Publications

Abstract

In normal conversation, speakers translate thoughts into words at high speed. To enable this speed, the retrieval of distinct types of linguistic knowledge has to be orchestrated with millisecond precision. The nature of this orchestration is still largely unknown. This report presents dynamic measures of the real-time activation of two basic types of linguistic knowledge, syntax and phonology. Electrophysiological data demonstrate that during noun-phrase production speakers retrieve the syntactic gender of a noun before its abstract phonological properties. This two-step process operates at high speed: the data show that phonological information is already available 40 milliseconds after syntactic properties have been retrieved.

Abstract

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Abstract

The syntactic structure of main and subordinate clauses is determined to a considerable extent by verb biases. For example, some English and Dutch ditransitive verbs have a preference for the prepositional object dative, whereas others are typically used with the double object dative. In this study, we compare the effect of these biases on structure selection in (S)VO and (S)OV dative clauses in the Corpus of Spoken Dutch (CGN). This comparison allowed us to make inferences about the size of the advance planning scope during spontaneous speaking: If the verb is an obligatory component of clause-level advance planning scope, as is claimed by the hypothesis of hierarchical incrementality, then biases should exert their influence on structure choices, regardless of early (VO) or late (OV) position of the verb in the clause. Conversely, if planning proceeds in a piecemeal fashion, strictly guided by lexical availability, as claimed by linear incrementality, then the verb and its associated biases can only influence structure choices in VO sentences. We tested these predictions by analyzing structure choices in the CGN, using mixed logit models. Our results support a combination of linear and hierarchical incrementality, showing a significant influence of verb bias on structure choices in VO, and a weaker (but still significant) effect in OV clauses

Abstract

An introductory study of the perception of stochastically specified events is reported. The initial problem was to determine whether the perceiver can split visual input data of this kind into random and determined components. The inability of subjects to do so with the stimulus material used (a filmlike sequence of dot patterns), led to the more general question of how subjects code this kind of visual material. To meet the difficulty of defining the subjects' responses, two experiments were designed. In both, patterns were presented as a rapid sequence of dots on a screen. The patterns were more or less disturbed by “noise,” i.e. the dots did not appear exactly at their proper places. In the first experiment the response was a rating on a semantic scale, in the second an identification from among a set of alternative patterns. The results of these experiments give some insight in the coding systems adopted by the subjects. First, noise appears to be detrimental to pattern recognition, especially to patterns with little spread. Second, this shows connections with the factors obtained from analysis of the semantic ratings, e.g. easily disturbed patterns show a large drop in the semantic regularity factor, when only a little noise is added.

Abstract

This study investigated whether the negative effect of complexity on artificial grammar learning could be compensated by adding semantics. Participants were exposed to exemplars from a simple or a complex finite state grammar presented with or without a semantic reference field. As expected, performance on a grammaticality judgment test was higher for the simple grammar than for the complex grammar. For the simple grammar, the results also showed that participants presented with a reference field and instructed to decode the meaning of each exemplar (decoding condition) did better than participants who memorized the exemplars without semantic referents (memorize condition). Contrary to expectations, however, there was no significant difference between the decoding condition and the memorize condition for the complex grammar. These findings indicated that the negative effect of complexity remained, despite the addition of semantics. To clarify how the presence of a reference field influenced the learning process, its effects on the acquisition of two types of knowledge (first- and second-order dependencies) and on participants’ awareness of their knowledge were examined. The results tentatively suggested that the reference field enhanced the learning of second-order dependencies. In addition, participants in the decoding condition realized when they had knowledge relevant to making a grammaticality judgment, whereas participants in the memorize condition demonstrated some knowledge of which they were unaware. These results are in line with the view that the reference field enhanced structure learning by making certain dependencies more salient. Moreover, our findings stress the influence of complexity on artificial grammar learning

