Publications

Abstract

In spoken interactions, interlocutors carefully plan and time their utterances, minimising gaps and overlaps between consecutive turns. Cross-linguistic comparison has indicated that spoken languages vary only minimally in terms of turn-timing, and language acquisition research has shown pre-linguistic vocal turn-taking in the first half year of life. These observations suggest that the turn-taking system may provide a fundamental basis for our linguistic capacities. The question remains however to what extent our capacity for rapid turn-taking is determined by modality constraints. The avoidance of overlapping turns could be motivated by the difficulty of hearing and speaking at the same time. If so, turn-taking in sign might show greater toleration for overlap. Alternatively, signed conversations may show a similar distribution of turn-timing as spoken languages, thus avoiding both gaps and overlaps. To address this question we look at turn-timing in question-answer sequences in spontaneous conversations of Sign Language of the Netherlands. The findings indicate that although there is considerable overlap in two or more signers' articulators in conversation, when proper allowance is made for onset preparation, post-utterance retraction and the intentional holding of signs for response, turn-taking latencies in sign look remarkably like those reported for spoken language. This is consistent with the possibility that, at least with regard to responses to questions, speakers and signers follow similar time courses in planning and producing their utterances in on-going conversation. This suggests that turn-taking systems may well be a shared cognitive infrastructure underlying all modern human languages, both spoken and signed.

Abstract

Artificial grammar learning constitutes a well-established model for the acquisition of grammatical knowledge in a natural setting. Previous neuroimaging studies demonstrated that Broca's area (left BA 44/45) is similarly activated by natural syntactic processing and artificial grammar learning. The current study was conducted to investigate the causal relationship between Broca's area and learning of an artificial grammar by means of transcranial direct current stimulation (tDCS). Thirty-eight healthy subjects participated in a between-subject design, with either anodal tDCS (20 min, 1 mA) or sham stimulation, over Broca's area during the acquisition of an artificial grammar. Performance during the acquisition phase, presented as a working memory task, was comparable between groups. In the subsequent classification task, detecting syntactic violations, and specifically, those where no cues to superficial similarity were available, improved significantly after anodal tDCS, resulting in an overall better performance. A control experiment where 10 subjects received anodal tDCS over an area unrelated to artificial grammar learning further supported the specificity of these effects to Broca's area. We conclude that Broca's area is specifically involved in rule-based knowledge, and here, in an improved ability to detect syntactic violations. The results cannot be explained by better tDCS-induced working memory performance during the acquisition phase. This is the first study that demonstrates that tDCS may facilitate acquisition of grammatical knowledge, a finding of potential interest for rehabilitation of aphasia.

Abstract

Recently, an increasing number of studies have suggested a role for the basal ganglia and related dopamine inputs in procedural learning, specifically when learning occurs through trial-by-trial feedback (Shohamy, Myers, Kalanithi, & Gluck. (2008). Basal ganglia and dopamine contributions to probabilistic category learning. Neuroscience and Biobehavioral Reviews, 32, 219–236). A necessary relationship has however only been demonstrated in patient studies. In the present study, we show for the first time that increasing dopamine levels in the brain improves the gradual acquisition of complex information in healthy participants. We implemented two artificial-grammar-learning tasks, one with and one without performance feedback. Learning was improved after levodopa intake for the feedback-based learning task only, suggesting that dopamine plays a specific role in trial-by-trial feedback-based learning. This provides promising directions for future studies on dopaminergic modulation of cognitive functioning.

Abstract

Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.

Abstract

Using event-related potentials (ERPs), this study examines how trait information inferred from behaviors is associated with person names. In linguistic discourses, person names were associated with descriptions of either positive or negative behaviors. In a subsequent explicit evaluation task, the previously described person names were presented in isolation, and the participants were asked to judge the emotional valence of these names. We found that the names associated with positive descriptions elicited a larger positivity in the ERP than the names associated with negative descriptions. The results indicate that the emotional valence of person names attached to person perception can be dynamically influenced by short descriptions of the target person, probably due to trait inference based on the provided behavioral descriptions

Abstract

Does the way a word is written influence its spoken production? Previous studies suggest that orthography is involved only when the orthographic representation is highly relevant during speaking (e.g., in reading-aloud tasks). To address this issue, we carried out two experiments using the blocked cyclic picture-naming paradigm. In both experiments, participants were asked to name pictures repeatedly in orthographically homogeneous or heterogeneous blocks. In the naming task, the written form was not shown; however, the radical of the first character overlapped between the four pictures in this block type. A facilitative orthographic effect was found when picture names shared part of their written forms, compared with the heterogeneous condition. This facilitative effect was independent of the position of orthographic overlap (i.e., the left, the lower, or the outer part of the character). These findings strongly suggest that orthography can influence speaking even when it is not highly relevant (i.e., during picture naming) and the orthographic effect is less likely to be attributed to strategic preparation.

