Publications

Abstract

Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12-14 of Foxp2; these exons encode the DNA-binding motif, a key functional domain. We demonstrate that early global Cre-mediated recombination yields a null allele, as shown by loss of the loxP-flanked exons at the RNA level and an absence of Foxp2 protein. Homozygous null mice display severe motor impairment, cerebellar abnormalities and early postnatal lethality, consistent with other Foxp2 mutants. When crossed to transgenic lines expressing Cre protein in a spatially and/or temporally controlled manner, these conditional mice will provide new insights into the contributions of Foxp2 to distinct neural circuits, and allow dissection of roles during development and in the mature brain.

Abstract

Disruptions of the FOXP2 gene cause a rare speech and language disorder, a discovery that has opened up novel avenues for investigating the relevant neural pathways. FOXP2 shows remarkably high conservation of sequence and neural expression in diverse vertebrates, suggesting that studies in other species are useful in elucidating its functions. Here we describe how investigations of mice that carry disruptions of Foxp2 provide insights at multiple levels: molecules, cells, circuits and behaviour. Work thus far has implicated the gene in key processes including neurite outgrowth, synaptic plasticity, sensorimotor integration and motor-skill learning.

Abstract

Cumulative tool-based culture underwrote our species' evolutionary success and tool-based nut-cracking is one of the strongest candidates for cultural transmission in our closest relatives, chimpanzees. However the social learning processes that may explain both the similarities and differences between the species remain unclear. A previous study of nut-cracking by initially naïve chimpanzees suggested that a learning chimpanzee holding no hammer nevertheless replicated hammering actions it witnessed. This observation has potentially important implications for the nature of the social learning processes and underlying motor coding involved. In the present study, model and observer actions were quantified frame-by-frame and analysed with stringent statistical methods, demonstrating synchrony between the observer's and model's movements, cross-correlation of these movements above chance level and a unidirectional transmission process from model to observer. These results provide the first quantitative evidence for motor mimicking underlain by motor coding in apes, with implications for mirror neuron function.

Abstract

Previous research on language development shows that children are tuned early on to the language-specific semantic and syntactic encoding of events in their native language. Here we ask whether language-specificity is also evident in children's early representations in gesture accompanying speech. In a longitudinal study, we examined the spontaneous speech and cospeech gestures of eight Turkish-speaking children aged one to three and focused on their caused motion event expressions. In Turkish, unlike in English, the main semantic elements of caused motion such as Action and Path can be encoded in the verb (e.g. sok- ‘put in’) and the arguments of a verb can be easily omitted. We found that Turkish-speaking children's speech indeed displayed these language-specific features and focused on verbs to encode caused motion. More interestingly, we found that their early gestures also manifested specificity. Children used iconic cospeech gestures (from 19 months onwards) as often as pointing gestures and represented semantic elements such as Action with Figure and/or Path that reinforced or supplemented speech in language-specific ways until the age of three. In the light of previous reports on the scarcity of iconic gestures in English-speaking children's early productions, we argue that the language children learn shapes gestures and how they get integrated with speech in the first three years of life.

Abstract

Discourse markers (DMs) are linguistic elements that index different relations and coherence between units of talk (Schiffrin, Deborah, 1987. Discourse Markers. Cambridge University Press, Cambridge). Most research on the development of these forms has focused on conversations rather than narratives and furthermore has not directly compared children's use of DMs to adult usage. This study examines the development of three DMs (şey ‘uuhh’, yani ‘I mean’, işte ‘y’know’) that mark interactional levels of discourse in oral Turkish narratives in 60 Turkish children (3-, 5- and 9-year-olds) and 20 Turkish-speaking adults. The results show that the frequency and functions of DMs change with age. Children learn şey, which mainly marks exchange level structures, earliest. However, yani and işte have multi-functions such as marking both information states and participation frameworks and are consequently learned later. Children also use DMs with different functions than adults. Overall, the results show that learning to use interactional DMs in narratives is complex and goes beyond age 9, especially for multi-functional DMs that index an interplay of discourse coherence at different levels.

Abstract

This study investigated how sentence formulation is influenced by a preceding discourse context. In two eye-tracking experiments, participants described pictures of two-character transitive events in Dutch (Experiment 1) and Chinese (Experiment 2). Focus was manipulated by presenting questions before each picture. In the Neutral condition, participants first heard ‘What is happening here?’ In the Object or Subject Focus conditions, the questions asked about the Object or Subject character (What is the policeman stopping? Who is stopping the truck?). The target response was the same in all conditions (The policeman is stopping the truck). In both experiments, sentence formulation in the Neutral condition showed the expected pattern of speakers fixating the subject character (policeman) before the object character (truck). In contrast, in the focus conditions speakers rapidly directed their gaze preferentially only to the character they needed to encode to answer the question (the new, or focused, character). The timing of gaze shifts to the new character varied by language group (Dutch vs. Chinese): shifts to the new character occurred earlier when information in the question can be repeated in the response with the same syntactic structure (in Chinese but not in Dutch). The results show that discourse affects the timecourse of linguistic formulation in simple sentences and that these effects can be modulated by language-specific linguistic structures such as parallels in the syntax of questions and declarative sentences.

