Publications

Abstract

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

Abstract

The current study investigated whether point-accompanying characteristics, like vocalizations and hand shape, differentiate infants' underlying motives of prelinguistic pointing. We elicited imperative (requestive) and declarative (expressive and informative) pointing acts in experimentally controlled situations, and analyzed accompanying characteristics. Experiment 1 revealed that prosodic characteristics of point-accompanying vocalizations distinguished requestive from both expressive and informative pointing acts, with little differences between the latter two. In addition, requestive points were more often realized with the whole hand than the index finger, while this was the opposite for expressive and informative acts. Experiment 2 replicated Experiment 1, revealing distinct prosodic characteristics for requestive pointing also when the referent was distal and when it had an index-finger shape. Findings reveal that beyond the social context, point-accompanying vocalizations give clues to infants' underlying intentions when pointing.

Abstract

The genetic determinants of cerebral asymmetries are unknown. Sex differences in asymmetry of the planum temporale, that overlaps Wernicke’s classical language area, have been inconsistently reported. Meta-analysis of previous studies has suggested that publication bias established this sex difference in the literature. Using probabilistic definitions of cortical regions we screened over the cerebral cortex for sexual dimorphisms of asymmetry in 2337 healthy subjects, and found the planum temporale to show the strongest sex-linked asymmetry of all regions, which was supported by two further datasets, and also by analysis with the Freesurfer package that performs automated parcellation of cerebral cortical regions. We performed a genome-wide association scan meta-analysis of planum temporale asymmetry in a pooled sample of 3095 subjects, followed by a candidate-driven approach which measured a significant enrichment of association in genes of the ´steroid hormone receptor activity´ and 'steroid metabolic process' pathways. Variants in the genes and pathways identified may affect the role of the planum temporale in language cognition.

Abstract

The study of phonetic contrasts and related phenomena, e.g. inter- and intra-speaker variability, often requires to analyse data in the form of measured time series, like f0 contours and formant trajectories. As a consequence, the investigator has to find suitable ways to reduce the raw and abundant numerical information contained in a bundle of time series into a small but sufficient set of numerical descriptors of their shape. This approach requires one to decide in advance which dynamic traits to include in the analysis and which not. For example, a rising pitch gesture may be represented by its duration and slope, hence reducing it to a straight segment, or by a richer coding specifying also whether (and how much) the rising contour is concave or convex, the latter being irrelevant in some context but crucial in others. Decisions become even more complex when a phenomenon is described by a multidimensional time series, e.g. by the first two formants. In this paper we introduce a methodology based on Functional Data Analysis (FDA) that allows the investigator to delegate most of the decisions involved in the quantitative description of multidimensional time series to the data themselves. FDA produces a data-driven parametrisation of the main shape traits present in the data that is visually interpretable, in the same way as slopes or peak heights are. These output parameters are numbers that are amenable to ordinary statistical analysis, e.g. linear (mixed effects) models. FDA is also able to capture correlations among different dimensions of a time series, e.g. between formants F1 and F2. We present FDA by means of an extended case study on diphthong – hiatus distinction in Spanish, a contrast that involves duration, formant trajectories and pitch contours.

Abstract

In order to make sense of the world, humans tend to see causation almost everywhere. Although most causal relations may seem straightforward, they are not always construed in the same way cross-culturally. In this study, we investigate concepts of ‘chance’, ‘coincidence’ or ‘randomness’ that refer to assumed relations between intention, action, and outcome in situations, and we ask how people from different cultures make sense of such non-law-like connections. Based on a framework proposed by Alicke (2000), we administered a task that aims to be a neutral tool for investigating causal construals cross-culturally and cross-linguistically. Members of four different cultural groups, rural Mayan Yucatec and Tseltal speakers from Mexico and urban students from Mexico and Germany, were presented with a set of scenarios involving various types of causal and non-causal relations and were asked to explain the described events. Three links varied as to whether they were present or not in the scenarios: Intention to Action, Action to Outcome, and Intention to Outcome. Our results show that causality is recognized in all four cultural groups. However, how causality and especially non-law-like causality are interpreted depends on the type of links, the cultural background and the language used. In all three groups, Action to Outcome is the decisive link for recognizing causality. Despite the fact that the two Mayan groups share similar cultural backgrounds, they display different ideologies regarding concepts of non-law causality. The data suggests that the concept of ‘chance’ is not universal, but seems to be an explanation that only some cultural groups draw on to make sense of specific situations. Of particular importance is the existence of linguistic concepts in each language that trigger ideas of causality in the responses from each cultural group

Abstract

When the dead come home… Remarks on ancestor worship among the Lowland Mayas. In Amerindian ethnographical literature, ancestor worship is often mentioned but evidence of its existence is lacking. This article will try to demonstrate that some Lowland Maya do worship ancestors ; it will use precise criteria taken from ethnological studies of societies where ancestor worship is common, compared to maya beliefs and practices. The All Souls’ Day, or hanal pixan, seems to be the most significant manifestation of this cult. Our approach will be comparative, through time – using colonial and ethnographical data of the twentieth century, and space – contemplating uses and beliefs of two maya groups, the Yucatec and the Lacandon Maya.

Abstract

Studies in relatives have generally yielded high heritability estimates for refractive error: twins 75–90%, families 15–70%. However, because related individuals often share a common environment, these estimates are inflated (via misallocation of unique/common environment variance). We calculated a lower-bound heritability estimate for refractive error free from such bias.
Between the ages 7 and 15 years, participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) underwent non-cycloplegic autorefraction at regular research clinics. At each age, an estimate of the variance in refractive error explained by single nucleotide polymorphism (SNP) genetic variants was calculated using genome-wide complex trait analysis (GCTA) using high-density genome-wide SNP genotype information (minimum N at each age=3,404).
The variance in refractive error explained by the SNPs (“SNP heritability”) was stable over childhood: Across age 7–15 years, SNP heritability averaged 0.28 (SE=0.08, p<0.001). The genetic correlation for refractive error between visits varied from 0.77 to 1.00 (all p<0.001) demonstrating that a common set of SNPs was responsible for the genetic contribution to refractive error across this period of childhood. Simulations suggested lack of cycloplegia during autorefraction led to a small underestimation of SNP heritability (adjusted SNP heritability=0.35; SE=0.09). To put these results in context, the variance in refractive error explained (or predicted) by the time participants spent outdoors was <0.005 and by the time spent reading was <0.01, based on a parental questionnaire completed when the child was aged 8–9 years old.
Genetic variation captured by common SNPs explained approximately 35% of the variation in refractive error between unrelated subjects. This value sets an upper limit for predicting refractive error using existing SNP genotyping arrays, although higher-density genotyping in larger samples and inclusion of interaction effects is expected to raise this figure toward twin- and family-based heritability estimates. The same SNPs influenced refractive error across much of childhood. Notwithstanding the strong evidence of association between time outdoors and myopia, and time reading and myopia, less than 1% of the variance in myopia at age 15 was explained by crude measures of these two risk factors, indicating that their effects may be limited, at least when averaged over the whole population.

Abstract

Analyses of gray matter concentration (GMC) deficits in patients with schizophrenia (Sz) have identified robust changes throughout the cortex. We assessed the relationships between diagnosis, overall symptom severity, and patterns of gray matter in the largest aggregated structural imaging dataset to date. We performed both source-based morphometry (SBM) and voxel-based morphometry (VBM) analyses on GMC images from 784 Sz and 936 controls (Ct) across 23 scanning sites in Europe and the United States. After correcting for age, gender, site, and diagnosis by site interactions, SBM analyses showed 9 patterns of diagnostic differences. They comprised separate cortical, subcortical, and cerebellar regions. Seven patterns showed greater GMC in Ct than Sz, while 2 (brainstem and cerebellum) showed greater GMC for Sz. The greatest GMC deficit was in a single pattern comprising regions in the superior temporal gyrus, inferior frontal gyrus, and medial frontal cortex, which replicated over analyses of data subsets. VBM analyses identified overall cortical GMC loss and one small cluster of increased GMC in Sz, which overlapped with the SBM brainstem component. We found no significant association between the component loadings and symptom severity in either analysis. This mega-analysis confirms that the commonly found GMC loss in Sz in the anterior temporal lobe, insula, and medial frontal lobe form a single, consistent spatial pattern even in such a diverse dataset. The separation of GMC loss into robust, repeatable spatial patterns across multiple datasets paves the way for the application of these methods to identify subtle genetic and clinical cohort effects.

Abstract

In two studies subjects were required to read Dutch sentences that in some cases contained a syntactic violation, in other cases a semantic violation. All syntactic violations were word category violations. The design excluded differential contributions of expectancy to influence the syntactic violation effects. The syntactic violations elicited an Anterior Negativity between 300 and 500 ms. This negativity was bilateral and had a frontal distribution. Over posterior sites the same violations elicited a P600/SPS starting at about 600 ms. The semantic violations elicited an N400 effect. The topographic distribution of the AN was more frontal than the distribution of the classical N400 effect, indicating that the underlying generators of the AN and the N400 are, at least to a certain extent, non-overlapping. Experiment 2 partly replicated the design of Experiment 1, but with differences in rate of presentation and in the distribution of items over subjects, and without semantic violations. The word category violations resulted in the same effects as were observed in Experiment 1, showing that they were independent of some of the specific parameters of Experiment 1. The discussion presents a tentative account of the functional differences in the triggering conditions of the AN and the P600/SPS.