Abstract

While listeners are recognizing words from the connected speech stream, they are also parsing information from the intonational contour. This contour may contain cues to word boundaries, particularly if a language has boundary tones that occur at a large proportion of word onsets. We investigate how useful the pitch rise at the beginning of an accentual phrase (APR) would be as a potential word-boundary cue for Japanese listeners. A corpus study shows that it should allow listeners to locate approximately 40–60% of word onsets, while causing less than 1% false positives. We then present a word-spotting study which shows that Japanese listeners can, indeed, use accentual phrase boundary cues during segmentation. This work shows that the prosodic patterns that have been found in the production of Japanese also impact listeners’ processing.

Abstract

Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

Abstract

Background: Several studies have investigated the effect of known adult body mass index (BMI) associated single nucleotide polymorphisms (SNPs) on BMI in childhood. There has been no genome-wide association study (GWAS) of BMI trajectories over childhood.
Methods: We conducted a GWAS meta-analysis of BMI trajectories from 1 to 17 years of age in 9377 children (77 967 measurements) from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Western Australian Pregnancy Cohort (Raine) Study. Genome-wide significant loci were examined in a further 3918 individuals (48 530 measurements) from Northern Finland. Linear mixed effects models with smoothing splines were used in each cohort for longitudinal modelling of BMI.
Results: A novel SNP, downstream from the FAM120AOS gene on chromosome 9, was detected in the meta-analysis of ALSPAC and Raine. This association was driven by a difference in BMI at 8 years (T allele of rs944990 increased BMI; PSNP = 1.52 × 10−8), with a modest association with change in BMI over time (PWald(Change) = 0.006). Three known adult BMI-associated loci (FTO, MC4R and ADCY3) and one childhood obesity locus (OLFM4) reached genome-wide significance (PWald < 1.13 × 10−8) with BMI at 8 years and/or change over time.
Conclusions: This GWAS of BMI trajectories over childhood identified a novel locus that warrants further investigation. We also observed genome-wide significance with previously established obesity loci, making the novel observation that these loci affected both the level and the rate of change in BMI. We have demonstrated that the use of repeated measures data can increase power to allow detection of genetic loci with smaller sample sizes.

Abstract

Exposure to high levels of environmental lead, or biomarker evidence of high body lead content, is associated with anaemia, developmental and neurological deficits in children, and increased mortality in adults. Adverse effects of lead still occur despite substantial reduction in environmental exposure. There is genetic variation between individuals in blood lead concentration but the polymorphisms contributing to this have not been defined. We measured blood or erythrocyte lead content, and carried out genome-wide association analysis, on population-based cohorts of adult volunteers from Australia and UK (N = 5433). Samples from Australia were collected in two studies, in 1993–1996 and 2002–2005 and from UK in 1991–1992. One locus, at ALAD on chromosome 9, showed consistent association with blood lead across countries and evidence for multiple independent allelic effects. The most significant single nucleotide polymorphism (SNP), rs1805313 (P = 3.91 × 10−14 for lead concentration in a meta-analysis of all data), is known to have effects on ALAD expression in blood cells but other SNPs affecting ALAD expression did not affect blood lead. Variants at 12 other loci, including ABO, showed suggestive associations (5 × 10−6 >} P {> 5 × 10−8). Identification of genetic polymorphisms affecting blood lead reinforces the view that genetic factors, as well as environmental ones, are important in determining blood lead levels. The ways in which ALAD variation affects lead uptake or distribution are still to be determined.

Abstract

An event-related brain potential experiment was carried out to investigate on-line thematic role assignment during sentence–picture matching in patients with Broca's aphasia. Subjects were presented with a picture that was followed by an auditory sentence. The sentence either matched the picture or mismatched the visual information depicted. Sentences differed in complexity, and ranged from simple active semantically irreversible sentences to passive semantically reversible sentences. ERPs were recorded while subjects were engaged in sentence–picture matching. In addition, reaction time and accuracy were measured. Three groups of subjects were tested: Broca patients (N = 10), non-aphasic patients with a right hemisphere (RH) lesion (N = 8), and healthy aged-matched controls (N = 15). The results of this study showed that, in neurologically unimpaired individuals, thematic role assignment in the context of visual information was an immediate process. This in contrast to patients with Broca's aphasia who demonstrated no signs of on-line sensitivity to the picture–sentence mismatches. The syntactic contribution to the thematic role assignment process seemed to be diminished given the reduction and even absence of P600 effects. Nevertheless, Broca patients showed some off-line behavioral sensitivity to the sentence–picture mismatches. The long response latencies of Broca's aphasics make it likely that off-line response strategies were used.

Abstract

Induced pluripotent stem cell (iPSC) technology has emerged as an important tool in understanding, and potentially reversing, disease pathology. This is particularly true in the case of neurodegenerative diseases, in which the affected cell types are not readily accessible for study. Since the first descriptions of iPSC-based disease modelling, considerable advances have been made in understanding the aetiology and progression of a diverse array of neurodegenerative conditions, including Parkinson's disease and Alzheimer's disease. To date, however, relatively few studies have succeeded in using iPSCs to model the neurodegeneration observed in cerebellar ataxia. Given the distinct neurodevelopmental phenotypes associated with certain types of ataxia, iPSC-based models are likely to provide significant insights, not only into disease progression, but also to the development of early-intervention therapies. In this review, we describe the existing iPSC-based disease models of this heterogeneous group of conditions and explore the challenges associated with generating cerebellar neurons from iPSCs, which have thus far hindered the expansion of this research.

