Publications

Abstract

Introduction The ability to identify individuals at increased genetic risk for Alzheimer's disease (AD) may streamline biomarker and drug trials and aid clinical and personal decision making. Methods We evaluated the discriminative ability of a genetic risk score (GRS) covering 22 published genetic risk loci for AD in 1162 Flanders-Belgian AD patients and 1019 controls and assessed correlations with family history, onset age, and cerebrospinal fluid (CSF) biomarkers (Aβ1-42, T-Tau, P-Tau181P). Results A GRS including all single nucleotide polymorphisms (SNPs) and age-specific APOE ε4 weights reached area under the curve (AUC) 0.70, which increased to AUC 0.78 for patients with familial predisposition. Risk of AD increased with GRS (odds ratio, 2.32 (95% confidence interval 2.08-2.58 per unit; P < 1.0e-15). Onset age and CSF Aβ1-42 decreased with increasing GRS (Ponset-age = 9.0e-11; PAβ = 8.9e-7). Discussion The discriminative ability of this 22-SNP GRS is still limited, but these data illustrate that incorporation of age-specific weights improves discriminative ability. GRS-phenotype correlations highlight the feasibility of identifying individuals at highest susceptibility. © 2015 The Authors.

Abstract

Speakers adapt their speech and gestures in various ways for their audience. We investigated further whether they use
ostensive signals (eye gaze, ostensive speech (e.g. like this, this) or a combination of both) in relation to their gestures
when talking to different addressees, i.e., to another adult or a child in a multimodal demonstration task. While adults used
more eye gaze towards their gestures with other adults than with children, they were more likely to use combined
ostensive signals for children than for adults. Thus speakers mark the communicative relevance of their gestures with different types of ostensive signals and by taking different types of addressees into account.

Abstract

Spinocerebellar ataxia type 23 is caused by mutations in PDYN, which encodes the opioid neuropeptide precursor protein, prodynorphin. Prodynorphin is processed into the opioid peptides, α-neoendorphin, and dynorphins A and B, that normally exhibit opioid-receptor mediated actions in pain signalling and addiction. Dynorphin A is likely a mutational hotspot for spinocerebellar ataxia type 23 mutations, and in vitro data suggested that dynorphin A mutations lead to persistently elevated mutant peptide levels that are cytotoxic and may thus play a crucial role in the pathogenesis of spinocerebellar ataxia type 23. To further test this and study spinocerebellar ataxia type 23 in more detail, we generated a mouse carrying the spinocerebellar ataxia type 23 mutation R212W in PDYN. Analysis of peptide levels using a radioimmunoassay shows that these PDYNR212W mice display markedly elevated levels of mutant dynorphin A, which are associated with climber fibre retraction and Purkinje cell loss, visualized with immunohistochemical stainings. The PDYNR212W mice reproduced many of the clinical features of spinocerebellar ataxia type 23, with gait deficits starting at 3 months of age revealed by footprint pattern analysis, and progressive loss of motor coordination and balance at the age of 12 months demonstrated by declining performances on the accelerating Rotarod. The pathologically elevated mutant dynorphin A levels in the cerebellum coincided with transcriptionally dysregulated ionotropic and metabotropic glutamate receptors and glutamate transporters, and altered neuronal excitability. In conclusion, the PDYNR212W mouse is the first animal model of spinocerebellar ataxia type 23 and our work indicates that the elevated mutant dynorphin A peptide levels are likely responsible for the initiation and progression of the disease, affecting glutamatergic signalling, neuronal excitability, and motor performance. Our novel mouse model defines a critical role for opioid neuropeptides in spinocerebellar ataxia, and suggests that restoring the elevated mutant neuropeptide levels can be explored as a therapeutic intervention.

Abstract

Language-mediated visual attention describes the interaction of two fundamental components of the human cognitive system, language and vision. Within this paper we present an amodal shared resource model of language-mediated visual attention that offers a description of the information and processes involved in this complex multimodal behavior and a potential explanation for how this ability is acquired. We demonstrate that the model is not only sufficient to account for the experimental effects of Visual World Paradigm studies but also that these effects are emergent properties of the architecture of the model itself, rather than requiring separate information processing channels or modular processing systems. The model provides an explicit description of the connection between the modality-specific input from language and vision and the distribution of eye gaze in language-mediated visual attention. The paper concludes by discussing future applications for the model, specifically its potential for investigating the factors driving observed individual differences in language-mediated eye gaze.

Abstract

Recent empirical evidence suggests that language-mediated eye gaze is partly determined by level of formal literacy training. Huettig, Singh and Mishra (2011) showed that high-literate individuals' eye gaze was closely time locked to phonological overlap between a spoken target word and items presented in a visual display. In contrast, low-literate individuals' eye gaze was not related to phonological overlap, but was instead strongly influenced by semantic relationships between items. Our present study tests the hypothesis that this behavior is an emergent property of an increased ability to extract phonological structure from the speech signal, as in the case of high-literates, with low-literates more reliant on more coarse grained structure. This hypothesis was tested using a neural network model, that integrates linguistic information extracted from the speech signal with visual and semantic information within a central resource. We demonstrate that contrasts in fixation behavior similar to those observed between high and low literates emerge when models are trained on speech signals of contrasting granularity.

Abstract

A quantitative model of human categorization behavior is proposed, which can be applied to 4-alternative forced-choice categorization data involving two binary classifications. A number of processing dependencies between the two classifications are explicitly formulated, such as the dependence of the location, orientation, and steepness of the class boundary for one classification on the outcome of the other classification. The significance of various types of dependencies can be tested statistically. Analyses of a data set from the literature shows that interesting dependencies in human speech recognition can be uncovered using the model.

Abstract

The temporal distribution of perceptually relevant information for consonant recognition in British English VCVs is investigated. The information distribution in the vicinity of consonantal closure and release was measured by presenting initial and final portions, respectively, of naturally produced VCV utterances to listeners for categorization. A multidimensional scaling analysis of the results provided highly interpretable, four-dimensional geometrical representations of the confusion patterns in the categorization data. In addition, transmitted information as a function of truncation point was calculated for the features manner place and voicing. The effects of speaker, vowel context, stress, and distinctive feature on the resulting information distributions were tested statistically. It was found that, although all factors are significant, the location and spread of the distributions depends principally on the distinctive feature, i.e., the temporal distribution of perceptually relevant information is very different for the features manner, place, and voicing.

Abstract

Previous research [9] suggests that Dutch learners of (British) English are not able to express sarcasm prosodically in their L2. The present study investigates whether explicit training on the prosodic markers of sarcasm in English can improve learners’ realisation of sarcasm. Sarcastic speech was elicited in short simulated telephone conversations between Dutch advanced learners of English and a native British English-speaking ‘friend’ in two sessions, fourteen days apart. Between the two sessions, participants were trained by means of (1) a presentation, (2) directed independent practice, and (3) evaluation of participants’ production and individual feedback in small groups. L1 British English-speaking raters subsequently evaluated the degree of sarcastic sounding in the participants’ responses on a five-point scale. It was found that significantly higher sarcasm ratings were given to L2 learners’ production obtained after the training than that obtained before the training; explicit training on prosody has a positive effect on learners’ production of sarcasm.