Abstract

According to the complementary learning systems (CLS) account of word learning, novel words are rapidly acquired (learning system 1), but slowly integrated into the mental lexicon (learning system 2). This two-step learning process has been shown to apply to novel word forms. In this study, we investigated whether novel word meanings are also gradually integrated after acquisition by measuring the extent to which newly learned words were able to prime semantically related words at two different time points. In addition, we investigated whether modality at study modulates this integration process. Sixty-four adult participants studied novel words together with written or spoken definitions. These words did not prime semantically related words directly following study, but did so after a 24-hour delay. This significant increase in the magnitude of the priming effect suggests that semantic integration occurs over time. Overall, words that were studied with a written definition showed larger priming effects, suggesting greater integration for the written study modality. Although the process of integration, reflected as an increase in the priming effect over time, did not significantly differ between study modalities, words studied with a written definition showed the most prominent positive effect after a 24-hour delay. Our data suggest that semantic integration requires time, and that studying in written format benefits semantic integration more than studying in spoken format. These findings are discussed in light of the CLS theory of word learning.

Abstract

As a preliminary to further research on musical consonance an explanatory investigation was made on the different modes of judgment of musical intervals. This was done by way of a semantic differential. Subjects rated 23 intervals against 10 scales. In a factor analysis three factors appeared: pitch, evaluation and fusion. The relation between these factors and some physical characteristics has been investigated. The scale consonant-dissonant showed to be purely evaluative (in opposition to Stumpf's theory). This evaluative connotation is not in accordance with the musicological meaning of consonance. Suggestions to account for this difference have been given.

Abstract

Within the first few years of life, children acquire many of the building blocks of their native language. This not only involves knowledge about the linguistic structure of spoken language, but also knowledge about the way in which this linguistic structure surfaces in their speech input. In this chapter, we review how infants and toddlers cope with differences between speakers and accents. Within the context of milestones in early speech perception, we examine how voice and accent characteristics are integrated during language processing, looking closely at the advantages and disadvantages of speaker and accent familiarity, surface-level deviation between two utterances, variability in the input, and prior speaker exposure. We conclude that although deviation from the child’s standard can complicate speech perception early in life, young listeners can overcome these additional challenges. This suggests that early spoken language processing is flexible and adaptive to the listening situation at hand.

Abstract

Speech requires precise motor control and rapid sequencing of highly complex vocal musculature. Despite its complexity, most people produce spoken language effortlessly. This is due to activity in distributed neuronal circuitry including cortico-striato-thalamic loops that control speech-motor output. Understanding the neuro-genetic mechanisms that encode these pathways will shed light on how humans can effortlessly and innately use spoken language and could elucidate what goes wrong in speech-language disorders.
FOXP2 was the first single gene identified to cause speech and language disorder. Individuals with FOXP2 mutations display a severe speech deficit that also includes receptive and expressive language impairments. The underlying neuro-molecular mechanisms controlled by FOXP2, which will give insight into our capacity for speech-motor control, are only beginning to be unraveled. Recently FOXP2 was found to regulate genes involved in retinoic acid signaling and to modify the cellular response to retinoic acid, a key regulator of brain development. Herein we explore the evidence that FOXP2 and retinoic acid signaling function in the same pathways. We present evidence at molecular, cellular and behavioral levels that suggest an interplay between FOXP2 and retinoic acid that may be important for fine motor control and speech-motor output.
We propose that retinoic acid signaling is an exciting new angle from which to investigate how neurogenetic mechanisms can contribute to the (spoken) language ready brain.

Abstract

Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG). Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms) duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process

Abstract

The present research investigates how consumer choice is affected by Terror Management Theory’s proposition of Mortality Salience increasing one’s cultural worldview defense and self-esteem striving. The study builds empirically upon prior theorizing by Arndt, Solomon, Kasser and Sheldon (2004). During an experiment, we manipulated Mortality Salience and measured product preferences for conspicuousness and familiarity. Participants primed with death were more likely to choose conspicuous products, corroborating previous research of mortality salience raising materialistic tendencies. In addition, participants showed a tendency to prefer familiar brands. These results are in line with the Terror Management Theory framework.

