Language-related Disorders Research Articles

From Sound to Meaning: Navigating Wernicke's Area in Language Processing.

Wernicke's area, a critical brain region associated with language comprehension, was first identified by Carl Wernicke in the late 19th century. Situated in the left hemisphere's posterior superior temporal gyrus, this area is essential for processing auditory and visual language inputs. It integrates semantic and syntactic information, playing a key role in meaningful communication. The development of Wernicke's area during infancy and childhood is marked by rapid growth and refinement influenced by early language exposure and environmental stimuli. Neuroplasticity, the brain's ability to reorganize and adapt, is crucial for recovery from language impairments such as Wernicke's aphasia. This capacity for reorganization includes synaptic plasticity and axonal sprouting, which facilitate recovery through targeted rehabilitation and enriched environments. Recent research utilizing advanced neuroimaging and neuroanatomical tracing techniques has elucidated the connectivity of Wernicke's area with other language-related regions, such as Broca's area. Functional studies have revealed its specialized roles in processing different aspects of language, including phonological, semantic, and syntactic features. Moreover, investigations into language disorders and potential therapeutic interventions underscore the importance of harnessing neuroplasticity for effective treatment. Emerging technologies, such as non-invasive brain stimulation and multimodal imaging, offer promising avenues for further exploration of Wernicke's area and its role in language functions. These innovations hold the potential to enhance our understanding of language processing and improve therapeutic strategies for language impairments. In conclusion, Wernicke's area is central to language comprehension, and genetic and environmental factors influence its development. Understanding neuroplasticity and leveraging advanced research technologies can significantly advance our ability to address language-related disorders and enhance patient outcomes.

Language and reading impairments are associated with increased prevalence of non-right-handedness.

Handedness has been studied for association with language-related disorders because of its link with language hemispheric dominance. No clear pattern has emerged, possibly because of small samples, publication bias, and heterogeneous criteria across studies. Non-right-handedness (NRH) frequency was assessed in N=2503 cases with reading and/or language impairment and N=4316 sex-matched controls identified from 10 distinct cohorts (age range 6-19 years old; European ethnicity) using a priori set criteria. A meta-analysis (Ncases =1994) showed elevated NRH % in individuals with language/reading impairment compared with controls (OR=1.21, CI=1.06-1.39, p=.01). The association between reading/language impairments and NRH could result from shared pathways underlying brain lateralization, handedness, and cognitive functions.

Genome-wide analysis of runs of homozygosity in Pakistani controls with no history of speech or language-related developmental phenotypes

Background Runs of homozygosity (ROHs) analysis of controls provide a convenient resource to minimize the association of false positive results of disease-associated ROHs and genetic variants for simple and complex disorders in individuals from the same population. Evidence for the value of ROHs to speech or language-related traits is restricted due to the absence of population-matched behaviourally defined controls and limited family-based studies. Aim This study aims to identify common ROHs in the Pakistani population, focussing on the total length and frequency of ROHs of variable sizes, shared ROHs, and their genomic distribution. Subjects and methods We performed homozygosity analysis (in PLINK) of 86 individuals (39 males, 47 females) with no history of speech or language-related phenotypes (controls) who had been genotyped with the Illumina Infinium QC Array-24. Results ROHs of 1-<4 megabases (Mb) were frequent in unrelated individuals. We observed ROHs over 20 Mb among six individuals. Over 30 percent of the identified ROHs were shared among several individuals, indicating consanguinity’s effect on the Pakistani population. Conclusion Our findings serve as a foundation for family-based genetic studies of consanguineous families with speech or language-related disorders to ultimately narrow the homozygosity regions of interest to identify pathogenic variants.

Hyperexcitable and immature-like neuronal activity in the auditory cortex of adult rats lacking the language-linked CNTNAP2 gene.