Abstract

The constraints that govern acceptable phoneme combinations in speech perception and production have considerable plasticity. We addressed whether sleep influences the acquisition of new constraints and their integration into the speech-production system. Participants repeated sequences of syllables in which two phonemes were artificially restricted to syllable onset or syllable coda, depending on the vowel in that sequence. After 48 sequences, participants either had a 90-min nap or remained awake. Participants then repeated 96 sequences so implicit constraint learning could be examined, and then were tested for constraint generalization in a forced-choice task. The sleep group, but not the wake group, produced speech errors at test that were consistent with restrictions on the placement of phonemes in training. Furthermore, only the sleep group generalized their learning to new materials. Polysomnography data showed that implicit constraint learning was associated with slow-wave sleep. These results show that sleep facilitates the integration of new linguistic knowledge with existing production constraints. These data have relevance for systems-consolidation models of sleep.

Abstract

A key function of attention is to select an appropriate subset of available information by facilitation of attended processes and/or inhibition of irrelevant processing. Functional imaging studies, using positron emission tomography, have during different experimental tasks revealed decreased neuronal activity in areas that process input from unattended sensory modalities. It has been hypothesized that these decreases reflect a selective inhibitory modulation of nonrelevant cortical processing. In this study we addressed this question using a continuous arithmetical task with and without concomitant disturbing auditory input (task-irrelevant speech). During the arithmetical task, irrelevant speech did not affect task-performance but yielded decreased activity in the auditory and midcingulate cortices and increased activity in the left posterior parietal cortex. This pattern of modulation is consistent with a top down inhibitory modulation of a nonattended input to the auditory cortex and a coexisting, attention-based facilitation of taskrelevant processing in higher order cortices. These findings suggest that task-related decreases in cortical activity may be of functional importance in the understanding of both attentional mechanisms and taskrelated information processing.

Abstract

Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a Genome-wide Association Scan (GWAS) meta-analysis using three richly characterised datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading- and language-related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected p≈10−7 for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on-going international efforts to identify genes contributing to reading and language skills.

Abstract

Irrelevant speech effect (ISE) is defined as a decrement in visually presented digit-list short-term memory performance due to exposure to irrelevant auditory material. Perhaps the most successful theoretical explanation of the effect is the changing state hypothesis. This hypothesis explains the effect in terms of confusion between amodal serial order cues, and represents a view based on the interference caused by the processing of similar order information of the visual and auditory materials. An alternative view suggests that the interference occurs as a consequence of the similarity between the visual and auditory contents of the stimuli. An important argument for the former view is the observation that ISE is almost exclusively observed in tasks that require memory for serial order. However, most short-term memory tasks require that both item and order information be retained in memory. An ideal task to investigate the sensitivity of maintenance of serial order to irrelevant speech would be one that calls upon order information but not item information. One task that is particularly suited to address this issue is serial recognition. In a typical serial recognition task, a list of items is presented and then probed by the same list in which the order of two adjacent items has been transposed. Due to the re-presentation of the encoding string, serial recognition requires primarily the serial order to be maintained while the content of the presented items is deemphasized. In demonstrating a highly significant ISE of changing versus steady-state auditory items in a serial recognition task, the present finding lends support for and extends previous empirical findings suggesting that irrelevant speech has the potential to interfere with the coding of the order of the items to be memorized.

Abstract

Using parametric and nonparametric techniques, our study investigated the presence of single locus and pairwise effects between 20 markers of the Genetic Analysis Workshop 15 (GAW15) North American Rheumatoid Arthritis Consortium (NARAC) candidate gene data set (Problem 2), analyzing 463 independent patients and 855 controls. Specifically, our work examined the correspondence between logistic regression (LR) analysis of single-locus and pairwise interaction effects, and random forest (RF) single and joint importance measures. For this comparison, we selected small but stable RFs (500 trees), which showed strong correlations (r~0.98) between their importance measures and those by RFs grown on 5000 trees. Both RF importance measures captured most of the LR single-locus and pairwise interaction effects, while joint importance measures also corresponded to full LR models containing main and interaction effects. We furthermore showed that RF measures were particularly sensitive to data imputation. The most consistent pairwise effect on rheumatoid arthritis was found between two markers within MAP3K7IP2/SUMO4 on 6q25.1, although LR and RFs assigned different significance levels. Within a hypothetical two-stage design, pairwise LR analysis of all markers with significant RF single importance would have reduced the number of possible combinations in our small data set by 61%, whereas joint importance measures would have been less efficient for marker pair reduction. This suggests that RF single importance measures, which are able to detect a wide range of interaction effects and are computationally very efficient, might be exploited as pre-screening tool for larger association studies. Follow-up analysis, such as by LR, is required since RFs do not indicate highrisk genotype combinations.

Abstract

Previous studies have described the existence of a phonotactic bias called the Labial–Coronal (LC) bias, corresponding to a tendency to produce more words beginning with a labial consonant followed by a coronal consonant (i.e. “bat”) than the opposite CL pattern (i.e. “tap”). This bias has initially been interpreted in terms of articulatory constraints of the human speech production system. However, more recently, it has been suggested that this presumably language-general LC bias in production might be accompanied by LC and CL biases in perception, acquired in infancy on the basis of the properties of the linguistic input. The present study investigates the origins of these perceptual biases, testing infants learning Japanese, a language that has been claimed to possess more CL than LC sequences, and comparing them with infants learning French, a language showing a clear LC bias in its lexicon. First, a corpus analysis of Japanese IDS and ADS revealed the existence of an overall LC bias, except for plosive sequences in ADS, which show a CL bias across counts. Second, speech preference experiments showed a perceptual preference for CL over LC plosive sequences (all recorded by a Japanese speaker) in 13- but not in 7- and 10-month-old Japanese-learning infants (Experiment 1), while revealing the emergence of an LC preference between 7 and 10 months in French-learning infants, using the exact same stimuli. These crosslinguistic behavioral differences, obtained with the same stimuli, thus reflect differences in processing in two populations of infants, which can be linked to differences in the properties of the lexicons of their respective native languages. These findings establish that the emergence of a CL/LC bias is related to exposure to a linguistic input.