Abstract

The primary goal of psycholinguistic research is to understand the architectures and mechanisms that underlie human language comprehension and production. This entails an understanding of how linguistic knowledge is represented and organized in the brain and a theory of how that knowledge is accessed when we use language. Research has traditionally emphasized purely linguistic aspects of on-line comprehension, such as the influence of lexical, syntactic, semantic and discourse constraints, and their tim -course. It has become increasingly clear, however, that nonlinguistic information, such as the visual environment, are also actively exploited by situated language comprehenders.

Abstract

Over 15% of probands in a large cohort of more than 1500 inherited retinal degeneration patients present with a clinical diagnosis of Stargardt disease (STGD1), a recessive form of macular dystrophy caused by biallelic variants in the ABCA4 gene. Participants were clinically examined and underwent either target capture sequencing of the exons and some pathogenic intronic regions of ABCA4, sequencing of the entire ABCA4 gene or whole genome sequencing. ABCA4 c.4539 + 2028C > T, p.[= ,Arg1514Leufs*36] is a pathogenic deep intronic variant that results in a retina-specific 345-nucleotide pseudoexon inclusion. Through analysis of the Irish STGD1 cohort, 25 individuals across 18 pedigrees harbour ABCA4 c.4539 + 2028C > T and another pathogenic variant. This includes, to the best of our knowledge, the only two homozygous patients identified to date. This provides important evidence of variant pathogenicity for this deep intronic variant, highlighting the value of homozygotes for variant interpretation. 15 other heterozygous incidents of this variant in patients have been reported globally, indicating significant enrichment in the Irish population. We provide detailed genetic and clinical characterization of these patients, illustrating that ABCA4 c.4539 + 2028C > T is a variant of mild to intermediate severity. These results have important implications for unresolved STGD1 patients globally with approximately 10% of the population in some western countries claiming Irish heritage. This study exemplifies that detection and characterization of founder variants is a diagnostic imperative.

Abstract

In this paper, we report an experiment on the naming of household containers in Dutch and Icelandic carried out as part of the Evolution of Semantic Systems project (EoSS; Majid et al., 2011). This naming experiment allows us to support and elaborate on a hypothesis by Malt et al. (2003) that productive morphology in the naming domain can have an influence on boundary placement within the extensional space. Specifically, we demonstrate that the Dutch diminutive -(t)je favours a cut between small items versus others, whereas Icelandic, which does not use the diminutive in this domain, favours a cut between large items and others. This is not a typological effect, as Dutch and Icelandic are both Germanic languages and both have diminutive morphology available in principle. We find no evidence that the diminutive produces a proliferation of terms and/or fine-grained nesting within the extensional domain. Rather, the Dutch diminutive favours a more even distribution of terms across the space whereas Icelandic favours broad inclusive terms with a number of narrower specialist terms. Further, the extensional space defined by the diminutive is not associated with its own clear prototypical exemplar. Using evidence from compounding and modification, we also consider which semantic features are prominent in differentiating categories within the domain. By far the most prominent in both languages is the inferred contents of the container. Other than contents, however, the languages differ in the range and prominence of features such as intended usage or material of composition. Our results demonstrate that in order to understand the processes that produce semantic divisions of basic object classes, we should consider fine-grained analyses of closely related languages alongside analyses of typologically different languages.

Abstract

Pointing gestures are recognised to be a primary manifestation of human social cognition and communicative capacity. The goal of this task is to collect empirical descriptions of pointing practices in different cultural settings.

Abstract

Although generally studied in isolation, language and action often co-occur in everyday life. Here we investigated one particular form of simultaneous language and action, namely speech and gestures that speakers use in everyday communication. In a functional magnetic resonance imaging study, we identified the neural networks involved in the integration of semantic information from speech and gestures. Verbal and/or gestural content could be integrated easily or less easily with the content of the preceding part of speech. Premotor areas involved in action observation (Brodmann area [BA] 6) were found to be specifically modulated by action information "mismatching" to a language context. Importantly, an increase in integration load of both verbal and gestural information into prior speech context activated Broca's area and adjacent cortex (BA 45/47). A classical language area, Broca's area, is not only recruited for language-internal processing but also when action observation is integrated with speech. These findings provide direct evidence that action and language processing share a high-level neural integration system.

Abstract

According to theories of embodied cognition, understanding a verb like throw involves unconsciously simulating the action of throwing, using areas of the brain that support motor planning. If understanding action words involves mentally simulating one’s own actions, then the neurocognitive representation of word meanings should differ for people with different kinds of bodies, who perform actions in systematically different ways. In a test of the body-specificity hypothesis, we used functional magnetic resonance imaging to compare premotor activity correlated with action verb understanding in right- and left-handers. Righthanders preferentially activated the left premotor cortex during lexical decisions on manual-action verbs (compared with nonmanual-action verbs), whereas left-handers preferentially activated right premotor areas. This finding helps refine theories of embodied semantics, suggesting that implicit mental simulation during language processing is body specific: Right- and lefthanders, who perform actions differently, use correspondingly different areas of the brain for representing action verb meanings.