Abstract

To understand spoken language requires that the brain provides rapid access to different kinds of knowledge, including the sounds and meanings of words, and syntax. Syntax specifies constraints on combining words in a grammatically well formed manner. Agrammatic patients are deficient in their ability to use these constraints, due to a lesion in the perisylvian area of the languagedominant hemisphere. We report a study on real-time auditory sentence processing in agrammatic comprehenders, examining
their ability to accommodate damage to the language system. We recorded event-related brain potentials (ERPs) in agrammatic comprehenders, nonagrammatic aphasics, and age-matched controls. When listening to sentences with grammatical violations, the agrammatic aphasics did not show the same syntax-related ERP effect as the two other subject groups. Instead, the waveforms of the agrammatic aphasics were dominated by a meaning-related ERP effect, presumably reflecting their attempts to achieve understanding by the use of semantic constraints. These data demonstrate that although agrammatic aphasics are impaired in their ability to exploit syntactic information in real time, they can reduce the consequences of a syntactic deficit by exploiting a semantic route. They thus provide evidence for the compensation of a syntactic deficit by a stronger reliance on another route in mapping
sound onto meaning. This is a form of plasticity that we refer to as multiple-route plasticity.

Abstract

A central and influential idea among researchers of language is that our language faculty is organized according to Fregean compositionality, which states that the meaning of an utterance is a function of the meaning of its parts and of the syntactic rules by which these parts are combined. Since the domain of syntactic rules is the sentence, the implication of this idea is that language interpretation takes place in a two-step fashion. First, the meaning of a sentence is computed. In a second step, the sentence meaning is integrated with information from prior discourse, world knowledge, information about the speaker and semantic information from extra-linguistic domains such as co-speech gestures or the visual world. Here, we present results from recordings of event-related brain potentials that are inconsistent with this classical two-step model of language interpretation. Our data support a one-step model in which knowledge about the context and the world, concomitant information from other modalities, and the speaker are brought to bear immediately, by the same fast-acting brain system that combines the meanings of individual words into a message-level representation. Underlying the one-step model is the immediacy assumption, according to which all available information will immediately be used to co-determine the interpretation of the speaker's message. Functional magnetic resonance imaging data that we collected indicate that Broca's area plays an important role in semantic unification. Language comprehension involves the rapid incorporation of information in a 'single unification space', coming from a broader range of cognitive domains than presupposed in the standard two-step model of interpretation.

Abstract

Syntax is one of the components in the architecture of language processing that allows the listener/reader to bind single-word information into a unified interpretation of multiword utterances. This paper discusses ERP effects that have been observed in relation to syntactic processing. The fact that these effects differ from the semantic N400 indicates that the brain honors the distinction between semantic and syntactic binding operations. Two models of syntactic processing attempt to account for syntax-related ERP effects. One type of model is serial, with a first phase that is purely syntactic in nature (syntax-first model). The other type of model is parallel and assumes that information immediately guides the interpretation process once it becomes available. This is referred to as the immediacy model. ERP evidence is presented in support of the latter model. Next, an explicit computational model is proposed to explain the ERP data. This Unification Model assumes that syntactic frames are stored in memory and retrieved on the basis of the spoken or written word form input. The syntactic frames associated with the individual lexical items are unified by a dynamic binding process into a structural representation that spans the whole utterance. On the basis of a meta-analysis of imaging studies on syntax, it is argued that the left posterior inferior frontal cortex is involved in binding syntactic frames together, whereas the left superior temporal cortex is involved in retrieval of the syntactic frames stored in memory. Lesion data that support the involvement of this left frontotemporal network in syntactic processing are discussed.

Abstract

This study investigated the effects of combined semantic and syntactic violations in relation to the effects of single semantic and single syntactic violations on language-related event-related brain potential (ERP) effects (N400 and P600/ SPS). Syntactic violations consisted of a mismatch in grammatical gender or number features of the definite article and the noun in sentence-internal or sentence-final noun phrases (NPs). Semantic violations consisted of semantically implausible adjective–noun combinations in the same NPs. Combined syntactic and semantic violations were a summation of these two respective violation types. ERPs were recorded while subjects read the sentences with the different types of violations and the correct control sentences. ERP effects were computed relative to ERPs elicited by the sentence-internal or sentence-final nouns. The size of the N400 effect to the semantic violation was increased by an additional syntactic violation (the syntactic boost). In contrast, the size of the P600/ SPS to the syntactic violation was not affected by an additional semantic violation. This suggests that in the absence of syntactic ambiguity, the assignment of syntactic structure is independent of semantic context. However, semantic integration is influenced by syntactic processing. In the sentence-final position, additional global processing consequences were obtained as a result of earlier violations in the sentence. The resulting increase in the N400 amplitude to sentence-final words was independent of the nature of the violation. A speeded anomaly detection task revealed that it takes substantially longer to detect semantic than syntactic anomalies. These results are discussed in relation to the latency and processing characteristics of the N400 and P600/SPS effects. Overall, the results reveal an asymmetry in the interplay between syntax and semantics during on-line sentence comprehension.

Abstract

In an ERP experiment we investigated how the recruitment and integration of world knowledge information relate to the integration of information within a current discourse context. Participants were presented with short discourse contexts which were followed by a sentence that contained a critical word that was correct or incorrect based on general world knowledge and the supporting discourse context, or was more or less acceptable based on the combination of general world knowledge and the specific local discourse context. Relative to the critical word in the correct world knowledge sentences following a neutral discourse, all other critical words elicited an N400 effect that began at about 300 ms after word onset. However, the magnitude of the N400 effect varied in a way that suggests an interaction between world knowledge and discourse context. The results indicate that both world knowledge and discourse context have an effect on sentence interpretation, but neither overrides the other.

Abstract

All natural languages develop devices to communicate who did what to whom. Elicited pantomime provides one model for studying this process, by providing a window into how humans (hearing non-signers) behave in a natural communicative modality (silent gesture) without established conventions from a grammar. Most studies in this paradigm focus on production, although they sometimes make assumptions about how comprehenders would likely behave. Here, we directly assess how naïve speakers of English (Experiments 1 & 2), Korean (Experiment 1), and Turkish (Experiment 2) comprehend pantomimed descriptions of transitive events, which are either semantically reversible (Experiments 1 & 2) or not (Experiment 2). Contrary to previous assumptions, we find no evidence that Person-Person-Action sequences are ambiguous to comprehenders, who simply adopt an agent-first parsing heuristic for all constituent orders. We do find that Person-Action-Person sequences yield the most consistent interpretations, even in native speakers of SOV languages. The full range of behavior in both production and comprehension provides counter-evidence to the notion that producers’ utterances are motivated by the needs of comprehenders. Instead, we argue that production and comprehension are subject to different sets of cognitive pressures, and that the dynamic interaction between these competing pressures can help explain synchronic and diachronic constituent order phenomena in natural human languages, both signed and spoken.

Abstract

Written language comprehension at the word and the sentence level was analysed by the combination of spatial and temporal analysis of functional magnetic resonance imaging (fMRI). Spatial analysis was performed via general linear modelling (GLM). Concerning the temporal analysis, local differences in neurovascular coupling may confound a direct comparison of blood oxygenation level-dependent (BOLD) response estimates between regions. To avoid this problem, we parametrically varied linguistic task demands and compared only task-induced within-region BOLD response differences across areas. We reasoned that, in a hierarchical processing system, increasing task demands at lower processing levels induce delayed onset of higher-level processes in corresponding areas. The flow of activation is thus reflected in the size of task-induced delay increases. We estimated BOLD response delay and duration for each voxel and each participant by fitting a model function to the event-related average BOLD response. The GLM showed increasing activations with increasing linguistic demands dominantly in the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG). The combination of spatial and temporal analysis allowed a functional differentiation of IFG subregions involved in written language comprehension. Ventral IFG region (BA 47) and STG subserve earlier processing stages than two dorsal IFG regions (BA 44 and 45). This is in accordance with the assumed early lexical semantic and late syntactic processing of these regions and illustrates the complementary information provided by spatial and temporal fMRI data analysis of the same data set.

Abstract

Ethnologue (http://www.ethnologue.com) is the most widely consulted inventory of the world’slanguages used today. The present review article looks carefully at the goals and description of the content of the Ethnologue’s 16th, 17th, and 18th editions, and reports on a comprehensive survey of the accuracy of the inventory itself. While hundreds of spurious and missing languages can be documented for Ethnologue, it is at present still better than any other nonderivative work of the same scope, in all aspects but one. Ethnologue fails to disclose the sources for the information presented, at odds with well-established scientific principles. The classification of languages into families in Ethnologue is also evaluated, and found to be far off from that argued in the specialist literature on the classification of individual languages. Ethnologue is frequently held to be splitting: that is, it tends to recognize more languages than an application of the criterion of mutual intelligibility would yield. By means of a random sample, we find that, indeed, with confidence intervals, the number of mutually unintelligible languages is on average 85% of the number found in Ethnologue. © 2015, Linguistic Society of America. All rights reserved.

