – independent of dyslexia diagnosis – showed weaker neural responses to phonological neighbourhood information in both hemispheres 200–500 ms after word onset and reduced sensitivity to written and spoken word frequency between 200 and 650 ms. Dyslexic readers showed weaker responses to written word frequency in particular compared to the control group, pointing towards an additional effect of print exposure on auditory word processing. Source space analysis localised phonological and lexico-semantic effect peaks to the left superior temporal gyrus, a key area that has been related to core deficits in dyslexia across a range of neuroimaging studies. The results provide comprehensive evidence that phonological deficits impact both sublexical and lexical stages of spoken word processing and that these deficits cannot be fully compensated through neural re-organization of lexical-distributional information at the single word level. Theoretical and practical implications for typical readers, dyslexic readers, and readers with developmental language disorder are discussed.
Neural correlates of statistical learning in developmental dyslexia: An electroencephalography study
2023, Biological Psychology
The human brain extracts statistical regularities from the surrounding environment in a process called statistical learning. Behavioural evidence suggests that developmental dyslexia affects statistical learning. However, surprisingly few studies have assessed how developmental dyslexia affects the neural processing underlying this type of learning. We used electroencephalography to explore the neural correlates of an important aspect of statistical learning – sensitivity to transitional probabilities – in individuals with developmental dyslexia. Adults diagnosed with developmental dyslexia (n = 17) and controls (n = 19) were exposed to a continuous stream of sound triplets. Every so often, a triplet ending had a low transitional probability given the triplet’s first two sounds (“statistical deviants”). Furthermore, every so often a triplet ending was presented from a deviant location (“acoustic deviants”). We examined mismatch negativity elicited by statistical deviants (sMMN), and MMN elicited by location deviants (i.e., acoustic changes). Acoustic deviants elicited a MMN which was larger in the control group than in the developmental dyslexia group. Statistical deviants elicited a small, yet significant, sMMN in the control group, but not in the developmental dyslexia group. However, the difference between the groups was not significant. Our findings indicate that the neural mechanisms underlying pre-attentive acoustic change detection and implicit statistical auditory learning are both affected in developmental dyslexia.
Increased top-down semantic processing in natural speech linked to better reading in dyslexia
2023, NeuroImage
Early research proposed that individuals with developmental dyslexia use contextual information to facilitate lexical access and compensate for phonological deficits. Yet at present there is no corroborating neuro-cognitive evidence. We explored this with a novel combination of magnetoencephalography (MEG), neural encoding and grey matter volume analyses. We analysed MEG data from 41 adult native Spanish speakers (14 with dyslexic symptoms) who passively listened to naturalistic sentences. We used multivariate Temporal Response Function analysis to capture online cortical tracking of both auditory (speech envelope) and contextual information. To compute contextual information tracking we used word-level Semantic Surprisal derived using a Transformer Neural Network language model. We related online information tracking to participants’ reading scores and grey matter volumes within the reading-linked cortical network. We found that right hemisphere envelope tracking was related to better phonological decoding (pseudoword reading) for both groups, with dyslexic readers performing worse overall at this task. Consistently, grey matter volume in the superior temporal and bilateral inferior frontal areas increased with better envelope tracking abilities. Critically, for dyslexic readers only, stronger Semantic Surprisal tracking in the right hemisphere was related to better word reading. These findings further support the notion of a speech envelope tracking deficit in dyslexia and provide novel evidence for top-down semantic compensatory mechanisms.
Neural phoneme discrimination in variable speech in newborns – Associations with dyslexia risk and later language skills
2023, Brain and Cognition
A crucial skill in infant language acquisition is learning of the native language phonemes. This requires the ability to group complex sounds into distinct auditory categories based on their shared features. Problems in phonetic learning have been suggested to underlie language learning difficulties in dyslexia, a developmental reading-skill deficit. We investigated auditory abilities important for language acquisition in newborns with or without a familial risk for dyslexia with electrophysiological mismatch responses (MMRs). We presented vowel changes in a sequence of acoustically varying vowels, requiring grouping of the stimuli to two phoneme categories. The vowel changes elicited an MMR which was significantly diminished in infants whose parents had the most severe dyslexia in our sample. Phoneme-MMR amplitude and its hemispheric lateralization were associated with language test outcomes assessed at 28 months, an age at which it becomes possible to behaviourally test children and several standardized tests are available. In addition, statistically significant MMRs to violations of a complex sound-order rule were only found in infants without dyslexia risk, but these results are very preliminary due to small sample size. The results demonstrate the relevance of the newborn infants’ readiness for phonetic learning for their emerging language skills. Phoneme extraction difficulties in infants at familial risk may contribute to the phonological deficits observed in dyslexia.
Neurodevelopmental oscillatory basis of speech processing in noise
2023, Developmental Cognitive Neuroscience
Citation Excerpt :
It is even at the core of the asymmetric sampling in time hypothesis, which argues that prosodic and syllabic information are preferentially processed in the right hemisphere, while phonemic information is preferentially processed in the left hemisphere or bilaterally (Poeppel, 2003). As previously argued (Giraud and Ramus, 2013), the fact that language brain functions become asymmetric in the course of development suggests asymmetry is a hallmark of maturity. Our results highlight two distinct neuromaturational effects related to the ability to perceive speech in babble noise.
Humans’ extraordinary ability to understand speech in noise relies on multiple processes that develop with age. Using magnetoencephalography (MEG), we characterize the underlying neuromaturational basis by quantifying how cortical oscillations in 144 participants (aged 5–27 years) track phrasal and syllabic structures in connected speech mixed with different types of noise. While the extraction of prosodic cues from clear speech was stable during development, its maintenance in a multi-talker background matured rapidly up to age 9 and was associated with speech comprehension. Furthermore, while the extraction of subtler information provided by syllables matured at age 9, its maintenance in noisy backgrounds progressively matured until adulthood. Altogether, these results highlight distinct behaviorally relevant maturational trajectories for the neuronal signatures of speech perception. In accordance with grain-size proposals, neuromaturational milestones are reached increasingly late for linguistic units of decreasing size, with further delays incurred by noise.

