Publications

Abstract

In the speech production model proposed by [Levelt, W. J. M., Roelofs, A., Meyer, A. S. (1999). A theory of lexical access in speech production. Behavioral and Brain Sciences, 22, pp. 1-75.], syllables play a crucial role at the interface of phonological and phonetic encoding. At this interface, abstract phonological syllables are translated into phonetic syllables. It is assumed that this translation process is mediated by a so-called Mental Syllabary. Rather than constructing the motor programs for each syllable on-line, the mental syllabary is hypothesized to provide pre-compiled gestural scores for the articulators. In order to find evidence for such a repository, we investigated syllable-frequency effects: If the mental syllabary consists of retrievable representations corresponding to syllables, then the retrieval process should be sensitive to frequency differences. In a series of experiments using a symbol-position association learning task, we tested whether highfrequency syllables are retrieved and produced faster compared to low-frequency syllables. We found significant syllable frequency effects with monosyllabic pseudo-words and disyllabic pseudo-words in which the first syllable bore the frequency manipulation; no effect was found when the frequency manipulation was on the second syllable. The implications of these results for the theory of word form encoding at the interface of phonological and phonetic encoding; especially with respect to the access mechanisms to the mental syllabary in the speech production model by (Levelt et al.) are discussed.

Abstract

Although most bilinguals can translate with relative ease, the underlying neuro-cognitive processes are poorly understood. Using event-related brain potentials (ERPs) we investigated the temporal course of word translation. Participants translated words from and to their first (L1, Dutch) and second (L2, English) language while ERPs were recorded. Interlingual homographs (IHs) were included to introduce language conflict. IHs share orthographic form but have different meanings in L1 and L2 (e.g., room in Dutch refers to cream). Results showed that the brain distinguished between translation directions as early as 200 ms after word presentation: the P2 amplitudes were more positive in the L1L2 translation direction. The N400 was also modulated by translation direction, with more negative amplitudes in the L2L1 translation direction. Furthermore, the IHs were translated more slowly, induced more errors, and elicited more negative N400 amplitudes than control words. In a naming experiment, participants read aloud the same words in L1 or L2 while ERPs were recorded. Results showed no effect of either IHs or language, suggesting that task schemas may be crucially related to language control in translation. Furthermore, translation appears to involve conceptual processing in both translation directions, and the task goal appears to influence how words are processed.

Abstract

In a semantic priming paradigm, the effects of different levels of processing on the N400 were assessed by changing the task demands. In the lexical decision task, subjects had to discriminate between words and nonwords and in the physical task, subjects had to discriminate between uppercase and lowercase letters. The proportion of related versus unrelated word pairs differed between conditions. A lexicality test on reaction times demonstrated that the physical task was performed nonlexically. Moreover, a semantic priming reaction time effect was obtained only in the lexical decision task. The level of processing clearly affected the event-related potentials. An N400 priming effect was only observed in the lexical decision task. In contrast, in the physical task a P300 effect was observed for either related or unrelated targets, depending on their frequency of occurrence. Taken together, the results indicate that an N400 priming effect is only evoked when the task performance induces the semantic aspects of words to become part of an episodic trace of the stimulus event.

Abstract

Dyslexia is a learning difficulty with neurodevelopmental origins, manifesting as reduced accuracy and speed in reading and spelling. It is substantially heritable and frequently co-occurs with other neurodevelopmental conditions, particularly attention deficit-hyperactivity disorder (ADHD). Here, we investigate the genetic structure underlying dyslexia and a range of psychiatric traits using results from genome-wide association studies of dyslexia, ADHD, autism, anorexia nervosa, anxiety, bipolar disorder, major depressive disorder, obsessive compulsive disorder,
schizophrenia, and Tourette syndrome. Genomic Structural Equation Modelling (GenomicSEM) showed heightened support for a model consisting of five correlated latent genomic factors described as: F1) compulsive disorders (including obsessive-compulsive disorder, anorexia nervosa, Tourette syndrome), F2) psychotic disorder (including bipolar disorder, schizophrenia), F3) internalising disorders (including anxiety disorder, major depressive disorder), F4) neurodevelopmental traits (including autism, ADHD), and F5) attention and learning difficulties (including ADHD, dyslexia). ADHD loaded more strongly on the attention and learning difficulties latent factor (F5) than on the neurodevelopmental traits latent factor (F4). The attention and learning difficulties latent factor (F5) was positively correlated with internalising disorders (.40), neurodevelopmental traits (.25) and psychotic disorders (.17) latent factors, and negatively correlated with the compulsive disorders (–.16) latent factor. These factor correlations are mirrored in genetic correlations observed between the attention and learning difficulties latent factor and other cognitive, psychological and wellbeing traits. We further investigated genetic variants underlying both dyslexia and ADHD, which implicated 49 loci (40 not previously found in GWAS of the individual traits) mapping to 174 genes (121 not found in GWAS of individual traits) as potential pleiotropic variants. Our study confirms the increased genetic relation between dyslexia and ADHD versus other psychiatric traits and uncovers novel pleiotropic variants affecting both traits. In future, analyses including additional co-occurring traits such as dyscalculia and dyspraxia will allow a clearer definition of the attention and learning difficulties latent factor, yielding further insights into factor structure and pleiotropic effects.

Abstract

Clashen proposes two distinct processing routes, for regularly and irregularly inflected forms, respectively, and thus is apparently making a psychological claim. We argue his position, which embodies a strictly linguistic perspective, does not constitute a psychological processing model.

Abstract

Recent theoretical models have demonstrated that phenotypic traits can support the non-random assortment of cooperators in a population, thereby permitting the evolution of cooperation. In these “tag-based models”, cooperators modulate cooperation according to an observable and hard-to-fake trait displayed by potential interaction partners. Socially acquired vocalizations in general, and speech accent among humans in particular, are frequently proposed as hard to fake and hard to hide traits that display sufficient cross-populational variability to reliably guide such social assortment in fission–fusion societies. Adults’ sensitivity to accent variation in social evaluation and decisions about cooperation is well-established in sociolinguistic research. The evolutionary and developmental origins of these biases are largely unknown, however. Here, we investigate the influence of speech accent on 5–10-year-old children's developing social and cooperative preferences across four Brazilian Amazonian towns. Two sites have a single dominant accent, and two sites have multiple co-existing accent varieties. We found that children's friendship and resource allocation preferences were guided by accent only in sites characterized by accent heterogeneity. Results further suggest that this may be due to a more sensitively tuned ear for accent variation. The demonstrated local-accent preference did not hold in the face of personal cost. Results suggest that mechanisms guiding tag-based assortment are likely tuned according to locally relevant tag-variation.

Abstract

The nature of the connection between musical and spatial processing is controversial. While pitch may be described in spatial terms such as “high” or “low”, it is unclear whether pitch and space are associated but separate dimensions or whether they share representational and processing resources. In the present study, we asked participants to judge whether a target vocal note was the same as (or different from) a preceding cue note. Importantly, target trials were presented as video clips where a singer sometimes gestured upward or downward while singing that target note, thus providing an alternative, concurrent source of spatial information. Our results show that pitch discrimination was significantly biased by the spatial movement in gesture, such that downward gestures made notes seem lower in pitch than they really were, and upward gestures made notes seem higher in pitch. These effects were eliminated by spatial memory load but preserved under verbal memory load conditions. Together, our findings suggest that pitch and space have a shared representation such that the mental representation of pitch is audiospatial in nature.

Abstract

Importance
Previous studies indicated that female sex might be a modifier in Stargardt disease, which is an ABCA4-associated retinopathy.

Objective
To investigate whether women are overrepresented among individuals with ABCA4-associated retinopathy who are carrying at least 1 mild allele or carrying nonmild alleles.

Data Sources
Literature data, data from 2 European centers, and a new study. Data from a Radboudumc database and from the Rotterdam Eye Hospital were used for exploratory hypothesis testing.

Study Selection
Studies investigating the sex ratio in individuals with ABCA4-AR and data from centers that collected ABCA4 variant and sex data. The literature search was performed on February 1, 2023; data from the centers were from before 2023.

Data Extraction and Synthesis
Random-effects meta-analyses were conducted to test whether the proportions of women among individuals with ABCA4-associated retinopathy with mild and nonmild variants differed from 0.5, including subgroup analyses for mild alleles. Sensitivity analyses were performed excluding data with possibly incomplete variant identification. χ2 Tests were conducted to compare the proportions of women in adult-onset autosomal non–ABCA4-associated retinopathy and adult-onset ABCA4-associated retinopathy and to investigate if women with suspected ABCA4-associated retinopathy are more likely to obtain a genetic diagnosis. Data analyses were performed from March to October 2023.

Main Outcomes and Measures
Proportion of women per ABCA4-associated retinopathy group. The exploratory testing included sex ratio comparisons for individuals with ABCA4-associated retinopathy vs those with other autosomal retinopathies and for individuals with ABCA4-associated retinopathy who underwent genetic testing vs those who did not.