Abstract

Atypical visual perception in people with autism spectrum disorders (ASD) is hypothesized to stem from an imbalance in excitatory and inhibitory processes in the brain. We used neuronal oscillations in the gamma frequency range (30 – 90 Hz), which emerge from a balanced interaction of excitation and inhibition in the brain, to assess contextual modulation processes in early visual perception. Electroencephalography was recorded in 12 high-functioning adults with ASD and 12 age- and IQ-matched control participants. Oscilla- tions in the gamma frequency range were analyzed in response to stimuli consisting of small line-like elements. Orientation-speci fi c contextual modulation was manipulated by parametrically increasing the amount of homogeneously oriented elements in the stimuli. The stimuli elicited a strong steady-state gamma response around the refresh-rate of 60 Hz, which was larger for controls than for participants with ASD. The amount of orientation homogeneity (contextual modulation) in fl uenced the gamma response in control subjects, while for subjects with ASD this was not the case. The atypical steady-state gamma response to contextual modulation in subjects with ASD may capture the link between an imbalance in excitatory and inhibitory neuronal processing and atypical visual processing in ASD

Abstract

Humans have a strong proclivity for structuring and patterning stimuli: Whether in space or time, we tend to mentally order stimuli in our environment and organize them into units with specific types of relationships. A crucial prerequisite for such organization is the cognitive ability to discern and process regularities among multiple stimuli. To investigate the evolutionary roots of this cognitive capacity, we tested chimpanzees—which, along with bonobos, are our closest living relatives—for simple, variable distance dependency processing in visual patterns. We trained chimpanzees to identify pairs of shapes either linked by an arbitrary learned association (arbitrary associative dependency) or a shared feature (same shape, feature-based dependency), and to recognize strings where items related to either of these ways occupied the first (leftmost) and the last (rightmost) item of the stimulus. We then probed the degree to which subjects generalized this pattern to new colors, shapes, and numbers of interspersed items. We found that chimpanzees can learn and generalize both types of dependency rules, indicating that the ability to encode both feature-based and arbitrary associative regularities over variable distances in the visual domain is not a human prerogative. Our results strongly suggest that these core components of human structural processing were already present in our last common ancestor with chimpanzees.

Abstract

Flexibly adapting social behavior to social and environmental challenges helps to alleviate glucocorticoid (GC) levels, which may have positive fitness implications for an individual. For primates, the predominant social behavior is grooming. Giving grooming to others is particularly efficient in terms of GC mitigation. However, grooming is confined by certain limitations such as time constraints or restricted access to other group members. For instance, dominance hierarchies may impact grooming partner availability in primate societies. Consequently specific grooming patterns emerge. In despotic species focusing grooming activity on preferred social partners significantly ameliorates GC levels in females of all ranks. In this study we investigated grooming patterns and GC management in Barbary macaques, a comparably relaxed species. We monitored changes in grooming behavior and cortisol (C) for females of different ranks. Our results show that the C‐amelioration associated with different grooming patterns had a gradual connection with dominance hierarchy: while higher‐ranking individuals showed lowest urinary C measures when they focused their grooming on selected partners within their social network, lower‐ranking individuals expressed lowest C levels when dispersing their grooming activity evenly across their social partners. We argue that the relatively relaxed social style of Barbary macaque societies allows individuals to flexibly adapt grooming patterns, which is associated with rank‐specific GC management. Am. J. Primatol. 77:688–700, 2015

Abstract

Aims/hypothesis Several forkhead box (FOX) transcription factor family members have important roles in controlling pancreatic cell fates and maintaining beta cell mass and function, including FOXA1, FOXA2 and FOXM1. In this study we have examined the importance of FOXP1, FOXP2 and FOXP4 of the FOXP subfamily in islet cell development and function. Methods Mice harbouring floxed alleles for Foxp1, Foxp2 and Foxp4 were crossed with pan-endocrine Pax6-Cre transgenic mice to generate single and compound Foxp mutant mice. Mice were monitored for changes in glucose tolerance by IPGTT, serum insulin and glucagon levels by radioimmunoassay, and endocrine cell development and proliferation by immunohistochemistry. Gene expression and glucose-stimulated hormone secretion experiments were performed with isolated islets. Results Only the triple-compound Foxp1/2/4 conditional knockout (cKO) mutant had an overt islet phenotype, manifested physiologically by hypoglycaemia and hypoglucagonaemia. This resulted from the reduction in glucagon-secreting alpha cell mass and function. The proliferation of alpha cells was profoundly reduced in Foxp1/2/4 cKO islets through the effects on mediators of replication (i.e. decreased Ccna2, Ccnb1 and Ccnd2 activators, and increased Cdkn1a inhibitor). Adult islet Foxp1/2/4 cKO beta cells secrete insulin normally while the remaining alpha cells have impaired glucagon secretion. Conclusions/interpretation Collectively, these findings reveal an important role for the FOXP1, 2, and 4 proteins in governing postnatal alpha cell expansion and function.

Abstract

The response exclusion account (REA), advanced by Mahon and colleagues, localises the distractor frequency effect and the semantic interference effect in picture naming at the level of the response output buffer. We derive four predictions from the REA: (1) the size of the distractor frequency effect should be identical to the frequency effect obtained when distractor words are read aloud, (2) the distractor frequency effect should not change in size when stimulus-onset asynchrony (SOA) is manipulated, (3) the interference effect induced by a distractor word (as measured from a nonword control distractor) should increase in size with increasing SOA, and (4) the word frequency effect and the semantic interference effect should be additive. The results of the picture-naming task in Experiment 1 and the word-reading task in Experiment 2 refute all four predictions. We discuss a tentative account of the findings obtained within a traditional selection-by-competition model in which both context effects are localised at the level of lexical selection.

Abstract

Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype

Abstract

The principle of common coding suggests that a joint representation is formed when actions are repeatedly paired with a specific perceptual event. Musicians are occupationally specialized with regard to the coupling between actions and their auditory effects. In the present study, we employed a novel paradigm to demonstrate automatic action–effect associations in pianists. Pianists and nonmusicians pressed keys according to aurally presented number sequences. Numbers were presented at pitches that were neutral, congruent, or incongruent with respect to pitches that would normally be produced by such actions. Response time differences were seen between congruent and incongruent sequences in pianists alone. A second experiment was conducted to determine whether these effects could be attributed to the existence of previously documented spatial/pitch compatibility effects. In a “stretched” version of the task, the pitch distance over which the numbers were presented was enlarged to a range that could not be produced by the hand span used in Experiment 1. The finding of a larger response time difference between congruent and incongruent trials in the original, standard, version compared with the stretched version, in pianists, but not in nonmusicians, indicates that the effects obtained are, at least partially, attributable to learned action effects.

Abstract

Relying on the methodology of conversation analysis, this article examines a practice in ordinary conversation characterized by the resaying of a word, phrase, or sentence. The article shows that multiple sayings such as "No no no" or "Alright alright alright" are systematic in both their positioning relative to the interlocutor's talk and in their function. Specifically, the findings are that multiple sayings are a resource speakers have to display that their turn is addressing an in progress course of action rather than only the just prior utterance. Speakers of multiple sayings communicate their stance that the prior speaker has persisted unnecessarily in the prior course of action and should properly halt course of action.

