Publications

Abstract

TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically diagnosed with Alzheimer's disease and a positive family history of ALS. We did not observe enrichment of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFκB induction. Of 3 common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13–1.9]; p-value 0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS cohorts. © 2017 The Author(s)

Abstract

Over 25 genes are known to affect the risk of developing Alzheimer disease (AD), the most common neurodegenerative dementia. However, mechanistic insights and improved disease management remains limited, due to difficulties in determining the functional consequences of genetic associations. Transcriptomics is increasingly being used to corroborate or enhance interpretation of genetic discoveries. These approaches, which include second and third generation sequencing, single-cell sequencing, and bioinformatics, reveal allele-specific events connecting AD risk genes to expression profiles, and provide converging evidence of pathophysiological pathways underlying AD. Simultaneously, they highlight brain region- and cell-type-specific expression patterns, and alternative splicing events that affect the straightforward relation between a genetic variant and AD, re-emphasizing the need for an integrated approach of genetics and transcriptomics in understanding AD. © 2018 The Authors

Abstract

Forkhead-box protein P2 is a transcription factor that has been associated with intriguing aspects of cognitive function in humans, non-human mammals, and song-learning birds. Heterozygous mutations of the human FOXP2 gene cause a monogenic speech and language disorder. Reduced functional dosage of the mouse version (Foxp2) causes deficient cortico-striatal synaptic plasticity and impairs motor-skill learning. Moreover, the songbird orthologue appears critically important for vocal learning. Across diverse vertebrate species, this well-conserved transcription factor is highly expressed in the developing and adult central nervous system. Very little is known about the mechanisms regulated by Foxp2 during brain development. We used an integrated functional genomics strategy to robustly define Foxp2-dependent pathways, both direct and indirect targets, in the embryonic brain. Specifically, we performed genome-wide in vivo ChIP–chip screens for Foxp2-binding and thereby identified a set of 264 high-confidence neural targets under strict, empirically derived significance thresholds. The findings, coupled to expression profiling and in situ hybridization of brain tissue from wild-type and mutant mouse embryos, strongly highlighted gene networks linked to neurite development. We followed up our genomics data with functional experiments, showing that Foxp2 impacts on neurite outgrowth in primary neurons and in neuronal cell models. Our data indicate that Foxp2 modulates neuronal network formation, by directly and indirectly regulating mRNAs involved in the development and plasticity of neuronal connections

Abstract

Mutations in the FOXP2 gene cause a severe communication disorder involving speech deficits (developmental verbal dyspraxia), accompanied by wide-ranging impairments in expressive and receptive language. The protein encoded by FOXP2 belongs to a divergent subgroup of forkhead-box transcription factors, with a distinctive DNA-binding domain and motifs that mediate hetero- and homodimerization. Here we report the first direct functional genetic investigation of missense and nonsense mutations in FOXP2 using human cell-lines, including a well-established neuronal model system. We focused on three unusual FOXP2 coding variants, uniquely identified in cases of verbal dyspraxia, assessing expression, subcellular localization, DNA-binding and transactivation properties. Analysis of the R553H forkhead-box substitution, found in all affected members of a large three-generation family, indicated that it severely affects FOXP2 function, chiefly by disrupting nuclear localization and DNA-binding properties. The R328X truncation mutation, segregating with speech/language disorder in a second family, yields an unstable, predominantly cytoplasmic product that lacks transactivation capacity. A third coding variant (Q17L) observed in a single affected child did not have any detectable functional effect in the present study. In addition, we used the same systems to explore the properties of different isoforms of FOXP2, resulting from alternative splicing in human brain. Notably, one such isoform, FOXP2.10+, contains dimerization domains, but no DNA-binding domain, and displayed increased cytoplasmic localization, coupled with aggresome formation. We hypothesize that expression of alternative isoforms of FOXP2 may provide mechanisms for post-translational regulation of transcription factor function.

Abstract

Mutations of the human FOXP2 gene have been shown to cause severe difficulties in learning to make coordinated sequences of articulatory gestures that underlie speech (developmental verbal dyspraxia or DVD). Affected individuals are impaired in multiple aspects of expressive and receptive linguistic processing and ­display abnormal grey matter volume and functional activation patterns in cortical and subcortical brain regions. The protein encoded by FOXP2 belongs to a divergent subgroup of forkhead-box transcription factors, with a distinctive DNA-binding domain and motifs that mediate hetero- and homodimerization. This chapter describes the successful use of FOXP2 as a unique molecular window into neurogenetic pathways that are important for speech and language development, adopting several complementary strategies. These include direct functional investigations of FOXP2 splice variants and the effects of etiological mutations. FOXP2’s role as a transcription factor also enabled the development of functional genomic routes for dissecting neurogenetic mechanisms that may be relevant for speech and language. By identifying downstream target genes regulated by FOXP2, it was possible to identify common regulatory themes in modulating synaptic plasticity, neurodevelopment, and axon guidance. These targets represent novel entrypoints into in vivo pathways that may be disturbed in speech and language disorders. The identification of FOXP2 target genes has also led to the discovery of a shared neurogenetic pathway between clinically distinct language disorders; the rare Mendelian form of DVD and a complex and more common form of language ­disorder known as Specific Language Impairment.