Abstract

OBJECTIVES: Deficits in response inhibition have been associated with attention-deficit/hyperactivity disorder (ADHD). Given the role of serotonin in ADHD and impulsivity, we postulated that genetic variants within the serotonin pathway might influence response inhibition. METHODS: We measured neural activation during stop-signal task performance in adolescents with ADHD (N = 185), their unaffected siblings (N = 111), and healthy controls (N = 124), and investigated the relationship of two serotonin gene polymorphisms (the rs6296 SNP of the HTR1B gene and HTTLPR variants of the 5-HTT gene) with the neural correlates of response inhibition. RESULTS: The whole-brain analyses demonstrated large scale neural activation differences in the inferior and medial frontal and temporal/parietal regions of the response inhibition network between the different variants of both the HTR1B and 5HTT genes. Activation in these regions was significantly associated with stop-task performance, but not with ADHD diagnosis or severity. No associations were found between HTR1B and 5HTT variants and ADHD or ADHD-related neural activation. CONCLUSIONS: These results provide novel evidence that serotonin may play an important role in the neurobiology of response inhibition. Although response inhibition is strongly linked to ADHD, serotonin linked genetic variants associated with response inhibition and its neural correlates do not explain variance of the ADHD phenotype.

Abstract

An important issue in current psycholinguistics is how the time course of utterance planning affects the generation of grammatical structures. The current study investigated the influence of parallel activation of the components of complex noun phrases on the generation of subject-verb agreement. Specifically, the lexical interference account (Gillespie, M. and Pearlmutter, N. J., 2011b and Solomon, E. S. and Pearlmutter, N. J., 2004) predicts more agreement errors (i.e., attraction) for subject phrases in which the head and local noun mismatch in number (e.g., the apple next to the pears) when nouns are planned in parallel than when they are planned in sequence. We used a speeded picture description task that yielded sentences such as the apple next to the pears is red. The objects mentioned in the noun phrase were either semantically related or unrelated. To induce agreement errors, pictures sometimes mismatched in number. In order to manipulate the likelihood of parallel processing of the objects and to test the hypothesized relationship between parallel processing and the rate of agreement errors, the pictures were either placed close together or far apart. Analyses of the participants' eye movements and speech onset latencies indicated slower processing of the first object and stronger interference from the related (compared to the unrelated) second object in the close than in the far condition. Analyses of the agreement errors yielded an attraction effect, with more errors in mismatching than in matching conditions. However, the magnitude of the attraction effect did not differ across the close and far conditions. Thus, spatial proximity encouraged parallel processing of the pictures, which led to interference of the associated conceptual and/or lexical representation, but, contrary to the prediction, it did not lead to more attraction errors.

Abstract

Objective: To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). Methods: We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared. Results: Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p < 0.001) but not in age at first nonvaccination-associated seizure, age at first report of developmental delay, or cognitive outcome. The risk of subsequent vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination. Conclusions: Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific.

Abstract

Recent research has put forward the idea that Chinese speech production is governed by the syllable as the fundamental phonological unit. However, it may be that onset priming might be more difficult to obtain in Mandarin Chinese. Therefore, in this study, the degree of overlap between prime and target was increased from C to CV (i.e., extending beyond the phoneme) as well as whether primes and targets had an overlapping structure (CV vs. CVN). Subsyllabic priming effects were found (i.e., onset + vowel overlap but not purely onset overlap), contrasting with the claim that the syllable is the compulsory building block in the initial construction of Mandarin Chinese phonology.

Abstract

The Microsoft KINECT is a 3D sensing device originally developed for the XBOX. The Microsoft KINECT opens up many exciting new opportunities for conducting experimental research on human behavior. We investigated some of these possibilities within the field of psycholinguistics (specifically: language production) by creating software, using C#, allowing for the KINECT to be used in a typical psycholinguistic experimental setting. The results of a naming experiment using this software confirmed that the KINECT was able to measure the effects of a robust psycholinguistic variable (word frequency) on naming latencies. However, although the current version of the software is able to measure psycholinguistic variables of interest, we also discuss several points where the software can still stand to be improved. The main aim of this paper is to make the software freely available for assessment and use by the psycholinguistic community and to illustrate the KINECT as a potentially valuable tool for investigating human behavior, especially in the field of psycholinguistics.