Abstract

Humans appear to rely on spatial mappings to represent and describe concepts. The conceptual cuing effect describes the tendency for participants to orient attention to a spatial location following the presentation of an unrelated cue word (e.g., orienting attention upward after reading the word sky). To date, such effects have predominately been explained within the embodied cognition framework, according to which people’s attention is oriented on the basis of prior experience (e.g., sky → up via perceptual simulation). However, this does not provide a compelling explanation for how abstract words have the same ability to orient attention. Why, for example, does dream also orient attention upward? We report on an experiment that investigated the role of language use (specifically, collocation between concept words and spatial words for up and down dimensions) and found that it predicted the cuing effect. The results suggest that language usage patterns may be instrumental in explaining conceptual cuing.

Abstract

Our recent studies suggest that congenitally blind adults have severely impaired thresholds in an auditory spatial bisection task, pointing to the importance of vision in constructing complex auditory spatial maps (Gon etal., 2014). To explore strategies that may improve the auditory spatial sense in visually impaired people, we investigated the impact of tactile feedback on spatial auditory localization in 48 blindfolded sighted subjects. We measured auditory spatial bisection thresholds before and after training, either with tactile feedback, verbal feedback, or no feedback. Audio thresholds were first measured with a spatial bisection task: subjects judged whether the second sound of a three sound sequence was spatially closer to the first or the third sound. The tactile feedback group underwent two audio-tactile feedback sessions of 100 trials, where each auditory trial was followed by the same spatial sequence played on the subject's forearm; auditory spatial bisection thresholds were evaluated after each session. In the verbal feedback condition, the positions of the sounds were verbally reported to the subject after each feedback trial.The no feedback group did the same sequence of trials, with no feedback. Performance improved significantly only after audio-tactile feedback. The results suggest that direct tactile feedback interacts with the auditory spatial localization system, possibly by a process of cross-sensory recalibration. Control tests with the subject rotated suggested that this effect occurs only when the tactile and acoustic sequences are spatially congruent. Our results suggest that the tactile system can be used to recalibrate the auditory sense of space. These results encourage the possibility of designing rehabilitation programs to help blind persons establish a robust auditory sense of space, through training with the tactile modality.

Abstract

The involvement of neural motor and sensory systems in the processing of language has so far mainly been studied in native (L1) speakers. In an fMRI experiment, we investigated whether non-native (L2) semantic representations are rich enough to allow for activation in motor and somatosensory brain areas. German learners of Dutch and a control group of Dutch native speakers made lexical decisions about visually presented Dutch motor and non-motor verbs. Region-of-interest (ROI) and whole-brain analyses indicated that L2 speakers, like L1 speakers, showed significantly increased activation for simple motor compared to non-motor verbs in motor and somatosensory regions. This effect was not restricted to Dutch-German cognate verbs, but was also present for non-cognate verbs. These results indicate that L2 semantic representations are rich enough for motor-related activations to develop in motor and somatosensory areas.

Abstract

In this functional magnetic resonance imaging (fMRI) long-lag priming study, we investigated the processing of Dutch semantically transparent, derived prefix verbs. In such words, the meaning of the word as a whole can be deduced from the meanings of its parts, e.g., wegleggen “put aside.” Many behavioral and some fMRI studies suggest that native (L1) speakers decompose transparent derived words. The brain region usually implicated in morphological decomposition is the left inferior frontal gyrus (LIFG). In non-native (L2) speakers, the processing of transparent derived words has hardly been investigated, especially in fMRI studies, and results are contradictory: some studies find more reliance on holistic (i.e., non-decompositional) processing by L2 speakers; some find no difference between L1 and L2 speakers. In this study, we wanted to find out whether Dutch transparent derived prefix verbs are decomposed or processed holistically by German L2 speakers of Dutch. Half of the derived verbs (e.g., omvallen “fall down”) were preceded by their stem (e.g., vallen “fall”) with a lag of 4–6 words (“primed”); the other half (e.g., inslapen “fall asleep”) were not (“unprimed”). L1 and L2 speakers of Dutch made lexical decisions on these visually presented verbs. Both region of interest analyses and whole-brain analyses showed that there was a significant repetition suppression effect for primed compared to unprimed derived verbs in the LIFG. This was true both for the analyses over L2 speakers only and for the analyses over the two language groups together. The latter did not reveal any interaction with language group (L1 vs. L2) in the LIFG. Thus, L2 speakers show a clear priming effect in the LIFG, an area that has been associated with morphological decomposition. Our findings are consistent with the idea that L2 speakers engage in decomposition of transparent derived verbs rather than processing them holistically

Abstract

The left and right sides of the human brain are specialized for different kinds of information processing, and much of our cognition is lateralized to an extent towards one side or the other. Handedness is a reflection of nervous system lateralization. Roughly ten percent of people are mixed- or left-handed, and they show an elevated rate of reductions or reversals of some cerebral functional asymmetries compared to right-handers. Brain anatomical correlates of left-handedness have also been suggested. However, the relationships of left-handedness to brain structure and function remain far from clear. We carried out a comprehensive analysis of cortical surface area differences between 106 left-handed subjects and 1960 right-handed subjects, measured using an automated method of regional parcellation (FreeSurfer, Destrieux atlas). This is the largest study sample that has so far been used in relation to this issue. No individual cortical region showed an association with left-handedness that survived statistical correction for multiple testing, although there was a nominally significant association with the surface area of a previously implicated region: the left precentral sulcus. Identifying brain structural correlates of handedness may prove useful for genetic studies of cerebral asymmetries, as well as providing new avenues for the study of relations between handedness, cerebral lateralization and cognition.