Abstract

Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p <} 0.001) and rheumatoid factor (RF) IgM (p {< 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates.

Abstract

This paper investigates whether individual speakers forming a homogeneous group differ in their choice and pronunciation of words when engaged in casual conversation, and if so, how they differ. More specifically, it examines whether the Balanced Winnow classifier is able to distinguish between the twenty speakers of the Ernestus Corpus of Spontaneous Dutch, who all have the same social background. To examine differences in choice and pronunciation of words, instead of characteristics of the speech signal itself, classification was based on lexical and pronunciation features extracted from hand-made orthographic and automatically generated broad phonetic transcriptions. The lexical features consisted of words and two-word combinations. The pronunciation features represented pronunciation variations at the word and phone level that are typical for casual speech. The best classifier achieved a performance of 79.9% and was based on the lexical features and on the pronunciation features representing single phones and triphones. The speakers must thus differ from each other in these features. Inspection of the relevant features indicated that, among other things, the words relevant for classification generally do not contain much semantic content, and that speakers differ not only from each other in the use of these words but also in their pronunciation.

Abstract

Treatment with serotonin reuptake inhibitors (SSRI) has been associated with an increased risk of preterm birth, but causality remains unclear. While placental CRH production is correlated with gestational length and preterm birth, it has been difficult to establish if psychological stress or mental health problems are associated with increased CRH levels. This study compared second trimester CRH serum concentrations in pregnant women on SSRI treatment (n=207) with untreated depressed women (n=56) and controls (n=609). A secondary aim was to investigate the combined effect of SSRI treatment and CRH levels on gestational length and risk for preterm birth. Women on SSRI treatment had significantly higher second trimester CRH levels than controls, and untreated depressed women. CRH levels and SSRI treatment were independently associated with shorter gestational length. The combined effect of SSRI treatment and high CRH levels yielded the highest risk estimate for preterm birth. SSRI treatment during pregnancy is associated with increased CRH levels. However, the elevated risk for preterm birth in SSRI users appear not to be mediated by increased placental CRH production, instead CRH appear as an independent risk factor for shorter gestational length and preterm birth.

Abstract

The epileptic encephalopathies are a clinically and aetiologically heterogeneous subgroup of epilepsy syndromes. Most epileptic encephalopathies have a genetic cause and patients are often found to carry a heterozygous de novo mutation in one of the genes associated with the disease entity. Occasionally recessive mutations are identified: a recent publication described a distinct neonatal epileptic encephalopathy (MIM 615905) caused by autosomal recessive mutations in the SLC13A5 gene. Here, we report eight additional patients belonging to four different families with autosomal recessive mutations in SLC13A5. SLC13A5 encodes a high affinity sodium-dependent citrate transporter, which is expressed in the brain. Neurons are considered incapable of de novo synthesis of tricarboxylic acid cycle intermediates; therefore they rely on the uptake of intermediates, such as citrate, to maintain their energy status and neurotransmitter production. The effect of all seven identified mutations (two premature stops and five amino acid substitutions) was studied in vitro, using immunocytochemistry, selective western blot and mass spectrometry. We hereby demonstrate that cells expressing mutant sodium-dependent citrate transporter have a complete loss of citrate uptake due to various cellular loss-of-function mechanisms. In addition, we provide independent proof of the involvement of autosomal recessive SLC13A5 mutations in the development of neonatal epileptic encephalopathies, and highlight teeth hypoplasia as a possible indicator for SLC13A5 screening. All three patients who tried the ketogenic diet responded well to this treatment, and future studies will allow us to ascertain whether this is a recurrent feature in this severe disorder.

Abstract

The present study was designed to examine the impact of bilingualism on the neuronal activity in different executive control processes namely conflict monitoring, control implementation (i.e., interference suppression and conflict resolution) and overcoming of inhibition. Twenty-two highly proficient but non-balanced successive French–German bilingual adults and 22 monolingual adults performed a combined Stroop/Negative priming task while event-related potential (ERP) were recorded online. The data revealed that the ERP effects were reduced in bilinguals in comparison to monolinguals but only in the Stroop task and limited to the N400 and the sustained fronto-central negative-going potential time windows. This result suggests that bilingualism may impact the process of control implementation rather than the process of conflict monitoring (N200). Critically, our study revealed a differential time course of the involvement of the anterior cingulate cortex (ACC) and the prefrontal cortex (PFC) in conflict processing. While the ACC showed major activation in the early time windows (N200 and N400) but not in the latest time window (late sustained negative-going potential), the PFC became unilaterally active in the left hemisphere in the N400 and the late sustained negative-going potential time windows. Taken together, the present electroencephalography data lend support to a cascading neurophysiological model of executive control processes, in which ACC and PFC may play a determining role.

Abstract

We used functional magnetic resonance imaging (fMRI) to longitudinally examine brain plasticity arising from long-term, intensive simultaneous interpretation training. Simultaneous interpretation is a bilingual task with heavy executive control demands. We compared brain responses observed during simultaneous interpretation with those observed during simultaneous speech repetition (shadowing) in a group of trainee simultaneous interpreters, at the beginning and at the end of their professional training program. Age, sex and language-proficiency matched controls were scanned at similar intervals. Using multivariate pattern classification, we found distributed patterns of changes in functional responses from the first to second scan that distinguished the interpreters from the controls. We also found reduced recruitment of the right caudate nucleus during simultaneous interpretation as a result of training. Such practice-related change is consistent with decreased demands on multilingual language control as the task becomes more automatized with practice. These results demonstrate the impact of simultaneous interpretation training on the brain functional response in a cerebral structure that is not specifically linguistic, but that is known to be involved in learning, in motor control, and in a variety of domain-general executive functions. Along with results of recent studies showing functional and structural adaptations in the caudate nuclei of experts in a broad range of domains, our results underline the importance of this structure as a central node in expertise-related networks. (C) 2015 Elsevier Inc. All rights reserved.

Abstract

We used functional magnetic resonance imaging (fMRI) to examine the neural basis of extreme multilingual language control in a group of 50 multilingual participants. Comparing brain responses arising during simultaneous interpretation (SI) with those arising during simultaneous repetition revealed activation of regions known to be involved in speech perception and production, alongside a network incorporating the caudate nucleus that is known to be implicated in domain-general cognitive control. The similarity between the networks underlying bilingual language control and general executive control supports the notion that the frequently reported bilingual advantage on executive tasks stems from the day-to-day demands of language control in the multilingual brain. We examined neural correlates of the management of simultaneity by correlating brain activity during interpretation with the duration of simultaneous speaking and hearing. This analysis showed significant modulation of the putamen by the duration of simultaneity. Our findings suggest that, during SI, the caudate nucleus is implicated in the overarching selection and control of the lexico-semantic system, while the putamen is implicated in ongoing control of language output. These findings provide the first clear dissociation of specific dorsal striatum structures in polyglot language control, roles that are consistent with previously described involvement of these regions in nonlinguistic executive control.

Abstract

Fast and automatic behavioral responses are required to avoid collision with an approaching stimulus. Accordingly, looming stimuli have been found to be highly salient and efficient attractors of attention due to the implication of potential collision and potential threat. Here, we address the question of whether looming motion is processed in the absence of any functional primary visual cortex and consequently without awareness. For this, we investigated a patient (TN) suffering from complete, bilateral damage to his primary visual cortex. Using an fMRI paradigm, we measured TN's brain activation during the presentation of looming, receding, rotating, and static point lights, of which he was unaware. When contrasted with other conditions, looming was found to produce bilateral activation of the middle temporal areas, as well as the superior temporal sulcus and inferior parietal lobe (IPL). The latter are generally thought to be involved in multisensory processing of motion in extrapersonal space, as well as attentional capture and saliency. No activity was found close to the lesioned V1 area. This demonstrates that looming motion is processed in the absence of awareness through direct subcortical projections to areas involved in multisensory processing of motion and saliency that bypass V-1.

Abstract

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10-33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction

Abstract

To accomplish a smooth transition in conversation from one speaker to the next, a tight coordination of interaction between speakers is required. Recent studies of adult conversation suggest that this close timing of interaction may well be a universal feature of conversation. In the present paper, we set out to assess the development of this close timing of turns in infancy in vocal exchanges between mothers and infants. Previous research has demonstrated an early sensitivity to timing in interactions (e.g. Murray & Trevarthen, 1985). In contrast, less is known about infants’ abilities to produce turns in a timely manner and existing findings are rather patchy. We conducted a longitudinal study of twelve mother-infant dyads in free-play interactions at the ages of 3, 4, 5, 9, 12 and 18 months. Based on existing work and the predictions made by the Interaction Engine Hypothesis (Levinson, 2006), we expected that infants would begin to develop the temporal properties of turn-taking early in infancy but that their timing of turns would slow down at 12 months, which is around the time when infants start to produce their first words. Findings were consistent with our predictions: Infants were relatively fast at timing their turn early in infancy but slowed down towards the end of the first year. Furthermore, the changes observed in infants’ turn-timing skills were not caused by changes in maternal timing, which remained stable across the 3-18 month period. However, the slowing down of turn-timing started somewhat earlier than predicted: at 9 months.