Abstract

When people request information, they have a variety of means for eliciting the information. In English two of the primary resources for eliciting information include asking questions, making statements about their interlocutor (thereby generating confirmation or revision). But within these types there are a variety of ways that these information elicitors can be designed. The goal of this task is to examine how different languages seek and provide information, the extent to which syntax vs prosodic resources are used (e.g., in questions), and the extent to which the design of information seeking actions and their responses display a structural preference to promote social solidarity.

Abstract

Presenting a comprehensive, state-of-the-art overview of theoretical and descriptive research in the field, The Handbook of Conversation Analysis brings together contributions by leading international experts to provide an invaluable information resource and reference for scholars of social interaction across the areas of conversation analysis, discourse analysis, linguistic anthropology, interpersonal communication, discursive psychology and sociolinguistics. Ideal as an introduction to the field for upper level undergraduates and as an in-depth review of the latest developments for graduate level students and established scholars Five sections outline the history and theory, methods, fundamental concepts, and core contexts in the study of conversation, as well as topics central to conversation analysis Written by international conversation analysis experts, the book covers a wide range of topics and disciplines, from reviewing underlying structures of conversation, to describing conversation analysis' relationship to anthropology, communication, linguistics, psychology, and sociology

Abstract

Human referential communication is often thought as coding-decoding a set of symbols, neglecting that establishing shared meanings requires a computational mechanism powerful enough to mutually negotiate them. Sharing the meaning of a novel symbol might rely on similar conceptual inferences across communicators or on statistical similarities in their sensorimotor behaviors. Using magnetoencephalography, we assess spectral, temporal, and spatial characteristics of neural activity evoked when people generate and understand novel shared symbols during live communicative interactions. Solving those communicative problems induced comparable changes in the spectral profile of neural activity of both communicators and addressees. This shared neuronal up-regulation was spatially localized to the right temporal lobe and the ventromedial prefrontal cortex and emerged already before the occurrence of a specific communicative problem. Communicative innovation relies on neuronal computations that are shared across generating and understanding novel shared symbols, operating over temporal scales independent from transient sensorimotor behavior.

Abstract

Magnetoencephalography (MEG) is measured above the head, which makes it sensitive to variations of the head position with respect to the sensors. Head movements blur the topography of the neuronal sources of the MEG signal, increase localization errors, and reduce statistical sensitivity. Here we describe two novel and readily applicable methods that compensate for the detrimental effects of head motion on the statistical sensitivity of MEG experiments. First, we introduce an online procedure that continuously monitors head position. Second, we describe an offline analysis method that takes into account the head position time-series. We quantify the performance of these methods in the context of three different experimental settings, involving somatosensory, visual and auditory stimuli, assessing both individual and group-level statistics. The online head localization procedure allowed for optimal repositioning of the subjects over multiple sessions, resulting in a 28% reduction of the variance in dipole position and an improvement of up to 15% in statistical sensitivity. Offline incorporation of the head position time-series into the general linear model resulted in improvements of group-level statistical sensitivity between 15% and 29%. These tools can substantially reduce the influence of head movement within and between sessions, increasing the sensitivity of many cognitive neuroscience experiments.

Abstract

In sign languages, where space is often used to talk about space, expressions of spatial relations (e.g., ON, IN, UNDER, BEHIND) may rely on analogue mappings of real space onto signing space. In contrast, spoken languages express space in mostly categorical ways (e.g. adpositions). This raises interesting questions about the role of language modality in the acquisition of expressions of spatial relations. However, whether and to what extent modality influences the acquisition of spatial language is controversial – mostly due to the lack of direct comparisons of Deaf children to Deaf adults and to age-matched hearing children in similar tasks. Furthermore, the previous studies have taken English as the only model for spoken language development of spatial relations.
Therefore, we present a balanced study in which spatial expressions by deaf and hearing children in two different age-matched groups (preschool children and school-age children) are systematically compared, as well as compared to the spatial expressions of adults. All participants performed the same tasks, describing angular (LEFT, RIGHT, FRONT, BEHIND) and non-angular spatial configurations (IN, ON, UNDER) of different objects (e.g. apple in box; car behind box).
The analysis of the descriptions with non-angular spatial relations does not show an effect of modality on the development of
locative expressions in TİD and Turkish. However, preliminary results of the analysis of expressions of angular spatial relations suggest that signers provide angular information in their spatial descriptions
more frequently than Turkish speakers in all three age groups, and thus showing a potentially different developmental pattern in this domain. Implications of the findings with regard to the development of relations in spatial language and cognition will be discussed.

Abstract

This study investigates whether spoken sentence comprehension deficits in Broca's aphasics results from their inability to access the subordinate meaning of ambiguous words (e.g. bank), or alternatively, from a delay in their selection of the contextually appropriate meaning. Twelve Broca's aphasics and twelve elderly controls were presented with lexical ambiguities in three context conditions, each followed by the same target words. In the concordant condition, the sentence context biased the meaning of the sentence final ambiguous word that was related to the target. In the discordant condition, the sentence context biased the meaning of the sentence final ambiguous word that was incompatible with the target.In the unrelated condition, the sentence-final word was unambiguous and unrelated to the target. The task of the subjects was to listen attentively to the stimuli The activational status of the ambiguous sentence-final words was inferred from the amplitude of the N399 to the targets at two inter-stimulus intervals (ISIs) (100 ms and 1250 ms). At the short ISI, the Broca's aphasics showed clear evidence of activation of the subordinate meaning. In contrast to elderly controls, however, the Broca's aphasics were not successful at selecting the appropriate meaning of the ambiguity in the short ISI version of the experiment. But at the long ISI, in accordance with the performance of the elderly controls, the patients were able to successfully complete the contextual selection process. These results indicate that Broca's aphasics are delayed in the process of contextual selection. It is argued that this finding of delayed selection is compatible with the idea that comprehension deficits in Broca's aphasia result from a delay in the process of integrating lexical information.

Abstract

General knowledge acquisition entails the extraction of statistical regularities from the environment. At high levels of complexity, this may involve the extraction, and consolidation, of associative regularities across event memories. The underlying neural mechanisms would likely involve a hippocampo-neocortical dialog, as proposed previously for system-level consolidation. To test these hypotheses, we assessed possible differences in consolidation between associative memories containing cross-episodic regularities and unique associative memories. Subjects learned face–location associations, half of which responded to complex regularities regarding the combination of facial features and locations, whereas the other half did not. Importantly, regularities could only be extracted over hippocampus-encoded, associative aspects of the items. Memory was assessed both immediately after encoding and 48 h later, under fMRI acquisition. Our results suggest that processes related to system-level reorganization occur preferentially for regular associations across episodes. Moreover, the build-up of general knowledge regarding regular associations appears to involve the coordinated activity of the hippocampus and mediofrontal regions. The putative cross-talk between these two regions might support a mechanism for regularity extraction. These findings suggest that the consolidation of cross-episodic regularities may be a key mechanism underlying general knowledge acquisition.

Abstract

This volume on Inuit speech follows the evolution of a native language of the North American Arctic, from its historical roots to its present-day linguistic structure and patterns of use from Alaska to Greenland. Drawing on a wide range of research from the fields of linguistics, anthropology, and sociology, Dorais integrates these diverse perspectives in a comprehensive view of native language development, maintenance, and use under conditions of marginalization due to social transition.