Abstract

Functional and anatomical asymmetries are prevalent features of the human brain, linked to gender, handedness, and cognition. However, little is known about the neurodevelopmental processes involved. In zebrafish, asymmetries arise in the diencephalon before extending within the central nervous system. We aimed to identify genes involved in the development of subtle, left-right volumetric asymmetries of human subcortical structures using large datasets. We first tested the feasibility of measuring left-right volume differences in such large-scale samples, as assessed by two automated methods of subcortical segmentation (FSL|FIRST and FreeSurfer), using data from 235 subjects who had undergone MRI twice. We tested the agreement between the first and second scan, and the agreement between the segmentation methods, for measures of bilateral volumes of six subcortical structures and the hippocampus, and their volumetric asymmetries. We also tested whether there were biases introduced by left-right differences in the regional atlases used by the methods, by analyzing left-right flipped images. While many bilateral volumes were measured well (scan-rescan r = 0.6-0.8), most asymmetries, with the exception of the caudate nucleus, showed lower repeatabilites. We meta-analyzed genome-wide association scan results for caudate nucleus asymmetry in a combined sample of 3,028 adult subjects but did not detect associations at genome-wide significance (P < 5 × 10-8). There was no enrichment of genetic association in genes involved in left-right patterning of the viscera. Our results provide important information for researchers who are currently aiming to carry out large-scale genome-wide studies of subcortical and hippocampal volumes, and their asymmetries

Abstract

A large body of evidence has shown that visual context information can rapidly modulate language comprehension for concrete sentences and when it is mediated by a referential or a lexical-semantic link. What has not yet been examined is whether visual context can also modulate comprehension of abstract sentences incrementally when it is neither referenced by, nor lexically associated with, the sentence. Three eye-tracking reading experiments examined the effects of spatial distance between words (Experiment 1) and objects (Experiment 2 and 3) on participants’ reading times for sentences that convey similarity or difference between two abstract nouns (e.g., ‘Peace and war are certainly different...’). Before reading the sentence, participants inspected a visual context with two playing cards that moved either far apart or close together. In Experiment 1, the cards turned and showed the first two nouns of the sentence (e.g., ‘peace’, ‘war’). In Experiments 2 and 3, they turned but remained blank. Participants’ reading times at the adjective (Experiment 1: first-pass reading time; Experiment 2: total times) and at the second noun phrase (Experiment 3: first-pass times) were faster for sentences that expressed similarity when the preceding words/objects were close together (vs. far apart) and for sentences that expressed dissimilarity when the preceding words/objects were far apart (vs. close together). Thus, spatial distance between words or entirely unrelated objects can rapidly and incrementally modulate the semantic interpretation of abstract sentences.

Abstract

All accounts of communicative behaviour in general, and communicative strategies in particular, mention gesture1 in relation to language acquisition (cf. Faerch & Kasper 1983 for an overview). However, few attempts have been made to investigate how spoken language and spontaneous gesture combine to determine discourse referents. Referential gesture and referential discourse will be of particular interest, since communicative strategies in second language discourse often involve labelling problems.

This paper will focus on two issues:

1) Within a cognitive account of communicative strategies, gesture will be seen to be part of conceptual or analysis-based strategies, in that relational features in the referents are exploited;

2) It will be argued that communication strategies can be seen in terms of cue manipulation in the same sense as sentence processing has been analysed in terms of competing cues. Strategic behaviour, and indeed the process of referring in general, are seen in terms of cues, combining or competing to determine discourse referents. Gesture can then be regarded as being such a cue at the discourse level, and as a cue-based communicative strategy, in that gesture functions by exploiting physically based cues which can be recognised as being part of the referent. The question of iconicity and motivation vs. the arbitrary qualities of gesture as a strategic cue will be addressed in connection with this.

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

Current views on the neurobiological underpinnings of language are discussed that deviate in a number of ways from the classical Wernicke–Lichtheim–Geschwind model. More areas than Broca's and Wernicke's region are involved in language. Moreover, a division along the axis of language production and language comprehension does not seem to be warranted. Instead, for central aspects of language processing neural infrastructure is shared between production and comprehension. Three different accounts of the role of Broca's area in language are discussed. Arguments are presented in favor of a dynamic network view, in which the functionality of a region is co-determined by the network of regions in which it is embedded at particular moments in time. Finally, core regions of language processing need to interact with other networks (e.g. the attentional networks and the ToM network) to establish full functionality of language and communication.

Abstract

A hallmark of human language is that we combine lexical building blocks retrieved from memory in endless new ways. This combinatorial aspect of language is referred to as unification. Here we focus on the neurobiological infrastructure for syntactic and semantic unification. Unification is characterized by a high-speed temporal profile including both prediction and integration of retrieved lexical elements. A meta-analysis of numerous neuroimaging studies reveals a clear dorsal/ventral gradient in both left inferior frontal cortex and left posterior temporal cortex, with dorsal foci for syntactic processing and ventral foci for semantic processing. In addition to core areas for unification, further networks need to be recruited to realize language-driven communication to its full extent. One example is the theory of mind network, which allows listeners and readers to infer the intended message (speaker meaning) from the coded meaning of the linguistic utterance. This indicates that sensorimotor simulation cannot handle all of language processing.