Abstract

The left-hemisphere dominance for language is a core example of the functional specialization of the cerebral hemispheres. The degree of left-hemisphere dominance for language depends on hand preference: Whereas the majority of right-handers show left-hemispheric language lateralization, this number is reduced in left-handers. Here, we assessed whether handedness analogously has an influence upon lateralization in the visual system. Using functional magnetic resonance imaging, we localized 4 more or less specialized extrastriate areas in left- and right-handers, namely fusiform face area (FFA), extrastriate body area (EBA), fusiform body area (FBA), and human motion area (human middle temporal [hMT]). We found that lateralization of FFA and EBA depends on handedness: These areas were right lateralized in right-handers but not in left-handers. A similar tendency was observed in FBA but not in hMT. We conclude that the relationship between handedness and hemispheric lateralization extends to functionally lateralized parts of visual cortex, indicating a general coupling between cerebral lateralization and handedness. Our findings indicate that hemispheric specialization is not fixed but can vary considerably across individuals even in areas engaged relatively early in the visual system.

Abstract

Although language is an effective vehicle for communication, it is unclear how linguistic and communicative abilities relate to each other. Some researchers have argued that communicative message generation involves perspective taking (mentalizing), and—crucially—that mentalizing depends on language. We employed a verbal communication paradigm to directly test whether the generation of a communicative action relies on mentalizing and whether the cerebral bases of communicative message generation are distinct from parts of cortex sensitive to linguistic variables. We found that dorsomedial prefrontal cortex, a brain area consistently associated with mentalizing, was sensitive to the communicative intent of utterances, irrespective of linguistic difficulty. In contrast, left inferior frontal cortex, an area known to be involved in language, was sensitive to the linguistic demands of utterances, but not to communicative intent. These findings show that communicative and linguistic abilities rely on cerebrally (and computationally) distinct mechanisms

Abstract

Here we review evidence from cognitive neuroscience for a tight relation between language and action in the brain. We focus on two types of relation between language and action. First, we investigate whether the perception of speech and speech sounds leads to activation of parts of the cortical motor system also involved in speech production. Second, we evaluate whether understanding action-related language involves the activation of parts of the motor system. We conclude that whereas there is considerable evidence that understanding language can involve parts of our motor cortex, this relation is best thought of as inherently flexible. As we explain, the exact nature of the input as well as the intention with which language is perceived influences whether and how motor cortex plays a role in language processing.

Abstract

Co-speech gestures embody a form of manual action that is tightly coupled to the language system. As such, the co-occurrence of speech and co-speech gestures is an excellent example of the interplay between language and action. There are, however, other ways in which language and action can be thought of as closely related. In this paper we will give an overview of studies in cognitive neuroscience that examine the neural underpinnings of links between language and action. Topics include neurocognitive studies of motor representations of speech sounds, action-related language, sign language and co-speech gestures. It will be concluded that there is strong evidence on the interaction between speech and gestures in the brain. This interaction however shares general properties with other domains in which there is interplay between language and action.

Abstract

According to embodied theories of language, people understand a verb like throw, at least in part, by mentally simulating throwing. This implicit simulation is often assumed to be similar or identical to motor imagery. Here we used fMRI totest whether implicit simulations of actions during language understanding involve the same cortical motor regions as explicit motor imagery Healthy participants were presented with verbs related to hand actions (e.g., to throw) and nonmanual actions (e.g., to kneel). They either read these verbs (lexical decision task) or actively imagined performing the actions named by the verbs (imagery task). Primary motor cortex showd effector-specific activation during imagery, but not during lexical decision. Parts of premotor cortex distinguished manual from nonmanual actions during both lexical decision and imagery, but there was no overlap or correlation between regions activated during the two tasks. These dissociations suggest that implicit simulation and explicit imagery cued by action verbs may involve different types of motor representations and that the construct of “mental simulation” should be distinguished from “mental imagery” in embodied theories of language.

Abstract

The human capacity to communicate has been hypothesized to be causally dependent upon language. Intuitively this seems plausible since most communication relies on language. Moreover, intention recognition abilities (as a necessary prerequisite for communication) and language development seem to co-develop. Here we review evidence from neuroimaging as well as from neuropsychology to evaluate the relationship between communicative and linguistic abilities. Our review indicates that communicative abilities are best considered as neurally distinct from language abilities. This conclusion is based upon evidence showing that humans rely on different cortical systems when designing a communicative message for someone else as compared to when performing core linguistic tasks, as well as upon observations of individuals with severe language loss after extensive lesions to the language system, who are still able to perform tasks involving intention understanding