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Neurogenetics and auditory processing in developmental dyslexia

Highlights

Introduction

Section snippets

Molecular genetics of dyslexia and related cognitive and brain phenotypes

Dyslexia candidate genes influence cortical neuronal migration and microcircuits

A mechanistic hypothesis for linking genetic cortical anomalies and the phonological impairment in dyslexia

Conclusion

References and recommended reading

Cross-national comparisons of developmental dyslexia in Italy and the United States

Child Dev

Developmental dyslexia

Lancet

Evidence for aberrant auditory anatomy in developmental dyslexia

Proc Natl Acad Sci U S A

Subcortical differentiation of stop consonants relates to reading and speech-in-noise perception

Proc Natl Acad Sci U S A

The genetic lexicon of dyslexia

Annu Rev Genomics Hum Genet

Identification of novel dyslexia candidate genes through the analysis of a chromosomal deletion

Am J Med Genet B Neuropsychiatr Genet

A theoretical molecular network for dyslexia: integrating available genetic findings

Mol Psychiatry

Association of the KIAA0319 dyslexia susceptibility gene with reading skills in the general population

Am J Psychiatry

Analysis of dyslexia candidate genes in the raine cohort representing the general Australian population

Genes Brain Behav

A haplotype spanning KIAA0319 and TTRAP is associated with normal variation in reading and spelling ability

Biol Psychiatry

DCDC2, KIAA0319 and CMIP are associated with reading-related traits

Biol Psychiatry

Dyslexia and DCDC2: normal variation in reading and spelling is associated with DCDC2 polymorphisms in an Australian population sample

Eur J Hum Genet

Dissection of genetic associations with language-related traits in population-based cohorts

J Neurodev Disord

Association of short-term memory with a variant within DYX1C1 in developmental dyslexia

Genes Brain Behav

DCDC2 genetic variants and susceptibility to developmental dyslexia

Psychiatr Genet

Dyslexia and DYX1C1: deficits in reading and spelling associated with a missense mutation

Mol Psychiatry

Genetic variance in a component of the language acquisition device: ROBO1 polymorphisms associated with phonological buffer deficits

Behav Genet

Mapping for dyslexia and related cognitive trait loci provides strong evidence for further risk genes on chromosome 6p21

Am J Med Genet B Neuropsychiatr Genet

Surface area accounts for the relation of gray matter volume to reading-related skills and history of dyslexia

Cereb Cortex

The contribution of white and gray matter differences to developmental dyslexia: insights from DTI and VBM at 3.0 T

Neuropsychologia

Polymorphism of DCDC2 reveals differences in cortical morphology of healthy individuals — a preliminary voxel based morphometry study

Brain Imaging Behav

Developmental dyslexia: four consecutive patients with cortical anomalies

Ann Neurol

Three dyslexia susceptibility genes, DYX1C1, DCDC2, and KIAA0319, affect temporo-parietal white matter structure

Biol Psychiatry

A tractography study in dyslexia: neuroanatomic correlates of orthographic, phonological and speech processing

Brain

Impaired semantic processing during sentence reading in children with dyslexia: combined fMRI and ERP evidence

Neuroimage

Neural correlates of temporal auditory processing in developmental dyslexia during german vowel length discrimination: an fMRI study

Brain Lang

Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions

J Neurosci

FOXP2 expression during brain development coincides with adult sites of pathology in a severe speech and language disorder

Brain

Foxp2 regulates gene networks implicated in neurite outgrowth in the developing brain

PLoS Genet

Imaging genetics of FOXP2 in dyslexia

Eur J Hum Genet