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

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

In the recent past the work on large-scale linguistic distributions across the globe has intensified considerably. Work on macro-areal relationships in Africa (Güldemann, 2010) suggests that the shape of convergence areas may be determined by climatic factors and geophysical features such as mountains, water bodies, coastlines, etc. Worldwide data is now available for geophysical features as well as linguistic features, including numeral systems and basic constituent order. We explore the possibility that the shape of areal aggregations of individual features in these two linguistic domains correlates with Köppen-Geiger climate zones. Furthermore, we test the hypothesis that the shape of such areal feature aggregations is determined by the contour of adjacent geophysical features like mountain ranges or coastlines. In these first basic tests, we do not find clear evidence that either Köppen-Geiger climate zones or the contours of geophysical features are major predictors for the linguistic data at hand

Abstract

While the notion of the ‘area’ or ‘Sprachbund’ has a long history in linguistics, with geographically-defined regions frequently cited as a useful means to explain typological distributions, the problem of delimiting areas has not been well addressed. Lists of general-purpose, largely independent ‘macro-areas’ (typically continent size) have been proposed as a step to rule out contact as an explanation for various large-scale linguistic phenomena. This squib points out some problems in some of the currently widely-used predetermined areas, those found in the World Atlas of Language Structures (Haspelmath et al., 2005). Instead, we propose a principled division of the world’s landmasses into six macro-areas that arguably have better geographical independence properties

Abstract

Whitesands is an Oceanic language of the southern Vanuatu subgroup. Like the related languages of southern Vanuatu, Whitesands has developed a clause-linkage system which monitors referent continuity on new clauses – typically contrasting with the previous clause. In this chapter I address how the construction interacts with topic continuity in discourse. I outline the morphosyntactic form of this anaphoric co-reference device. From a functionalist perspective, I show how the system is used in natural discourse and discuss its restrictions with respect to relative and complement clauses. I conclude with a discussion on its interactions with theoretical notions of information structure – in particular the nature of presupposed versus asserted clauses, information back- and foregrounding and how these affect the use of the switch-reference system

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

All primates learn things from conspecifics socially, but it is not clear whether they conform to the behavior of these conspecifics—if conformity is defined as overriding individually acquired behavioral tendencies in order to copy peers’ behavior. In the current study, chimpanzees, orangutans, and 2-year-old human children individually acquired a problem-solving strategy. They then watched several conspecific peers demonstrate an alternative strategy. The children switched to this new, socially demonstrated strategy in roughly half of all instances, whereas the other two great-ape species almost never adjusted their behavior to the majority’s. In a follow-up study, children switched much more when the peer demonstrators were still present than when they were absent, which suggests that their conformity arose at least in part from social motivations. These results demonstrate an important difference between the social learning of humans and great apes, a difference that might help to account for differences in human and nonhuman cultures

Abstract

Bilingual listeners comprehend speech-in-noise better in their native than non-native language. This native-language benefit is thought to arise from greater use of top-down linguistic information to assist degraded speech comprehension. Using functional magnetic resonance imaging, we recently showed that left angular gyrus activation is modulated when semantic context is used to assist native language speech-in-noise comprehension (Golestani, Hervais-Adelman, Obleser, & Scott, 2013). Here, we extend the previous work, by reanalyzing the previous data alongside the results obtained in the non-native language of the same late bilingual participants. We found a behavioral benefit of semantic context in processing speech-in-noise in the native language only, and the imaging results also revealed a native language context effect in the left angular gyrus. We also find a complementary role of lower-level auditory regions during stimulus-driven processing. Our findings help to elucidate the neural basis of the established native language behavioral benefit of speech-in-noise processing. (C) 2014 Elsevier Inc. All rights reserved.

Abstract

Superiority in visual search for individuals diagnosed with autism spectrum disorder (ASD) is a well-reported finding. We administered two visual search tasks to individuals with ASD and matched controls. One showed no difference between the groups, and one did show the expected superior performance for individuals with ASD. These results offer an explanation, formulated in terms of load theory. We suggest that there is a limit to the superiority in visual search for individuals with ASD, related to the perceptual load of the stimuli. When perceptual load becomes so high that no additional task-(ir)relevant information can be processed, performance will be based on single stimulus identification, in which no differences between individuals with ASD and controls have been demonstrated

Abstract

Theories of embodied language comprehension have proposed that language is understood through perceptual simulation of the sensorimotor characteristics of its meaning. Strong support for this claim requires demonstration of encoding-based activation of sensorimotor representations that is distinct from task-related or goal-driven processes. Participants in 3 eye-tracking experiments were presented with triplets of either numbers or object and animal names. In Experiment 1, participants indicated whether the size of the referent of the middle object or animal name was in between the size of the 2 outer items. In Experiment 2, the object and animal names were encoded for an immediate recognition memory task. In Experiment 3, participants completed the same comparison task of Experiment 1 for both words and numbers. During the comparison tasks, word and number decision times showed a symbolic distance effect, such that response time was inversely related to the size difference between the items. A symbolic distance effect was also observed for animal and object encoding times in cases where encoding time likely reflected some goal-driven processes as well. When semantic size was irrelevant to the task (Experiment 2), it had no effect on word encoding times. Number encoding times showed a numerical distance priming effect: Encoding time increased with numerical difference between items. Together these results suggest that while activation of numerical magnitude representations is encoding-based as well as goal-driven, activation of size information associated with words is goal-driven and does not occur automatically during encoding. This conclusion challenges strong theories of embodied cognition which claim that language comprehension consists of activation of analog sensorimotor representations irrespective of higher level processes related to context or task-specific goals