Results
Women were significantly overrepresented in the mild variant group (proportion, 0.59; 95% CI, 0.56-0.62; P < .001) but not in the nonmild variant group (proportion, 0.50; 95% CI, 0.46-0.54; P = .89). Sensitivity analyses confirmed these results. Subgroup analyses on mild variants showed differences in the proportions of women. Furthermore, in the Radboudumc database, the proportion of adult women among individuals with ABCA4-associated retinopathy (652/1154 = 0.56) was 0.10 (95% CI, 0.05-0.15) higher than among individuals with other retinopathies (280/602 = 0.47).

Conclusions and Relevance
This meta-analysis supports the likelihood that sex is a modifier in developing ABCA4-associated retinopathy for individuals with a mild ABCA4 allele. This finding may be relevant for prognosis predictions and recurrence risks for individuals with ABCA4-associated retinopathy. Future studies should further investigate whether the overrepresentation of women is caused by differences in the disease mechanism, by differences in health care–seeking behavior, or by health care discrimination between women and men with ABCA4-AR.

Abstract

To answer a question, speakers must determine their response and formulate it in words. But do they decide on a response before formulation, or do they formulate different potential answers before selecting one? We addressed this issue in a verbal question-answering experiment. Participants answered questions more quickly when they had one potential answer (e.g., Which tourist attraction in Paris is very tall?) than when they had multiple potential answers (e.g., What is the name of a Shakespeare play?). Participants also answered more quickly when the set of potential answers were on average short rather than long, regardless of whether there was only one or multiple potential answers. Thus, participants were not affected by the linguistic complexity of unselected but plausible answers. These findings suggest that participants select a single answer before formulation.

Abstract

Research suggests that interlocutors manage the timing demands of conversation by preparing what they want to say early. In three experiments, we used a verbal question-answering task to investigate what aspects of their response speakers prepare early. In all three experiments, participants answered more quickly when the critical content (here, barks) necessary for answer preparation occurred early (e.g., Which animal barks and is also a common household pet?) rather than late (e.g., Which animal is a common household pet and also barks?). In the individual experiments, we found no convincing evidence that participants were slower to produce longer answers, consisting of multiple words, than shorter answers, consisting of a single word. There was also no interaction between these two factors. A combined analysis of the first two experiments confirmed this lack of interaction, and demonstrated that participants were faster to answer questions when the critical content was available early rather than late and when the answer was short rather than long. These findings provide tentative evidence for an account in which interlocutors prepare the content of their answer as soon as they can, but sometimes do not prepare its length (and thus form) until they are ready to speak.

Abstract

Name agreement (NA) refers to the degree to which speakers agree on a picture’s name. A robust finding is that speakers are faster to name pictures with high agreement (HA) than those with low agreement (LA). This NA effect is thought to occur because LA pictures strongly activate several names, and so speakers need time to select one. HA pictures, in contrast, strongly activate a single name and so there is no need to select one name out of several alternatives. Recent models of lexical access suggest that the structure of the mental lexicon changes with experience. Thus, speakers should consider a range of names when naming LA pictures, but the extent to which they consider each of these names should change with experience. We tested these hypotheses in two picture-naming experiments. In Experiment 1, participants were faster to name LA than HA pictures when they named each picture once. Importantly, they were faster to produce modal names (provided by most participants) than alternative names for LA pictures, consistent with the view that speakers activate multiple names for LA pictures. In Experiment 2, participants were familiarised with the modal name before the experiment and named each picture three times. Although there was still an NA effect when participants named the pictures the first time, it was reduced in comparison to Experiment 1 and was further reduced with each picture repetition.Thus, familiarisation and repetition reduced the NA effect, but did not eliminate it, suggesting speakers activate a range of plausible names.

Abstract

The pubertal height growth spurt is a distinctive feature of childhood growth reflecting both the central onset of puberty and local growth factors. Although little is known about the underlying genetics, growth variability during puberty correlates with adult risks for hormone-dependent cancer and adverse cardiometabolic health. The only gene so far associated with pubertal height growth, LIN28B, pleiotropically influences childhood growth, puberty and cancer progression, pointing to shared underlying mechanisms. To discover genetic loci influencing pubertal height and growth and to place them in context of overall growth and maturation, we performed genome-wide association meta-analyses in 18 737 European samples utilizing longitudinally collected height measurements. We found significant associations (P < 1.67 × 10(-8)) at 10 loci, including LIN28B. Five loci associated with pubertal timing, all impacting multiple aspects of growth. In particular, a novel variant correlated with expression of MAPK3, and associated both with increased prepubertal growth and earlier menarche. Another variant near ADCY3-POMC associated with increased body mass index, reduced pubertal growth and earlier puberty. Whereas epidemiological correlations suggest that early puberty marks a pathway from rapid prepubertal growth to reduced final height and adult obesity, our study shows that individual loci associating with pubertal growth have variable longitudinal growth patterns that may differ from epidemiological observations. Overall, this study uncovers part of the complex genetic architecture linking pubertal height growth, the timing of puberty and childhood obesity and provides new information to pinpoint processes linking these traits.

Abstract

Until recently, imaging the infant brain was very challenging. Functional Near InfraRed Spectroscopy (fNIRS) is a promising, relatively novel technique, whose use is rapidly expanding. As an emergent field, it is particularly important to share methodological knowledge to ensure replicable and robust results. In this paper, we present a community-augmented database which will facilitate precisely this exchange. We tabulated articles and theses reporting empirical fNIRS research carried out on infants below three years of age along several methodological variables. The resulting spreadsheet has been uploaded in a format allowing individuals to continue adding new results, and download the most recent version of the table. Thus, this database is ideal to carry out systematic reviews. We illustrate its academic utility by focusing on the factors affecting three key variables: infant attrition, the reliability of oxygenated and deoxygenated responses, and signal-to-noise ratios. We then discuss strengths and weaknesses of the DBIfNIRS, and conclude by suggesting a set of simple guidelines aimed to facilitate methodological convergence through the standardization of reports.

Abstract

Over the first year of life, infant perception changes radically as the child learns the phonology of the ambient language from the speech she is exposed to. Since infant-directed speech attracts the child's attention more than other registers, it is necessary to describe that input in order to understand language development, and to address questions of learnability. In this review, evidence from corpora analyses, experimental studies, and observational paradigms is brought together to outline the first comprehensive empirical picture of infant-directed speech and its effects on language acquisition. The ensuing landscape suggests that infant-directed speech provides an emotionally and linguistically rich input to language acquisition

Abstract

A core property of language is the ability to generalize beyond observed examples. In two experiments, we explore how listeners generalize implicitly learned sound patterns to new nonwords and to new sounds, with the goal of shedding light on how similarity affects treatment of potential generalization targets. During the exposure phase, listeners heard nonwords whose onset consonant was restricted to a subset of a natural class (e.g., /d g v z Z/). During the test phase, listeners were presented with new nonwords and asked to judge how frequently they had been presented before; some of the test items began with a consonant from the exposure set (e.g., /d/), and some began with novel consonants with varying relations to the exposure set (e.g., /b/, which is highly similar to all onsets in the training set; /t/, which is highly similar to one of the training onsets; and /p/, which is less similar than the other two). The exposure onset was rated most frequent, indicating that participants encoded onset attestation in the exposure set, and generalized it to new nonwords. Participants also rated novel consonants as somewhat frequent, indicating generalization to onsets that did not occur in the exposure phase. While generalization could be accounted for in terms of featural distance, it was insensitive to natural class structure. Generalization to new sounds was predicted better by models requiring prior linguistic knowledge (either traditional distinctive features or articulatory phonetic information) than by a model based on a linguistically naïve measure of acoustic similarity.

Abstract

First paragraph: Motivated by his quest to characterize the society of the last common ancestor of humans and other great apes, Toshisada Nishida set out as a graduate student to the Mahale Mountains on the eastern shore of Lake Tanganyika, Tanzania. This book is a story of his 45 years with the Mahale chimpanzees, or as he calls it, their ethnography. Beginning with his accounts of meeting the Tongwe people and the challenges of provisioning the chimpanzees for habituation, Nishida reveals how he slowly unravelled the unit group and community basis of chimpanzee social organization. The book begins and ends with a feeling of chronological order, starting with his arrival at Mahale and ending with an eye towards the future, with concrete recommendations for protecting wild chimpanzees. However, the bulk of the book is topically organized with chapters on feeding behaviour, growth and development, play and exploration, communication, life histories, sexual strategies, politics and culture.

Abstract

To meet their exhibition, conservation, education, and scientific goals, members of the American Zoo and Aquarium Association (AZA) collaborate to manage their living collections as single species populations. These cooperative population management programs, Species Survival Planss (SSP) and Population Management Plans (PMP), issue specimen-by-specimen recommendations aimed at perpetuating captive populations by maintaining genetic diversity and demographic stability. Species Survival Plans and PMPs differ in that SSP participants agree to complete recommendations, whereas PMP participants need only take recommendations under advisement. We evaluated the effect of program type and the number of participating institutions on the success of actions recommended by the Population Management Center (PMC): transfers of specimens between institutions, breeding, and target number of offspring. We analyzed AZA studbook databases for the occurrence of recommended or unrecommended transfers and births during the 1-year period after the distribution of standard AZA Breeding-and-Transfer Plans. We had three major findings: 1) on average, both SSPs and PMPs fell about 25% short of their target; however, as the number of participating institutions increased so too did the likelihood that programs met or exceeded their target; 2) SSPs exhibited significantly greater transfer success than PMPs, although transfer success for both program types was below 50%; and 3) SSPs exhibited significantly greater breeding success than PMPs, although breeding success for both program types was below 20%. Together, these results indicate that the science and sophistication behind genetic and demographic management of captive populations may be compromised by the challenges of implementation.