Abstract

We previously discovered that mutations of the human FOXP2 gene cause a monogenic communication disorder, primarily characterized by difficulties in learning to make coordinated sequences of articulatory gestures that underlie speech. Affected people have deficits in expressive and receptive linguistic processing and display structural and/or functional abnormalities in cortical and subcortical brain regions. FOXP2 provides a unique window into neural processes involved in speech and language. In particular, its role as a transcription factor gene offers powerful functional genomic routes for dissecting critical neurogenetic mechanisms. Here, we employ chromatin immunoprecipitation coupled with promoter microarrays (ChIP-chip) to successfully identify genomic sites that are directly bound by FOXP2 protein in native chromatin of human neuron-like cells. We focus on a subset of downstream targets identified by this approach, showing that altered FOXP2 levels yield significant changes in expression in our cell-based models and that FOXP2 binds in a specific manner to consensus sites within the relevant promoters. Moreover, we demonstrate significant quantitative differences in target expression in embryonic brains of mutant mice, mediated by specific in vivo Foxp2-chromatin interactions. This work represents the first identification and in vivo verification of neural targets regulated by FOXP2. Our data indicate that FOXP2 has dual functionality, acting to either repress or activate gene expression at occupied promoters. The identified targets suggest roles in modulating synaptic plasticity, neurodevelopment, neurotransmission, and axon guidance and represent novel entry points into in vivo pathways that may be disturbed in speech and language disorders.

Abstract

This paper investigates the effects of novel words on a cognitively plausible computational model of word learning. The model is first familiarized with a set of words, achieving high recognition scores and subsequently offered novel words for training. We show that the model is able to recognize the novel words as different from the previously seen words, based on a measure of novelty that we introduce. We then propose a procedure analogous to novelty preference in infants. Results from simulations of word learning show that adding this procedure to our model speeds up training and helps the model attain higher recognition rates.

Abstract

In this paper an overview of the knowledge components needed for extensive documentation of small languages is given. The Language Archive is striving to offer all these tools to the linguistic community. The major tools in relation to the knowledge components are described. Followed by a discussion on what is currently lacking and possible strategies to move forward.

Abstract

This study examines the influence of orthography on the processing of reduced word forms. For this purpose, we compared the impact of phonological variation with the impact of spelling-sound consistency on the processing of words that may be produced with or without the vowel schwa. Participants learnt novel French words in which the vowel schwa was present or absent in the first syllable. In Experiment 1, the words were consistently produced without schwa or produced in a variable manner (i.e., sometimes produced with and sometimes produced without schwa). In Experiment 2, words were always produced in a consistent manner, but an orthographic exposure phase was included in which words that were produced without schwa were either spelled with or without the letter . Results from naming and eye-tracking tasks suggest that both phonological variation and spelling-sound consistency influence the processing of spoken novel words. However, the influence of phonological variation outweighs the effect of spelling-sound consistency. Our findings therefore suggest that the influence of orthography on the processing of reduced word forms is relatively small.

Abstract

A central question in the study of the mental lexicon is how morphologically complex words are processed. We consider this question from the viewpoint of statistical models of morphology. As an indicator of the mental processing cost in the brain, we use reaction times to words in a visual lexical decision task on Finnish nouns. Statistical correlation between a model and reaction times is employed as a goodness measure of the model. In particular, we study Morfessor, an unsupervised method for learning concatenative morphology. The results for a set of inflected and monomorphemic Finnish nouns reveal that the probabilities given by Morfessor, especially the Categories-MAP version, show considerably higher correlations to the reaction times than simple word statistics such as frequency, morphological family size, or length. These correlations are also higher than when any individual test subject is viewed as a model.

Abstract

Before infants become mature speakers of their native language, they must acquire a robust word-recognition system which allows them to strike the balance between allowing some variation (mood, voice, accent) and recognizing variability that potentially changes meaning (e.g. cat vs hat). The current meta-analysis quantifies how the latter, termed mispronunciation sensitivity, changes over infants’ first three years, testing competing predictions of mainstream language acquisition theories. Our results show that infants were sensitive to mispronunciations, but accepted them as labels for target objects. Interestingly, and in contrast to predictions of mainstream theories, mispronunciation sensitivity was not modulated by infant age, suggesting that a sufficiently flexible understanding of native language phonology is in place at a young age.

Abstract

Rede uitgesproken bij de aanvaarding van het ambt van hoogleraar in de Psycholinguïstiek aan de Faculteit der Letteren van de Katholieke Universiteit Nijmegen op vrijdag 18 mei 2001

Abstract

We meta‐analyzed the effectiveness of incidental second language word learning from spoken input. Our sample contained 105 effect sizes from 32 primary studies employing meaning‐focused word‐learning activities with 1,964 participants with typical cognitive functioning. The random‐effects meta‐analysis yielded a mean effect size of g = 1.05, reflecting generally large vocabulary gains from spoken input in meaning‐focused activities. A meta‐regression with three substantive and two methodological predictors also revealed that adult participants outperformed children in terms of word learning and that interactive learning tasks were more effective than noninteractive ones. Furthermore, learning scores were higher when measured with recognition than with recall tests. Methodologically, the use of a no‐input control group seemed to protect against an overestimation of learning effects, evidenced by smaller effect sizes. Finally, whether a pretest–posttest design was used did not influence effect sizes. All data and the analysis script are publicly available.