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant risk gene thought to play a role in the genetic etiology of language-related disorders, such as autism spectrum disorder and developmental language disorder. Despite its candidacy for influencing language development, few preclinical studies have examined the role of CNTNAP2 in auditory processing. Using in vivo and in vitro electrophysiological recordings in a rat model with translational validity, we report that a loss of the Cntnap2 gene function caused immature-like cortical evoked potentials, delayed multiunit response latencies to acoustic stimuli, impaired temporal processing, and led to a pattern of hyperexcitability in both multiunit and single cell recordings in adulthood. These collective results provide direct evidence that a constitutive loss of Cntnap2 gene function in rats can cause auditory processing impairments similar to those seen in language-related human disorders, indicating that its contribution in maintaining cortical neuron excitability may underlie the cortical activity alterations observed in Cntnap2-/- rats.

MIPA: A theory of phonological acquisition and speech motor control

Despite long-standing interest in the relation of early speech production and phonological development, little is known about how speech motor skills develop in tandem with emerging phonological representations in childhood. Recent experimental work in our laboratory has shown that better speech motor control at young ages is associated with better outcomes at later ages in phonological sensitivity. In this talk we will advance a new, theoretical model to account for these findings. It is termed MIPA (Motor Involvement in Phonological Acquisition) and proposes that highly developed sensorimotor maps for speech support the acquisition of detailed phonological representations. We will begin by providing an overview of the model, its core predictions, and compare it to existing frameworks. We will then describe experimental studies designed to explore the conceptual merits of the model by testing children longitudinally on a set of measures assessing the coordination of vocal-tract gestures, phonological sensitivity, and the relationship between those two skills. Application of the model to the study and treatment of children with developmental disabilities that affect speech production, such as stuttering, as well as language-related disorders arising from poor sensitivity to phonological structure, such as dyslexia, will also be briefly described.

Whole-genome sequencing identifies functional noncoding variation in SEMA3C that cosegregates with dyslexia in a multigenerational family

Dyslexia is a common heritable developmental disorder involving impaired reading abilities. Its genetic underpinnings are thought to be complex and heterogeneous, involving common and rare genetic variation. Multigenerational families segregating apparent monogenic forms of language-related disorders can provide useful entrypoints into biological pathways. In the present study, we performed a genome-wide linkage scan in a three-generational family in which dyslexia affects 14 of its 30 members and seems to be transmitted with an autosomal dominant pattern of inheritance. We identified a locus on chromosome 7q21.11 which cosegregated with dyslexia status, with the exception of two cases of phenocopy (LOD = 2.83). Whole-genome sequencing of key individuals enabled the assessment of coding and noncoding variation in the family. Two rare single-nucleotide variants (rs144517871 and rs143835534) within the first intron of the SEMA3C gene cosegregated with the 7q21.11 risk haplotype. In silico characterization of these two variants predicted effects on gene regulation, which we functionally validated for rs144517871 in human cell lines using luciferase reporter assays. SEMA3C encodes a secreted protein that acts as a guidance cue in several processes, including cortical neuronal migration and cellular polarization. We hypothesize that these intronic variants could have a cis-regulatory effect on SEMA3C expression, making a contribution to dyslexia susceptibility in this family.

Misunderstandings about developmental dyslexia: a historical overview.

Developmental dyslexia is a reading disorder unrelated to intellectual disability, inadequate teaching systems or poor motivation for schooling. The first attempts to understand such difficulty of learning to read, connected the problem to a primary ‘visual defect’. Since then, several models have been developed. In the last decades, autopsy and histopathological studies on the brain of developmental dyslexics provided neuroanatomical evidence of structural and morphological differences between the normal and dyslexic brains. Furthermore, neuroimaging studies allowed to understand the neural systems of reading and dyslexia. According to more recent studies, developmental dyslexia appears as a language-related neurodevelopmental disorder with a deficit in phonological decoding and visuospatial organization of the language code. Therefore, dyslexia is viewed as a multicomponential and complex disorder. Consequently, rehabilitation should be aimed at both the recovery of linguistic decoding processes and the improvement of visuo-spatial and attentional processes. This brief overview should be a valuable tool for a deeper understanding of dyslexic disorder. Literature searches in Medline, PsycINFO, EMBASE, Scopus, PubMed, Web of Science identified one hundred articles focusing attention on how this disorder has been considered over the years.