Abstract

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5–90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8–80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9–25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5–40 and 40–90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Abstract

Previous research has shown that, in a phoneme detection task, vowels produce longer reaction times than consonants, suggesting that they are harder to perceive. One possible explanation for this difference is based upon their respective acoustic/articulatory characteristics. Another way of accounting for the findings would be to relate them to the differential functioning of vowels and consonants in the syllabic structure of words. In this experiment, we examined the second possibility. Targets were two pairs of phonemes, each containing a vowel and a consonant with similar phonetic characteristics. Subjects heard lists of English words had to press a response key upon detecting the occurrence of a pre-specified target. This time, the phonemes which functioned as vowels in syllabic structure yielded shorter reaction times than those which functioned as consonants. This rules out an explanation for response time difference between vowels and consonants in terms of function in syllable structure. Instead, we propose that consonantal and vocalic segments differ with respect to variability of tokens, both in the acoustic realisation of targets and in the representation of targets by listeners.

Abstract

The mapping of phonetic information to lexical representations in second-language (L2) listening was examined using an eyetracking paradigm. Japanese listeners followed instructions in English to click on pictures in a display. When instructed to click on a picture of a rocket, they experienced interference when a picture of a locker was present, that is, they tended to look at the locker instead. However, when instructed to click on the locker, they were unlikely to look at the rocket. This asymmetry is consistent with a similar asymmetry previously observed in Dutch listeners’ mapping of English vowel contrasts to lexical representations. The results suggest that L2 listeners may maintain a distinction between two phonetic categories of the L2 in their lexical representations, even though their phonetic processing is incapable of delivering the perceptual discrimination required for correct mapping to the lexical distinction. At the phonetic processing level, one of the L2 categories is dominant; the present results suggest that dominance is determined by acoustic–phonetic proximity to the nearest L1 category. At the lexical processing level, representations containing this dominant category are more likely than representations containing the non-dominant category to be correctly contacted by the phonetic input.

Abstract

In three experiments, the processing of lexical tone in Cantonese was examined. Cantonese listeners more often accepted a nonword as a word when the only difference between the nonword and the word was in tone, especially when the F0 onset difference between correct and erroneous tone was small. Same–different judgments by these listeners were also slower and less accurate when the only difference between two syllables was in tone, and this was true whether the F0 onset difference between the two tones was large or small. Listeners with no knowledge of Cantonese produced essentially the same same-different judgment pattern as that produced by the native listeners, suggesting that the results display the effects of simple perceptual processing rather than of linguistic knowledge. It is argued that the processing of lexical tone distinctions may be slowed, relative to the processing of segmental distinctions, and that, in speeded-response tasks, tone is thus more likely to be misprocessed than is segmental structure.

Abstract

SPEECH, in any language, is continuous; speakers provide few reliable cues to the boundaries of words, phrases, or other meaningful units. To understand speech, listeners must divide the continuous speech stream into portions that correspond to such units. This segmentation process is so basic to human language comprehension that psycholinguists long assumed that all speakers would do it in the same way. In previous research1,2, however, we reported that segmentation routines can be language-specific: speakers of French process spoken words syllable by syllable, but speakers of English do not. French has relatively clear syllable boundaries and syllable-based timing patterns, whereas English has relatively unclear syllable boundaries and stress-based timing; thus syllabic segmentation would work more efficiently in the comprehension of French than in the comprehension of English. Our present study suggests that at this level of language processing, there are limits to bilingualism: a bilingual speaker has one and only one basic language.

Abstract

Research on the exploitation of prosodic information in the recognition of spoken language is reviewed. The research falls into three main areas: the use of prosody in the recognition of spoken words, in which most attention has been paid to the question of whether the prosodic structure of a word plays a role in initial contact with stored lexical representations; the use of prosody in the computation of syntactic structure, in which the resolution of global and local ambiguities has formed the central focus; and the role of prosody in the processing of discourse structure, in which there has been a preponderance of work on the contribution of accentuation and deaccentuation to integration of concepts with an existing discourse model. The review reveals that in each area progress has been made towards new conceptions of prosody's role in processing, and in particular this has involved abandonment of previously held deterministic views of the relationship between prosodic structure and other aspects of linguistic structure

Abstract

Psycholinguists strive to construct a model of human language processing in general. But this does not imply that they should confine their research to universal aspects of linguistic structure, and avoid research on language-specific phenomena. First, even universal characteristics of language structure can only be accurately observed cross-linguistically. This point is illustrated here by research on the role of the syllable in spoken-word recognition, on the perceptual processing of vowels versus consonants, and on the contribution of phonetic assimilation phonemena to phoneme identification. In each case, it is only by looking at the pattern of effects across languages that it is possible to understand the general principle. Second, language-specific processing can certainly shed light on the universal model of language comprehension. This second point is illustrated by studies of the exploitation of vowel harmony in the lexical segmentation of Finnish, of the recognition of Dutch words with and without vowel epenthesis, and of the contribution of different kinds of lexical prosodic structure (tone, pitch accent, stress) to the initial activation of candidate words in lexical access. In each case, aspects of the universal processing model are revealed by analysis of these language-specific effects. In short, the study of spoken-language processing by human listeners requires cross-linguistic comparison.

Abstract

Language production and comprehension are intimately interrelated; and models of production and comprehension should, we argue, be constrained by common architectural guidelines. Levelt et al.'s target article adopts as guiding principle Ockham's razor: the best model of production is the simplest one. We recommend adoption of the same principle in comprehension, with consequent simplification of some well-known types of models.

Abstract

Segmentation of continuous speech into its component words is a nontrivial task for listeners. Previous work has suggested that listeners develop heuristic segmentation procedures based on experience with the structure of their language; for English, the heuristic is that strong syllables (containing full vowels) are most likely to be the initial syllables of lexical words, whereas weak syllables (containing central, or reduced, vowels) are nonword-initial, or, if word-initial, are grammatical words. This hypothesis is here tested against natural and laboratory-induced missegmentations of continuous speech. Precisely the expected pattern is found: listeners erroneously insert boundaries before strong syllables but delete them before weak syllables; boundaries inserted before strong syllables produce lexical words, while boundaries inserted before weak syllables produce grammatical words.

Abstract

Three experiments addressed the question of whether pitch-accent information may be exploited in the process of recognizing spoken words in Tokyo Japanese. In a two-choice classification task, listeners judged from which of two words, differing in accentual structure, isolated syllables had been extracted ~e.g., ka from baka HL or gaka LH!; most judgments were correct, and listeners’ decisions were correlated with the fundamental frequency characteristics of the syllables. In a gating experiment, listeners heard initial fragments of words and guessed what the words were; their guesses overwhelmingly had the same initial accent structure as the gated word even when only the beginning CV of the stimulus ~e.g., na- from nagasa HLL or nagashi LHH! was presented. In addition, listeners were more confident in guesses with the same initial accent structure as the stimulus than in guesses with different accent. In a lexical decision experiment, responses to spoken words ~e.g., ame HL! were speeded by previous presentation of the same word ~e.g., ame HL! but not by previous presentation of a word differing only in accent ~e.g., ame LH!. Together these findings provide strong evidence that accentual information constrains the activation and selection of candidates for spoken-word recognition.

Abstract

A model of speech segmentation in a stress language is proposed, according to which the occurrence of a strong syllable triggers segmentation of the speech signal, whereas occurrence of a weak syllable does not trigger segmentation. We report experiments in which listeners detected words embedded in nonsense bisyllables more slowly when the bisyllable had two strong syllables than when it had a strong and a weak syllable; mint was detected more slowly in mintayve than in mintesh. According to our proposed model, this result is an effect of segmentation: When the second syllable is strong, it is segmented from the first syllable, and successful detection of the embedded word therefore requires assembly of speech material across a segmentation position. Speech recognition models involving phonemic or syllabic recoding, or based on strictly left-to-right processes, do not predict this result. It is argued that segmentation at strong syllables in continuous speech recognition serves the purpose of detecting the most efficient locations at which to initiate lexical access. (C) 1988 by the American Psychological Association

Abstract

Monolingual French speakers employ a syllable-based procedure in speech segmentation; monolingual English speakers use a stress-based segmentation procedure and do not use the syllable-based procedure. In the present study French-English bilinguals participated in segmentation experiments with English and French materials. Their results as a group did not simply mimic the performance of English monolinguals with English language materials and of French monolinguals with French language materials. Instead, the bilinguals formed two groups, defined by forced choice of a dominant language. Only the French-dominant group showed syllabic segmentation and only with French language materials. The English-dominant group showed no syllabic segmentation in either language. However, the English-dominant group showed stress-based segmentation with English language materials; the French-dominant group did not. We argue that rhythmically based segmentation procedures are mutually exclusive, as a consequence of which speech segmentation by bilinguals is, in one respect at least, functionally monolingual.

Abstract

PURPOSE: We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina. METHODS: An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated. RESULTS: Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA. CONCLUSIONS: This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.

