Publications

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

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 carried out the first study on the relationship between individual language aptitude and structural connectivity of language pathways in the adult brain. We measured four components of language aptitude (vocabulary learning, VocL; sound recognition, SndRec; sound-symbol correspondence, SndSym; and grammatical inferencing, GrInf) using the LLAMA language aptitude test (Meara, 2005). Spatial working memory (SWM), verbal working memory (VWM) and IQ were also measured as control factors. Diffusion Tensor Imaging (DTI) was employed to investigate the structural connectivity of language pathways in the perisylvian language network. Principal Component Analysis (PCA) on behavioural measures suggests that a general ability might be important to the first stages of L2 acquisition. It also suggested that VocL, SndSy and SWM are more closely related to general IQ than SndRec and VocL, and distinguished the tasks specifically designed to tap into L2 acquisition (VocL, SndRec,SndSym and GrInf) from more generic measures (IQ, SWM and VWM). Regression analysis suggested significant correlations between most of these behavioural measures and the structural connectivity of certain language pathways, i.e., VocL and BA47-Parietal pathway, SndSym and inter-hemispheric BA45 pathway, GrInf and BA45-Temporal pathway and BA6-Temporal pathway, IQ and BA44-Parietal pathway, BA47-Parietal pathway, BA47-Temporal pathway and inter-hemispheric BA45 pathway, SWM and inter-hemispheric BA6 pathway and BA47-Parietal pathway, and VWM and BA47-Temporal pathway. These results are discussed in relation to relevant findings in the literature.

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

Four experiments investigated the role of the syllable in Chinese spoken word production. Chen, Chen and Ferrand (2003) reported a syllable priming effect when primes and targets shared the first syllable using a masked priming paradigm in Chinese. Our Experiment 1 was a direct replication of Chen et al.'s (2003) Experiment 3 employing CV (e. g., /ba2.ying2/, strike camp) and CVG (e. g., /bai2.shou3/, white haired) syllable types. Experiment 2 tested the syllable priming effect using different syllable types: e. g., CV (/qi4.qiu2/, balloon) and CVN (/qing1.ting2/, dragonfly). Experiment 3 investigated this issue further using line drawings of common objects as targets that were preceded either by a CV (e. g., /qi3/, attempt), or a CVN (e. g., /qing2/, affection) prime. Experiment 4 further examined the priming effect by a comparison between CV or CVN priming and an unrelated priming condition using CV-NX (e. g., /mi2.ni3/, mini) and CVN-CX (e. g., /min2.ju1/, dwellings) as target words. These four experiments consistently found that CV targets were named faster when preceded by CV primes than when they were preceded by CVG, CVN or unrelated primes, whereas CVG or CVN targets showed the reverse pattern. These results indicate that the priming effect critically depends on the match between the structure of the prime and that of the first syllable of the target. The effect obtained in this study was consistent across different stimuli and different tasks (word and picture naming), and provides more conclusive and consistent data regarding the role of the syllable in Chinese speech production.

Abstract

This article reports on results from a broad crosslinguistic study based on data from thirty-five signed languages around the world. The study is the first of its kind, and the typological generalizations presented here cover the domain of interrogative structures as they appear across a wide range of geographically and genetically distinct signed languages. Manual and nonmanual ways of marking basic types of questions in signed languages are investigated. As a result, it becomes clear that the range of crosslinguistic variation is extensive for some subparameters, such as the structure of question-word paradigms, while other parameters, such as the use of nonmanual expressions in questions, show more similarities across signed languages. Finally, it is instructive to compare the findings from signed language typology to relevant data from spoken languages at a more abstract, crossmodality level.

Abstract

This article presents a typology of negative constructions across a substantial number of sign languages from around the globe. After situating the topic within the wider context of linguistic typology, the main negation strategies found across sign languages are described. Nonmanual negation includes the use of head movements and facial expressions for negation and is of great importance in sign languages as well as particularly interesting from a typological point of view. As far as manual signs are concerned, independent negative particles represent the dominant strategy, but there are also instances of irregular negation in most sign languages. Irregular negatives may take the form of suppletion, cliticisation, affixing, or internal modification of a sign. The results of the study lead to interesting generalisations about similarities and differences between negatives in signed and spoken languages.

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

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

Semantic unification, the process by which small blocks of semantic information are combined into a coherent utterance, has been studied with various types of tasks. However, whether the brain activations reported in these studies are attributed to semantic unification per se or to other task-induced concomitant processes still remains unclear. The neural basis for semantic unification in sentence comprehension was examined using event-related potentials (ERP) and functional Magnetic Resonance Imaging (fMRI). The semantic unification load was manipulated by varying the goodness of fit between a critical word and its preceding context (in high cloze, low cloze and violation sentences). The sentences were presented in a serial visual presentation mode. The participants were asked to perform one of three tasks: semantic congruency judgment (SEM), silent reading for comprehension (READ), or font size judgment (FONT), in separate sessions. The ERP results showed a similar N400 amplitude modulation by the semantic unification load across all of the three tasks. The brain activations associated with the semantic unification load were found in the anterior left inferior frontal gyrus (aLIFG) in the FONT task and in a widespread set of regions in the other two tasks. These results suggest that the aLIFG activation reflects a semantic unification, which is different from other brain activations that may reflect task-specific strategic processing.

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

How does language comprehension interact with motor activity? We investigated the conditions under which comprehending an action sentence affects people's balance. We performed two experiments to assess whether sentences describing forward or backward movement modulate the lateral movements made by subjects who made sensibility judgments about the sentences. In one experiment subjects were standing on a balance board and in the other they were seated on a balance board that was mounted on a chair. This allowed us to investigate whether the action compatibility effect (ACE) is robust and persists in the face of salient incompatibilities between sentence content and subject movement. Growth-curve analysis of the movement trajectories produced by the subjects in response to the sentences suggests that the ACE is indeed robust. Sentence content influenced movement trajectory despite salient inconsistencies between implied and actual movement. These results are interpreted in the context of the current discussion of embodied, or grounded, language comprehension and meaning representation.

Abstract

This paper explores the expression of multiple entities in Turkish Sign Language (Türk İşaret Dili; TİD), a less well-studied sign language. It aims to provide a comprehensive description of the ways and frequencies in which entity plurality in this language is expressed, both within and outside the noun phrase. We used a corpus that includes both elicited and spontaneous data from native signers. The results reveal that most of the expressions of multiple entities in TİD are iconic, spatial strategies (i.e. localization and spatial plural predicate inflection) none of which, we argue, should be considered as genuine plural marking devices with the main aim of expressing plurality. Instead, the observed devices for localization and predicate inflection allow for a plural interpretation when multiple locations in space are used. Our data do not provide evidence that TİD employs (productive) morphological plural marking (i.e. reduplication) on nouns, in contrast to some other sign languages and many spoken languages. We relate our findings to expression of multiple entities in other signed languages and in spoken languages and discuss these findings in terms of modality effects on expression of multiple entities in human language.

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.