Frequency-Dependent Intrinsic Electrophysiological Functional Architecture of the Human Verbal Language Network.

Functional magnetic resonance imaging (fMRI) allowed the spatial characterization of the resting-state verbal language network (vLN). While other resting-state networks (RSNs) were matched with their electrophysiological equivalents at rest and could be spectrally defined, such correspondence is lacking for the vLN. This magnetoencephalography (MEG) study aimed at defining the spatio-spectral characteristics of the neuromagnetic intrinsic functional architecture of the vLN. Neuromagnetic activity was recorded at rest in 100 right-handed healthy adults (age range: 18–41 years). Band-limited power envelope correlations were performed within and across frequency bands (θ, α, β, and low γ) from a seed region placed in the left Broca’s area, using static orthogonalization as leakage correction. K-means clustering was used to segregate spatio-spectral clusters of resting-state functional connectivity (rsFC). Remarkably, unlike other RSNs, within-frequency long-range rsFC from the left Broca’s area was not driven by one main carrying frequency but was characterized by a specific spatio-spectral pattern segregated along the ventral (predominantly θ and α) and dorsal (β and low-γ bands) vLN streams. In contrast, spatial patterns of cross-frequency vLN functional integration were spectrally more widespread and involved multiple frequency bands. Moreover, the static intrinsic functional architecture of the neuromagnetic human vLN involved clearly left-hemisphere-dominant vLN interactions as well as cross-network interactions with the executive control network and postero-medial nodes of the DMN. Overall, this study highlighted the involvement of multiple modes of within and cross-frequency power envelope couplings at the basis of long-range electrophysiological vLN functional integration. As such, it lays the foundation for future works aimed at understanding the pathophysiology of language-related disorders.

Language competence of four-year-old children with immigration background in Hesse: quo vadis?

A sustainable integration of persons with immigration background is more topical than ever before. The importance of language as one of the key aspects of integration is beyond discussion. In 2018, ca. 1 091 000 persons with the non-German citizenship were registered in the German state of Hesse. One third of all Hessian inhabitants and a half of those of preschool age had an immigration background. The tendency is increasing due to, first, ongoing immigration and, second, higher birth rates in non-German families. Consequently, the numbers of preschoolers with minimal German language skills and with language-related disorders such as hearing disorders are also rising. This study aimed to analyze the German language competence of Hessian four-year-old children with immigration background. The assessment was carried out by the validated, standardized test "Kindersprachscreening". For children who were classified as needing additional medical assistance in acquiring German, following variables were analyzed: participation in therapies, known diagnoses of impairments and illnesses, parents' and kindergarten teachers' awareness of the child's need for additional medical assistance in acquiring German.

The Multidimensional Battery of Prosody Perception (MBOPP)

Prosody can be defined as the rhythm and intonation patterns spanning words, phrases and sentences. Accurate perception of prosody is an important component of many aspects of language processing, such as parsing grammatical structures, recognizing words, and determining where emphasis may be placed. Prosody perception is important for language acquisition and can be impaired in language-related developmental disorders. However, existing assessments of prosodic perception suffer from some shortcomings. These include being unsuitable for use with typically developing adults due to ceiling effects, or failing to allow the investigator to distinguish the unique contributions of individual acoustic features such as pitch and temporal cues. Here we present the Multi-Dimensional Battery of Prosody Perception (MBOPP), a novel tool for the assessment of prosody perception. It consists of two subtests: Linguistic Focus, which measures the ability to hear emphasis or sentential stress, and Phrase Boundaries, which measures the ability to hear where in a compound sentence one phrase ends, and another begins. Perception of individual acoustic dimensions (Pitch and Time) can be examined separately, and test difficulty can be precisely calibrated by the experimenter because stimuli were created using a continuous voice morph space. We present validation analyses from a sample of 57 individuals and discuss how the battery might be deployed to examine perception of prosody in various populations.