Abstract

Impaired emotion regulation may underlie exaggerated emotional reactivity in patients with obsessive compulsive disorder (OCD), yet instructed emotion regulation has never been studied in the disorder. METHOD: This study aimed to assess the neural correlates of emotion processing and regulation in 43 medication-free OCD patients and 38 matched healthy controls, and additionally test if these can be modulated by stimulatory (patients) and inhibitory (controls) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (dlPFC). Participants performed an emotion regulation task during functional magnetic resonance imaging before and after a single session of randomly assigned real or sham rTMS. Effect of group and rTMS were assessed on self-reported distress ratings and brain activity in frontal-limbic regions of interest. RESULTS: Patients had higher distress ratings than controls during emotion provocation, but similar rates of distress reduction after voluntary emotion regulation. OCD patients compared with controls showed altered amygdala responsiveness during symptom provocation and diminished left dlPFC activity and frontal-amygdala connectivity during emotion regulation. Real v. sham dlPFC stimulation differentially modulated frontal-amygdala connectivity during emotion regulation in OCD patients. CONCLUSIONS: We propose that the increased emotional reactivity in OCD may be due to a deficit in emotion regulation caused by a failure of cognitive control exerted by the dorsal frontal cortex. Modulatory rTMS over the left dlPFC may influence automatic emotion regulation capabilities by influencing frontal-limbic connectivity.

Abstract

In three cross-modal priming experiments we asked whether adaptation to a foreign-accented speaker is automatic, and whether adaptation can be seen after a long delay between initial exposure and test. Dutch listeners were exposed to a Hebrew-accented Dutch speaker with two types of Dutch words: those that contained [ɪ] (globally accented words), and those in which the Dutch [i] was shortened to [ɪ] (specific accent marker words). Experiment 1, which served as a baseline, showed that native Dutch participants showed facilitatory priming for globally accented, but not specific accent, words. In experiment 2, participants performed a 3.5-minute phoneme monitoring task, and were tested on their comprehension of the accented speaker 24 hours later using the same cross-modal priming task as in experiment 1. During the phoneme monitoring task, listeners were asked to detect a consonant that was not strongly accented. In experiment 3, the delay between exposure and test was extended to 1 week. Listeners in experiments 2 and 3 showed facilitatory priming for both globally accented and specific accent marker words. Together, these results show that adaptation to a foreign-accented speaker can be rapid and automatic, and can be observed after a prolonged delay in testing.

Abstract

The modality learning effect, according to Mayer (2001), proposes that learning is enhanced when information is presented in both the visual and auditory domain (e.g., pictures and spoken information), compared to presenting information solely in the visual channel (e.g., pictures and written text). Most of the evidence for this effect comes from adults in a laboratory setting. Therefore, we tested the modality effect with 80 children in the highest grade of elementary school, in a naturalistic setting. In a between-subjects design children either saw representational pictures with speech or representational pictures with text. Retention and transfer knowledge was tested at three moments: immediately after the intervention, one day after, and after one week. The present study did not find any evidence for a modality effect in children when the lesson is learner-paced. Instead, we found a reversed modality effect directly after the intervention for retention. A reversed modality effect was also found for the transfer questions one day later. This effect was robust, even when controlling for individual differences.

Abstract

Languages are among the most complex systems that evolution has created. With an unforeseen speed many of these unique results of evolution are currently disappearing: every two weeks one of the 6500 still spoken languages is dying and many are subject to extreme changes due to globalization. Experts understood the need to document the languages and preserve the cultural and linguistic treasures embedded in them for future generations. Also linguistic theory will need to consider the variation of the linguistic systems encoded in languages to improve our understanding of how human minds process language material, thus accessibility to all types of resources is increasingly crucial. Deeper insights into human language processing and a higher degree of integration and interoperability between resources will also improve our language processing technology. The DOBES programme is focussing on the documentation and preservation of language material. The Max Planck Institute developed the Language Archiving Technology to help researchers when creating, archiving and accessing language resources. The recently started CLARIN research infrastructure has as main goals to achieve a broad visibility and an easy
accessibility of language resources.

Abstract

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = −0.59, P = 2.10E−04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

Abstract

In het onderwijs wordt aangenomen dat hardop en stillezen dezelfde processen zijn. In dit onderzoek wordt gekeken naar het verschil tussen hardop en stillezen wat betreft leessnelheid en tekstbegrip bij 90 kinderen uit groep 4. Ook wordt de invloed van de cognitieve vaardigheden fonologisch bewustzijn, benoemsnelheid en visuele aandachtsspanne op de verschillende leesmodi onderzocht. De participanten lazen stil sneller, maar begrepen de tekst beter hardop. De cognitieve vaardigheden correleerden met hardop en stillezen wat betreft leessnelheid, maar hingen in beide leesmodi niet samen met tekstbegrip. Hoewel hardop en stillezen samenhangen, onderstrepen deze bevindingen dat het verschillende leesmodi zijn.

Abstract

Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions.