Abstract

The relationship between the production and the comprehension systems has recently become a topic of interest for many psycholinguists. It has been argued that these systems are tightly linked and in particular that listeners use the production system to predict upcoming content. In this study, we tested how similar production and prediction processes are in a novel version of the visual world paradigm. Dutch speaking participants (native speakers in Experiment 1; German-Dutch bilinguals in Experiment 2) listened to mathematical equations while looking at a clock face featuring the numbers 1 to 12. On alternating trials, they either heard a complete equation ("three plus eight is eleven") or they heard the first part ("three plus eight is") and had to produce the result ("eleven") themselves. Participants were encouraged to look at the relevant numbers throughout the trial. Their eye movements were recorded and analyzed. We found that the participants' eye movements in the two tasks were overall very similar. They fixated the first and second number of the equations shortly after they were mentioned, and fixated the result number well before they named it on production trials and well before the recorded speaker named it on comprehension trials. However, all fixation latencies were shorter on production than on comprehension trials. These findings suggest that the processes involved in planning to say a word and anticipating hearing a word are quite similar, but that people are more aroused or engaged when they intend to respond than when they merely listen to another person.

Abstract

Interaction includes moments of silence. When all participants forgo the option to speak, the silence can be called a “lapse.” This article builds on existing work on lapses and other kinds of silences (gaps, pauses, and so on) to examine how participants reach a point where lapsing is a possibility and how they orient to the lapse that subsequently develops. Drawing from a wide range of activities and settings, I will show that participants may treat lapses as (a) the relevant cessation of talk, (b) the allowable development of silence, or (c) the conspicuous absence of talk. Data are in American and British English.

Abstract

Recipients process information from speech and co-speech gestures, but it is currently unknown how this processing is influenced by the presence of other important social cues, especially gaze direction, a marker of communicative intent. Such cues may modulate neural activity in regions associated either with the processing of ostensive cues, such as eye gaze, or with the processing of semantic information, provided by speech and gesture.
Participants were scanned (fMRI) while taking part in triadic communication involving two recipients and a speaker. The speaker uttered sentences that
were and were not accompanied by complementary iconic gestures. Crucially, the speaker alternated her gaze direction, thus creating two recipient roles: addressed (direct gaze) vs unaddressed (averted gaze) recipient. The comprehension of Speech&Gesture relative to SpeechOnly utterances recruited middle occipital, middle temporal and inferior frontal gyri, bilaterally. The calcarine sulcus and posterior cingulate cortex were sensitive to differences between direct and averted gaze. Most importantly, Speech&Gesture utterances, but not SpeechOnly utterances, produced additional activity in the right middle temporal gyrus when participants were addressed. Marking communicative intent with gaze direction modulates the processing of speech–gesture utterances in cerebral areas typically associated with the semantic processing of multi-modal communicative acts.

Abstract

One of the most intriguing aspects of human communication is its turn-taking system. It requires the ability to process on-going turns at talk while planning the next, and to launch this next turn without considerable overlap or delay. Recent research has investigated the eye movements of observers of dialogues to gain insight into how we process turns at talk. More specifically, this research has focused on the extent to which we are able to anticipate the end of current and the beginning of next turns. At the same time, there has been a call for shifting experimental paradigms exploring social-cognitive processes away from passive observation towards online processing. Here, we present research that responds to this call by situating state-of-the-art technology for tracking interlocutors’ eye movements within spontaneous, face-to-face conversation. Each conversation involved three native speakers of English. The analysis focused on question-response sequences involving just two of those participants, thus rendering the third momentarily unaddressed. Temporal analyses of the unaddressed participants’ gaze shifts from current to next speaker revealed that unaddressed participants are able to anticipate next turns, and moreover, that they often shift their gaze towards the next speaker before the current turn ends. However, an analysis of the complex structure of turns at talk revealed that the planning of these gaze shifts virtually coincides with the points at which the turns first become recog-nizable as possibly complete. We argue that the timing of these eye movements is governed by an organizational principle whereby unaddressed participants shift their gaze at a point that appears interactionally most optimal: It provides unaddressed participants with access to much of the visual, bodily behavior that accompanies both the current speaker’s and the next speaker’s turn, and it allows them to display recipiency with regard to both speakers’ turns.

Abstract

Objective: To evaluate cognitive outcome in adult survivors of bacterial meningitis. Methods: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls. Results: Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p<0.001) and tended to be cognitively slower than survivors of meningococcal meningitis (p = 0.08). We found a diffuse pattern of cognitive impairment in which cognitive speed played the most important role. Cognitive performance was not related to time since meningitis; however, there was a positive association between time since meningitis and self-reported physical impairment (p<0.01). The frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar. Conclusions: Adult survivors of bacterial meningitis are at risk of cognitive impairment, which consists mainly of cognitive slowness. The loss of cognitive speed is stable over time after bacterial meningitis; however, there is a significant improvement in subjective physical impairment in the years after bacterial meningitis. The use of dexamethasone was not associated with cognitive impairment.

Abstract

Here, we report evidence for oscillatory bi-directional interactions between the nucleus accumbens and the neocortex in humans. Six patients performed a demanding covert visual attention task while we simultaneously recorded brain activity from deep-brain electrodes implanted in the nucleus accumbens and the surface electroencephalogram (EEG). Both theta and alpha oscillations were strongly coherent with the frontal and parietal EEG during the task. Theta-band coherence increased during processing of the visual stimuli. Granger causality analysis revealed that the nucleus accumbens was communicating with the neocortex primarily in the theta-band, while the cortex was communicating the nucleus accumbens in the alpha-band. These data are consistent with a model, in which theta- and alpha-band oscillations serve dissociable roles: Prior to stimulus processing, the cortex might suppress ongoing processing in the nucleus accumbens by modulating alpha-band activity. Subsequently, upon stimulus presentation, theta oscillations might facilitate the active exchange of stimulus information from the nucleus accumbens to the cortex.

Abstract

Creativity is crucial to the progression of human civilization and has led to important scientific discoveries. Especially, individuals are more likely to have scientific discoveries if they possess certain personality traits of creativity (trait creativity), including imagination, curiosity, challenge and risk-taking. This study used voxel-based morphometry to identify the brain regions underlying individual differences in trait creativity, as measured by the Williams creativity aptitude test, in a large sample (n = 246). We found that creative individuals had higher gray matter volume in the right posterior middle temporal gyrus (pMTG), which might be related to semantic processing during novelty seeking (e.g. novel association, conceptual integration and metaphor understanding). More importantly, although basic personality factors such as openness to experience, extroversion, conscientiousness and agreeableness (as measured by the NEO Personality Inventory) all contributed to trait creativity, only openness to experience mediated the association between the right pMTG volume and trait creativity. Taken together, our results suggest that the basic personality trait of openness might play an important role in shaping an individual’s trait creativity.

Abstract

Experiments 1 and 2 examined the time-course of retrieval of phonological, visual-shape and semantic knowledge as Dutch participants listened to sentences and looked at displays of four pictures. Given a sentence with beker, `beaker', for example, the display contained phonological (a beaver, bever), shape (a bobbin, klos), and semantic (a fork, vork) competitors. When the display appeared at sentence onset, fixations to phonological competitors preceded fixations to shape and semantic competitors. When display onset was 200 ms before (e.g.) beker, fixations were directed to shape and then semantic competitors, but not phonological competitors. In Experiments 3 and 4, displays contained the printed names of the previously-pictured entities; only phonological competitors were fixated preferentially. These findings suggest that retrieval of phonological, shape and semantic knowledge in the spoken-word and picture-recognition systems is cascaded, and that visual attention shifts are co-determined by the time-course of retrieval of all three knowledge types and by the nature of the information in the visual environment.

Abstract

Visual attention can be directed immediately, as a spoken word unfolds, towards conceptually related but nonassociated objects, even if they mismatch on other dimensions that would normally determine which objects in the scene were appropriate referents for the unfolding word (Huettig & Altmann, 2005). Here we demonstrate that the mapping between language and concurrent visual objects can also be mediated by visual-shape relations. On hearing "snake", participants directed overt attention immediately, within a visual display depicting four objects, to a picture of an electric cable, although participants had viewed the visual display with four objects for approximately 5 s before hearing the target word - sufficient time to recognize the objects for what they were. The time spent fixating the cable correlated significantly with ratings of the visual similarity between snakes in general and this particular cable. Importantly, with sentences contextually biased towards the concept snake, participants looked at the snake well before the onset of "snake", but they did not look at the visually similar cable until hearing "snake". Finally, we demonstrate that such activation can, under certain circumstances (e.g., during the processing of dominant meanings of homonyms), constrain the direction of visual attention even when it is clearly contextually inappropriate. We conclude that language-mediated attention can be guided by a visual match between spoken words and visual objects, but that such a match is based on lexical input and may not be modulated by contextual appropriateness.