Abstract

Sign Language of the Netherlands (NGT) is a visual-gestural language in which linguistic information is conveyed through manual as well as non-manual channels; not only the hands, but also body position, head position and facial expression are important for the language structure. Facial expressions serve grammatical functions in the marking of topics, yes/no questions, and wh-questions (Coerts, 1992). Furthermore, facial expression is used nonlinguistically in the expression of affect (Ekman, 1979). Consequently, at the phonetic level obligatory marking of grammar using facial expression may conflict with the expression of affect. In this study, I investigated the interplay of linguistic and affective functions of brow movements in NGT. Three hypotheses were tested in this thesis. The first is that the affective markers of eyebrows would dominate over the linguistic markers. The second hypothesis predicts that the grammatical markers dominate over the affective brow movements. A third possibility is that a Phonetic Sum would occur in which both functions are combined simultaneously. I elicited sentences combining grammatical and affective functions of eyebrows using a randomised design. Five sentence types were included: declarative sentences, topic sentences, yes-no questions, wh-questions with the wh-sign sentence-final and wh-questions with the wh-sign sentence-initial. These sentences were combined with neutral, surprised, angry, and distressed affect. The brow movements were analysed using the Facial Action Coding System (Ekman, Friesen, & Hager, 2002a). In these sentences, the eyebrows serve a linguistic function, an affective function, or both. One of the possibilities in the latter cases was that a Phonetic Sum would occur that combines both functions simultaneously. Surprisingly, it was found that a Phonetic Sum occurs in which the phonetic weight of Action Unit 4 appears to play an important role. The results show that affect displays may alter question signals in NGT.

Abstract

How do new languages develop systematic ways to talk about sensory experiences, such as color? To what extent is the evolution of color terms guided by societal factors? This paper describes the color lexicon of a rural sign language called Kata Kolok which emerged approximately one century ago in a Balinese village. Kata Kolok has four color signs: black, white, red and a blue-green term. In addition, two non-conventionalized means are used to provide color descriptions: naming relevant objects, and pointing to objects in the vicinity. Comparison with Balinese culture and spoken Balinese brings to light discrepancies between the systems, suggesting that neither cultural practices nor language contact have driven the formation of color signs in Kata Kolok. The few lexicographic investigations from other rural sign languages report limitations in the domain of color. On the other hand, larger, urban signed languages have extensive systems, for example, Australian Sign Language has up to nine color terms (Woodward 1989: 149). These comparisons support the finding that, rural sign languages like Kata Kolok fail to provide the societal pressures for the lexicon to expand further.

Abstract

Noticing the hole (NTH) occurs when speakers want to say something, but realise they do not know the right word(s). Such awareness of lacking knowledge supposedly facilitates the acquisition of the unknown word(s) from later input (Swain, 1993). We tested this claim by experimentally inducing NTH in a second language (L2) for some participants (experimental), but not others (control). Then, in a price comparison game, all participants were exposed to spoken L2 input containing the to-be-learned words. They were unaware of taking part in an L2 study. Post-tests showed that participants who had noticed holes in their vocabulary had indeed learned more words compared to participants who had not. This held both for the experimental group as well as those participants in the control group who later reported to have noticed holes. Thus, when we become aware of vocabulary holes, the first step to improve our vocabulary is already taken.

Abstract

Metaphors occur frequently in literary texts. Deliberate Metaphor Theory (DMT; e.g., Steen, 2017) proposes that metaphors that serve a communicative function as metaphor are radically different from metaphors that do not have this function. We investigated differences in processing between deliberate and non-deliberate metaphors, compared to non-metaphorical words in literary reading. Using the Deliberate Metaphor Identification Procedure (Reijnierse et al., 2018), we identified metaphors in two literary stories. Then, eye-tracking was used to investigate participants’ (N = 72) reading behavior. Deliberate metaphors were read slower than non-deliberate metaphors, and both metaphor types were read slower than non-metaphorical words. Differences were controlled for several psycholinguistic variables. Differences in reading behavior were related to individual differences in reading experience and absorption and appreciation of the story. These results are in line with predictions from DMT and underline the importance of distinguishing between metaphor types in the experimental study of literary reading.

Abstract

Language acquisition in both natural and artificial language learning settings crucially depends on extracting information from sequence input. A shared sequence learning mechanism is thus assumed to underlie both natural and artificial language learning. A growing body of empirical evidence is consistent with this hypothesis. By means of artificial language learning experiments, we may therefore gain more insight in this shared mechanism. In this paper, we review empirical evidence from artificial language learning and computational modelling studies, as well as natural language data, and suggest that there are two key factors that help determine processing complexity in sequence learning, and thus in natural language processing. We propose that the specific ordering of non-adjacent dependencies (i.e., nested or crossed), as well as the number of non-adjacent dependencies to be resolved simultaneously (i.e., two or three) are important factors in gaining more insight into the boundaries of human sequence learning; and thus, also in natural language processing. The implications for theories of linguistic competence are discussed.