Abstract

Learning new words is an increasingly common necessity in everyday life. External factors, among which music and social interaction are particularly debated, are claimed to facilitate this task. Due to their influence on the learner’s temporal behavior, these stimuli are able to drive the learner’s attention to the correct referent of new words at the correct point in time. However, do music and social interaction impact learning behavior in the same way? The current study aims to answer this question. Native German speakers (N = 80) were requested to learn new words (pseudo-words) during a contextual learning game. This learning task was performed alone with a computer or with a partner, with or without music. Results showed that music and social interaction had a different impact on the learner’s behavior: Participants tended to temporally coordinate their behavior more with a partner than with music, and in both cases more than with a computer. However, when both music and social interaction were present, this temporal coordination was hindered. These results suggest that while music and social interaction do influence participants’ learning behavior, they have a different impact. Moreover, impaired behavior when both music and a partner are present suggests that different mechanisms are employed to coordinate with the two types of stimuli. Whether one or the other approach is more efficient for word learning, however, is a question still requiring further investigation, as no differences were observed between conditions in a retrieval phase, which took place immediately after the learning session. This study contributes to the literature on word learning in adults by investigating two possible facilitating factors, and has important implications for situations such as music therapy, in which music and social interaction are present at the same time.

Abstract

The classic account of language is that language processing occurs in isolation from other cognitive systems, like perception, motor action, and emotion. The central theme of this paper is the relationship between a participant’s emotional state and language comprehension. Does emotional context affect how we process neutral words? Recent studies showed that processing of word meaning – traditionally conceived as an automatic process – is affected by emotional state. The influence of emotional state on syntactic processing is less clear. One study reported a mood-related P600 modulation, while another study did not observe an effect of mood on syntactic processing. The goals of this study were: First, to clarify whether and if so how mood affects syntactic processing. Second, to shed light on the underlying mechanisms by separating possible effects of mood from those of attention on syntactic processing. Event-related potentials (ERPs) were recorded while participants read syntactically correct or incorrect sentences. Mood (happy vs. sad) was manipulated by presenting film clips. Attention was manipulated by directing attention to syntactic features vs. physical features. The mood induction was effective. Interactions between mood, attention and syntactic correctness were obtained, showing that mood and attention modulated P600. The mood manipulation led to a reduction in P600 for sad as compared to happy mood when attention was directed at syntactic features. The attention manipulation led to a reduction in P600 when attention was directed at physical features compared to syntactic features for happy mood. From this we draw two conclusions: First, emotional state does affect syntactic processing. We propose mood-related differences in the reliance on heuristics as the underlying mechanism. Second, attention can contribute to emotion-related ERP effects in syntactic language processing. Therefore, future studies on the relation between language and emotion will have to control for effects of attention

Abstract

Languages combine arbitrary and iconic signals. How do iconic signals emerge and when do they persist? We present an experimental study of the role of iconicity in the emergence of structure in an artificial language. Using an iterated communication game in which we control the signalling medium as well as the meaning space, we study the evolution of communicative signals in transmission chains. This sheds light on how affordances of the communication medium shape and constrain the mappability and transmissibility of form-meaning pairs. We find that iconic signals can form the building blocks for wider compositional patterns

Abstract

The last four decades have seen huge progress in the description and analysis of cross-linguistic diversity in the encoding of motion (Talmy 1985, 1991, Slobin 1996, 2004). Comparisons between satellite-framed and verb-framed languages suggest that satellite-framed languages typically have a larger manner of motion verb lexicon (swim, dash), while verb-framed languages typically have a larger path of motion verb lexicon (enter, cross) (Slobin 2004, Verkerk 2013, 2014b). This paper investigates how differences between the motion verb lexicons of satellite-framed and verb-framed languages emerge. Phylogenetic comparative methods adopted from biology and an etymological study are used to investigate manner verb lexicons and path verb lexicons in an Indo-European dataset. I show that manner verbs and path verbs typically have different types of etymological origins and that manner verbs emerge faster in satellite-framed subgroups, while path verbs emerge faster in verb-framed subgroups.