Abstract

Diffusion tensor imaging (DTI) and a longitudinal language learning approach were applied to investigate the relationship between the achieved second language (L2) proficiency during L2 learning and the reorganization of structural connectivity between core language areas. Language proficiency tests and DTI scans were obtained from German students before and after they completed an intensive 6-week course of the Dutch language. In the initial learning stage, with increasing L2 proficiency, the hemispheric dominance of the BA6-temporal pathway (mainly along the arcuate fasciculus) shifted from the left to the right hemisphere. With further increased proficiency, however, lateralization dominance was again found in the left BA6-temporal pathway. This result is consistent with reports in the literature that imply a stronger involvement of the right hemisphere in L2-processing especially for less proficient L2-speakers. This is the first time that a L2-proficiency-dependent laterality shift in structural connectivity of language pathways during L2 acquisition has been observed to shift from left to right, and back to left hemisphere dominance with increasing L2-proficiency. We additionally find that changes in fractional anisotropy values after the course are related to the time elapsed between the two scans. The results suggest that structural connectivity in (at least part of) the perisylvian language network may be subject to fast dynamic changes following language learning

Abstract

We performed a resting-state functional connectivity study to investigate directly the functional correlations within the perisylvian language networks by seeding from 3 subregions of Broca's complex (pars opercularis, pars triangularis, and pars orbitalis) and their right hemisphere homologues. A clear topographical functional connectivity pattern in the left middle frontal, parietal, and temporal areas was revealed for the 3 left seeds. This is the first demonstration that a functional connectivity topology can be observed in the perisylvian language networks. The results support the assumption of the functional division for phonology, syntax, and semantics of Broca's complex as proposed by the memory, unification, and control (MUC) model and indicated a topographical functional organization in the perisylvian language networks, which suggests a possible division of labor for phonological, syntactic, and semantic function in the left frontal, parietal, and temporal areas.

Abstract

In face-to-face communication, multimodal cues such as prosody, gestures, and mouth movements can play a crucial role in language processing. While several studies have addressed how these cues contribute to native (L1) language processing, their impact on non-native (L2) comprehension is largely unknown. Comprehension of naturalistic language by L2 comprehenders may be supported by the presence of (at least some) multimodal cues, as these provide correlated and convergent information that may aid linguistic processing. However, it is also the case that multimodal cues may be less used by L2 comprehenders because linguistic processing is more demanding than for L1 comprehenders, leaving more limited resources for the processing of multimodal cues. In this study, we investigated how L2 comprehenders use multimodal cues in naturalistic stimuli (while participants watched videos of a speaker), as measured by electrophysiological responses (N400) to words, and whether there are differences between L1 and L2 comprehenders. We found that prosody, gestures, and informative mouth movements each reduced the N400 in L2, indexing easier comprehension. Nevertheless, L2 participants showed weaker effects for each cue compared to L1 comprehenders, with the exception of meaningful gestures and informative mouth movements. These results show that L2 comprehenders focus on specific multimodal cues – meaningful gestures that support meaningful interpretation and mouth movements that enhance the acoustic signal – while using multimodal cues to a lesser extent than L1 comprehenders overall.

Abstract

Osteoblast induction and differentiation in developing long bones is dynamically controlled by the opposing action of transcriptional activators and repressors. In contrast to the long list of activators that have been discovered over past decades, the network of repressors is not well-defined. Here we identify the expression of Foxp1/2/4 proteins, comprised of Forkhead-box (Fox) transcription factors of the Foxp subfamily, in both perichondrial skeletal progenitors and proliferating chondrocytes during endochondral ossification. Mice carrying loss-of-function and gain-of-function Foxp mutations had gross defects in appendicular skeleton formation. At the cellular level, over-expression of Foxp1/2/4 in chondroctyes abrogated osteoblast formation and chondrocyte hypertrophy. Conversely, single or compound deficiency of Foxp1/2/4 in skeletal progenitors or chondrocytes resulted in premature osteoblast differentiation in the perichondrium, coupled with impaired proliferation, survival, and hypertrophy of chondrocytes in the growth plate. Foxp1/2/4 and Runx2 proteins interacted in vitro and in vivo, and Foxp1/2/4 repressed Runx2 transactivation function in heterologous cells. This study establishes Foxp1/2/4 proteins as coordinators of osteogenesis and chondrocyte hypertrophy in developing long bones and suggests that a novel transcriptional repressor network involving Foxp1/2/4 may regulate Runx2 during endochondral ossification.

Abstract

Background: Developmental language disorder (DLD) is a condition that significantly affects children's achievement but has been understudied. We aim to estimate the prevalence of DLD in Shanghai, compare the co-occurrence of difficulties between children with DLD and those with typical development (TD), and investigate the early risk factors for DLD.

Methods: We estimated DLD prevalence using data from a population-based survey with a cluster random sampling design in Shanghai, China. A subsample of children (aged 5-6 years) received an onsite evaluation, and each child was categorized as TD or DLD. The proportions of children with socio-emotional behavior (SEB) difficulties, low non-verbal IQ (NVIQ), and poor school readiness were calculated among children with TD and DLD. We used multiple imputation to address the missing values of risk factors. Univariate and multivariate regression models adjusted with sampling weights were used to estimate the correlation of each risk factor with DLD.