Abstract

Humans can easily extract the rhythm of a complex sound, like music, and move to its regular beat, like in dance. These abilities are modulated by musical training and vary significantly in untrained individuals. The causes of this variability are multidimensional and typically hard to grasp in single tasks. To date we lack a comprehensive model capturing the rhythmic fingerprints of both musicians and non-musicians. Here we harnessed machine learning to extract a parsimonious model of rhythmic abilities, based on behavioral testing (with perceptual and motor tasks) of individuals with and without formal musical training (n = 79). We demonstrate that variability in rhythmic abilities and their link with formal and informal music experience can be successfully captured by profiles including a minimal set of behavioral measures. These findings highlight that machine learning techniques can be employed successfully to distill profiles of rhythmic abilities, and ultimately shed light on individual variability and its relationship with both formal musical training and informal musical experiences.

Abstract

Human cognition is traditionally studied in experimental conditions wherein confounding complexities of the natural environment are intentionally eliminated. Thus, it remains unknown how a brain region involved in a particular experimental condition is engaged in natural conditions. Here we use electrocorticography to address this uncertainty in three participants implanted with intracranial electrodes and identify activations of neuronal populations within the intraparietal sulcus region during an experimental arithmetic condition. In a subsequent analysis, we report that the same intraparietal sulcus neural populations are activated when participants, engaged in social conversations, refer to objects with numerical content. Our prototype approach provides a means for both exploring human brain dynamics as they unfold in complex social settings and reconstructing natural experiences from recorded brain signals.

Abstract

In psycholinguistic studies using error rates as a response measure, response times (RT) are most often analyzed independently of the error rate, although it is widely recognized that they are related. In this paper we present a mixed effects logistic regression model for the error rate that uses RT as a trial-level fixed- and random-effect regression input. Production data from a translation–recall experiment are analyzed as an example. Several model comparisons reveal that RT improves the fit of the regression model for the error rate. Two simulation studies then show how the mixed effects regression model can identify individual participants for whom (a) faster responses are more accurate, (b) faster responses are less accurate, or (c) there is no relation between speed and accuracy. These results show that this type of model can serve as a useful adjunct to traditional techniques, allowing psycholinguistic researchers to examine more closely the relationship between RT and accuracy in individual subjects and better account for the variability which may be present, as well as a preliminary step to more advanced RT–accuracy modeling.

Abstract

The tracking of entities in discourse is known to be a bimodal phenomenon. Speakers achieve cohesion in speech by alternating between full lexical forms, pronouns, and zero anaphora as they track referents. They also track referents in co-speech gestures. In this study, we explored how viewpoint is deployed in reference tracking, focusing on representations of animate entities in German narrative discourse. We found that gestural viewpoint systematically varies depending on discourse context. Speakers predominantly use character viewpoint in maintained contexts and observer viewpoint in reintroduced contexts. Thus, gestural viewpoint seems to function as a cohesive device in narrative discourse. The findings expand on and provide further evidence for the coordination between speech and gesture on the discourse level that is crucial to understanding the tight link between the two modalities.

Abstract

It is usually assumed that modern language is a recent phenomenon, coinciding with the emergence of modern humans themselves. Many assume as well that this is the result of a single, sudden mutation giving rise to the full “modern package”. However, we argue here that recognizably modern language is likely an ancient feature of our genus pre-dating at least the common ancestor of modern humans and Neandertals about half a million years ago. To this end, we adduce a broad range of evidence from linguistics, genetics, palaeontology and archaeology clearly suggesting that Neandertals shared with us something like modern speech and language. This reassessment of the antiquity of modern language, from the usually quoted 50,000-100,000 years to half a million years, has profound consequences for our understanding of our own evolution in general and especially for the sciences of speech and language. As such, it argues against a saltationist scenario for the evolution of language, and towards a gradual process of culture-gene co-evolution extending to the present day. Another consequence is that the present-day linguistic diversity might better reflect the properties of the design space for language and not just the vagaries of history, and could also contain traces of the languages spoken by other human forms such as the Neandertals.

Abstract

Understanding the patterns and causes of differential structural stability is an area of major interest for the study of language change and evolution. It is still debated whether structural features have intrinsic stabilities across language families and geographic areas, or if the processes governing their rate of change are completely dependent upon the specific context of a given language or language family. We conducted an extensive literature review and selected seven different approaches to conceptualising and estimating the stability of structural linguistic features, aiming at comparing them using the same dataset, the World Atlas of Language Structures. We found that, despite profound conceptual and empirical differences between these methods, they tend to agree in classifying some structural linguistic features as being more stable than others. This suggests that there are intrinsic properties of such structural features influencing their stability across methods, language families and geographic areas. This finding is a major step towards understanding the nature of structural linguistic features and their interaction with idiosyncratic, lineage- and area-specific factors during language change and evolution.

Abstract

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Abstract

Next-generation sequencing is set to transform the discovery of genes underlying neurodevelopmental disorders, and so off er important insights into the biological bases of spoken language. Success will depend on functional assessments in neuronal cell lines, animal models and humans themselves.

Abstract

Desmet, Brysbaert, and De Baecke (2002a) showed that the production of relative clauses following two potential attachment hosts (e.g., ‘Someone shot the servant of the actress who was on the balcony’) was influenced by the animacy of the first host. These results were important because they refuted evidence from Dutch against experience-based accounts of syntactic ambiguity resolution, such as the tuning hypothesis. However, Desmet et al. did not provide direct evidence in favour of tuning, because their study focused on production and did not include reading experiments. In the present paper this line of research was extended. A corpus analysis and an eye-tracking experiment revealed that when taking into account lexical properties of the NP host sites (i.e., animacy and concreteness) the frequency pattern and the on-line comprehension of the relative clause attachment ambiguity do correspond. The implications for exposure-based accounts of sentence processing are discussed.

Abstract

Ependymal cells in the lateral ventricular wall are considered to be post-mitotic but can give rise to neuroblasts and astrocytes after stroke in adult mice due to insult-induced suppression of Notch signaling. The transcription factor FoxJ1, which has been used to characterize mouse ependymal cells, is also expressed by a subset of astrocytes. Cells expressing FoxJ1, which drives the expression of motile cilia, contribute to early postnatal neurogenesis in mouse olfactory bulb. The distribution and progeny of FoxJ1-expressing cells in rat forebrain are unknown. Here we show using immunohistochemistry that the overall majority of FoxJ1-expressing cells in the lateral ventricular wall of adult rats are ependymal cells with a minor population being astrocytes. To allow for long-term fate mapping of FoxJ1-derived cells, we used the piggyBac system for in vivo gene transfer with electroporation. Using this method, we found that FoxJ1-expressing cells, presumably the astrocytes, give rise to neuroblasts and mature neurons in the olfactory bulb both in intact and stroke-damaged brain of adult rats. No significant contribution of FoxJ1-derived cells to stroke-induced striatal neurogenesis was detected. These data indicate that in the adult rat brain, FoxJ1-expressing cells contribute to the formation of new neurons in the olfactory bulb but are not involved in the cellular repair after stroke.

Abstract

Developing efficient electromagnetic interference shielding materials has become significantly important in present times. This paper reports a series of (Ba1-xCax)(Ti0.9Sn0.1)O3 (BCTS) ((x =0, 0.01, 0.05, & 0.1)ceramics synthesized by conventional method which were studied for electromagnetic interference shielding (EMI) applications in X-band (8-12.4 GHz). EMI shielding properties and all S parameters (S11 & S12) of BCTS ceramic pellets were measured in the frequency range (8-12.4 GHz) using a Vector Network Analyser (VNA). The BCTS ceramic pellets for x = 0.05 showed maximum total effective shielding of 46 dB indicating good shielding behaviour for high-frequency applications. However, the development of lead-free ceramics with different concentrations usually requires iterative experiments resulting in, longer development cycles and higher costs. To address this, we used a machine learning (ML) strategy to predict the EMI shielding for different concentrations and experimentally verify the concentration predicted to give the best EMI shielding. The ML model predicted BCTS ceramics with concentration (x = 0.06, 0.07, 0.08, and 0.09) to have higher shielding values. On experimental verification, a shielding value of 58 dB was obtained for x = 0.08, which was significantly higher than what was obtained experimentally before applying the ML approach. Our results show the potential of using ML in accelerating the process of optimal material development, reducing the need for repeated experimental measures significantly.

Abstract

Human language offers a variety of ways to create meaning, one of which is referring to entities, objects, or events in the world. One such meaning maker is understanding to whom or to what a pronoun in a discourse refers to. To understand a pronoun, the brain must access matching entities or concepts that have been encoded in memory from previous linguistic context. Models of language processing propose that internally stored linguistic concepts, accessed via exogenous cues such as phonological input of a word, are represented as (a)synchronous activities across a population of neurons active at specific frequency bands. Converging evidence suggests that delta band activity (1–3 Hz) is involved in temporal and representational integration during sentence processing. Moreover, recent advances in the neurobiology of memory suggest that recollection engages neural dynamics similar to those which occurred during memory encoding. Integrating from these two research lines, we here tested the hypothesis that neural dynamic patterns, especially in delta frequency range, underlying referential meaning representation, would be reinstated during pronoun resolution. By leveraging neural decoding techniques (i.e., representational similarity analysis) on a magnetoencephalogram data set acquired during a naturalistic story-listening task, we provide evidence that delta-band activity underlies referential meaning representation. Our findings suggest that, during spoken language comprehension, endogenous linguistic representations such as referential concepts may be proactively retrieved and represented via activation of their underlying dynamic neural patterns.