Abstract

The present study investigated the interplay between selective inhibition (the ability to suppress specific competing responses) and nonselective inhibition (the ability to suppress any inappropriate response) during single word production. To this end, we combined two well-established research paradigms: the picture-word interference task and the stop-signal task. Selective inhibition was assessed by instructing participants to name target pictures (e.g., dog) in the presence of semantically related (e.g., cat) or unrelated (e.g., window) distractor words. Nonselective inhibition was tested by occasionally presenting a visual stop-signal, indicating that participants should withhold their verbal response. The stop-signal was presented early (250 ms) aimed at interrupting the lexical selection stage, and late (325 ms) to influence the word-encoding stage of the speech production process. We found longer naming latencies for pictures with semantically related distractors than with unrelated distractors (semantic interference effect). The results further showed that, at both delays, stopping latencies (i.e., stop-signal RTs) were prolonged for naming pictures with semantically related distractors compared to pictures with unrelated distractors. Taken together, our findings suggest that selective and nonselective inhibition, at least partly, share a common inhibitory mechanism during different stages of the speech production process.

Abstract

The role of attentional control in lexical ambiguity resolution was examined in two patients with damage to the left inferior frontal gyrus (LIFG) and one control patient with non-LIFG damage. Experiment 1 confirmed that the LIFG patients had attentional control deficits compared to normal controls while the non-LIFG patient was relatively unimpaired. Experiment 2 showed that all three patients did as well as normal controls in using biasing sentence context to resolve lexical ambiguities involving balanced ambiguous words, but only the LIFG patients took an abnormally long time on lexical ambiguities that resolved toward a subordinate meaning of biased ambiguous words. Taken together, the results suggest that attentional control plays an important role in the resolution of certain lexical ambiguities – those that induce strong interference from context-inappropriate meanings (i.e., dominant meanings of biased ambiguous words).

Abstract

The distribution of energy across the noise spectrum provides the primary cues for the identification of a fricative. Formant transitions have been reported to play a role in identification of some fricatives, but the combined results so far are conflicting. We report five experiments testing the hypothesis that listeners differ in their use of formant transitions as a function of the presence of spectrally similar fricatives in their native language. Dutch, English, German, Polish, and Spanish native listeners performed phoneme monitoring experiments with pseudowords containing either coherent or misleading formant transitions for the fricatives / s / and / f /. Listeners of German and Dutch, both languages without spectrally similar fricatives, were not affected by the misleading formant transitions. Listeners of the remaining languages were misled by incorrect formant transitions. In an untimed labeling experiment both Dutch and Spanish listeners provided goodness ratings that revealed sensitivity to the acoustic manipulation. We conclude that all listeners may be sensitive to mismatching information at a low auditory level, but that they do not necessarily take full advantage of all available systematic acoustic variation when identifying phonemes. Formant transitions may be most useful for listeners of languages with spectrally similar fricatives.

Abstract

Readers and listeners actively predict upcoming words during language processing. These predictions might serve to support the unification of incoming words into sentence context and thus rely on interactions between areas in the language network. In the current magnetoencephalography study, participants read sentences that varied in contextual constraints so that the predictability of the sentence-final words was either high or low. Before the sentence-final words, we observed stronger alpha power suppression for the highly compared with low constraining sentences in the left inferior frontal cortex, left posterior temporal region, and visual word form area. Importantly, the temporal and visual word form area alpha power correlated negatively with left frontal gamma power for the highly constraining sentences. We suggest that the correlation between alpha power decrease in temporal language areas and left prefrontal gamma power reflects the initiation of an anticipatory unification process in the language network.

Abstract

Using magnetoencephalography, the current study examined gamma activity associated with language prediction. Participants read high- and low-constraining sentences in which the final word of the sentence was either expected or unexpected. Although no consistent gamma power difference induced by the sentence-final words was found between the expected and unexpected conditions, the correlation of gamma power during the prediction and activation intervals of the sentence-final words was larger when the presented words matched with the prediction compared with when the prediction was violated or when no prediction was available. This suggests that gamma magnitude relates to the match between predicted and perceived words. Moreover, the expected words induced activity with a slower gamma frequency compared with that induced by unexpected words. Overall, the current study establishes that prediction is related to gamma power correlations and a slowing of the gamma frequency.

Abstract

The blocked cyclic naming paradigm has been increasingly employed to investigate the mechanisms underlying spoken word production. Semantic homogeneity typically elicits longer naming latencies than heterogeneity; however, it is debated whether competitive lexical selection or incremental learning underlies this effect. The current study manipulated both semantic and phonological homogeneity and used behavioural and electrophysiological measurements to provide evidence that can distinguish between the two accounts. Results show that naming latencies are longer in semantically homogeneous blocks, but shorter in phonologically homogeneous blocks, relative to heterogeneity. The semantic factor significantly modulates electrophysiological waveforms from 200 ms and the phonological factor from 350 ms after picture presentation. A positive component was demonstrated in both manipulations, possibly reflecting a task-related top-down bias in performing blocked cyclic naming. These results provide novel insights into the neural correlates of blocked cyclic naming and further contribute to the understanding of spoken word production.

Abstract

To highlight relevant information in dialogues, both wh-question context and pitch accent in answers can be used, such that focused information gains more attention and is processed more elaborately. To evaluate the relative influence of context and pitch accent on the depth of semantic processing, we measured Event-Related Potentials (ERPs) to auditorily presented wh-question-answer pairs. A semantically incongruent word in the answer occurred either in focus or non-focus position as determined by the context, and this word was either accented or unaccented. Semantic incongruency elicited different N400 effects in different conditions. The largest N400 effect was found when the question-marked focus was accented, while the other three conditions elicited smaller N400 effects. The results suggest that context and accentuation interact. Thus accented focused words were processed more deeply compared to conditions where focus and accentuation mismatched, or when the new information had no marking. In addition, there seems to be sex differences in the depth of semantic processing. For males, a significant N400 effect was observed only when the question-marked focus was accented, reduced N400 effects were found in the other dialogues. In contrast, females produced similar N400 effects in all the conditions. These results suggest that regardless of external cues, females tend to engage in more elaborate semantic processing compared to males.