Findings: Of 1082 children who were approached for the onsite evaluation, 974 (90.0%) completed the language ability assessments, of whom 74 met the criteria for DLD, resulting in a prevalence of 8.5% (95% CI 6.3-11.5) when adjusted with sampling weights. Compared with TD children, children with DLD had higher rates of concurrent difficulties, including SEB (total difficulties score at-risk: 156 [17.3%] of 900 TD vs. 28 [37.8%] of 74 DLD, p < 0.0001), low NVIQ (3 [0.3%] of 900 TD vs. 8 [10.8%] of 74 DLD, p < 0.0001), and poor school readiness (71 [7.9%] of 900 TD vs. 13 [17.6%] of 74 DLD, p = 0.0040). After accounting for all other risk factors, a higher risk of DLD was associated with a lack of parent-child interaction diversity (adjusted odds ratio [aOR] = 3.08, 95% CI = 1.29-7.37; p = 0.012) and lower kindergarten levels (compared to demonstration and first level: third level (aOR = 6.15, 95% CI = 1.92-19.63; p = 0.0020)).

Interpretation: The prevalence of DLD and its co-occurrence with other difficulties suggest the need for further attention. Family and kindergarten factors were found to contribute to DLD, suggesting that multi-sector coordinated efforts are needed to better identify and serve DLD populations at home, in schools, and in clinical settings.

Funding: The study was supported by Shanghai Municipal Education Commission (No. 2022you1-2, D1502), the Innovative Research Team of High-level Local Universities in Shanghai (No. SHSMU-ZDCX20211900), Shanghai Municipal Health Commission (No.GWV-10.1-XK07), and the National Key Research and Development Program of China (No. 2022YFC2705201).

Abstract

Face-selective regions (FSRs) are among the most widely studied functional regions in the human brain. However, individual variability of the FSRs has not been well quantified. Here we use functional magnetic resonance imaging (fMRI) to localize the FSRs and quantify their spatial and functional variabilities in 202 healthy adults. The occipital face area (OFA), posterior and anterior fusiform face areas (pFFA and aFFA), posterior continuation of the superior temporal sulcus (pcSTS), and posterior and anterior STS (pSTS and aSTS) were delineated for each individual with a semi-automated procedure. A probabilistic atlas was constructed to characterize their interindividual variability, revealing that the FSRs were highly variable in location and extent across subjects. The variability of FSRs was further quantified on both functional (i.e., face selectivity) and spatial (i.e., volume, location of peak activation, and anatomical location) features. Considerable interindividual variability and rightward asymmetry were found in all FSRs on these features. Taken together, our work presents the first effort to characterize comprehensively the variability of FSRs in a large sample of healthy subjects, and invites future work on the origin of the variability and its relation to individual differences in behavioral performance. Moreover, the probabilistic functional atlas will provide an adequate spatial reference for mapping the face network.

Abstract

Celiac disease (CD) is an intolerance to dietary proteins of wheat, barley, and rye. CD may have substantial morbidity, yet it is quite common with a prevalence of 1%-2% in Western populations. It is not clear why the CD phenotype is so prevalent despite its negative effects on human health, especially because appropriate treatment in the form of a gluten-free diet has only been available since the 1950s, when dietary gluten was discovered to be the triggering factor. The high prevalence of CD might suggest that genes underlying this disease may have been favored by the process of natural selection. We assessed signatures of selection for ten confirmed CD-associated loci in several genome-wide data sets, comprising 8154 controls from four European populations and 195 individuals from a North African population, by studying haplotype lengths via the integrated haplotype score (iHS) method. Consistent signs of positive selection for CD-associated derived alleles were observed in three loci: IL12A, IL18RAP, and SH2B3. For the SH2B3 risk allele, we also show a difference in allele frequency distribution (F(st)) between HapMap phase II populations. Functional investigation of the effect of the SH2B3 genotype in response to lipopolysaccharide and muramyl dipeptide revealed that carriers of the SH2B3 rs3184504*A risk allele showed stronger activation of the NOD2 recognition pathway. This suggests that SH2B3 plays a role in protection against bacteria infection, and it provides a possible explanation for the selective sweep on SH2B3, which occurred sometime between 1200 and 1700 years ago.

Abstract

Genome-wide association studies using thousands to hundreds of thousands of single nucleotide polymorphism (SNP) markers and region-wide association studies using a dense panel of SNPs are already in use to identify disease susceptibility genes and to predict disease risk in individuals. Because these tasks become increasingly important, three different data sets were provided for the Genetic Analysis Workshop 15, thus allowing examination of various novel and existing data mining methods for both classification and identification of disease susceptibility genes, gene by gene or gene by environment interaction. The approach most often applied in this presentation group was random forests because of its simplicity, elegance, and robustness. It was used for prediction and for screening for interesting SNPs in a first step. The logistic tree with unbiased selection approach appeared to be an interesting alternative to efficiently select interesting SNPs. Machine learning, specifically ensemble methods, might be useful as pre-screening tools for large-scale association studies because they can be less prone to overfitting, can be less computer processor time intensive, can easily include pair-wise and higher-order interactions compared with standard statistical approaches and can also have a high capability for classification. However, improved implementations that are able to deal with hundreds of thousands of SNPs at a time are required.