Abstract

It is now well-established that anticipation of up-coming input is a key characteristic of spoken language comprehension. It has also frequently been observed that literacy influences spoken language processing. Here we investigated whether anticipatory spoken language processing is related to individuals’ word reading abilities. Dutch adults with dyslexia and a control group participated in two eye-tracking experiments. Experiment 1 was conducted to assess whether adults with dyslexia show the typical language-mediated eye gaze patterns. Eye movements of both adults with and without dyslexia closely replicated earlier research: spoken language is used to direct attention to relevant objects in the environment in a closely time-locked manner. In Experiment 2, participants received instructions (e.g., "Kijk naar deCOM afgebeelde pianoCOM", look at the displayed piano) while viewing four objects. Articles (Dutch “het” or “de”) were gender-marked such that the article agreed in gender only with the target and thus participants could use gender information from the article to predict the target object. The adults with dyslexia anticipated the target objects but much later than the controls. Moreover, participants' word reading scores correlated positively with their anticipatory eye movements. We conclude by discussing the mechanisms by which reading abilities may influence predictive language processing.

Abstract

The notion that prediction is a fundamental principle of human information processing has been en vogue over recent years. The investigation of language processing may be particularly illuminating for testing this claim. Linguists traditionally have argued prediction plays only a minor role during language understanding because of the vast possibilities available to the language user as each word is encountered. In the present review I consider four central questions of anticipatory language processing: Why (i.e. what is the function of prediction in language processing)? What (i.e. what are the cues used to predict up-coming linguistic information and what type of representations are predicted)? How (what mechanisms are involved in predictive language processing and what is the role of possible mediating factors such as working memory)? When (i.e. do individuals always predict up-coming input during language processing)? I propose that prediction occurs via a set of diverse PACS (production-, association-, combinatorial-, and simulation-based prediction) mechanisms which are minimally required for a comprehensive account of predictive language processing. Models of anticipatory language processing must be revised to take multiple mechanisms, mediating factors, and situational context into account. Finally, I conjecture that the evidence considered here is consistent with the notion that prediction is an important aspect but not a fundamental principle of language processing.

Abstract

This paper reports on ongoing research on the role of various kinds of potential substrate languages in the development of the semantic structures of Ndyuka (Eastern Suriname Creole). A set of 100 senses of noun, verb, and other lexemes in Ndyuka were compared with senses of corresponding lexemes in three kinds of languages of the former Slave Coast and Gold Coast areas, and immediately adjoining hinterland: (a) Gbe languages; (b) other Kwa languages, specifically Akan and Ga; (c) non-Kwa Niger-Congo languages. The results of this process provide some evidence for the importance of the Gbe languages in the formation of the Suriname creoles, but also for the importance of other languages, and for the areal nature of some of the collocations studied, rendering specific identification of a single substrate source impossible and inappropriate. These results not only provide information about the role of Gbe and other languages in the formation of Ndyuka, but also give evidence for effects of substrate languages spoken by late arrivals some time after the "founders" of a given creole-speaking society. The conclusions are extrapolated beyond Suriname to creole genesis generally.

Abstract

This study investigates how listeners cope with gradient forms of deletion of word-final /t/ when recognising words in a phonological context that makes /t/-deletion viable. A corpus study confirmed a high incidence of /t/-deletion in an /st#b/ context in Dutch. A discrimination study showed that differences between released /t/, unreleased /t/ and fully deleted /t/ in this specific /st#b/ context were salient. Two on-line experiments were carried out to investigate whether lexical activation might be affected by this form variation. Even though unreleased and released variants were processed equally fast by listeners, a detailed analysis of the unreleased condition provided evidence for gradient activation. Activating a target ending in /t/ is slowest for the most reduced variant because phonological context has to be taken into account. Importantly, activation for a target with /t/ in the absence of cues for /t/ is reduced if there is a surface-matching lexical competitor.

Abstract

In this study we investigate whether speakers, in line with the predictions of the Hyper- and Hypospeech theory, speed up most during the least informative parts and less during the more informative parts, when they are asked to speak faster. We expected listeners to benefit from these changes in timing, and our main goal was to find out whether making the temporal organisation of artificially time-compressed speech more like that of natural fast speech would improve intelligibility over linear time compression. Our production study showed that speakers reduce unstressed syllables more than stressed syllables, thereby making the prosodic pattern more pronounced. We extrapolated fast speech timing to even faster rates because we expected that the more salient prosodic pattern could be exploited in difficult listening situations. However, at very fast speech rates, applying fast speech timing worsens intelligibility. We argue that the non-uniform way of speeding up may not be due to an underlying communicative principle, but may result from speakers’ inability to speed up otherwise. As both prosodic and segmental information contribute to word recognition, we conclude that extrapolating fast speech timing to extremely fast rates distorts this balance between prosodic and segmental information.

Abstract

Children who start formal education in a second language may experience slower vocabulary growth in that language and subsequently experience disadvantages in literacy acquisition. The current study asked whether lexical specificity training can stimulate bilingual children's phonological awareness, which is considered to be a precursor to literacy. Therefore, Dutch monolingual and Turkish-Dutch bilingual children were taught new Dutch words with only minimal acoustic-phonetic differences. As a result of this training, the monolingual and the bilingual children improved on phoneme blending, which can be seen as an early aspect of phonological awareness. During training, the bilingual children caught up with the monolingual children on words with phonological overlap between their first language Turkish and their second language Dutch. It is concluded that learning minimal pair words fosters phoneme awareness, in both first and second language preliterate children, and that for second language learners phonological overlap between the two languages positively affects training outcomes, likely due to linguistic transfer

Abstract

Successful navigation is facilitated by the presence of landmarks. Previous functional magnetic resonance imaging (fMRI) evidence indicated that the human parahippocampal gyrus automatically distinguishes between landmarks placed at navigationally relevant (decision points) and irrelevant locations (nondecision points). This storage of navigational relevance can provide a neural mechanism underlying successful navigation. However, an efficient wayfinding mechanism requires that important spatial information is learned quickly and maintained over time. The present study investigates whether the representation of navigational relevance is modulated by time and practice. Participants learned 2 film sequences through virtual mazes containing objects at decision and at nondecision points. One maze was shown one time, and the other maze was shown 3 times. Twenty-four hours after study, event-related fMRI data were acquired during recognition of the objects. The results showed that activity in the parahippocampal gyrus was increased for objects previously placed at decision points as compared with objects placed at nondecision points. The decision point effect was not modulated by the number of exposures to the mazes and independent of explicit memory functions. These findings suggest a persistent representation of navigationally relevant information, which is stable after only one exposure to an environment. These rapidly induced and long-lasting changes in object representation provide a basis for successful wayfinding.

Abstract

The human brain distinguishes between landmarks placed at navigationally relevant and irrelevant locations. However, to provide a successful wayfinding mechanism not only landmarks but also the routes between them need to be stored. We examined the neural representation of a memory for route direction and a memory for relevant landmarks. Healthy human adults viewed objects along a route through a virtual maze. Event-related functional magnetic resonance imaging (fMRI) data were acquired during a subsequent subliminal priming recognition task. Prime-objects either preceded or succeeded a target-object on a preciously learned route. Our results provide evidence that the parahippocampal gyri distinguish between relevant and irrelevant landmarks whereas the inferior parietal gyrus, the anterior cingulate gyrus as well as the right caudate nucleus are involved in the coding of route direction. These data show that separated memory systems store different spatial information. A memory for navigationally relevant object information and a memory for route direction exist.

Abstract

A. Caramazza, A. Costa, M. Miozzo, and Y. Bi(2001) reported a series of experiments demonstrating that the ease of producing a word depends only on the frequency of that specific word but not on the frequency of a homophone twin. A. Caramazza, A. Costa, et al. concluded that homophones have separate word form representations and that the absence of frequency-inheritance effects for homophones undermines an important argument in support of 2-stage models of lexical access, which assume that syntactic (lemma) representations mediate between conceptual and phonological representations. The authors of this article evaluate the empirical basis of this conclusion, report 2 experiments demonstrating a frequency-inheritance effect, and discuss other recent evidence. It is concluded that homophones share a common word form and that the distinction between lemmas and word forms should be upheld.

Abstract

The neural mechanism of leader emergence is not well understood. This study investigated (i) whether interpersonal neural synchronization (INS) plays an important role in leader emergence, and (ii) whether INS and leader emergence are associated with the frequency or the quality of communications. Eleven three-member groups were asked to perform a leaderless group discussion (LGD) task, and their brain activities were recorded via functional near infrared spectroscopy (fNIRS)-based hyperscanning. Video recordings of the discussions were coded for leadership and communication. Results showed that the INS for the leader–follower (LF) pairs was higher than that for the follower–follower (FF) pairs in the left temporo-parietal junction (TPJ), an area important for social mentalizing. Although communication frequency was higher for the LF pairs than for the FF pairs, the frequency of leader-initiated and follower-initiated communication did not differ significantly. Moreover, INS for the LF pairs was significantly higher during leader-initiated communication than during follower-initiated communications. In addition, INS for the LF pairs during leader-initiated communication was significantly correlated with the leaders’ communication skills and competence, but not their communication frequency. Finally, leadership could be successfully predicted based on INS as well as communication frequency early during the LGD (before half a minute into the task). In sum, this study found that leader emergence was characterized by high-level neural synchronization between the leader and followers and that the quality, rather than the frequency, of communications was associated with synchronization. These results suggest that leaders emerge because they are able to say the right things at the right time.