Abstract

Neurodevelopmental disorders have a strong genetic component, but despite widespread efforts, the specific genetic factors underlying these disorders remain undefined for a large proportion of affected individuals. Given the accessibility of exome-sequencing, this problem has thus far been addressed from a protein-centric standpoint; however, protein-coding regions only make up ∼1-2% of the human genome. With the advent of whole-genome sequencing we are in the midst of a paradigm shift as it is now possible to interrogate the entire sequence of the human genome (coding and non-coding) to fill in the missing heritability of complex disorders. These new technologies bring new challenges, as the number of non-coding variants identified per individual can be overwhelming, making it prudent to focus on non-coding regions of known function, for which the effects of variation can be predicted and directly tested to assess pathogenicity. The 3’UTRome is a region of the non-coding genome that perfectly fulfils these criteria and is of high interest when searching for pathogenic variation related to complex neurodevelopmental disorders. Herein, we review the regulatory roles of the 3’UTRome as binding sites for microRNAs, RNA binding proteins or during alternative polyadenylation. We detail existing evidence that these regions contribute to neurodevelopmental disorders and outline strategies for identification and validation of novel putatively pathogenic variation in these regions. This evidence suggests that studying the 3’UTRome will lead to the identification of new risk factors, new candidate disease genes and a better understanding of the molecular mechanisms contributing to NDDs.

Abstract

This study, following up on work on Dutch by Warner, Jongman, Sereno, and Kemps (2004. Journal of Phonetics, 32, 251–276), investigates the influence of orthographic distinctions and underlying morphological distinctions on the small sub-phonemic durational differences that have been called incomplete neutralization. One part of the previous work indicated that an orthographic geminate/singleton distinction could cause speakers to produce an incomplete neutralization effect. However, one interpretation of the materials in that experiment is that they contain an underlying difference in the phoneme string at the level of concatenation of morphemes, rather than just an orthographic difference. Thus, the previous effect might simply be another example of incomplete neutralization of a phonemic distinction. The current experiment, also on Dutch, uses word pairs which have the same underlying morphological contrast, but do not differ in orthography. These new materials show no incomplete neutralization, and thus support the hypothesis that orthography, but not underlying morphological differences, can cause incomplete neutralization effects.

Abstract

In processing connected speech, listeners must parse a highly variable signal. We investigate processing of a particular type of production variability, namely epenthetic stops between nasals and obstruents. Using a phoneme monitoring task and a dictation task, we test listeners' perception of epenthetic stops (which are not part of the string of segments intended by the speaker). We confirm that the epenthetic stop perceived is the one predicted by articulatory accounts of how such stops are produced, and that the likelihood of an epenthetic stop being perceived as a real stop is related to the strength of acoustic cues in the signal. We show that the probability of listeners mis-parsing epenthetic stops as real is influenced by language-specific syllable structure constraints, and depends on processing demands. We further show, through reaction time data, that even when epenthetic stops are perceived, they impose a greater processing load than stops which were intended by the speaker. These results show that processing of phonetic variability is affected by several factors, including language-specific phonology, even though the mis-timing of articulations that creates epenthetic stops is universally possible.

Abstract

In this paper, we use articulatory measures to determine whether Dutch schwa epenthesis is an abstract phonological process or a concrete phonetic process depending on articulatory timing. We examine tongue position during /l/ before underlying schwa and epenthetic schwa and in coda position. We find greater tip raising before both types of schwa, indicating light /l/ before schwa and dark /l/ in coda position. We argue that the ability of epenthetic schwa to condition the /l/ alternation shows that Dutch schwa epenthesis is an abstract phonological process involving insertion of some unit, and cannot be accounted for within Articulatory Phonology.

Abstract

Articulatory data are used to address the question of whether Dutch schwa insertion is a phonological or a phonetic process. By investigating tongue tip raising and dorsal lowering, we show that /l/ when it appears before inserted schwa is a light /l/, just as /l/ before an underlying schwa is, and unlike the dark /l/ before a consonant in non-insertion productions of the same words. The fact that inserted schwa can condition the light/dark /l/ alternation shows that schwa insertion involves the phonological insertion of a segment rather than phonetic adjustments to articulations.

Abstract

This study investigates whether the mora is used in controlling timing in Japanese speech, or is instead a structural unit in the language not involved in timing. Unlike most previous studies of mora-timing in Japanese, this article investigates timing in spontaneous speech. Predictability of word duration from number of moras is found to be much weaker than in careful speech. Furthermore, the number of moras predicts word duration only slightly better than number of segments. Syllable structure also has a significant effect on word duration. Finally, comparison of the predictability of whole words and arbitrarily truncated words shows better predictability for truncated words, which would not be possible if the truncated portion were compensating for remaining moras. The results support an accumulative model of variance with a final lengthening effect, and do not indicate the presence of any compensation related to mora-timing. It is suggested that the rhythm of Japanese derives from several factors about the structure of the language, not from durational compensation.