The Neurocognition of Developmental Disorders of Language.

Developmental disorders of language include developmental language disorder, dyslexia, and motor-speech disorders such as articulation disorder and stuttering. These disorders have generally been explained by accounts that focus on their behavioral rather than neural characteristics; their processing rather than learning impairments; and each disorder separately rather than together, despite their commonalities and comorbidities. Here we update and review a unifying neurocognitive account-the Procedural circuit Deficit Hypothesis (PDH). The PDH posits that abnormalities of brain structures underlying procedural memory (learning and memory that rely on the basal ganglia and associated circuitry) can explain numerous brain and behavioral characteristics across learning and processing, in multiple disorders, including both commonalities and differences. We describe procedural memory, examine its role in various aspects of language, and then present the PDH and relevant evidence across language-related disorders. The PDH has substantial explanatory power, and both basic research and translational implications.

Prevalence of communication disorders in a rural population at taluq level of Gujarat, India

ObjectivesThe main objective of the study was to estimate the prevalence of communication disorders between genders and across age groups. MethodsThe All India Institute of Speech and Hearing, Mysore conducted a Speech and Hearing camp as a part of the annual activity of National Service Scheme (NSS) in Sinor Taluq, Vadodara district, Gujarat State of India. Speech and Hearing camp was conducted in 15 villages of Sinor Taluq. These villages were selected randomly and the population of these villages was 28,954 (twenty eight thousand nine hundred fifty-four). ResultsAmong the 28,954 individuals surveyed, 1187 (4.09%) individuals were found to have communication disorder. The overall prevalence of ear-related disorders was 3.30% (male – 1.66%, female – 1.63%) and prevalence of speech- and language-related disorder was 0.79% (male – 0.60%, female – 0.24%). ConclusionThe results of the present study could be used to plan and execute policies for the identification, management, and rehabilitation of individuals with communication disorders.

Cortical speech and non-speech discrimination in relation to cognitive measures in preschool children.

Effective speech sound discrimination at preschool age is known to be a prerequisite for the development of language skills and later literacy acquisition. However, the speech specificity of cortical discrimination skills in small children is currently not known, as previous research has either studied speech functions without comparison with non-speech sounds, or used much simpler sounds such as harmonic or sinusoidal tones as control stimuli. We investigated the cortical discrimination of five syllable features (consonant, vowel, vowel duration, fundamental frequency, and intensity), covering both segmental and prosodic phonetic changes, and their acoustically matched non-speech counterparts in 63 6-year-old typically developed children, by using a multi-feature mismatch negativity (MMN) paradigm. Each of the five investigated features elicited a unique pattern of differentiating negativities: an early differentiating negativity, MMN, and a late differentiating negativity. All five studied features showed speech-related enhancement of at least one of these responses, suggesting experience-related neural commitment in both phonetic and prosodic speech processing. In addition, the cognitive performance and language skills of the children were tested extensively. The speech-related neural enhancement was positively associated with the level of performance in several neurocognitive tasks, indicating a relationship between successful establishment of cortical memory traces for speech and enhanced cognitive functioning. The results contribute to the understanding of typical developmental trajectories of linguistic vs. non-linguistic auditory skills, and provide a reference for future studies investigating deficits in language-related disorders at preschool age.

Understanding Language from a Genomic Perspective.

Language is a defining characteristic of the human species, but its foundations remain mysterious. Heritable disorders offer a gateway into biological underpinnings, as illustrated by the discovery that FOXP2 disruptions cause a rare form of speech and language impairment. The genetic architecture underlying language-related disorders is complex, and although some progress has been made, it has proved challenging to pinpoint additional relevant genes with confidence. Next-generation sequencing and genome-wide association studies are revolutionizing understanding of the genetic bases of other neurodevelopmental disorders, like autism and schizophrenia, and providing fundamental insights into the molecular networks crucial for typical brain development. We discuss how a similar genomic perspective, brought to the investigation of language-related phenotypes, promises to yield equally informative discoveries. Moreover, we outline how follow-up studies of genetic findings using cellular systems and animal models can help to elucidate the biological mechanisms involved in the development of brain circuits supporting language.