Abstract

Two eye-tracking experiments were conducted in which the manual response mode typically used in lexical decision tasks (LDTs) was replaced with an eye-movement response through a sequence of 3 words. This ocular LDT combines the explicit control of task goals found in LDTs with the highly practiced ocular response used in reading text. In Experiment 1, forward saccades indicated an affirmative lexical decision (LD) on each word in the triplet. In Experiment 2, LD responses were delayed until all 3 letter strings had been read. The goal of the study was to evaluate the contribution of task goals and response mode to semantic priming. Semantic priming is very robust in tasks that involve recognition of words in isolation, such as LDT, but limited during text reading, as measured using eye movements. Gaze durations in both experiments showed robust semantic priming even though ocular response times were much shorter than manual LDs for the same words in the English Lexicon Project. Ex-Gaussian distribution fits revealed that the priming effect was concentrated in estimates of tau (τ), meaning that priming was most pronounced in the slow tail of the distribution. This pattern shows differential use of the prime information, which may be more heavily recruited in cases in which the LD is difficult, as indicated by longer response times. Compared with the manual LD responses, ocular LDs provide a more sensitive measure of this task-related influence on word recognition as measured by the LDT.

Abstract

Participants in interaction routinely orient to gaze, bodily comportment, and nonlexical vocalizations as salient for developing an analysis of the unfolding course of action. In this article, I address the respiratory phenomenon of sighing, the aim being to describe sighing as a situated practice that contributes to the achievement of particular actions in interaction. I report on the various actions sighs implement or construct and how their positioning and delivery informs participants’ understandings of their significance for interaction. Data are in American English

Abstract

Background: Individuals with autism spectrum disorder (ASD) and their parents demonstrate impaired performance in rapid automatized naming (RAN), a task that recruits a variety of linguistic and executive processes. Though the basic processes that contribute to RAN differences remain unclear, eye-voice relationships, as measured through eye tracking, can provide insight into cognitive and perceptual processes contributing to RAN performance. For example, in RAN, eye-voice span (EVS), the distance ahead the eyes are when articulation of a target item's label begins, is an indirect measure of automaticity of the processes underlying RAN. The primary objective of this study was to investigate automaticity in naming processes, as indexed by EVS during RAN. The secondary objective was to characterize RAN difficulties in individuals with ASD and their siblings. Methods: Participants (aged 15 – 33 years) included 21 individuals with ASD, 23 siblings of individuals with ASD, and 24 control subjects, group-matched on chronological age. Naming time, frequency of errors, and EVS were measured during a RAN task and compared across groups. Results: A stepwise pattern of RAN performance was observed, with individuals with ASD demonstrating the slowest naming across all RAN conditions, controls demonstrating the fastest naming, and siblings demonstrating intermediate performance. Individuals with ASD exhibited smaller EVSs than controls on all RAN conditions, and siblings exhibited smaller EVSs during number naming (the most highly automatized type of naming). EVSs were correlated with naming times in controls only, and only in the more automatized conditions. Conclusions: These results suggest that reduced automaticity in the component processes of RAN may underpin differences in individuals with ASD and their siblings. These findings also provide further support that RAN abilities are impacted by genetic liability to ASD. This study has important implications for understanding the underlying skills contributing to language-related deficits in ASD.

Abstract

In human face-to-face communication, language comprehension is a multi-modal, situated activity. However, little is known about how we combine information from different modalities during comprehension, and how perceived communicative intentions, often signaled through visual signals, influence this process. We explored this question by simulating a multi-party communication context in which a speaker alternated her gaze between two recipients. Participants viewed speech-only or speech + gesture object-related messages when being addressed (direct gaze) or unaddressed (gaze averted to other participant). They were then asked to choose which of two object images matched the speaker’s preceding message. Unaddressed recipients responded significantly more slowly than addressees for speech-only utterances. However, perceiving the same speech accompanied by gestures sped unaddressed recipients up to a level identical to that of addressees. That is, when unaddressed recipients’ speech processing suffers, gestures can enhance the comprehension of a speaker’s message. We discuss our findings with respect to two hypotheses attempting to account for how social eye gaze may modulate multi-modal language comprehension.

Abstract

The FOXP2 transcription factor is one of the most well-known genes to have been implicated in developmental speech and language disorders. Rare mutations disrupting the function of this gene have been described in different families and cases. In a large three-generation family carrying a missense mutation, neuroimaging studies revealed significant effects on brain structure and function, most notably in the inferior frontal gyrus, caudate nucleus and cerebellum. After the identification of rare disruptive FOXP2 variants impacting on brain structure, several reports proposed that common variants at this locus may also have detectable effects on the brain, extending beyond disorder into normal phenotypic variation. These neuroimaging genetics studies used groups of between 14 and 96 participants. The current study assessed effects of common FOXP2 variants on neuroanatomy using voxel-based morphometry and volumetric techniques in a sample of >1300 people from the general population. In a first targeted stage we analyzed single nucleotide polymorphisms (SNPs) claimed to have effects in prior smaller studies (rs2253478, rs12533005, rs2396753, rs6980093, rs7784315, rs17137124, rs10230558, rs7782412, rs1456031), beginning with regions proposed in the relevant papers, then assessing impact across the entire brain. In the second gene-wide stage, we tested all common FOXP2 variation, focusing on volumetry of those regions most strongly implicated from analyses of rare disruptive mutations. Despite using a sample that is more than ten times that used for prior studies of common FOXP2 variation, we found no evidence for effects of SNPs on variability in neuroanatomy in the general population. Thus, the impact of this gene on brain structure may be largely limited to extreme cases of rare disruptive alleles. Alternatively, effects of common variants at this gene exist but are too subtle to be detected with standard volumetric techniques

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

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

At present, more than one-fifth of humanity is unable to read and write. We critically examine experimental evidence and theories of how (il)literacy affects the human mind. In our discussion we show that literacy has significant cognitive consequences that go beyond the processing of written words and sentences. Thus, cultural inventions such as reading shape general cognitive processing in non-trivial ways. We suggest that this has important implications for educational policy and guidance as well as research into cognitive processing and brain functioning.