Abstract

This article examines the relation between ideophones and gestures in a corpus of everyday discourse in Siwu, a richly ideophonic language spoken in Ghana. The overall frequency of ideophone-gesture couplings in everyday speech is lower than previously suggested, but two findings shed new light on the relation between ideophones and gesture. First, discourse type makes a difference: ideophone-gesture couplings are more frequent in narrative contexts, a finding that explains earlier claims, which were based not on everyday language use but on elicited narratives. Second, there is a particularly strong coupling between ideophones and one type of gesture: iconic gestures. This coupling allows us to better understand iconicity in relation to the affordances of meaning and modality. Ultimately, the connection between ideophones and iconic gestures is explained by reference to the depictive nature of both. Ideophone and iconic gesture are two aspects of the process of depiction

Abstract

A word like Huh?–used as a repair initiator when, for example, one has not clearly heard what someone just said– is found in roughly the same form and function in spoken languages across the globe. We investigate it in naturally occurring conversations in ten languages and present evidence and arguments for two distinct claims: that Huh? is universal, and that it is a word. In support of the first, we show that the similarities in form and function of this interjection across languages are much greater than expected by chance. In support of the second claim we show that it is a lexical, conventionalised form that has to be learnt, unlike grunts or emotional cries. We discuss possible reasons for the cross-linguistic similarity and propose an account in terms of convergent evolution. Huh? is a universal word not because it is innate but because it is shaped by selective pressures in an interactional environment that all languages share: that of other-initiated repair. Our proposal enhances evolutionary models of language change by suggesting that conversational infrastructure can drive the convergent cultural evolution of linguistic items.

Abstract

The robustness and flexibility of human language is underpinned by a machinery of interactive repair. Repair is deeply intertwined with two core properties of human language: reflexivity (it can communicate about itself) and accountability (it is used to publicly enforce social norms). We review empirical and theoretical advances from across the cognitive sciences that mark interactive repair as a domain of pragmatic universals, a key place to study metacognition in interaction, and a system that enables collective computation. This provides novel insights on the role of repair in comparative cognition, language development and human-computer interaction. As an always-available fallback option and an infrastructure for negotiating social commitments, interactive repair is foundational to the resilience, complexity, and flexibility of human language.

Abstract

Do people who speak different languages think differently, even when they are not using language? To find out, we used nonlinguistic psychophysical tasks to compare mental representations of musical pitch in native speakers of Dutch and Farsi. Dutch speakers describe pitches as high (hoog) or low (laag), whereas Farsi speakers describe pitches as thin (na-zok) or thick (koloft). Differences in language were reflected in differences in performance on two pitch-reproduction tasks, even though the tasks used simple, nonlinguistic stimuli and responses. To test whether experience using language influences mental representations of pitch, we trained native Dutch speakers to describe pitch in terms of thickness, as Farsi speakers do. After the training, Dutch speakers’ performance on a nonlinguistic psychophysical task resembled the performance of native Farsi speakers. People who use different linguistic space-pitch metaphors also think about pitch differently. Language can play a causal role in shaping nonlinguistic representations of musical pitch.

Abstract

Prediction-based accounts of language acquisition have the potential to explain several different effects in child language acquisition and adult language processing. However, evidence regarding the developmental predictions of such accounts is mixed. Here, we consider several predictions of these accounts in two large-scale developmental studies of syntactic priming of the English dative alternation. Study 1 was a cross-sectional study (N = 140) of children aged 3−9 years, in which we found strong evidence of abstract priming and the lexical boost, but little evidence that either effect was moderated by age. We found weak evidence for a prime surprisal effect; however, exploratory analyses revealed a protracted developmental trajectory for verb-structure biases, providing an explanation as for why prime surprisal effects are more elusive in developmental populations. In a longitudinal study (N = 102) of children in tightly controlled age bands at 42, 48, and 54 months, we found priming effects emerged on trials with verb overlap early but did not observe clear evidence of priming on trials without verb overlap until 54 months. There was no evidence of a prime surprisal effect at any time point and none of the effects were moderated by age. The results relating to the emergence of the abstract priming and lexical boost effects are consistent with prediction-based models, while the absence of age-related effects appears to reflect the structure-specific challenges the dative presents to English-acquiring children. Overall, our complex pattern of findings demonstrates the value of developmental data sets in testing psycholinguistic theory.

Abstract

The Levelt, Noort and Drenth Committees make their sole and final rejoinder to criticisms of their report on the Stapel fraud

Abstract

This paper presents a study of the spontaneous pre-sentential negations
of ten English-speaking children between the ages of 1; 6 and 3; 4 which
supports the hypothesis that child English nonanaphoric pre-sentential
negation is a form of metalinguistic exclamatory sentence negation. A
detailed discourse analysis reveals that children's pre-sentential negatives
like No Nathaniel a king (i) are characteristically echoic, and (it)
typically express objection and rectification, two characteristic functions
of exclamatory negation in adult discourse, e.g. Don't say 'Nathaniel's a
king'! A comparison of children's pre-sentential negations with their
internal predicate negations using not and don't reveals that the two
negative constructions are formally and functionally distinct. I argue
that children's nonanaphoric pre-sentential negatives constitute an
independent, well-formed class of discourse negation. They are not
'primitive' constructions derived from the miscategorization of emphatic
no in adult speech or children's 'inventions'. Nor are they an
early derivational variant of internal sentence negation. Rather, these
negatives reflect young children's competence in using grammatical
negative constructions appropriately in discourse.

Abstract

This paper presents the methods of language documentation as applied in the Awetí Language Documentation Project, one of the projects in the Documentation of Endangered Languages Programme (DOBES). It describes the steps of how a large digital corpus of annotated multi-media data is built. Special attention is devoted to the format of annotation of linguistic data. The Advanced Glossing format is presented and justified

Abstract

The Aslian branch of Austroasiatic is recognised as the oldest recoverable language family in the Malay Peninsula, predating the now dominant Austronesian languages present today. In this paper we address the dynamics of the prehistoric spread of Aslian languages across the peninsula, including the languages spoken by Semang foragers, traditionally associated with the 'Negrito' phenotype. The received view of an early and uniform tripartite break-up of proto-Aslian in the Early Neolithic period, and subsequent differentiation driven by societal modes is challenged. We present a Bayesian phylogeographic analysis of our dataset of vocabulary from 28 Aslian varieties. An explicit geographic model of diffusion is combined with a cognate birth-word death model of lexical evolution to infer the location of the major events of Aslian cladogenesis. The resultant phylogenetic trees are calibrated against dates in the historical and archaeological record to extrapolate a detailed picture of Aslian language history. We conclude that a binary split between Southern Aslian and the rest of Aslian took place in the Early Neolithic (4000 BP). This was followed much later in the Late Neolithic (2000-3000 BP) by a tripartite branching into Central Aslian, Jah Hut and Northern Aslian. Subsequent internal divisions within these sub-clades took place in the Early Metal Phase (post-2000 BP). Significantly, a split in Northern Aslian between Ceq Wong and the languages of the Semang was a late development and is proposed here to coincide with the adoption of Aslian by the Semang foragers. Given the difficulties involved in associating archaeologically recorded activities with linguistic events, as well as the lack of historical sources, our results remain preliminary. However, they provide sufficient evidence to prompt a rethinking of previous models of both clado- and ethno-genesis within the Malay Peninsula.

Abstract

Although there is a large body of research assessing whether exposure to narratives boosts social cognition immediately afterward, not much research has investigated the underlying mechanism of this putative effect. This experiment investigates the possibility that reading a narrative increases social curiosity directly afterward, which might explain the short-term boosts in social cognition reported by some others. We developed a novel measure of state social curiosity and collected data from participants (N = 222) who were randomly assigned to read an excerpt of narrative fiction or expository nonfiction. Contrary to our expectations, we found that those who read a narrative exhibited less social curiosity afterward than those who read an expository text. This result was not moderated by trait social curiosity. An exploratory analysis uncovered that the degree to which texts present readers with social targets predicted less social curiosity. Our experiment demonstrates that reading narratives, or possibly texts with social content in general, may engage and fatigue social-cognitive abilities, causing a temporary decrease in social curiosity. Such texts might also temporarily satisfy the need for social connection, temporarily reducing social curiosity. Both accounts are in line with theories describing how narratives result in better social cognition over the long term.

Abstract

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.

Abstract

Migraine is a disabling common brain disorder typically characterized by attacks of severe headache and associated with autonomic and neurological symptoms. Its etiology is far from resolved. This review will focus on evidence that epigenetic mechanisms play an important role in disease etiology. Epigenetics comprise both DNA methylation and post-translational modifications of the tails of histone proteins, affecting chromatin structure and gene expression. Besides playing a role in establishing cellular and developmental stage-specific regulation of gene expression, epigenetic processes are also important for programming lasting cellular responses to environmental signals. Epigenetic mechanisms may explain how non-genetic endogenous and exogenous factors such as female sex hormones, stress hormones and inflammation trigger may modulate attack frequency. Developing drugs that specifically target epigenetic mechanisms may open up exciting new avenues for the prophylactic treatment of migraine.