Abstract

Brain oscillations are prevalent in all species and are involved in numerous perceptual operations. α oscillations are thought to facilitate processing through the inhibition of task-irrelevant networks, while β oscillations are linked to the putative reactivation of content representations. Can the proposed functional role of α and β oscillations be generalized from low-level operations to higher-level cognitive processes? Here we address this question focusing on naturalistic spoken language comprehension. Twenty-two (18 female) Dutch native speakers listened to stories in Dutch and French while MEG was recorded. We used dependency parsing to identify three dependency states at each word: the number of (1) newly opened dependencies, (2) dependencies that remained open, and (3) resolved dependencies. We then constructed forward models to predict α and β power from the dependency features. Results showed that dependency features predict α and β power in language-related regions beyond low-level linguistic features. Left temporal, fundamental language regions are involved in language comprehension in α, while frontal and parietal, higher-order language regions, and motor regions are involved in β. Critically, α- and β-band dynamics seem to subserve language comprehension tapping into syntactic structure building and semantic composition by providing low-level mechanistic operations for inhibition and reactivation processes. Because of the temporal similarity of the α-β responses, their potential functional dissociation remains to be elucidated. Overall, this study sheds light on the role of α and β oscillations during naturalistic spoken language comprehension, providing evidence for the generalizability of these dynamics from perceptual to complex linguistic processes.

Abstract

Neural correlates of lexical stress were studied using the mismatch negativity (MMN) component in event-related potentials. The MMN responses were expected to reveal the encoding of stress information into long-term memory and the contributions of prosodic features such as fundamental frequency (F0) and intensity toward lexical access. In a passive oddball paradigm, neural responses to changes in F0, intensity, and in both features together were recorded for words and pseudowords. The findings showed significant differences not only between words and pseudowords but also between prosodic features. Early processing of prosodic information in words was indexed by an intensity-related MMN and an F0-related P200. These effects were stable at right-anterior and mid-anterior regions. At a later latency, MMN responses were recorded for both words and pseudowords at the mid-anterior and posterior regions. The P200 effect observed for F0 at the early latency for words developed into an MMN response. Intensity elicited smaller MMN for pseudowords than for words. Moreover, a larger brain area was recruited for the processing of words than for the processing of pseudowords. These findings suggest earlier and higher sensitivity to prosodic changes in words than in pseudowords, reflecting a language-related process. The present study, therefore, not only establishes neural correlates of lexical stress but also confirms the presence of long-term memory traces for prosodic information in the brain.

Abstract

Research into the neural foundation of perception asserts a model where top-down predictions modulate the bottom-up processing of sensory input. Despite becoming increasingly influential in cognitive neuroscience, the precise account of this predictive coding framework remains debated. In this study, we aim to contribute to this debate by investigating how predictions about prosody facilitate speech perception, and to shed light especially on lexical access influenced by simultaneous predictions in different domains, inter alia, prosodic and semantic. Using a passive auditory oddball paradigm, we examined neural responses to prosodic changes, leading to a semantic change as in Dutch nouns canon [ˈkaːnɔn] ‘cannon’ vs kanon [kaːˈnɔn] ‘canon’, and used acoustically identical pseudowords as controls. Results from twenty-eight native speakers of Dutch (age range 18–32 years) indicated an enhanced P50/N100 complex to prosodic change in pseudowords as well as an MMN response to both words and pseudowords. The enhanced P50/N100 response to pseudowords is claimed to indicate that all relevant auditory information is still processed by the brain, whereas the reduced response to words might reflect the suppression of information that has already been encoded. The MMN response to pseudowords and words, on the other hand, is best justified by the unification of previously established prosodic representations with sensory and semantic input respectively. This pattern of results is in line with the predictive coding framework acting on multiple levels and is of crucial importance to indicate that predictions about linguistic prosodic information are utilized by the brain as early as 50 ms.

Abstract

Language is used in communicative contexts to identify and successfully transmit new information that should be later remembered. In three studies, we used question–answer pairs, a naturalistic device for focusing information, to examine how properties of conversations inform later item memory. In Experiment 1, participants viewed three pictures while listening to a recorded question–answer exchange between two people about the locations of two of the displayed pictures. In a memory recognition test conducted online a day later, participants recognized the names of pictures that served as answers more accurately than the names of pictures that appeared as questions. This suggests that this type of focus indeed boosts memory. In Experiment 2, participants listened to the same items embedded in declarative sentences. There was a reduced memory benefit for the second item, confirming the role of linguistic focus on later memory beyond a simple serial-position effect. In Experiment 3, two participants asked and answered the same questions about objects in a dialogue. Here, answers continued to receive a memory benefit, and this focus effect was accentuated by language production such that information-seekers remembered the answers to their questions better than information-givers remembered the questions they had been asked. Combined, these studies show how people’s memory for conversation is modulated by the referential status of the items mentioned and by the speaker’s roles of the conversation participants.

Abstract

Sign language lexicography has thus far been a relatively obscure area in the world of lexicography. Therefore, this article will contain background information on signed languages and the communities in which they are used, on the lexicography of sign languages, the situation in the Netherlands as well as a review of a sign language dictionary that has recently been published in the Netherlands.