Abstract

This chapter investigates the fit of genetic, phenotypic, and linguistic data to two well-known models of population history. The first of these models, termed the population fissions model, emphasizes population splitting, isolation, and independent evolution. It predicts that genetic and linguistic data will be perfectly tree-like. The second model, termed isolation by distance, emphasizes genetic exchange among geographically proximate populations. It predicts a monotonic decline in genetic similarity with increasing geographic distance. While these models are overly simplistic, deviations from them were expected to provide important insights into the population history of northern Island Melanesia. The chapter finds scant support for either model because the prehistory of the region has been so complex. Nonetheless, the genetic and linguistic data are consistent with an early radiation of proto-Papuan speakers into the region followed by a much later migration of Austronesian speaking peoples. While these groups subsequently experienced substantial genetic and cultural exchange, this exchange has been insufficient to erase this history of separate migrations.

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

Neurocognitive studies of language production have provided sufficient evidence on both the spatial and the temporal patterns of brain activation to allow tentative and in some cases not so tentative conclusions about function-structure relationships. This chapter reports meta-analysis results that identify reliable activation areas for a range of word, sentence, and narrative production tasks both in the native language and a second language. Based on a theoretically motivated analysis of language production tasks it is possible to specify relationships between brain areas and functional processing components of language production that could not have been derived from the data provided by any single task.

Abstract

Hickok's enterprise to unify psycholinguistic and motor control models is highly stimulating. Nonetheless, there are problems of the model with respect to the time course of neural activation in word production, the flexibility for continuous speech, and the need for non-motor feedback.

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

Many older listeners report difficulties in understanding speech in noisy situations. Working memory and other cognitive skills may modulate, however, older listeners’ ability to use context information to alleviate the effects of noise on spoken-word recognition. In the present study, we investigated whether working memory predicts older adults’ ability to immediately use context information in the recognition of words embedded in sentences, presented in different listening conditions. In a phoneme-monitoring task, older adults were asked to detect as fast and as accurately as possible target phonemes in sentences spoken by a target speaker. Target speech was presented without noise, with fluctuating speech-shaped noise, or with competing speech from a single distractor speaker. The gradient measure of contextual probability (derived from a separate offline rating study) mainly affected the speed of recognition, with only a marginal effect on detection accuracy. Contextual facilitation was modulated by older listeners’ working memory and age across listening conditions. Working memory and age, as well as hearing loss, were also the most consistent predictors of overall listening performance. Older listeners’ immediate benefit from context in spoken-word recognition thus relates to their ability to keep and update a semantic representation of the sentence content in working memory.

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

Visual cues to the individual segments of speech and to sentence prosody guide speech recognition. The present study tested whether visual suprasegmental cues to the stress patterns of words can also constrain recognition. Dutch listeners use acoustic suprasegmental cues to lexical stress (changes in duration, amplitude, and pitch) in spoken-word recognition. We asked here whether they can also use visual suprasegmental cues. In two categorization experiments, Dutch participants saw a speaker say fragments of word pairs that were segmentally identical but differed in their stress realization (e.g., 'ca-vi from cavia "guinea pig" vs. 'ka-vi from kaviaar "caviar"). Participants were able to distinguish between these pairs from seeing a speaker alone. Only the presence of primary stress in the fragment, not its absence, was informative. Participants were able to distinguish visually primary from secondary stress on first syllables, but only when the fragment-bearing target word carried phrase-level emphasis. Furthermore, participants distinguished fragments with primary stress on their second syllable from those with secondary stress on their first syllable (e.g., pro-'jec from projector "projector" vs. 'pro-jec from projectiel "projectile"), independently of phrase-level emphasis. Seeing a speaker thus contributes to spoken-word recognition by providing suprasegmental information about the presence of primary lexical stress.

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

Recent behavioral and electrophysiological evidence has highlighted the long-term importance for language skills of an early ability to recognize words in continuous speech. We here present further tests of this long-term link in the form of follow-up studies conducted with two (separate) groups of infants who had earlier participated in speech segmentation tasks. Each study extends prior follow-up tests: Study 1 by using a novel follow-up measure that taps into online processing, Study 2 by assessing language performance relationships over a longer time span than previously tested. Results of Study 1 show that brain correlates of speech segmentation ability at 10 months are positively related to 16-month-olds’ target fixations in a looking-while-listening task. Results of Study 2 show that infant speech segmentation ability no longer directly predicts language profiles at the age of five. However, a meta-analysis across our results and those of similar studies (Study 3) reveals that age at follow-up does not moderate effect size. Together, the results suggest that infants’ ability to recognize words in speech certainly benefits early vocabulary development; further observed relationships of later language skills to early word recognition may be consequent upon this vocabulary size effect.