Abstract

We investigate differences of cerebral activation in 12 right-handed and left-handed participants, respectively, using a sentence-processing task. Functional MRI shows activation of left-frontal and inferior-parietal speech areas (BA 44, BA9, BA 40) in both groups, but a stronger bilateral activation in left-handers. Direct group comparison reveals a stronger activation in right-frontal cortex (BA 47, BA 6) and left cerebellum in left-handers. Laterality indices for the inferior-frontal cortex are less asymmetric in left-handers and are not related to the degree of handedness. Thus, our results show that sentence-processing induced enhanced activation involving a bilateral network in left-handed participants.

Abstract

Purpose: Factors affecting the efficacy of therapeutic monoclonal antibodies (mAb) directed to the epidermal growth factor receptor (EGFR) remain relatively unknown, especially in glioma. Experimental Design: We examined the efficacy of two EGFR-specific mAbs (mAbs 806 and 528) against U87MG-derived glioma xenografts expressing EGFR variants. Using this approach allowed us to change the form of the EGFR while keeping the genetic background constant. These variants included the de2-7 EGFR (or EGFRvIII), a constitutively active mutation of the EGFR expressed in glioma. Results: The efficacy of the mAbs correlated with EGFR number; however, the most important factor was receptor activation. Whereas U87MG xenografts expressing the de2-7 EGFR responded to therapy, those exhibiting a dead kinase de2-7 EGFR were refractory. A modified de2-7 EGFR that was kinase active but autophosphorylation deficient also responded, suggesting that these mAbs function in de2-7 EGFR–expressing xenografts by blocking transphosphorylation. Because de2-7 EGFR–expressing U87MG xenografts coexpress the wild-type EGFR, efficacy of the mAbs was also tested against NR6 xenografts that expressed the de2-7 EGFR in isolation. Whereas mAb 806 displayed antitumor activity against NR6 xenografts, mAb 528 therapy was ineffective, suggesting that mAb 528 mediates its antitumor activity by disrupting interactions between the de2-7 and wild-type EGFR. Finally, genetic disruption of Src in U87MG xenografts expressing the de2-7 EGFR dramatically enhanced mAb 806 efficacy. Conclusions: The effective use of EGFR-specific antibodies in glioma will depend on identifying tumors with activated EGFR. The combination of EGFR and Src inhibitors may be an effective strategy for the treatment of glioma.

Abstract

The Possible Word Constraint limits the number of lexical candidates considered in speech recognition by stipulating that input should be parsed into a string of lexically viable chunks. For instance, an isolated single consonant is not a feasible word candidate. Any segmentation containing such a chunk is disfavored. Five experiments using the head-turn preference procedure investigated whether, like adults, 12-month-olds observe this constraint in word recognition. In Experiments 1 and 2, infants were familiarized with target words (e.g., rush), then tested on lists of nonsense items containing these words in “possible” (e.g., “niprush” [nip + rush]) or “impossible” positions (e.g., “prush” [p + rush]). The infants listened significantly longer to targets in “possible” versus “impossible” contexts when targets occurred at the end of nonsense items (rush in “prush”), but not when they occurred at the beginning (tan in “tance”). In Experiments 3 and 4, 12-month-olds were similarly familiarized with target words, but test items were real words in sentential contexts (win in “wind” versus “window”). The infants listened significantly longer to words in the “possible” condition regardless of target location. Experiment 5 with targets at the beginning of isolated real words (e.g., win in “wind”) replicated Experiment 2 in showing no evidence of viability effects in beginning position. Taken together, the findings suggest that, in situations in which 12-month-olds are required to rely on their word segmentation abilities, they give evidence of observing lexical viability constraints in the way that they parse fluent speech.

Abstract

Whereas it has long been assumed that most linguistic processes underlying language production happen automatically, accumulating evidence suggests that some form of attention is required. Here, we investigated the contribution of sustained attention, which is the ability to maintain alertness over time. First, the sustained attention ability of participants was measured using auditory and visual continuous performance tasks. Next, the participants described pictures using simple noun phrases while their response times (RTs) and gaze durations were measured. Earlier research has suggested that gaze duration reflects language planning processes up to and including phonological encoding. Individual differences in sustained attention ability correlated with individual differences in the magnitude of the tail of the RT distribution, reflecting the proportion of very slow responses, but not with individual differences in gaze duration. These results suggest that language production requires sustained attention, especially after phonological encoding.

Abstract

It has previously been shown that language production, performed simultaneously with a nonlinguistic task, involves sustained attention. Sustained attention concerns the ability to maintain alertness over time. Here, we aimed to replicate the previous finding by showing that individuals call upon sustained attention when they plan single noun phrases (e.g., "the carrot") and perform a manual arrow categorization task. In addition, we investigated whether speakers also recruit sustained attention when they produce conjoined noun phrases (e.g., "the carrot and the bucket") describing two pictures, that is, when both the first and second task are linguistic. We found that sustained attention correlated with the proportion of abnormally slow phrase-production responses. Individuals with poor sustained attention displayed a greater number of very slow responses than individuals with better sustained attention. Importantly, this relationship was obtained both for the production of single phrases while performing a nonlinguistic manual task, and the production of noun phrase conjunctions in referring to two spatially separated objects. Inhibition and updating abilities were also measured. These scores did not correlate with our measure of sustained attention, suggesting that sustained attention and executive control are distinct. Overall, the results suggest that planning conjoined noun phrases involves sustained attention, and that language production happens less automatically than has often been assumed.

Abstract

Lateralization is an important aspect of the functional brain architecture for language and other cognitive faculties. The molecular genetic basis of human brain lateralization is unknown, and recent studies have suggested that gene expression in the cerebral cortex is bilaterally symmetrical. Here we have re-analyzed two transcriptomic datasets derived from post mortem human cerebral cortex, with a specific focus on superior temporal and auditory language cortex in adults. We applied an empirical Bayes approach to model differential left-right expression, together with gene ontology analysis and meta-analysis. There was robust and reproducible lateralization of individual genes and gene ontology groups that are likely to fine-tune the electrophysiological and neurotransmission properties of cortical circuits, most notably synaptic transmission, nervous system development and glutamate receptor activity. Our findings anchor the cerebral biology of language to the molecular genetic level. Future research in model systems may determine how these molecular signatures of neurophysiological lateralization effect fine-tuning of cerebral cortical function, differently in the two hemispheres.

Abstract

Second-language learners often experience major difficulties in producing non-native speech sounds. This paper introduces a training method that uses a real-time analysis of the acoustic properties of vowels produced by non-native speakers to provide them with immediate, trial-by-trial visual feedback about their articulation alongside that of the same vowels produced by native speakers. The Mahalanobis acoustic distance between non-native productions and target native acoustic spaces was used to assess L2 production accuracy. The experiment shows that 1 h of training per vowel improves the production of four non-native Danish vowels: the learners' productions were closer to the corresponding Danish target vowels after training. The production performance of a control group remained unchanged. Comparisons of pre- and post-training vowel discrimination performance in the experimental group showed improvements in perception. Correlational analyses of training-related changes in production and perception revealed no relationship. These results suggest, first, that this training method is effective in improving non-native vowel production. Second, training purely on production improves perception. Finally, it appears that improvements in production and perception do not systematically progress at equal rates within individuals. (C) 2015 Acoustical Society of America.

Abstract

A comprehensive theory of language acquisition must explain how human infants can learn any one of the world’s 7000 or so languages. As such, an important part of understanding how languages are learned is to investigate acquisition across a range of diverse languages and sociocultural contexts. To this end, cross-linguistic and cross-cultural language research has been pervasive in the field of first language acquisition since the early 1980s. In groundbreaking work, Slobin (1985) noted that the study of acquisition in cross-linguistic perspective can be used to reveal both developmental universals and language-specific acquisition patterns. Since this observation there have been several waves of cross-linguistic first language acquisition research, and more recently we have seen a rise in research investigating lesser-known languages. This special issue brings together work on several such languages, spoken in minority contexts. It is the first collection of language development research dedicated to the acquisition of under-studied or little-known languages and by extension, different cultures. Why lesser-known languages, and why minority contexts? First and foremost, acquisition theories need data from different languages, language families and cultural groups across the broadest typological array possible, and yet many theories of acquisition have been developed through analyses of English and other major world languages. Thus they are likely to be skewed by sampling bias. Languages of European origin constitute a small percentage of the total number of languages spoken worldwide. The Ethnologue (2015) lists 7102 languages spoken across the world. Of these, only 286 languages are languages of European origin, a mere 4% of the total number of languages spoken across the planet, and representing approximately only 26% of the total number of language speakers alive today. Compare this to the languages of the Pacific. The Ethnologue lists 1313 languages spoken in the Pacific, constituting 18.5% of the world’s languages. Of these, very few have been described, and even fewer have child language data available. Lieven and Stoll (2010) note that only around 70–80 languages have been the focus of acquisition studies (around 1% of the world’s languages). This somewhat alarming statistic suggests that the time is now ripe for researchers working on lesser-known languages to contribute to the field’s knowledge about how children learn a range of very different languages across differing cultures, and in doing so, for this research to make a contribution to language acquisition theory. The potential benefits are many. First, decades of descriptive work in linguistic typology have culminated in strong challenges to the existence of a Universal Grammar (Evans & Levinson, 2009), a long-held axiom of formal language acquisition theory. To be sure, cross-linguistic work in acquisition has long fuelled this debate (e.g. MacWhinney & Bates, 1989), but only as we collect a greater number of data points will we move closer toward a better understanding of the initial state of the human capacity for language and the types of social and cultural contexts in which language is successfully transmitted. A focus on linguistic diversity enables the investigation and postulation of universals in language acquisition, if and in whatever form they exist. In doing so, we can determine the sorts of things that are evident in child-directed speech, in children’s language production and in adult language, teasing out the threads at the intersection of language, culture and cognition. The study and dissemination of research into lesser-known, under-described languages with small communities significantly contributes to this aim because it not only reflects the diversity of languages present in the world, but provides a better representation of the social and economic conditions under which the majority of the world’s population acquire language (Heinrich, Heins, & Norenzayan, 2010). Related to this point, the study of smaller languages has taken on intense urgency in the past few decades due to the rapid extinction of these languages (Evans, 2010). The Language Documentation movement has toiled tirelessly in the pursuit of documenting languages before they disappear, an effort to which child language researchers have much to offer. Many children acquire smaller and minority languages in rich multilingual environments, where the influence of dominant languages affects acquisition (e.g., Stoll, Zakharko, Moran, Schikowski, & Bickel, 2015). Understanding the acquisition process where systems compete and may be in flux due to language contact, while no small task, will help us understand the social and economic conditions which favour successful preservation of minority languages, which could ultimately equip communities with the tools to stem the flow of language loss. With these points in mind we now turn to the articles in this special issue.