Abstract

Although children's knowledge of the sound patterns of words has been a focus of debate for many years, little is known about the lexical representations very young children use in word recognition. In particular, researchers have questioned the degree of specificity encoded in early lexical representations. The current study addressed this issue by presenting 18–23-month-olds with object labels that were either correctly pronounced, or mispronounced. Mispronunciations involved replacement of one segment with a similar segment, as in ‘baby–vaby’. Children heard sentences containing these words while viewing two pictures, one of which was the referent of the sentence. Analyses of children's eye movements showed that children recognized the spoken words in both conditions, but that recognition was significantly poorer when words were mispronounced. The effects of mispronunciation on recognition were unrelated to age or to spoken vocabulary size. The results suggest that children's representations of familiar words are phonetically well-specified, and that this specification may not be a consequence of the need to differentiate similar words in production.

Abstract

The roles which word class (open/closed) and sentential stress play in the sentence comprehension processes of both agrammatic (Broca's) aphasics and normal listeners were examined with a word monitoring task. Overall, normal listeners responded more quickly to stressed than to unstressed items, but showed no effect of word class. Aphasics also responded more quickly to stressed than to unstressed materials, but, unlike the normals, responded faster to open than to closed class words regardless of their stress. The results are interpreted as support for the theory that Broca's aphasics lack the functional underlying open/closed class word distinction used in word recognition by normal listeners.

Abstract

A growing number of researchers in the sentence processing community are using eye movements to address issues in spoken language comprehension. Experiments using this paradigm have shown that visually presented referential information, including properties of referents relevant to specific actions, influences even the earliest moments of syntactic processing. Methodological concerns about task-specific strategies and the linking hypothesis between eye movements and linguistic processing are identified and discussed. These concerns are addressed in a review of recent studies of spoken word recognition which introduce and evaluate a detailed linking hypothesis between eye movements and lexical access. The results provide evidence about the time course of lexical activation that resolves some important theoretical issues in spoken-word recognition. They also demonstrate that fixations are sensitive to properties of the normal language-processing system that cannot be attributed to task-specific strategies

Abstract

The rates of overspecification of color, pattern, and size are compared, to investigate how salience and absoluteness contribute to the production of overspecification. Color and pattern are absolute and salient attributes, whereas size is relative and less salient. Additionally, a tendency toward consistent responses is assessed. Using a within-participants design, we find similar rates of color and pattern overspecification, which are both higher than the rate of size overspecification. Using a between-participants design, however, we find similar rates of pattern and size overspecification, which are both lower than the rate of color overspecification. This indicates that although many speakers are more likely to include color than pattern (probably because color is more salient), they may also treat pattern like color due to a tendency toward consistency. We find no increase in size overspecification when the salience of size is increased, suggesting that speakers are more likely to include absolute than relative attributes. However, we do find an increase in size overspecification when mentioning the attributes is triggered, which again shows that speakers tend to refer in a consistent manner, and that there are circumstances in which even size overspecification is frequently produced.

Abstract

Although visual imagery is argued to be an essential component of autobiographical memory, there have been surprisingly few studies on autobiographical memory processes in blind individuals, who have had no or limited visual input. The purpose of the present study was to investigate how blindness affects retrieval and phenomenology of autobiographical memories. We asked 48 congenital/early blind and 48 sighted participants to recall autobiographical memories in response to six cue words, and to fill out the Autobiographical Memory Questionnaire measuring a number of variables including imagery, belief and recollective experience associated with each memory. Blind participants retrieved fewer memories and reported higher auditory imagery at retrieval than sighted participants. Moreover, within the blind group, participants with total blindness reported higher auditory imagery than those with some light perception. Blind participants also assigned higher importance, belief and recollection ratings to their memories than sighted participants. Importantly, these group differences remained the same for recent as well as childhood memories.

Abstract

This paper presents a quantitative analysis of the
turn-taking mechanism evidenced in 93 telephone
dialogues that were taken from the 9-million-word
Spoken Dutch Corpus. While the first part of the paper
focuses on the temporal phenomena of turn taking, such
as durations of pauses and overlaps of turns in the
dialogues, the second part explores the discoursefunctional
aspects of utterances in a subset of 8
dialogues that were annotated especially for this
purpose. The results show that speakers adapt their turntaking
behaviour to the interlocutor’s behaviour.
Furthermore, the results indicate that male-male dialogs
show a higher proportion of overlapping turns than
female-female dialogues.

Abstract

Content and temporal cues have been shown to interact during audio-visual (AV) speech identification. Typically, the most reliable unimodal cue is used more strongly to identify specific speech features; however, visual cues are only used if the AV stimuli are presented within a certain temporal window of integration (TWI). This suggests that temporal cues denote whether unimodal stimuli belong together, that is, whether they should be integrated. It is not known whether temporal cues also provide information about the identity of a syllable. Since spoken syllables have naturally varying AV onset asynchronies, we hypothesize that for suboptimal AV cues presented within the TWI, information about the natural AV onset differences can aid in speech identification. To test this, we presented low-intensity auditory syllables concurrently with visual speech signals, and varied the stimulus onset asynchronies (SOA) of the AV pair, while participants were instructed to identify the auditory syllables. We revealed that specific speech features (e.g., voicing) were identified by relying primarily on one modality (e.g., auditory). Additionally, we showed a wide window in which visual information influenced auditory perception, that seemed even wider for congruent stimulus pairs. Finally, we found a specific response pattern across the SOA range for syllables that were not reliably identified by the unimodal cues, which we explained as the result of the use of natural onset differences between AV speech signals. This indicates that temporal cues not only provide information about the temporal integration of AV stimuli, but additionally convey information about the identity of AV pairs. These results provide a detailed behavioral basis for further neuro-imaging and stimulation studies to unravel the neurofunctional mechanisms of the audio-visual-temporal interplay within speech perception.

Abstract

This paper presents DIANA, a new computational model of human speech processing. It is the first model that simulates the complete processing chain from the on-line processing of an acoustic signal to the execution of a response, including reaction times. Moreover it assumes minimal modularity. DIANA consists of three components. The activation component computes a probabilistic match between the input acoustic signal and representations in DIANA’s lexicon, resulting in a list of word hypotheses changing over time as the input unfolds. The decision component operates on this list and selects a word as soon as sufficient evidence is available. Finally, the execution component accounts for the time to execute a behavioral action. We show that DIANA well simulates the average participant in a word recognition experiment.

Abstract

DIANA is an end-to-end computational model of speech processing, which takes as input the speech signal, and provides as output the orthographic transcription of the stimulus, a word/non-word judgment and the associated estimated reaction time. So far, the model has only been tested for Dutch. In this paper, we extend DIANA such that it can also process North American English. The model is tested by having it simulate human participants in a large scale North American English lexical decision experiment. The simulations show that DIANA can adequately approximate the reaction times of an average participant (r = 0.45). In addition, they indicate that DIANA does not yet adequately model the cognitive processes that take place after stimulus offset.

Abstract

On the basis of two-speaker spontaneous conversations, it is shown that the distributions of both pauses and speech-overlaps of telephone and faceto-face dialogues have different statistical properties. Pauses in a face-to-face
dialogue last up to 4 times longer than pauses in telephone conversations in functionally comparable conditions. There is a high correlation (0.88 or larger) between the average pause duration for the two speakers across face-to-face
dialogues and telephone dialogues. The data provided form a first quantitative analysis of the complex turn-taking mechanism evidenced in the dialogues available in the 9-million-word Spoken Dutch Corpus.