Abstract

Most words that infants hear occur within fluent speech. To compile a vocabulary, infants therefore need to segment words from speech contexts. This study is the first to investigate whether infants (here: 10-month-olds) can recognize words when both initial exposure and test presentation are in continuous speech. Electrophysiological evidence attests that this indeed occurs: An increased extended negativity (word recognition effect) appears for familiarized target words relative to control words. This response proved constant at the individual level: Only infants who showed this negativity at test had shown such a response, within six repetitions after first occurrence, during familiarization.

Abstract

Day-to-day interpretations of “space” are enmeshed in specific cultural and linguistic practices. For example, many cultures have an association between vertical height and social standing; more powerful people may be placed literally higher than others at social gatherings, and be spoken of as having higher status. This questionnaire is a guide for exploring relationships between space, language, and social structure. The goal is to better understand how space is organised in the focus community, and to investigate the extent to which space is used as a model for reproducing social forms.

Abstract

The relocation of animals can induce stress when animals are placed in novel environmental conditions. The movement of captive animals among facilities is common, especially for non-human primates used in research. The stress response begins with the activation of the hypothalamic-pituitary-adrenal (HPA) axis which results in the release of glucocorticoid hormones (GC), which at chronic levels could lead to deleterious physiological effects. There is a substantial body of data concerning GC levels affecting reproduction, and rank and aggression in primates. However, the effect of transport has received much less attention. Fecal samples from eight (four male and four female) captive-bred cotton-top tamarins (Saguinus oedipus) were collected at four different time points (two pre-transport and two post-transport). The fecal samples were analyzed using an immunoassay to determine GC levels. A repeated measures analysis of variance (ANOVA) demonstrated that GC levels differed among transport times (p = 0.009), but not between sexes (p = 0.963). Five of the eight tamarins exhibited an increase in GC levels after transport. Seven of the eight tamarins exhibited a decrease in GC levels from three to six days post-transport to three weeks post-transport. Most values returned to pre-transport levels after three weeks. The results indicate that these tamarins experienced elevated GC levels following transport, but these increases were of short duration. This outcome would suggest that the negative effects of elevated GC levels were also of short duration.

Abstract

One of the major challenges in acquiring a language is being able to use morphology as an adult would, and thus, a considerable amount of acquisition research has focused on morphological production and comprehension. Most of this research, however, has focused on the acquisition of morphology in isolating languages, or languages (such as English) with limited inflectional morphology. The nature of the learning task is different, and potentially more challenging, when the child is learning a polysynthetic language – a language in which words are highly morphologically complex, expressing in a single word what in English takes a multi-word clause. To date, there has been no cross-linguistic survey of how children approach this puzzle and learn polysynthetic languages. This paper aims to provide such a survey, including a discussion of some of the general findings in the literature regarding the acquisition of polysynthetic systems

Abstract

We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β-C-telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMDC ). CTX and mid-tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (β=0.19 [0.13, 0.24]) (coefficient=SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMDC (β=-0.46 [-0.52,-0.40]) and cortical thickness [β=-0.11 (-0.18, -0.03)]. CTX was positively related to bone strength as reflected by the strength-strain index (SSI) (β=0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single-nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p<}0.05 cut-off) (n=2379). Subsequently, we performed a meta-analysis of associations between these SNPs and PC in ALSPAC (n=3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n=938), and the Young Finns Study (YFS) (n=1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (p{<0.05 cut-off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion.

Abstract

Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.

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 is an abridged version (in Dutch) of an in-press article by the same author (Kempen, G. (2008/9). Clausal coordination and coordinate ellipsis in a model of the speaker. To be published in: Linguistics). The two papers present a psycholinguistically inspired approach to the syntax of clause-level coordination and coordinate ellipsis. It departs from the assumption that coordinations are structurally similar to so-called appropriateness repairs Ñ an important type of self-repairs in spontaneous speech. Coordinate structures and appropriateness repairs can both be viewed as ÒupdateÓ con-structions. Updating is defined as a special sentence production mode that efficiently revises or augments existing sentential structure in response to modifications in the speakerÕs communicative intention. This perspective is shown to offer an empirically satisfactory and theoretically parsimonious account of two prominent types of coordinate ellipsis, in particular Forward Conjunction Reduction (FCR) and Gapping (including Long-Distance Gapping and Subgapping). They are analyzed as different manifestations of Òincremental updatingÓ Ñ efficient updating of only part of the existing sentential structure. Based on empirical data from Dutch and German, novel treatments are proposed for both types of clausal coordinate ellipsis. Two other forms of coordinate ellipsis Ñ SGF (ÒSubject Gap in Finite clauses with fronted verbÓ), and Backward Conjunction Reduction (BCR; also known as Right Node Raising or RNR) Ñ are shown to be incompatible with the notion of incremental updating. Alternative theoretical interpretations of these phenomena are proposed. The four types of clausal coordinate ellipsis Ñ SGF, Gapping, FCR and BCR Ñ are argued to originate in four different stages of sentence production: Intending (i.e. preparing the communicative intention), Conceptualization, Grammatical Encoding, and Phonological Encoding, respectively.

Abstract

Comments on a study by Frazier and others on Dutch-language lexical processing. Claims that the control condition in the experiment was inadequate and that an assumption made by Frazier about closed class verbal items is inaccurate, and proposes an alternative account of a subset of the data from the experiment

Abstract

Raises objections to L. Frazier et al's (see record 1994-32229-001) report of an experimental study intended to test Schreuder's (1990) Morphological Integration (MI) model concerning the processing of separable and inseparable verbs and shows that the logic of the experiment is flawed. The problem is rooted in the notion of a separable complex verb. The conclusion is drawn that Frazier et al's experimental data cannot be taken as evidence for the theoretical propositions they develop about the MI model.