Abstract

Hand gestures and speech form a single integrated system of meaning during language comprehension, but is gesture processed with speech in a unique fashion? We had subjects watch multimodal videos that presented auditory (words) and visual (gestures and actions on objects) information. Half of the subjects related the audio information to a written prime presented before the video, and the other half related the visual information to the written prime. For half of the multimodal video stimuli, the audio and visual information contents were congruent, and for the other half, they were incongruent. For all subjects, stimuli in which the gestures and actions were incongruent with the speech produced more errors and longer response times than did stimuli that were congruent, but this effect was less prominent for speech-action stimuli than for speech-gesture stimuli. However, subjects focusing on visual targets were more accurate when processing actions than gestures. These results suggest that although actions may be easier to process than gestures, gestures may be more tightly tied to the processing of accompanying speech.

Abstract

When you compare the behavior of two different age groups which are trying to master the same sensori-motor or cognitive skill, you are likely to discover varying learning routes: different stages, different intervals between stages, or even different orderings of stages. Such heterogeneous learning trajectories may be caused by at least six different types of factors: (1) Initial state: the kinds and levels of skills the learners have available at the onset of the learning episode. (2) Learning mechanisms: rule-based, inductive, connectionist, parameter setting, and so on. (3) Input and feedback characteristics: learning stimuli, information about success and failure. (4) Information processing mechanisms: capacity limitations, attentional biases, response preferences. (5) Energetic variables: motivation, emotional reactions. (6) Final state: the fine-structure of kinds and levels of subskills at the end of the learning episode. This applies to language acquisition as well. First and second language learners probably differ on all six factors. Nevertheless, the debate between advocates and opponents of the Fundamental Difference Hypothesis concerning L1 and L2 acquisition have looked almost exclusively at the first two factors. Those who believe that L1 learners have access to Universal Grammar whereas L2 learners rely on language processing strategies, postulate different learning mechanisms (UG parameter setting in L1, more general inductive strategies in L2 learning). Pienemann opposes this view and, based on his Processability Theory, argues that L1 and L2 learners start out from different initial states: they come to the grammar learning task with different structural hypotheses (SOV versus SVO as basic word order of German).

Abstract

This paper presents a theory of the syntactic aspects of human sentence production. An important characteristic of unprepared speech is that overt pronunciation of a sentence can be initiated before the speaker has completely worked out the meaning content he or she is going to express in that sentence. Apparently, the speaker is able to build up a syntactically coherent utterance out of a series of syntactic fragments each rendering a new part of the meaning content. This incremental, left-to-right mode of sentence production is the central capability of the proposed Incremental Procedural Grammar (IPG). Certain other properties of spontaneous speech, as derivable from speech errors, hesitations, self-repairs, and language pathology, are accounted for as well. The psychological plausibility thus gained by the grammar appears compatible with a satisfactory level of linguistic plausibility in that sentences receive structural descriptions which are in line with current theories of grammar. More importantly, an explanation for the existence of configurational conditions on transformations and other linguistics rules is proposed. The basic design feature of IPG which gives rise to these psychologically and linguistically desirable properties, is the “Procedures + Stack” concept. Sentences are built not by a central constructing agency which overlooks the whole process but by a team of syntactic procedures (modules) which work-in parallel-on small parts of the sentence, have only a limited overview, and whose sole communication channel is a stock. IPG covers object complement constructions, interrogatives, and word order in main and subordinate clauses. It handles unbounded dependencies, cross-serial dependencies and coordination phenomena such as gapping and conjunction reduction. It is also capable of generating self-repairs and elliptical answers to questions. IPG has been implemented as an incremental Dutch sentence generator written in LISP.

Abstract

In a recent Cognition paper (Cognition 85 (2002) B21), Bornkessel, Schlesewsky, and Friederici report ERP data that they claim “show that online processing difficulties induced by word order variations in German cannot be attributed to the relative infrequency of the constructions in question, but rather appear to reflect the application of grammatical principles during parsing” (p. B21). In this commentary we demonstrate that the posited contrast between grammatical principles and construction (in)frequency as sources of parsing problems is artificial because it is based on factually incorrect assumptions about the grammar of German and on inaccurate corpus frequency data concerning the German constructions involved.

Abstract

Remarques sur les facteurs intervenant dans le processus de formulation des énoncés.

Abstract

The psychology of language as developed by Wilhelm Wundt in his fundamental work Die Sprache (1900) has a strongly mentalistic character. The dominating positions held by behaviorism in psychology and structuralism in linguistics have overruled Wundt’s language theory to the effect that it has remained relatively unknown. This situation has changed recently under the influence of transformational linguistics and cognitive psychology. The paper discusses how Wundt applied the basic psychological concepts of apperception and association to language behavior, in particular to the construction and production of sentences during unprepared speech. The final part of the paper is devoted to the work, published in 1917, of the Dutch linguistic scholar Jacques van Ginneken, who elaborated Wundt’s ideas towards an explanation of some syntactic phenomena during the language acquisition of children.

Abstract

The practices of other-initiation of repair provide speakers with a set of solutions to one of the most basic problems in conversation: troubles of speaking, hearing, and understanding. Based on a collection of 227 cases systematically identified in a corpus of English conversation, this article describes the formats and practices of other-initiations of repair attested in the corpus and reports their quantitative distribution. In addition to straight other-initiations of repair, the identification of all possible cases also yielded a substantial proportion in which speakers use other-initiations to perform other actions, including non-serious actions, such as jokes and teases, preliminaries to dispreferred responses, and displays of surprise and disbelief. A distinction is made between other-initiations that perform additional actions concurrently and those that formally resemble straight other-initiations but analyzably do not initiate repair as an action.

Abstract

The transitions between turns at talk in conversation tend to occur quickly, with only a slight gap of approximately 100 to 300 ms between them. This estimate of central tendency, however, hides a wealth of complex variation, as a number of factors, such as the type of turns involved, have been shown to influence the timing of turn transitions. This article considers one specific type of turn that does not conform to the statistical trend, namely turns that deal with troubles of speaking, hearing, and understanding, known as other-initiations of repair. The results of a quantitative analysis of 169 other-initiations of repair in face-to-face conversation reveal that the most frequent cases occur after gaps of approximately 700 ms. Furthermore, other-initiations of repair that locate a source of trouble in a prior turn specifically tend to occur after shorter gaps than those that do not, and those that correct errors in a prior turn, while rare, tend to occur without delay. An analysis of the transitions before other-initiations of repair, using methods of conversation analysis, suggests that speakers use the extra time (i) to search for a late recognition of the problematic turn, (ii) to provide an opportunity for the speaker of the problematic turn to resolve the trouble independently, (iii) and to produce visual signals, such as facial gestures. In light of these results, it is argued that other-initiations of repair take priority over other turns at talk in conversation and therefore are not subject to the same rules and constraints that motivate fast turn transitions in general

Abstract

Conversation-analytic research has argued that the timing and construction of preferred responding actions (e.g., acceptances) differ from that of dispreferred responding actions (e.g., rejections), potentially enabling early response prediction by recipients. We examined 195 preferred and dispreferred responding actions in telephone corpora and found that the timing of the most frequent cases of each type did not differ systematically. Only for turn transitions of 700 ms or more was the proportion of dispreferred responding actions clearly greater than that of preferreds. In contrast, an analysis of the timing that included turn formats (i.e., those with or without qualification) revealed clearer differences. Small departures from a normal gap duration decrease the likelihood of a preferred action in a preferred turn format (e.g., a simple “yes”). We propose that the timing of a response is best understood as a turn-constructional feature, the first virtual component of a preferred or dispreferred turn format.