Abstract

Temporal cues can be used to selectively attend to relevant information during abundant sensory stimulation. However, such cues differ vastly in the accuracy of their temporal estimates, ranging from very predictable to very unpredictable. When cues are strongly predictable, attention may facilitate selective processing by aligning relevant incoming information to high neuronal excitability phases of ongoing low-frequency oscillations. However, top-down effects on ongoing oscillations when temporal cues have some predictability, but also contain temporal uncertainties, are unknown. Here, we experimentally created such a situation of mixed predictability and uncertainty: A target could occur within a limited time window after cue but was always unpredictable in exact timing. Crucially to assess top-down effects in such a mixed situation, we manipulated target probability. High target likelihood, compared with low likelihood, enhanced delta oscillations more strongly as measured by evoked power and intertrial coherence. Moreover, delta phase modulated detection rates for probable targets. The delta frequency range corresponds with half-a-period to the target occurrence window and therefore suggests that low-frequency phase reset is engaged to produce a long window of high excitability when event timing is uncertain within a restricted temporal window.

Abstract

The role of oscillatory phase for perceptual and cognitive processes is being increasingly acknowledged. To date, little is known about the direct role of phase in categorical perception. Here we show in two separate experiments that the identification of ambiguous syllables that can either be perceived as / da/ or / ga/ is biased by the underlying oscillatory phase as measured with EEG and sensory entrainment to rhythmic stimuli. The measured phase difference in which perception is biased toward / da/ or / ga/ exactly matched the different temporal onset delays in natural audiovisual speech between mouth movements and speech sounds, which last 80 ms longer for / ga/ than for / da/. These results indicate the functional relationship between prestimulus phase and syllable identification, and signify that the origin of this phase relationship could lie in exposure and subsequent learning of unique audiovisual temporal onset differences.

Abstract

This paper describes a computational model of speech comprehension that takes the acoustic signal as input and predicts reaction times as observed in an auditory lexical decision task. By doing so, we explore a new generation of end-to-end computational models that are able to simulate the behaviour of human subjects participating in a psycholinguistic experiment. So far, nearly all computational models of speech comprehension do not start from the speech signal itself, but from abstract representations of the speech signal, while the few existing models that do start from the acoustic signal cannot directly model reaction times as obtained in comprehension experiments. The main functional components in our model are the perception stage, which is compatible with the psycholinguistic model Shortlist B and is implemented with techniques from automatic speech recognition, and the decision stage, which is based on the linear ballistic accumulation decision model. We successfully tested our model against data from 20 participants performing a largescale auditory lexical decision experiment. Analyses show that the model is a good predictor for the average judgment and reaction time for each word.

Abstract

Apraxia of Speech (AOS) is a motor speech disorder whose precise nature is still poorly understood. A recent behavioural experiment featuring a noise masking paradigm suggests that AOS reflects a disruption of feedforward control, whereas feedback control is spared and plays a more prominent role in achieving and maintaining segmental contrasts [10]. In the present study, we set out to validate the interpretation of AOS as a feedforward impairment by means of a series of computational simulations with the DIVA model [6, 7] mimicking the behavioural experiment. Simulation results showed a larger reduction in vowel spacing and a smaller vowel dispersion in the masking condition compared to the no-masking condition for the simulated feedforward deficit, whereas the other groups showed an opposite pattern. These results mimic the patterns observed in the human data, corroborating the notion that AOS can be conceptualized as a deficit in feedforward control

Abstract

This work presents a salvage grammar of the Biri language of Eastern Central Queensland, a Pama-Nyungan language belonging to the large Maric subgroup. As the language is no longer used, the grammatical description is based on old written sources and on recordings made by linguists in the 1960s and 1970s. Biri is in many ways typical of the Pama-Nyungan languages of Southern Queensland. It has split case marking systems, marking nouns according to an ergative/absolutive system and pronouns according to a nominative/accusative system. Unusually for its area, Biri also has bound pronouns on its verb, cross-referencing the person, number and case of core participants. As far as it is possible, the grammatical discussion is ‘theory neutral’. The first four chapters deal with the phonology, morphology, and syntax of the language. The last two chapters contain a substantial discussion of Biri’s place in the Pama-Nyungan family. In chapter 6 the numerous dialects of the Biri language are discussed. In chapter 7 the close linguistic relationship between Biri and the surrounding languages is examined.

Abstract

In many areas of language acquisition, researchers have suggested that semantic generality plays an important role in determining the order of acquisition of particular lexical forms. However, generality is typically confounded with the effects of input frequency and it is therefore unclear to what extent semantic generality or input frequency determines the early acquisition of particular lexical items. The present study evaluates the relative influence of semantic status and properties of the input on the acquisition of verbs and their argument structures in the early speech of 9 English-speaking children from 2;0 to 3;0. The children's early verb utterances are examined with respect to (1) the order of acquisition of particular verbs in three different constructions, (2) the syntactic diversity of use of individual verbs, (3) the relative proportional use of semantically general verbs as a function of total verb use, and (4) their grammatical accuracy. The data suggest that although measures of semantic generality correlate with various measures of early verb use, once the effects of verb use in the input are removed, semantic generality is not a significant predictor of early verb use. The implications of these results for semantic-based theories of verb argument structure acquisition are discussed.

Abstract

To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a parahippocampal area, which decreased with time. In turn, mPFC-parahippocampal connectivity increased progressively. These findings support a model in which thalamic midline nuclei serve as a hub linking hippocampus, mPFC, and posterior representational areas during memory retrieval at an early (2 h) stage of consolidation, extending classical systems consolidation models by attributing a transient role to midline thalamic nuclei.

Abstract

A forum devoted to the relationship between music and language begins with an implicit assumption: There is at least one common principle that is central to all human musical systems and all languages, but that is not characteristic of (most) other domains. Why else should these two categories be paired together for analysis? We propose that one candidate for a common principle is their structure. In this chapter, we explore the nature of that structure—and its consequences for psychological and neurological processing mechanisms—within and across these two domains.

Abstract

Infants expect people to direct actions toward objects, and they respond to actions directed to themselves, but do they have expectations about actions directed to third parties? In two experiments, we used eye tracking to investigate 1- and 2-year-olds’ expectations about communicative actions addressed to a third party. Experiment 1 presented infants with videos where an adult (the Emitter) either uttered a sentence or produced non-speech sounds. The Emitter was either face-to-face with another adult (the Recipient) or the two were back-to-back. The Recipient did not respond to any of the sounds. We found that 2-, but not 1-year-olds looked quicker and longer at the Recipient following speech than non-speech, suggesting that they expected her to respond to speech. These effects were specific to the face-to-face context. Experiment 2 presented 1-year-olds with similar face-to-face exchanges but modified to engage infants and minimize task demands. The infants looked quicker to the Recipient following speech than non-speech, suggesting that they expected a response to speech. The study suggests that by 1 year of age infants expect communicative actions to be directed at a third-party listener.