Abstract

Social interaction relies on the ability to react to communication signals. Although cortical sensory–motor “mirror” networks are thought to play a key role in visual aspects of primate communication, evidence for a similar generic role for auditory–motor interaction in primate nonverbal communication is lacking. We demonstrate that a network of human premotor cortical regions activated during facial movement is also involved in auditory processing of affective nonverbal vocalizations. Within this auditory–motor mirror network, distinct functional subsystems respond preferentially to emotional valence and arousal properties of heard vocalizations. Positive emotional valence enhanced activation in a left posterior inferior frontal region involved in representation of prototypic actions, whereas increasing arousal enhanced activation in presupplementary motor area cortex involved in higher-order motor control. Our findings demonstrate that listening to nonverbal vocalizations can automatically engage preparation of responsive orofacial gestures, an effect that is greatest for positive-valence and high-arousal emotions. The automatic engagement of responsive orofacial gestures by emotional vocalizations suggests that auditory–motor interactions provide a fundamental mechanism for mirroring the emotional states of others during primate social behavior. Motor facilitation by positive vocal emotions suggests a basic neural mechanism for establishing cohesive bonds within primate social groups.

Abstract

An event-related brain potential experiment was carried out to investigate on-line thematic role assignment during sentence–picture matching in patients with Broca's aphasia. Subjects were presented with a picture that was followed by an auditory sentence. The sentence either matched the picture or mismatched the visual information depicted. Sentences differed in complexity, and ranged from simple active semantically irreversible sentences to passive semantically reversible sentences. ERPs were recorded while subjects were engaged in sentence–picture matching. In addition, reaction time and accuracy were measured. Three groups of subjects were tested: Broca patients (N = 10), non-aphasic patients with a right hemisphere (RH) lesion (N = 8), and healthy aged-matched controls (N = 15). The results of this study showed that, in neurologically unimpaired individuals, thematic role assignment in the context of visual information was an immediate process. This in contrast to patients with Broca's aphasia who demonstrated no signs of on-line sensitivity to the picture–sentence mismatches. The syntactic contribution to the thematic role assignment process seemed to be diminished given the reduction and even absence of P600 effects. Nevertheless, Broca patients showed some off-line behavioral sensitivity to the sentence–picture mismatches. The long response latencies of Broca's aphasics make it likely that off-line response strategies were used.

Abstract

The establishment of a reliable model for the study of Purkinje cells in vitro is of particular importance, given their central role in cerebellar function and pathology. Recent advances in induced pluripotent stem cell (iPSC) technology offer the opportunity to generate multiple neuronal subtypes for study in vitro. However, to date, only a handful of studies have generated Purkinje cells from human pluripotent stem cells, with most of these protocols proving challenging to reproduce. Here, we describe a simplified method for the reproducible generation of Purkinje cells from human iPSCs. After 21 days of treatment with factors selected to mimic the self-inductive properties of the isthmic organiser—insulin, fibroblast growth factor 2 (FGF2), and the transforming growth factor β (TGFβ)-receptor blocker SB431542—hiPSCs could be induced to form En1-positive cerebellar progenitors at efficiencies of up to 90%. By day 35 of differentiation, subpopulations of cells representative of the two cerebellar germinal zones, the rhombic lip (Atoh1-positive) and ventricular zone (Ptf1a-positive), could be identified, with the latter giving rise to cells positive for Purkinje cell progenitor-specific markers, including Lhx5, Kirrel2, Olig2 and Skor2. Further maturation was observed following dissociation and co-culture of these cerebellar progenitors with mouse cerebellar cells, with 10% of human cells staining positive for the Purkinje cell marker calbindin by day 70 of differentiation. This protocol, which incorporates modifications designed to enhance cell survival and maturation and improve the ease of handling, should serve to make existing models more accessible, in order to enable future advances in the field.

Abstract

In two eye-tracking experiments the role of contrastive pitch accents during the on-line determination of referents was examined. In both experiments, German listeners looked earlier at the picture of a referent belonging to a contrast pair (red scissors, given purple scissors) when instructions to click on it carried a contrastive accent on the color adjective (L + H*) than when the adjective was not accented. In addition to this prosodic facilitation, a general preference to interpret adjectives contrastively was found in Experiment 1: Along with the contrast pair, a noncontrastive referent was displayed (red vase) and listeners looked more often at the contrastive referent than at the noncontrastive referent even when the adjective was not focused. Experiment 2 differed from Experiment 1 in that the first member of the contrast pair (purple scissors) was introduced with a contrastive accent, thereby strengthening the salience of the contrast. In Experiment 2, listeners no longer preferred a contrastive interpretation of adjectives when the accent in a subsequent instruction was not contrastive. In sum, the results support both an early role for prosody in reference determination and an interpretation of contrastive focus that is dependent on preceding prosodic context.

Abstract

Highly proficient German users of English as a second language, and native speakers of American English, listened to nonsense sequences and responded whenever they detected an embedded English word. The responses of both groups were equivalently facilitated by preceding context that both by English and by German phonotactic constraints forced a boundary at word onset (e.g., lecture was easier to detect in moinlecture than in gorklecture, and wish in yarlwish than in plookwish. The American L1 speakers’ responses were strongly facilitated, and the German listeners’ responses almost as strongly facilitated, by contexts that forced a boundary in English but not in German thrarshlecture, glarshwish. The German listeners’ responses were significantly facilitated also by contexts that forced a boundary in German but not in English )moycelecture, loitwish, while L1 listeners were sensitive to acoustic boundary cues in these materials but not to the phonotactic sequences. The pattern of results suggests that proficient L2 listeners can acquire the phonotactic probabilities of an L2 and use them to good effect in segmenting continuous speech, but at the same time they may not be able to prevent interference from L1 constraints in their L2 listening.