Abstract

Since the 1990s, the field of sign language typology has shown that sign languages exhibit typological variation at all relevant levels of linguistic description. These initial typological comparisons were heavily skewed toward the urban sign languages of developed countries, mostly in the Western world. This review reports on the recent contributions made by rural signing varieties, that is, sign languages that have evolved in village communities, often in developing countries, due to a high incidence of deafness. With respect to a number of structural properties, rural sign languages fit into previously established typological classifications. However, they also exhibit unique and typologically marked features that challenge received views on possible sign languages. At the same time, the shared features of geographically dispersed rural signing varieties provide a unique window into the social dynamics that may shape the structures of modern human languages.

Abstract

Signed utterances are densely packed with pointing signs, reaching a frequency of one in six signs in spontaneous conversations (de Vos, 2012; Johnston, 2013a; Morford & MacFarlane, 2003). These pointing signs attain a wide range of functions and are formally highly diversified. Based on corpus analysis of spontaneous pointing signs in Kata Kolok, a rural signing variety of Bali, this paper argues that the full meaning potentials of pointing signs come about through the integration of a varied set of linguistic and extralinguistic cues. Taking this hybrid nature of point- ing phenomena into account, it is argued that pointing signs may become an intrinsic aspect of sign language grammars through two mechanisms: morphemization and syntactic integration. Although not entailed in this research, this approach could implicate that some highly systema- tized pointing systems of speaking communities may to a degree be grammatical as well.

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

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

Distributional vowel training for adults has been reported as “effective” for Spanish and Bulgarian learners of Dutch vowels, in studies using a behavioural task. A recent study did not yield a similar clear learning effect for Dutch learners of the English vowel contrast /æ/~/ε/, as measured with event-related potentials (ERPs). The present study aimed to examine the possibility that the latter result was related to the method. As in the ERP study, we tested whether distributional training improved Dutch adult learners’ perception of English /æ/~/ε/. However, we measured behaviour instead of ERPs, in a design identical to that used in the previous studies with Spanish learners. The results do not support an effect of distributional training and thus “replicate” the ERP study. We conclude that it remains unclear whether distributional vowel training is effective for Dutch adults.

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

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

Recent studies using phoneme detection tasks have shown that spoken-language processing is neither facilitated nor interfered with by optional assimilation, but is inhibited by violation of obligatory assimilation. Interpretation of these results depends on an assessment of their generality, specifically, whether they also obtain when listeners are processing nonnative language. Two separate experiments are presented in which native listeners of German and native listeners of Dutch had to detect a target fricative in legal monosyllabic Dutch nonwords. All of the nonwords were correct realisations in standard Dutch. For German listeners, however, half of the nonwords contained phoneme strings which violate the German fricative assimilation rule. Whereas the Dutch listeners showed no significant effects, German listeners detected the target fricative faster when the German fricative assimilation was violated than when no violation occurred. The results might suggest that violation of assimilation rules does not have to make processing more difficult per se.

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

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

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

In the word-learning domain, both adults and young children are able to find the correct referent of a word from highly ambiguous contexts that involve many words and objects by computing distributional statistics across the co-occurrences of words and referents at multiple naming moments (Yu & Smith, 2007; Smith & Yu, 2008). However, there is still debate regarding how learners accumulate distributional information to learn object labels in natural learning environments, and what underlying learning mechanism learners are most likely to adopt. Using the Human Simulation Paradigm (Gillette, Gleitman, Gleitman & Lederer, 1999), we found that participants’ learning performance gradually improved and that their ability to remember and carry over partial knowledge from past learning instances facilitated subsequent learning. These results support the statistical learning model that word learning is a continuous process.

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

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.