Abstract

Written information is often of limited accessibility to deaf people who use sign language. The eSign project was undertaken as a response to the need for technologies enabling efficient production and distribution over the Internet of sign language content. By using an avatar-independent scripting notation for signing gestures and a client-side web browser plug-in to translate this notation into motion data for an avatar, we achieve highly efficient delivery of signing, while avoiding the inflexibility of video or motion capture. Tests with members of the deaf community have indicated that the method can provide an acceptable quality of signing.

Abstract

Speech is structured into parts by syntactic and prosodic breaks. In locally syntactic ambiguous sentences, the detection of a syntactic break necessarily follows detection of a corresponding prosodic break, making an investigation of the immediate interplay of syntactic and prosodic information impossible when studying sentences in isolation. This problem can be solved, however, by embedding sentences in a discourse context that induces the expectation of either the presence or the absence of a syntactic break right at a prosodic break. Event-related potentials (ERPs) were compared to acoustically identical sentences in these different contexts. We found in two experiments that the closure positive shift, an ERP component known to be elicited by prosodic breaks, was reduced in size when a prosodic break was aligned with a syntactic break. These results establish that the brain matches prosodic information against syntactic information immediately.

Abstract

The current study investigated the role of cross-linguistic influence in Cantonese–English bilingual children's comprehension of subject- and object-extracted relative clauses (RCs). Twenty simultaneous Cantonese–English bilingual children (Mage = 8;11, SD = 2;6) and 20 vocabulary-matched Cantonese monolingual children (Mage = 6;4, SD = 1;3) completed a test of Cantonese RC comprehension. The bilingual children also completed a test of English RC comprehension. The results showed that, whereas the monolingual children were equally competent on subject and object RCs, the bilingual children performed significantly better on subject RCs. Error analyses suggested that the bilingual children were most often correctly assigning thematic roles in object RCs, but were incorrectly choosing the RC subject as the head referent. This pervasive error was interpreted to be due to the fact that both Cantonese and English have canonical SVO word order, which creates competition with structures that compete with an object RC analysis.

Abstract

This paper reports on two studies investigating children's and adults' processing of sentences containing ambiguity of prepositional phrase (PP) attachment. Study 1 used corpus data to investigate whether cues argued to be used by adults to resolve PP-attachment ambiguities are available in child-directed speech. Study 2 was an on-line reaction time study investigating the role of lexical and referential biases in syntactic ambiguity resolution by children and adults. Forty children (mean age 8;4) and 37 adults listened to V-NP-PP sentences containing temporary ambiguity of PP-attachment. The sentences were manipulated for (i) verb semantics, (ii) the definiteness of the object NP, and (iii) PP-attachment site. The children and adults did not differ qualitatively from each other in their resolution of the ambiguity. A verb semantics by attachment interaction suggested that different attachment analyses were pursued depending on the semantics of the verb. There was no influence of the definiteness of the object NP in either children's or adults' parsing preferences. The findings from the on-line task matched up well with the corpus data, thus identifying a role for the input in the development of parsing strategies.

Abstract

We present the results from four studies, two corpora and two experimental, which suggest that English- and German-speaking children (3;1–4;9 years) use multiple constraints to process and produce object relative clauses. Our two corpora studies show that children produce object relatives that reflect the distributional and discourse regularities of the input. Specifically, the results show that when children produce object relatives they most often do so with (a) an inanimate head noun, and (b) a pronominal relative clause subject. Our experimental findings show that children use these constraints to process and produce this construction type. Moreover, when children were required to repeat the object relatives they most often use in naturalistic speech, the subject-object asymmetry in processing of relative clauses disappeared. We also report cross-linguistic differences in children's rate of acquisition which reflect properties of the input language. Overall, our results suggest that children are sensitive to the same constraints on relative clause processing as adults.

Abstract

Eisenberg (2002) presents data from an experiment investigating three- and four-year-old children's comprehension of restrictive relative clauses (RC). From the results she argues, contrary to Hamburger & Crain (1982), that children do not have discourse knowledge of the felicity conditions of RCs before acquiring the syntax of relativization. This note evaluates this conclusion on the basis of the methodology used, and proposes that an account of syntactic development needs to be sensitive to the real-time processing requirements acquisition places on the learner.

Abstract

Although there is strong evidence for shared abstract grammatical structure in bilingual speakers from studies of sentence production, comparable evidence from studies of comprehension is lacking. Twenty-seven (N = 27) English-German bilingual adults participated in a structural priming study where unambiguous English subject and object relative clause (RC) structures were used to prime corresponding subject and object RC interpretations of structurally ambiguous German RCs. The results showed that English object RCs primed significantly greater object RC interpretations in German in comparison to baseline and subject RC prime conditions, but that English subject RC primes did not change the participants’ baseline preferences. This is the first study to report abstract crosslinguistic priming in comprehension. The results specifically suggest that word order overlap supports the integration of syntactic structures from different languages in bilingual speakers, and that these shared representations are used in comprehension as well as production

Abstract

Gestures that accompany speech are known to be tightly coupled with speech production. However little is known about the cognitive processes that underlie this link. Previous cross-linguistic research has provided preliminary evidence for online interaction between the two systems based on the systematic co-variation found between how different languages syntactically package Manner and Path information of a motion event and how gestures represent Manner and Path. Here we elaborate on this finding by testing whether speakers within the same language gesturally express Manner and Path differently according to their online choice of syntactic packaging of Manner and Path, or whether gestural expression is pre-determined by a habitual conceptual schema congruent with the linguistic typology. Typologically congruent and incongruent syntactic structures for expressing Manner and Path (i.e., in a single clause or multiple clauses) were elicited from English speakers. We found that gestural expressions were determined by the online choice of syntactic packaging rather than by a habitual conceptual schema. It is therefore concluded that speech and gesture production processes interface online at the conceptual planning phase. Implications of the findings for models of speech and gesture production are discussed

Abstract

Gestures that spontaneously accompany speech convey information coordinated with the concurrent speech. There has been considerable theoretical disagreement about the process by which this informational coordination is achieved. Some theories predict that the information encoded in gesture is not influenced by how information is verbally expressed. However, others predict that gestures encode only what is encoded in speech. This paper investigates this issue by comparing informational coordination between speech and gesture across different languages. Narratives in Turkish, Japanese, and English were elicited using an animated cartoon as the stimulus. It was found that gestures used to express the same motion events were influenced simultaneously by (1) how features of motion events were expressed in each language, and (2) spatial information in the stimulus that was never verbalized. From this, it is concluded that gestures are generated from spatio-motoric processes that interact on-line with the speech production process. Through the interaction, spatio-motoric information to be expressed is packaged into chunks that are verbalizable within a processing unit for speech formulation. In addition, we propose a model of speech and gesture production as one of a class of frameworks that are compatible with the data.

Abstract

In a way, the entire history of linguistic thought from the Antiquity to present days is a series of variations on two key themes: 1. In a certain sense, language and cognition are the same, and 2. In a certain sense, all languages are the same. What varies is the way in which “in a certain sense” is spelled out. Interpretations oscillate between radical positions such as the idea that thinking without speaking is impossible to the idea that it is just language which vexes our cognition and hence makes it rather impossible, and similarly between the idea that all differences between natural languages are nothing but irrelevant variations in the “vox”, the “external form” to the idea that it our thought is massively shaped by the particular structural features of the language we happen to speak. It is remarkable how little agreement has been reached on these issues after more than 2500 years of discussion. This, it is argued, has mainly two reasons: (a) The entire argument is largely confined to a few lexical and morphological properties of human languages, and (b) the discussion is rarely based on empirical research on “language at work” - how do we manage to solve those many little tasks for which human languages are designed in the first place.

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neuropsychiatric disorder with a complex genetic background. The G protein-coupled receptor kinase interacting ArfGAP 1 (GIT1) gene was previously associated with ADHD. We aimed at replicating the association of GIT1 with ADHD and investigated its role in cognitive and brain phenotypes. Gene-wide and single variant association analyses for GIT1 were performed for three cohorts: (1) the ADHD meta-analysis data set of the Psychiatric Genomics Consortium (PGC, N=19,210), (2) the Dutch cohort of the International Multicentre persistent ADHD CollaboraTion (IMpACT-NL, N=225), and (3) the Brain Imaging Genetics cohort (BIG, N=1,300). Furthermore, functionality of the rs550818 variant as an expression quantitative trait locus (eQTL) for GIT1 was assessed in human blood samples. By using Drosophila melanogaster as a biological model system, we manipulated Git expression according to the outcome of the expression result and studied the effect of Git knockdown on neuronal morphology and locomotor activity. Association of rs550818 with ADHD was not confirmed, nor did a combination of variants in GIT1 show association with ADHD or any related measures in either of the investigated cohorts. However, the rs550818 risk-genotype did reduce GIT1 expression level. Git knockdown in Drosophila caused abnormal synapse and dendrite morphology, but did not affect locomotor activity. In summary, we could not confirm GIT1 as an ADHD candidate gene, while rs550818 was found to be an eQTL for GIT1. Despite GIT1's regulation of neuronal morphology, alterations in gene expression do not appear to have ADHD-related behavioral consequences