Abstract

Four phoneme-detection studies tested the conclusion from recent research that spoken-language processing is inhibited by violation of obligatory assimilation processes in the listeners’ native language. In Experiment 1, native listeners of German detected a target fricative in monosyllabic Dutch nonwords, half of which violated progressive German fricative place assimilation. In contrast to the earlier findings, listeners detected the fricative more quickly when assimilation was violated than when no violation occurred. This difference was not due to purely acoustic factors, since in Experiment 2 native Dutch listeners, presented with the same materials, showed no such effect. In Experiment 3, German listeners again detected the fricative more quickly when violation occurred in both monosyllabic and bisyllabic native nonwords, further ruling out explanations based on non-native input or on syllable structure. Finally Experiment 4 tested whether the direction in which the rule operates (progressive or regressive) controls the direction of the effect on phoneme detection responses.When regressive German place assimilation for nasals was violated, German listeners detected stops more slowly, exactly as had been observed in previous studies of regressive assimilation. It is argued that a combination of low expectations in progressive assimilation and novel popout causes facilitation of processing,whereas not fulfilling high expectations in regressive assimilation causes inhibition.

Abstract

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

Abstract

Two cross-modal priming studies investigated the recognition of English words spoken with a foreign accent. Auditory English primes were either typical of a Dutch accent or typical of a Japanese accent in English and were presented to both Dutch and Japanese L2 listeners. Lexical-decision times to subsequent visual target words revealed that foreign-accented words can facilitate word recognition for L2 listeners if at least one of two requirements is met: the foreign-accented production is in accordance with the language background of the L2 listener, or the foreign accent is perceptually confusable with the standard pronunciation for the L2 listener. If neither one of the requirements is met, no facilitatory effect of foreign accents on L2 word recognition is found. Taken together, these findings suggest that linguistic experience with a foreign accent affects the ability to recognize words carrying this accent, and there is furthermore a general benefit for L2 listeners for recognizing foreign-accented words that are perceptually confusable with the standard pronunciation.

Abstract

An eye-tracking experiment examined whether prosodic cues can affect the interpretation of grammatical functions in the absence of clear morphological information. German listeners were presented with scenes depicting three potential referents while hearing temporarily ambiguous SVO and OVS sentences. While case marking on the first noun phrase (NP) was ambiguous, clear case marking on the second NP disambiguated sentences towards SVO or OVS. Listeners interpreted caseambiguous NP1s more often as Subject, and thus expected an Object as upcoming argument, only when sentence beginnings carried an SVO-type intonation. This was revealed by more anticipatory eye movements to suitable Patients (Objects) than Agents (Subjects) in the visual scenes. No such preference was found when sentence beginnings had a clearly OVS-type intonation. Prosodic cues were integrated rapidly enough to affect listeners’ interpretation of grammatical function before disambiguating case information was available. We conclude that in addition to manipulating attachment ambiguities, prosody can influence the interpretation of constituent order ambiguities.

Abstract

In a visual-world study, we examined spoken-wordrecognition in Spanish. Spanish listeners followed spoken instructions to click on pictures while their eye movements were monitored. When instructed to click on the picture of a door (puerta), they experienced interference from the picture of a pig (p u e r c o ). The same interference from phonologically related items was observed when the displays contained printed names or a combination of pictures with their names printed underneath, although the effect was strongest for displays with printed names. Implications of the finding that the interference effect can be induced with standard pictorial displays as well as with orthographic displays are discussed.

Abstract

Reports of an advantage of bilingualism on brain structure in young adult participants
are inconsistent. Abutalebi et al. (2012) reported more efficient monitoring of conflict during the
Flanker task in young bilinguals compared to young monolingual speakers. The present study
compared young adult (mean age = 24) Cantonese-English bilinguals in Hong Kong and young
adult monolingual speakers. We expected (a) differences in metabolites in neural tissue to result
from bilingual experience, as measured by 1H-MRS at 3T, (b) correlations between metabolic
levels and Flanker conflict and interference effects (c) different associations in bilingual and
monolingual speakers. We found evidence of metabolic differences in the ACC due to bilingualism,
specifically in metabolites Cho, Cr, Glx and NAA. However, we found no significant correlations
between metabolic levels and conflict and interference effects and no significant evidence of
differential relationships between bilingual and monolingual speakers. Furthermore, we found no
evidence of significant differences in the mean size of conflict and interference effects between
groups i.e. no bilingual advantage. Lower levels of Cho, Cr, Glx and NAA in bilingual adults
compared to monolingual adults suggest that the brains of bilinguals develop greater adaptive
control during conflict monitoring because of their extensive bilingual experience.

Abstract

This paper provides a description of body part terminology used in Savosavo, a Papuan language of the Solomon Islands. The first part of the paper lists the known terms and discusses their meanings. This is followed by an analysis of their structural properties. Finally, the paper discusses partonomic relations in Savosavo and argues that it is difficult to structure the body part terminology hierarchically, because there is no linguistic evidence for part–whole relations between body parts.