Abstract

Germline mutations in PTEN, which encodes a widely expressed phosphatase, was mapped to 10q23 and identified as the susceptibility gene for Cowden syndrome, characterized by macrocephaly and high risks of breast, thyroid, and other cancers. The phenotypic spectrum of PTEN mutations expanded to include autism with macrocephaly only 10 years ago. Neurological studies of patients with PTEN-associated autism spectrum disorder (ASD) show increases in cortical white matter and a distinctive cognitive profile, including delayed language development with poor working memory and processing speed. Once a germline PTEN mutation is found, and a diagnosis of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome made, the clinical outlook broadens to include higher lifetime risks for multiple cancers, beginning in childhood with thyroid cancer. First described as a tumor suppressor, PTEN is a major negative regulator of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway—controlling growth, protein synthesis, and proliferation. This canonical function combines with less well-understood mechanisms to influence synaptic plasticity and neuronal cytoarchitecture. Several excellent mouse models of Pten loss or dysfunction link these neural functions to autism-like behavioral abnormalities, such as altered sociability, repetitive behaviors, and phenotypes like anxiety that are often associated with ASD in humans. These models also show the promise of mTOR inhibitors as therapeutic agents capable of reversing phenotypes ranging from overgrowth to low social behavior. Based on these findings, therapeutic options for patients with PTEN hamartoma tumor syndrome and ASD are coming into view, even as new discoveries in PTEN biology add complexity to our understanding of this master regulator.

Abstract

We are often in a bilingual situation (e.g., overhearing a conversation in the train). We investigated whether first (L1) and second language (L2) phonologies are automatically activated. A masked priming paradigm was used, with Russian words as targets and either Russian or English words as primes. Event-related potentials (ERPs) were recorded while Russian (L1) – English (L2) bilinguals read aloud L1 target words (e.g. РЕЙС /reis/ ‘fl ight’) primed with either L1 (e.g. РАНА /rana/ ‘wound’) or L2 words (e.g. PACK). Target words were read faster when they were preceded by phonologically related L1 primes but not by orthographically related L2 primes. ERPs showed orthographic priming in the 125-200 ms time window. Thus, both L1 and L2 phonologies are simultaneously activated during L1 reading. The results provide support for non-selective models of bilingual reading, which assume automatic activation of the non-target language phonology even when it is not required by the task.

Abstract

The neural response to a stimulus is influenced by endogenous factors such as expectation and attention. Current research suggests that expectation and attention exert their effects in opposite directions, where expectation decreases neural activity in sensory areas, while attention increases it. However, expectation and attention are usually studied either in isolation or confounded with each other. A recent study suggests that expectation and attention may act jointly on sensory processing, by increasing the neural response to expected events when they are attended, but decreasing it when they are unattended. Here we test this hypothesis in an auditory temporal cueing paradigm using magnetoencephalography in humans. In our study participants attended to, or away from, tones that could arrive at expected or unexpected moments. We found a decrease in auditory beta band synchrony to expected (versus unexpected) tones if they were unattended, but no difference if they were attended. Modulations in beta power were already evident prior to the expected onset times of the tones. These findings suggest that expectation and attention jointly modulate sensory processing.

Abstract

Stem cell-based approaches to restore function after stroke through replacement of dead neurons require the generation of specific neuronal subtypes. Loss of neurons in the cerebral cortex is a major cause of stroke-induced neurological deficits in adult humans. Reprogramming of adult human somatic cells to induced pluripotent stem cells is a novel approach to produce patient-specific cells for autologous transplantation. Whether such cells can be converted to functional cortical neurons that survive and give rise to behavioural recovery after transplantation in the stroke-injured cerebral cortex is not known. We have generated progenitors in vitro, expressing specific cortical markers and giving rise to functional neurons, from long-term self-renewing neuroepithelial-like stem cells, produced from adult human fibroblast-derived induced pluripotent stem cells. At 2 months after transplantation into the stroke-damaged rat cortex, the cortically fated cells showed less proliferation and more efficient conversion to mature neurons with morphological and immunohistochemical characteristics of a cortical phenotype and higher axonal projection density as compared with non-fated cells. Pyramidal morphology and localization of the cells expressing the cortex-specific marker TBR1 in a certain layered pattern provided further evidence supporting the cortical phenotype of the fated, grafted cells, and electrophysiological recordings demonstrated their functionality. Both fated and non-fated cell-transplanted groups showed bilateral recovery of the impaired function in the stepping test compared with vehicle-injected animals. The behavioural improvement at this early time point was most likely not due to neuronal replacement and reconstruction of circuitry. At 5 months after stroke in immunocompromised rats, there was no tumour formation and the grafted cells exhibited electrophysiological properties of mature neurons with evidence of integration in host circuitry. Our findings show, for the first time, that human skin-derived induced pluripotent stem cells can be differentiated to cortical neuronal progenitors, which survive, differentiate to functional neurons and improve neurological outcome after intracortical implantation in a rat stroke model.

Abstract

In this study, we investigate the timing of pre-answer inbreaths in order to shed light on the time course of response planning and execution in conversational turn-taking. Using acoustic and inductive plethysmography recordings of seven dyadic conversations in Dutch, we show that pre-answer inbreaths in conversation typically begin briefly after the end of questions. We also show that the presence of a pre-answer inbreath usually co-occurs with substantially delayed answers, with a modal latency of 576 ms vs. 100 ms for answers not preceded by an inbreath. Based on previously reported minimal latencies for internal intercostal activation and the production of speech sounds, we propose that vocal responses, either in the form of a pre-utterance inbreath or of speech proper when an inbreath is not produced, are typically launched in reaction to information present in the last portion of the interlocutor’s turn. We also show that short responses are usually made on residual breath, while longer responses are more often preceded by an inbreath. This relation of inbreaths to answer length suggests that by the time an inbreath is launched, typically during the last few hundred milliseconds of the question, the length of the answer is often prepared to some extent. Together, our findings are consistent with a two-stage model of response planning in conversational turn-taking: early planning of content often carried out in overlap with the incoming turn, and late launching of articulation based on the identification of turn-final cues

Abstract

This article describes how the tonal elements of two common Spanish intonation contours –the falling statement and the low-rising-falling request– align with the segmental string in broad-focus utterances differing in number of prosodic words. Using an imitation-and-completion task, we show that (i) the last stressed syllable of the utterance, traditionally viewed as carrying the ‘nuclear’ accent, associates with either a high or a low tonal element depending on phrase length (ii) that certain tonal elements can be realized or omitted depending on the availability of specific metrical positions in their intonational phrase, and (iii) that the high tonal element of the request contour associates with either a stressed syllable or an intonational phrase edge depending on phrase length. On the basis of these facts, and in contrast to previous descriptions of Spanish intonation relying on obligatory and constant nuclear contours (e.g., L* L% for all neutral statements), we argue for a less constrained intonational morphology involving tonal units linked to the segmental string via contour-specific principles.

Abstract

We investigate the extent to which French polar questions and continuation statements, two types of utterances with similar morphosyntactic and intonational forms but different pragmatic functions, can be distinguished in conversational data based on phonetic and visual bodily information. We show that the two utterance types can be distinguished well over chance level by automatic classification models including several phonetic and visual cues. We also show that a considerable amount of relevant phonetic and visual information is present before the last portion of the utterances, potentially assisting early speech act recognition by addressees. These findings indicate that bottom-up phonetic and visual cues may play an important role during the production and recognition of speech acts alongside top-down contextual information.