The Cognitive and Behavioral Phenotype of the 16p11.2 Deletion in a Clinically Ascertained Population

BackgroundDeletion of the recurrent ~600 kb BP4-BP5 chromosomal region 16p11.2 has been associated with a wide range of neurodevelopmental outcomes. MethodsTo clarify the phenotype of 16p11.2 deletion, we examined the psychiatric and developmental presentation of predominantly clinically referred individuals, with a particular emphasis on broader autism phenotype characteristics in individuals with recurrent ~600 kb chromosome 16p11.2 deletions. Using an extensive standardized assessment battery across three clinical sites, 85 individuals with the 16p11.2 deletion and 153 familial control subjects were evaluated for symptom presentation and clinical diagnosis. ResultsIndividuals with the 16p11.2 deletion presented with a high frequency of psychiatric and developmental disorders (>90%). The most commonly diagnosed conditions were developmental coordination disorder, phonologic processing disorder, expressive and receptive language disorders (71% of individuals >3 years old with a speech and language–related disorder), and autism spectrum disorder. Individuals with the 16p11.2 deletion not meeting diagnostic criteria for autism spectrum disorder had a significantly higher prevalence of autism-related characteristics compared with the familial noncarrier control group. Individuals with the 16p11.2 deletion had a range of intellectual ability, but IQ scores were 26 points lower than noncarrier family members on average. ConclusionsClinically referred individuals with the 16p11.2 deletion have high rates of psychiatric and developmental disorders and provide a genetically well-defined group to study the emergence of developmental difficulties, particularly associated with the broader autism phenotype.

Hemispheric Asymmetry in Auditory Processing of Speech Envelope Modulations in Prereading Children

The temporal envelope of speech is an important cue contributing to speech intelligibility. Theories about the neural foundations of speech perception postulate that the left and right auditory cortices are functionally specialized in analyzing speech envelope information at different time scales: the right hemisphere is thought to be specialized in processing syllable rate modulations, whereas a bilateral or left hemispheric specialization is assumed for phoneme rate modulations. Recently, it has been found that this functional hemispheric asymmetry is different in individuals with language-related disorders such as dyslexia. Most studies were, however, performed in adults and school-aged children, and only a little is known about how neural auditory processing at these specific rates manifests and develops in very young children before reading acquisition. Yet, studying hemispheric specialization for processing syllable and phoneme rate modulations in preliterate children may reveal early neural markers for dyslexia. In the present study, human cortical evoked potentials to syllable and phoneme rate modulations were measured in 5-year-old children at high and low hereditary risk for dyslexia. The results demonstrate a right hemispheric preference for processing syllable rate modulations and a symmetric pattern for phoneme rate modulations, regardless of hereditary risk for dyslexia. These results suggest that, while hemispheric specialization for processing syllable rate modulations seems to be mature in prereading children, hemispheric specialization for phoneme rate modulation processing may still be developing. These findings could have important implications for the development of phonological and reading skills.

Distribution of language‐related Cntnap2 protein in neural circuits critical for vocal learning

Variants of the contactin associated protein-like 2 (Cntnap2) gene are risk factors for language-related disorders including autism spectrum disorder, specific language impairment, and stuttering. Songbirds are useful models for study of human speech disorders due to their shared capacity for vocal learning, which relies on similar cortico-basal ganglia circuitry and genetic factors. Here we investigate Cntnap2 protein expression in the brain of the zebra finch, a songbird species in which males, but not females, learn their courtship songs. We hypothesize that Cntnap2 has overlapping functions in vocal learning species, and expect to find protein expression in song-related areas of the zebra finch brain. We further expect that the distribution of this membrane-bound protein may not completely mirror its mRNA distribution due to the distinct subcellular localization of the two molecular species. We find that Cntnap2 protein is enriched in several song control regions relative to surrounding tissues, particularly within the adult male, but not female, robust nucleus of the arcopallium (RA), a cortical song control region analogous to human layer 5 primary motor cortex. The onset of this sexually dimorphic expression coincides with the onset of sensorimotor learning in developing males. Enrichment in male RA appears due to expression in projection neurons within the nucleus, as well as to additional expression in nerve terminals of cortical projections to RA from the lateral magnocellular nucleus of the nidopallium. Cntnap2 protein expression in zebra finch brain supports the hypothesis that this molecule affects neural connectivity critical for vocal learning across taxonomic classes.