Abstract

Purpose of review: Migraine is a prevalent neurovascular brain disorder with a strong genetic component, and different methodological approaches have been implemented to identify the genes involved. This review focuses on pearls and pitfalls of these approaches and genetic findings in migraine. Summary: Common forms of migraine (i.e. migraine with and without aura) are thought to have a polygenic make-up, whereas rare familial hemiplegic migraine (FHM) presents with a monogenic pattern of inheritance. Until a few years ago only studies in FHM yielded causal genes, which were identified by a classical linkage analysis approach. Functional analyses of FHM gene mutations in cellular and transgenic animal models suggest abnormal glutamatergic neurotransmission as a possible key disease mechanism. Recently, a number of genes were discovered for the common forms of migraine using a genome-wide association (GWA) approach, which sheds first light on the pathophysiological mechanisms involved. Conclusions: Novel technological strategies such as next-generation sequencing, which can be implemented in future genetic migraine research, may aid the identification of novel FHM genes and promote the search for the missing heritability of common migraine.

Abstract

Genetic investigations of people with speech and language disorders can provide windows into key aspects of human biology. Most genomic research into impaired speech development has so far focused on childhood apraxia of speech (CAS), a rare neurodevelopmental disorder characterized by difficulties with coordinating rapid fine motor sequences that underlie proficient speech. In 2001, pathogenic variants of FOXP2 provided the first molecular genetic accounts of CAS aetiology. Since then, disruptions in several other genes have been implicated in CAS, with a substantial proportion of cases being explained by high-penetrance variants. However, the genetic architecture underlying other speech-related disorders remains less well understood. Thus, in the present study, we used systematic DNA sequencing methods to investigate idiopathic speech delay, as characterized by delayed speech development in the absence of a motor speech diagnosis (such as CAS), a language/reading disorder, or intellectual disability. We performed genome sequencing in a cohort of 23 children with a rigorous diagnosis of idiopathic speech delay. For roughly half of the sample (ten probands), sufficient DNA was also available for genome sequencing in both parents, allowing discovery of de novo variants. In the thirteen singleton probands, we focused on identifying loss-of-function and likely damaging missense variants in genes intolerant to such mutations. We found that one speech delay proband carried a pathogenic frameshift deletion in SETD1A, a gene previously implicated in a broader variable monogenic syndrome characterized by global developmental problems including delayed speech and/or language development, mild intellectual disability, facial dysmorphisms, and behavioural and psychiatric symptoms. Of note, pathogenic SETD1A variants have been independently reported in children with CAS in two separate studies. In other probands in our speech delay cohort, likely pathogenic missense variants were identified affecting highly conserved amino acids in key functional domains of SPTBN1 and ARF3. Overall, this study expands the phenotype spectrum associated with pathogenic SETD1A variants, to also include idiopathic speech delay without CAS or intellectual disability, and suggests additional novel potential candidate genes that may harbour high-penetrance variants that can disrupt speech development.

Abstract

Perceptual representations of phonemes are flexible and adapt rapidly to accommodate idiosyncratic articulation in the speech of a particular talker. This letter addresses whether such adjustments remain stable over time and under exposure to other talkers. During exposure to a story, listeners learned to interpret an ambiguous sound as [f] or [s]. Perceptual adjustments measured after 12 h were as robust as those measured immediately after learning. Equivalent effects were found when listeners heard speech from other talkers in the 12 h interval, and when they had the opportunity to consolidate learning during sleep.

Abstract

The perception of speech sounds can be re-tuned rapidly through a mechanism of lexically-driven learning (Norris et al 2003, Cogn.Psych. 47). Here we investigated this type of learning for English voiced stop consonants which are commonly de-voiced in word final position by Dutch learners of English . Specifically, this study asked under which conditions the change in pre-lexical representation encodes phonological information about the position of the critical sound within a word. After exposure to a Dutch learner’s productions of de-voiced stops in word-final position (but not in any other positions), British English listeners showed evidence of perceptual learning in a subsequent cross-modal priming task, where auditory primes with voiceless final stops (e.g., ‘seat’), facilitated recognition of visual targets with voiced final stops (e.g., SEED). This learning generalized to test pairs where the critical contrast was in word-initial position, e.g. auditory primes such as ‘town’ facilitated recognition of visual targets like DOWN (Experiment 1). Control listeners, who had not heard any stops by the speaker during exposure, showed no learning effects. The generalization to word-initial position did not occur when participants had also heard correctly voiced, word-initial stops during exposure (Experiment 2), and when the speaker was a native BE speaker who mimicked the word-final devoicing (Experiment 3). These results suggest that word position can be encoded in the pre-lexical adjustment to the accented phoneme contrast. Lexcially-guided feedback, distributional properties of the input, and long-term representations of accents all appear to modulate the pre-lexical re-tuning of phoneme categories.

Abstract

The domain of the human body is an ideal focus for semantic typology, since the body is a physical universal and all languages have terms referring to its parts. Previous research on body part terms has depended on secondary sources (e.g. dictionaries), and has lacked sufficient detail or clarity for a thorough understanding of these terms’ semantics. The present special issue is the outcome of a collaborative project aimed at improving approaches to investigating the semantics of body part terms, by developing materials to elicit information that provides for cross-linguistic comparison. The articles in this volume are original fieldwork-based descriptions of terminology for parts of the body in ten languages. Also included are an elicitation guide and experimental protocol used in gathering data. The contributions provide inventories of body part terms in each language, with analysis of both intensional and extensional aspects of meaning, differences in morphological complexity, semantic relations among terms, and discussion of partonomic structure within the domain.

Abstract

This document is intended for use as an elicitation guide for the field linguist consulting with native speakers in collecting terms for parts of the body, and in the exploration of their semantics.

Abstract

Abstract: This paper reviews current discussion of the issue of just what is lost when a language dies. Special reference is made to the current situation in Laos, a country renowned for its considerable cultural and linguistic diversity. It focuses on the historical, anthropological and ecological knowledge that a language can encode, and the social and cultural consequences of the loss of such traditional knowledge when a language is no longer passed on. Finally, the article points out the paucity of studies and obstacles to field research on minority languages in Laos, which seriously hamper their documentation.

Abstract

This article presents a description of nominal expressions for parts of the human body conventionalised in Lao, a Southwestern Tai language spoken in Laos, Northeast Thailand, and Northeast Cambodia. An inventory of around 170 Lao expressions is listed, with commentary where some notability is determined, usually based on explicit comparison to the metalanguage, English. Notes on aspects of the grammatical and semantic structure of the set of body part terms are provided, including a discussion of semantic relations pertaining among members of the set of body part terms. I conclude that the semantic relations which pertain between terms for different parts of the body not only include part/whole relations, but also relations of location, connectedness, and general association. Calling the whole system a ‘partonomy’ attributes greater centrality to the part/whole relation than is warranted.

Abstract

The study of language in relation to anthropological questions has deep and varied roots, from Humboldt and Boas, Malinowski and Vygotsky, Sapir and Whorf, Wittgenstein and Austin, through to the linguistic anthropologists of now. A recent book by the linguist Daniel Everett, language: the cultural tool (2012), aims to bring some of the issues to a popular audience, with a focus on the idea that language is a tool for social action. I argue in this essay that the book does not represent the state of the art in this field, falling short on three central desiderata of a good account for the social functions of language and its relation to culture. I frame these desiderata in terms of three questions, here termed the cognition question, the causality question, and the culture question. I look at the relevance of this work for socio-cultural anthropology, in the context of a major interdisciplinary pendulum swing that is incipient in the study of language today, a swing away from formalist, innatist perspectives, and towards functionalist, empiricist perspectives. The role of human diversity and culture is foregrounded in all of this work. To that extent, Everett’s book is representative, but the quality of his argument is neither strong in itself nor representative of a movement that ought to be of special interest to socio-cultural anthropologists.

Abstract

Review of the books "Virtually you. The dangerous powers of the e-personality", by Elias Aboujaoude; "The big disconnect. The story of technology and loneliness", by Giles Slade; and "Net smart. How to thrive online", by Howard Rheingold.

Abstract

Purpose:
Stuttering is a speech condition that can have a major impact on a person's quality of life. This descriptive study aimed to identify subgroups of people who stutter (PWS) based on stuttering burden and to investigate differences between these subgroups on psychosocial aspects of life.

Method:
The study included 618 adult participants who stutter. They completed a detailed survey examining stuttering symptomatology, impact of stuttering on anxiety, education and employment, experience of stuttering, and levels of depression, anxiety, and stress. A two-step cluster analytic procedure was performed to identify subgroups of PWS, based on self-report of stuttering frequency, severity, affect, and anxiety, four measures that together inform about stuttering burden.

Results:
We identified a high- (n = 230) and a low-burden subgroup (n = 372). The high-burden subgroup reported a significantly higher impact of stuttering on education and employment, and higher levels of general depression, anxiety, stress, and overall impact of stuttering. These participants also reported that they trialed more different stuttering therapies than those with lower burden.