Abstract

Violations of the maxims of Quantity occur when utterances provide more (over-specified) or less (under-specified) information than strictly required for referent identification. While behavioural datasuggest that under-specified expressions lead to comprehension difficulty and communicative failure, there is no consensus as to whether over-specified expressions are also detrimental to comprehension. In this study we shed light on this debate, providing neurophysiological evidence supporting the view that extra information facilitates comprehension. We further present novel evidence that referential failure due to under-specification is qualitatively different from explicit cases of referential failure, when no matching referential candidate is available in the context.

Abstract

Purpose: To determine clinical phenotypes, evolution and genetic background of a large family with a combination of two unusual forms of reflex epilepsies. Method: Phenotyping was performed in eighteen family members (10 F, 8 M) including standardized EEG recordings with intermittent photic stimulation (IPS). Genetic analyses (linkage scans, Whole Exome Sequencing (WES) and Functional studies) were performed using photoparoxysmal EEG responses (PPRs) as affection status. Results: The proband suffered from speaking induced jaw-jerks and increasing limb jerks evoked by flickering sunlight since about 50 years of age. Three of her family members had the same phenotype. Generalized PPRs were found in seven members (six above 50 years of age) with myoclonus during the PPR. Evolution was typical: Sensitivity to lights with migraine-like complaints around adolescence, followed by jerks evoked by lights and spontaneously with dropping of objects, and strong increase of light sensitivity and onset of talking induced jaw jerks around 50 years. Linkage analysis showed suggestive evidence for linkage to four genomic regions. All photosensitive family members shared a heterozygous R129C mutation in the SCNM1 gene that regulates splicing of voltage gated ion channels. Mutation screening of 134 unrelated PPR patients and 95 healthy controls, did not replicate these findings. Conclusion: This family presents a combination of two rare reflex epilepsies. Genetic analysis favors four genomic regions and points to a shared SCNM1 mutation that was not replicated in a general cohort of photosensitive subjects. Further genetic studies in families with similar combination of features are warranted. (C) 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Abstract

Objective: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task-related brain networks. We investigated this hypothesis by studying task-related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task. Methods: Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n-back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions-of-interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task-related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks. Results: PD patients, compared with controls, showed trend-significantly decreased task accuracy, significantly increased task-related activity in the left DLPFC and a trend-significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task-related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network. Interpretation: These findings suggest that the increase in working memory-related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits. Hum Brain Mapp 36:1554-1566, 2015. (c) 2015 Wiley Periodicals, Inc.

Abstract

Numerous studies have revealed an asymmetry tied to the perception of coronal place of articulation: participants accept a labial mispronunciation of a coronal target, but not vice versa. Whether or not this asymmetry is based on language-general properties or arises from language-specific experience has been a matter of debate. The current study suggests a bias of the first type by documenting an early, cross-linguistic asymmetry related to coronal place of articulation. Japanese and Dutch 4- and 6-month-old infants showed evidence of discrimination if they were habituated to a labial and then tested on a coronal sequence, but not vice versa. This finding has important implications for both phonological theories and infant speech perception research

Abstract

German and French differ in a number of aspects. Regarding the prosody-pragmatics interface, German is said to have a direct focus-to-accent mapping, which is largely absent in French – owing to strong structural constraints. We used a semi-spontaneous dialogue setting to investigate the intonational marking of Verum Focus, a focus on the polarity of an utterance in the two languages (e.g. the child IS tearing the banknote as an opposite claim to the child is not tearing the banknote). When Verum Focus applies to auxiliaries, pragmatic aspects (i.e. highlighting the contrast) directly compete with structural constraints (e.g. avoiding an accent on phonologically weak elements such as monosyllabic function words). Intonational analyses showed that auxiliaries were predominantly accented in German, as expected. Interestingly, we found a high number of (as yet undocumented) focal accents on phrase-initial auxiliaries in French Verum Focus contexts. When French accent patterns were equally distributed across information structural contexts, relative prominence (in terms of peak height) between initial and final accents was shifted towards initial accents in Verum Focus compared to non-Verum Focus contexts. Our data hence suggest that French also may mark Verum Focus by focal accents but that this tendency is partly overridden by strong structural constraints.

Abstract

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.

Abstract

Adipose-derived stromal/stem cells (ASC) are multipotent with abilities to differentiate into multiple lineages including connective tissue and neural cells. Despite unlimited opportunity and needs for human and veterinary regenerative medicine, applications of adipose-derived stromal/stem cells are at present very limited. Furthermore, the fundamental biological factors regulating stemness in ASC and their stable differentiation into other tissue cells are not fully understood. The objective of this review was to provide an update on the current knowledge of the nature and isolation, molecular and epigenetic determinants of the potency, and applications of adipose-derived stromal/stem cells, as well as challenges and future directions. The first quarter of the review focuses on the nature of ASC, namely their definition, origin, isolation and sorting methods and multilineage differentiation potential, often with a comparison to mesenchymal stem cells of bone marrow. Due to the indisputable role of epigenetic regulation on cell identities, epigenetic modifications (DNA methylation, chromatin remodeling and microRNAs) are described broadly in stem cells but with a focus on ASC. The final sections provide insights into the current and potential applications of ASC in human and veterinary regenerative medicine.

Abstract

In this dissertation the perceptual relevance of prevoicing in Dutch was investigated. Prevoicing is the presence of vocal fold vibration during the closure of initial voiced plosives (negative voice onset time). The presence or absence of prevoicing is generally used to describe the difference between voiced and voiceless Dutch plosives. The first experiment described in this dissertation showed that prevoicing is frequently absent in Dutch and that several factors affect the production of prevoicing. A detailed acoustic analysis of the voicing distinction identified several acoustic correlates of voicing. Prevoicing appeared to be by far the best predictor. Perceptual classification data revealed that prevoicing was indeed the strongest cue that listeners use when classifying plosives as voiced or voiceless. In the cases where prevoicing was absent, other acoustic cues influenced classification, such that some of these tokens were still perceived as being voiced. In the second part of this dissertation the influence of prevoicing variation on spoken-word recognition was examined. In several cross-modal priming experiments two types of prevoicing variation were contrasted: a difference between the presence and absence of prevoicing (6 versus 0 periods of prevoicing) and a difference in the amount of prevoicing (12 versus 6 periods). All these experiments indicated that primes with 12 and 6 periods of prevoicing had the same effect on lexical decisions to the visual targets. The primes without prevoicing had a different effect, but only when their voiceless counterparts were real words. Phonetic detail appears to influence lexical access only when it is useful: In Dutch, the presence versus absence of prevoicing is informative, while the amount of prevoicing is not.

Abstract

An event-related brain potential experiment was carried out to investigate the influence of semantic and syntactic context constraints on lexical selection and integration in spoken-word comprehension. Subjects were presented with constraining spoken sentences that contained a critical word that was either (a) congruent, (b) semantically and syntactically incongruent, but beginning with the same initial phonemes as the congruent critical word, or (c) semantically and syntactically incongruent, beginning with phonemes that differed from the congruent critical word. Relative to the congruent condition, an N200 effect reflecting difficulty in the lexical selection process was obtained in the semantically and syntactically incongruent condition where word onset differed from that of the congruent critical word. Both incongruent conditions elicited a large N400 followed by a left anterior negativity (LAN) time-locked to the moment of word category violation and a P600 effect. These results would best fit within a cascaded model of spoken-word processing, proclaiming an optimal use of contextual information during spokenword identification by allowing for semantic and syntactic processing to take place in parallel after bottom-up activation of a set of candidates, and lexical integration to proceed with a limited number of candidates that still match the acoustic input.