The Impacts of Language Background and Language-Related Disorders in Auditory Processing Assessment

To examine the impact of language background and language-related disorders (LRDs--dyslexia and/or language impairment) on performance in English speech and nonspeech tests of auditory processing (AP) commonly used in the clinic. A clinical database concerning 133 multilingual children (mostly with English as an additional language) and 71 monolingual children (7- to 12-year-old native English speakers) with listening concerns was analyzed retrospectively. Language background had no significant effect on the 3 nonspeech AP tests, but the multilingual group performed worse in most of the speech tests. Children with LRDs generally performed more poorly than those without, except for the masking level difference. Although language background affects performance in AP tasks that use speech, the effect of LRDs appears to be more wide-ranging insofar as the majority of the AP tests--speech and nonspeech--were significantly affected by their presence. The effects of language background are probably mediated directly through the effects of language expertise, whereas those associated with LRDs appear to arise from associated deficits in memory and attention. The vast majority of so-called AP tests tap abilities far beyond those typically thought of as specifically auditory; thus, they are poor measures of an AP disorder.

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

Recent advances in the field of language-related disorders have led to the identification of candidate genes for specific language impairment (SLI) and dyslexia. Replication studies have been conducted in independent samples including population-based cohorts, which can be characterised for a large number of relevant cognitive measures. The availability of a wide range of phenotypes allows us to not only identify the most suitable traits for replication of genetic association but also to refine the associated cognitive trait. In addition, it is possible to test for pleiotropic effects across multiple phenotypes which could explain the extensive comorbidity observed across SLI, dyslexia and other neurodevelopmental disorders. The availability of genome-wide genotype data for such cohorts will facilitate this kind of analysis but important issues, such as multiple test corrections, have to be taken into account considering that small effect sizes are expected to underlie such associations.

Unravelling neurogenetic networks implicated in developmental language disorders

Childhood syndromes disturbing language development are common and display high degrees of heritability. In most cases, the underlying genetic architecture is likely to be complex, involving multiple chromosomal loci and substantial heterogeneity, which makes it difficult to track down the crucial genomic risk factors. Investigation of rare Mendelian phenotypes offers a complementary route for unravelling key neurogenetic pathways. The value of this approach is illustrated by the discovery that heterozygous FOXP2 (where FOX is forkhead box) mutations cause an unusual monogenic disorder, characterized by problems with articulating speech along with deficits in expressive and receptive language. FOXP2 encodes a regulatory protein, belonging to the forkhead box family of transcription factors, known to play important roles in modulating gene expression in development and disease. Functional genetics using human neuronal models suggest that the different FOXP2 isoforms generated by alternative splicing have distinct properties and may act to regulate each other's activity. Such investigations have also analysed the missense and nonsense mutations found in cases of speech and language disorder, showing that they alter intracellular localization, DNA binding and transactivation capacity of the mutated proteins. Moreover, in the brains of mutant mice, aetiological mutations have been found to disrupt the synaptic plasticity of Foxp2-expressing circuitry. Finally, although mutations of FOXP2 itself are rare, the downstream networks which it regulates in the brain appear to be broadly implicated in typical forms of language impairment. Thus, through ongoing identification of regulated targets and interacting co-factors, this gene is providing the first molecular entry points into neural mechanisms that go awry in language-related disorders.