Conclusions:
Our results emphasize the need to be attentive to the diverse experiences and needs of PWS, rather than treating them as a homogeneous group. Our findings also stress the importance of personalized therapeutic strategies for individuals with stuttering, considering all aspects that could influence their stuttering burden. People with high-burden stuttering might, for example, have a higher need for psychological therapy to reduce stuttering-related anxiety. People with less emotional reactions but severe speech distortions may also have a moderate to high burden, but they may have a higher need for speech techniques to communicate with more ease. Future research should give more insights into the therapeutic needs of people highly burdened by their stuttering.

Abstract

Listeners show a remarkable ability to quickly adjust to degraded speech input. Here, we aimed to identify the neural mechanisms of such short-term perceptual adaptation. In a sparse-sampling, cardiac-gated functional magnetic resonance imaging (fMRI) acquisition, human listeners heard and repeated back 4-band-vocoded sentences (in which the temporal envelope of the acoustic signal is preserved, while spectral information is highly degraded). Clear-speech trials were included as baseline. An additional fMRI experiment on amplitude modulation rate discrimination quantified the convergence of neural mechanisms that subserve coping with challenging listening conditions for speech and non-speech. First, the degraded speech task revealed an “executive” network (comprising the anterior insula and anterior cingulate cortex), parts of which were also activated in the non-speech discrimination task. Second, trial-by-trial fluctuations in successful comprehension of degraded speech drove hemodynamic signal change in classic “language” areas (bilateral temporal cortices). Third, as listeners perceptually adapted to degraded speech, downregulation in a cortico-striato-thalamo-cortical circuit was observable. The present data highlight differential upregulation and downregulation in auditory–language and executive networks, respectively, with important subcortical contributions when successfully adapting to a challenging listening situation.

Abstract

In mainstream phonology, contrastive properties, like stem-final voicing, are simply listed in the lexicon. This article reviews experimental evidence that such contrastive properties may be predictable to some degree and that the relevant statistically gradient generalizations form an inherent part of the grammar. The evidence comes from the underlying voice specification of stem-final obstruents in Dutch. Contrary to received wisdom, this voice specification is partly predictable from the obstruent’s manner and place of articulation and from the phonological properties of the preceding segments. The degree of predictability, which depends on the exact contents of the lexicon, directs speakers’ guesses of underlying voice specifications. Moreover, existing words that disobey the generalizations are disadvantaged by being recognized and produced more slowly and less accurately, also under natural conditions.We discuss how these observations can be accounted for in two types of different approaches to grammar, Stochastic Optimality Theory and exemplar-based modeling.

Abstract

Acoustic duration and degree of vowel reduction are known to correlate with a word’s frequency of occurrence. The present study broadens the research on the role of frequency in speech production to voice assimilation. The test case was regressive voice assimilation in Dutch. Clusters from a corpus of read speech were more often perceived as unassimilated in lower-frequency words and as either completely voiced regressive assimilation or, unexpectedly, as completely voiceless progressive assimilation in higher-frequency words. Frequency did not predict the voice classifications over and above important acoustic cues to voicing, suggesting that the frequency effects on the classifications were carried exclusively by the acoustic signal. The duration of the cluster and the period of glottal vibration during the cluster decreased while the duration of the release noises increased with frequency. This indicates that speakers reduce articulatory effort for higher-frequency words, with some acoustic cues signaling more voicing and others less voicing. A higher frequency leads not only to acoustic reduction but also to more assimilation.

Abstract

This study examines the effect of L2 and L3 proficiency on L3 word learning. Native speakers of Spanish with different proficiencies in L2 English and L3 Dutch and a control group of Dutch native speakers participated in a Dutch word learning task involving minimal and non-minimal word pairs. The minimal word pairs were divided into ‘minimal-easy’ and ‘minimal-difficult’ pairs on the basis of whether or not they are known to pose perceptual problems for L1 Spanish learners. Spanish speakers’ proficiency in Dutch and English was independently established by their scores on general language comprehension tests. All participants were trained and subsequently tested on the mapping between pseudo-words and non-objects. The results revealed that, first, both native and non-native speakers produced more errors and longer reaction times for minimal than for non-minimal word pairs, and secondly, Spanish learners had more errors and longer reaction times for minimal-difficult than for minimal-easy pairs. The latter finding suggests that there is a strong continuity between sound perception and L3 word recognition. With respect to proficiency, only the learner’s proficiency in their L2, namely English, predicted their accuracy on L3 minimal pairs. This shows that learning an L2 with a larger vowel inventory than the L1 is also beneficial for word learning in an L3 with a similarly large vowel inventory.

Abstract

Genetic variation affecting absorption, distribution or excretion of essential trace elements may lead to health effects related to sub-clinical deficiency. We have tested for allelic effects of single-nucleotide polymorphisms (SNPs) on blood copper, selenium and zinc in a genome-wide association study using two adult cohorts from Australia and the UK. Participants were recruited in Australia from twins and their families and in the UK from pregnant women. We measured erythrocyte Cu, Se and Zn (Australian samples) or whole blood Se (UK samples) using inductively coupled plasma mass spectrometry. Genotyping was performed with Illumina chips and > 2.5 m SNPs were imputed from HapMap data. Genome-wide significant associations were found for each element. For Cu, there were two loci on chromosome 1 (most significant SNPs rs1175550, P = 5.03 × 10(-10), and rs2769264, P = 2.63 × 10(-20)); for Se, a locus on chromosome 5 was significant in both cohorts (combined P = 9.40 × 10(-28) at rs921943); and for Zn three loci on chromosomes 8, 15 and X showed significant results (rs1532423, P = 6.40 × 10(-12); rs2120019, P = 1.55 × 10(-18); and rs4826508, P = 1.40 × 10(-12), respectively). The Se locus covers three genes involved in metabolism of sulphur-containing amino acids and potentially of the analogous Se compounds; the chromosome 8 locus for Zn contains multiple genes for the Zn-containing enzyme carbonic anhydrase. Where potentially relevant genes were identified, they relate to metabolism of the element (Se) or to the presence at high concentration of a metal-containing protein (Cu).

Abstract

Author SummaryThe standard approach in genome-wide association studies is to analyse the relationship between genetic variants and disease one marker at a time. Significant associations between markers and disease are then used as evidence to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically only explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates than single markers, and then use these scores to data mine genome-wide association studies. We show how allelic scores derived from known variants as well as allelic scores derived from hundreds of thousands of genetic markers across the genome explain significant portions of the variance in body mass index, levels of C-reactive protein, and LDLc cholesterol, and many of these scores show expected correlations with disease. Power calculations confirm the feasibility of scaling our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. Our method represents a simple way in which tens of thousands of molecular phenotypes could be screened for potential causal relationships with disease.

Abstract

Studies of the impact of brain injury on memory processes often focus on the quantity and episodic richness of those recollections. Here, we argue that the organization of one's recollections offers critical insights into the impact of brain injury on functional memory. It is well-established in studies of word list memory that free recall of unrelated words exhibits a clear temporal organization. This temporal contiguity effect refers to the fact that the order in which word lists are recalled reflects the original presentation order. Little is known, however, about the organization of recall for semantically rich materials, nor how recall organization is impacted by hippocampal damage and memory impairment. The present research is the first study, to our knowledge, of temporal organization in semantically rich narratives in three groups: (1) Adults with bilateral hippocampal damage and severe declarative memory impairment, (2) adults with bilateral ventromedial prefrontal cortex (vmPFC) damage and no memory impairment, and (3) demographically matched non-brain-injured comparison participants. We find that although the narrative recall of adults with bilateral hippocampal damage reflected the temporal order in which those narratives were experienced above chance levels, their temporal contiguity effect was significantly attenuated relative to comparison groups. In contrast, individuals with vmPFC damage did not differ from non-brain-injured comparison participants in temporal contiguity. This pattern of group differences yields insights into the cognitive and neural systems that support the use of temporal organization in recall. These data provide evidence that the retrieval of temporal context in narrative recall is hippocampal-dependent, whereas damage to the vmPFC does not impair the temporal organization of narrative recall. This evidence of limited but demonstrable organization of memory in participants with hippocampal damage and amnesia speaks to the power of narrative structures in supporting meaningfully organized recall despite memory impairment.

Abstract

A principal components analysis of the ten scales of the Worry Questionnaire revealed the existence of major worry factors or domains of social evaluation and physical threat, and these factors were confirmed in a subsequent item analysis. Those high in trait anxiety had much higher scores on the Worry Questionnaire than those low in trait anxiety, especially on those scales relating to social evaluation. Scores on the Marlowe-Crowne Social Desirability Scale were negatively related to worry frequency. However, groups of low-anxious and repressed individucores did not differ in worry. It was concluded that worry, especals formed on the basis of their trait anxiety and social desirability sially in the social evaluation domain, is of fundamental importance to trait anxiety.

Abstract

The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3–90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The multivariate fractional polynomial regression (MFPR) emerged as the preferred algorithm, optimised with non-linear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3000 study participants. This model can inform about the biological and behavioural implications of deviations from typical age-related neuroanatomical changes and support future study designs. The model and scripts described here are freely available through CentileBrain.