Abstract

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

Abstract

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

Abstract

Majority influences have long been a subject of great interest for social psychologists and, more recently, for researchers investigating social influences in nonhuman primates. Although this empirical endeavor has culminated in the conclusion that some ape and monkey species show “conformist” tendencies, the current approach seems to suffer from two fundamental limitations: (a) majority influences have not been operationalized in accord with any of the existing definitions, thereby compromising the validity of cross-species comparisons, and (b) the results have not been systematically scrutinized in light of alternative explanations. In this review, we aim to address these limitations theoretically. First, we will demonstrate how the experimental designs used in nonhuman primate studies cannot test for conformity unambiguously and address alternative explanations and potential confounds for the presented results in the form of primacy effects, frequency exposure, and perception ambiguity. Second, we will show how majority influences have been defined differently across disciplines and, therefore, propose a set of definitions in order to streamline majority influence research, where conformist transmission and conformity will be put forth as operationalizations of the overarching denominator majority influences. Finally, we conclude with suggestions to foster the study of majority influences by clarifying the empirical scope of each proposed definition, exploring compatible research designs and highlighting how majority influences are inherently contingent on situational trade-offs.

Abstract

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

Abstract

We report on a prospective longitudinal research programme exploring the connection between language acquisition deficits and dyslexia. The language development profile of children at-risk for dyslexia is compared to that of age-matched controls as well as of children who have been diagnosed with specific language impairment (SLI). The experiments described concern the perception and production of grammatical morphology, categorical perception of speech sounds, phonological processing (non-word repetition), mispronunciation detection, and rhyme detection. The results of each of these indicate that the at-risk children as a group underperform in comparison to the controls, and that, in most cases, they approach the SLI group. It can be concluded that dyslexia most likely has precursors in language development, also in domains other than those traditionally considered conditional for the acquisition of literacy skills. The dyslexia-SLI connection awaits further, particularly qualitative, analyses.

Abstract

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

Abstract

Chimpanzees have been shown to be adept learners, both individually and socially. Yet, sometimes their conservative nature seems to hamper the flexible adoption of superior alternatives, even to the extent that they persist in using entirely ineffective strategies. In this study, we investigated chimpanzees’ behavioural flexibility in two different conditions under which social animals have been predicted to abandon personal preferences and adopt alternative strategies: i) under influence of majority demonstrations (i.e. conformity), and ii) in the presence of superior reward contingencies (i.e. maximizing payoffs). Unlike previous nonhuman primate studies, this study disentangled the concept of conformity from the tendency to maintain one’s first-learned strategy. Studying captive (n=16) and semi-wild (n=12) chimpanzees in two complementary exchange paradigms, we found that chimpanzees did not abandon their behaviour in order to match the majority, but instead remained faithful to their first-learned strategy (Study 1a and 1b). However, the chimpanzees’ fidelity to their first-learned strategy was overridden by an experimental upgrade of the profitability of the alternative strategy (Study 2). We interpret our observations in terms of chimpanzees’ relative weighing of behavioural options as a function of situation-specific trade-offs. More specifically, contrary to previous findings, chimpanzees in our study abandoned their familiar behaviour to maximize payoffs, but not to conform to a majority.

Abstract

The present study focuses on the role of grammatical aspect in event construal and its function in encoding the specificity of an event. We investigate whether advanced L2 learners (L1 German) acquire target-like patterns of use of progressive aspect in Dutch, a language in which use of aspect depends on specific situation types. We analyze use of progressive markers and patterns in information selection, relating to specific features of agents or actions in dynamic event scenes. L2 event descriptions are compared with L1 Dutch and L1 German data. The L2 users display the complex situation-dependent patterns of use of aspect in Dutch, but they do not select the aspectual viewpoint (aan he construction) to the same extent as native speakers. Moreover, the encoding of specificity of the events (mentioning of specific agent and action features) reflects L1 transfer, as well as target-like performance in specific domains.

Abstract

This volume contains 13 papers dealing with various aspects of information structure in a wide variety of African languages. They form the proceedings of a workshop organized by the Collaborative Research Center on Information Structure (University of Potsdam and Humboldt University, Berlin). In the introduction, the editors define the main contribution of this volume in terms of “the spectrum of information-structural notions and phenomena discussed, the investigation of information structure in several relatively unfamiliar languages and the genealogical width of the African languages studied.” (vii–viii emphasis added). In this sense it complements the previous volume on information structure in African languages published by the Collaborative Research Center and the University of Amsterdam (Aboh, Hartmann & Zimmermann, 2007), which was more theoryoriented.

Abstract

The aim of this thesis was to gain more insight into spoken-word comprehension and the influence of sentence-contextual information on these processes using ERPs. By manipulating critical words in semantically constraining sententes, in semantic or syntactic sense, and examining the consequences in the electrophysiological signal (e.g., elicitation of ERP components such as the N400, N200, LAN, and P600), three questions were tackled: I At which moment is context information used in the spoken-word recognition process? II What is the temporal relationship between lexical selection and integration of the meaning of a spoken word into a higher-order level representeation of the preceding sentence? III What is the time course of the processing of different sources of linguistic information obtained from the context, such as phonological, semantic and syntactic information, during spoken-word comprehension? From the results of this thesis it can be concluded that sentential context already exerts an influence on spoken-word processing at approximately 200 ms after word onset. In addition, semantic integration is attempted before a spoken word can be selected on the basis of the acoustic signal, i.e. before lexical selection is completed. Finally, knowledge of the syntactic category of a word is not needed before semantic integration can take place. These findings, therefore, were interpreted as providing evidence for an account of cascaded spoken-word processing that proclaims an optimal use of contextual information during spoken-word identification. Optimal use is accomplished by allowing for semantic and syntactic processing to take place in parallel after bottom-up activation of a set of candidates, and lexical integration to proceed with a limited number of candidates that still match the acoustic input

Abstract

Three experiments investigated the voicing distinction in Dutch initial labial and alveolar plosives. The difference between voiced and voiceless Dutch plosives is generally described in terms of the presence or absence of prevoicing (negative voice onset time). Experiment 1 showed, however, that prevoicing was absent in 25% of voiced plosive productions across 10 speakers. The production of prevoicing was influenced by place of articulation of the plosive, by whether the plosive occurred in a consonant cluster or not, and by speaker sex. Experiment 2 was a detailed acoustic analysis of the voicing distinction, which identified several acoustic correlates of voicing. Prevoicing appeared to be by far the best predictor. Perceptual classification data revealed that prevoicing was indeed the strongest cue that listeners use when classifying plosives as voiced or voiceless. In the cases where prevoicing was absent, other acoustic cues influenced classification, such that some of these tokens were still perceived as being voiced. These secondary cues were different for the two places of articulation. We discuss the paradox raised by these findings: although prevoicing is the most reliable cue to the voicing distinction for listeners, it is not reliably produced by speakers.