Abstract

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption, we performed a population-based genome-wide association study of 'age at first tooth' and 'number of teeth' using 5998 and 6609 individuals, respectively, from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2 446 724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of 15 independent loci, with 10 loci reaching genome-wide significance (P < 5 × 10(-8)) for 'age at first tooth' and 11 loci for 'number of teeth'. Together, these associations explain 6.06% of the variation in 'age of first tooth' and 4.76% of the variation in 'number of teeth'. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including an SNP in the protein-coding region of BMP4 (rs17563, P = 9.080 × 10(-17)). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development.

Abstract

Strong and weak syllables in English can be distinguished on the basis of vowel quality, of stress, or of both factors. Critical for deciding between these factors are syllables containing unstressed unreduced vowels, such as the first syllable of automata. In this study 12 speakers produced sentences containing matched sets of words with initial vowels ranging from stressed to reduced, at normal and at fast speech rates. Measurements of the duration, intensity, F0, and spectral characteristics of the word-initial vowels showed that unstressed unreduced vowels differed significantly from both stressed and reduced vowels. This result held true across speaker sex and dialect. The vowels produced by one speaker were then cross-spliced across the words within each set, and the resulting words' acceptability was rated by listeners. In general, cross-spliced words were only rated significantly less acceptable than unspliced words when reduced vowels interchanged with any other vowel. Correlations between rated acceptability and acoustic characteristics of the cross-spliced words demonstrated that listeners were attending to duration, intensity, and spectral characteristics. Together these results suggest that unstressed unreduced vowels in English pattern differently from both stressed and reduced vowels, so that no acoustic support for a binary categorical distinction exists; nevertheless, listeners make such a distinction, grouping unstressed unreduced vowels by preference with stressed vowels

Abstract

This article focuses on “perceptual syntax”, the faculty to process patterns in sensory stimuli. Specifically, this study addresses the ability to perceptually connect elements that are: (1) of the same sensory modality; (2) spatially and temporally non-adjacent; or (3) within multiple sensorial domains. The underlying hypothesis is that in each animal species, this core cognitive faculty enables the perception of the environment-world (Umwelt) and consequently the possibility to survive within it. Importantly, it is suggested that in doing so, perceptual syntax determines (and guides) each species’ ontological access to the world. In support of this hypothesis, research on perceptual syntax in nonverbal individuals (preverbal infants and nonhuman animals) and humans is reviewed. This comparative approach results in theoretical remarks on human cognition and ontology, pointing to the conclusion that the ability to map cross-modal connections through verbal language is what makes humans’ form of life species-typical.

Abstract

The aim of this paper is to help refine the definition of humans as “linguistic animals” in light of a comparative approach on nonhuman animals’ cognitive systems. As Uexküll & Kriszat (1934/1992) have theorized, the epistemic access to each species-specific environment (Umwelt) is driven by different biocognitive processes. Within this conceptual framework, I identify the salient cognitive process that distinguishes each species typical perception of the world as the faculty of language meant in the following operational definition: the ability to connect different elements according to structural rules. In order to draw some conclusions about humans’ specific faculty of language, I review different empirical studies on nonhuman animals’ ability to recognize formal patterns of tokens. I suggest that what differentiates human language from other animals’ cognitive systems is the ability to categorize the units of a pattern, going beyond its perceptual aspects. In fact, humans are the only species known to be able to combine semantic units within a network of combinatorial logical relationships (Deacon 1997) that can be linked to the state of affairs in the external world (Wittgenstein 1922). I assume that this ability is the core cognitive process underlying a) the capacity to speak (or to reason) in verbal propositions and b) the general human faculty of language expressed, for instance, in the ability to draw visual conceptual maps or to compute mathematical expressions. In light of these considerations, I conclude providing some research questions that could lead to a more detailed comparative exploration of the faculty of language.

Abstract

Family and twin studies of developmental dyslexia have consistently shown that there is a significant heritable component for this disorder. However, any genetic basis for the trait is likely to be complex, involving reduced penetrance, phenocopy, heterogeneity and oligogenic inheritance. This complexity results in reduced power for traditional parametric linkage analysis, where specification of the correct genetic model is important. One strategy is to focus on large multigenerational pedigrees with severe phenotypes and/or apparent simple Mendelian inheritance, as has been successfully demonstrated for speech and language impairment. This approach is limited by the scarcity of such families. An alternative which has recently become feasible due to the development of high-throughput genotyping techniques is the analysis of large numbers of sib-pairs using allele-sharing methodology. This paper outlines our strategy for conducting a systematic genome-wide search for genes involved in dyslexia in a large number of affected sib-pair familites from the UK. We use a series of psychometric tests to obtain different quantitative measures of reading deficit, which should correlate with different components of the dyslexia phenotype, such as phonological awareness and orthographic coding ability. This enable us to use QTL (quantitative trait locus) mapping as a powerful tool for localising genes which may contribute to reading and spelling disability.

Abstract

Recent application of nonparametric-linkage analysis to reading disability has implicated a putative quantitative-trait locus (QTL) on the short arm of chromosome 6. In the present study, we use QTL methods to evaluate linkage to the 6p25-21.3 region in a sample of 181 sib pairs from 82 nuclear families that were selected on the basis of a dyslexic proband. We have assessed linkage directly for several quantitative measures that should correlate with different components of the phenotype, rather than using a single composite measure or employing categorical definitions of subtypes. Our measures include the traditional IQ/reading discrepancy score, as well as tests of word recognition, irregular-word reading, and nonword reading. Pointwise analysis by means of sib-pair trait differences suggests the presence, in 6p21.3, of a QTL influencing multiple components of dyslexia, in particular the reading of irregular words (P=.0016) and nonwords (P=.0024). A complementary statistical approach involving estimation of variance components supports these findings (irregular words, P=.007; nonwords, P=.0004). Multipoint analyses place the QTL within the D6S422-D6S291 interval, with a peak around markers D6S276 and D6S105 consistently identified by approaches based on trait differences (irregular words, P=.00035; nonwords, P=.0035) and variance components (irregular words, P=.007; nonwords, P=.0038). Our findings indicate that the QTL affects both phonological and orthographic skills and is not specific to phoneme awareness, as has been previously suggested. Further studies will be necessary to obtain a more precise localization of this QTL, which may lead to the isolation of one of the genes involved in developmental dyslexia.

Abstract

We have constructed two YAC contigs in the Xp11.23-p11.22 interval of the human X chromosome, a region that was previously poorly characterized. One contig, of at least 1.4 Mb, links the pseudogene OATL1 to the genes GATA1, TFE3, and SYP and also contains loci implicated in Wiskott-Aldrich syndrome and synovial sarcoma. A second contig, mapping proximal to the first, is estimated to be over 2.1 Mb and links the hypervariable locus DXS255 to DXS146, and also contains a chloride channel gene that is responsible for hereditary nephrolithiasis. We have used plasmid rescue, inverse PCR, and Alu-PCR to generate 20 novel markers from this region, 1 of which is polymorphic, and have positioned these relative to one another on the basis of YAC analysis. The order of previously known markers within our contigs, Xpter-OATL1-GATA-TFE3-SYP-DXS255146- Xcen, agrees with genomic pulsed-field maps of the region. In addition, we have constructed a rare-cutter restriction map for a 710-kb region of the DXS255-DXS146 contig and have identified three CPG islands. These contigs and new markers will provide a useful resource for more detailed analysis of Xp11.23-p11.22, a region implicated in several genetic diseases.

Abstract

State-of-the-art DNA sequencing is providing ever more detailed insights into the genomes of humans, extant apes, and even extinct hominins (1–3), offering unprecedented opportunities to uncover the molecular variants that make us human. A common assumption is that the emergence of behaviorally modern humans after 200,000 years ago required—and followed—a specific biological change triggered by one or more genetic mutations. For example, Klein has argued that the dawn of human culture stemmed from a single genetic change that “fostered the uniquely modern ability to adapt to a remarkable range of natural and social circumstance” (4). But are evolutionary changes in our genome a cause or a consequence of cultural innovation (see the figure)?

Abstract

Dent disease, an X-linked familial renal tubular disorder, is a form of Fanconi syndrome associated with proteinuria, hypercalciuria, nephrocalcinosis, kidney stones, and eventual renal failure. We have previously used positional cloning to identify the 3' part of a novel kidney-specific gene (initially termed hClC-K2, but now referred to as CLCN5), which is deleted in patients from one pedigree segregating Dent disease. Mutations that disrupt this gene have been identified in other patients with this disorder. Here we describe the isolation and characterization of the complete open reading frame of the human CLCN5 gene, which is predicted to encode a protein of 746 amino acids, with significant homology to all known members of the ClC family of voltage-gated chloride channels. CLCN5 belongs to a distinct branch of this family, which also includes the recently identified genes CLCN3 and CLCN4. We have shown that the coding region of CLCN5 is organized into 12 exons, spanning 25-30 kb of genomic DNA, and have determined the sequence of each exon-intron boundary. The elucidation of the coding sequence and exon-intron organization of CLCN5 will both expedite the evaluation of structure/function relationships of these ion channels and facilitate the screening of other patients with renal tubular dysfunction for mutations at this locus.