Abstract

This paper describes how reciprocity is expressed in the Papuan (i.e. non-Austronesian­) language Savosavo, spoken in the Solomon Islands. The main strategy is to use the reciprocal nominal mapamapa, which can occur in different NP positions and always triggers default third person singular masculine agreement, regardless of the number and gender of the referents. After a description of this as well as another strategy that is occasionally used (the ‘joint activity construction’), the paper will provide a detailed analysis of data elicited with set of video stimuli and show that the main strategy is used to describe even clearly asymmetric situations, as long as more than one person acts on more than one person in a joint activity.

Abstract

This follow-up study of the European Dexamethasone Study was designed to examine the potential harmful effect of adjunctive dexamethasone treatment on long-term neuropsychological outcome in adults with bacterial meningitis. METHODS: Neurological, audiological, and neuropsychological examinations were performed in adults who survived pneumococcal or meningococcal meningitis. RESULTS: Eighty-seven of 99 (88%) eligible patients were included in the follow-up study; 46 (53%) were treated with dexamethasone and 41 (47%) with placebo. Median time between meningitis and testing was 99 months. Neuropsychological evaluation showed no significant differences between patients treated with dexamethasone and placebo. The proportions of patients with persisting neurological sequelae or hearing loss were similar in the dexamethasone and placebo groups. The overall rate of cognitive dysfunction did not differ significantly between patients and control subjects; however, patients after pneumococcal meningitis had a higher rate of cognitive dysfunction (21 vs 6%; p = 0.05) and experienced more impairment of everyday functioning due to physical problems (p = 0.05) than those after meningococcal meningitis. INTERPRETATION: Treatment with adjunctive dexamethasone is not associated with an increased risk for long-term cognitive impairment. Adults who survive pneumococcal meningitis are at significant risk for long-term neuropsychological abnormalities.

Abstract

Objectives To assess cognitive outcome and quality of life in patients with moderate disability after bacterial meningitis as compared to patients with good recovery. Methods Neuropsychological evaluation was performed in 40 adults after pneumococcal meningitis; 20 patients with moderate disability at discharge on the glasgow outcome scale (GOS score 4) and 20 with good recovery (GOS score 5). Results Patients with GOS score 4 had similar test results as compared to patients with GOS score 5 for the neuropsychological domains ‘intelligence’, ‘memory’ and ‘attention and executive functioning’. Patients with GOS score 4 showed less cognitive slowness than patients with GOS score 5. In a linear regression analysis cognitive speed was related to current intelligence, years of education and time since meningitis. Overall performance on the speed composite score correlated significantly with time since meningitis (−0.62; P<0.001). Therefore, difference between both groups may have been related to a longer time between meningitis and testing for GOS four patients (29 vs. 12 months; P<0.001). Conclusions Patients with moderate disability after bacterial meningitis are not at higher risk for neuropsychological abnormalities than patients with good recovery. In addition, cognitive slowness after bacterial meningitis may be reversible in time.

Abstract

In 2001, a point mutation in the forkhead box P2 (FOXP2) coding sequence was identified as the basis of an inherited speech and language disorder suffered by members of the family known as "KE." This mini-symposium review focuses on recent findings and research-in-progress, primarily from five laboratories. Each aims at capitalizing on the FOXP2 discovery to build a neurobiological bridge between molecule and phenotype. Below, we describe genetic through behavioral techniques used currently to investigate FoxP2 in birds, rodents, and humans for discovery of the neural bases of vocal learning and language.

Abstract

Early language development is known to be under genetic influence, but the genes affecting normal variation in the general population remain largely elusive. Recent studies of disorder reported that variants of the CNTNAP2 gene are associated both with language deficits in specific language impairment (SLI) and with language delays in autism. We tested the hypothesis that these CNTNAP2 variants affect communicative behavior, measured at 2 years of age in a large epidemiological sample, the Western Australian Pregnancy Cohort (Raine) Study. Singlepoint analyses of 1149 children (606 males, 543 emales) revealed patterns of association which were strikingly reminiscent of those observed in previous investigations of impaired language, centered on the same genetic markers, and with a consistent direction of effect (rs2710102, p = .0239; rs759178, p = .0248). Based on these findings we performed analyses of four-marker haplotypes of rs2710102- s759178-rs17236239-rs2538976, and identified significant association (haplotype TTAA, p = .049; haplotype GCAG, p = .0014). Our study suggests that common variants in the exon 13-15 region of CNTNAP2 influence early language acquisition, as assessed at age 2, in the general population. We propose that these CNTNAP2 variants increase susceptibility to SLI or autism when they occur together with other risk factors.

Abstract

Common ground is an essential prerequisite for coordination in social interaction, including language use. When referring back to a referent in discourse, this referent is ‘given information’ and therefore in the interactants’ common ground. When a referent is being referred to for the first time, a speaker introduces ‘new information’. The analyses reported here are on gestures that accompany such references when they include definite and indefinite grammatical determiners. The main finding from these analyses is that referents referred to by definite and indefinite articles were equally often accompanied by gesture, but speakers tended to accompany definite references with gestures focusing on action information and indefinite references with gestures focusing on entity information. The findings suggest that speakers use speech and gesture together to design utterances appropriate for speakers with whom they share common ground.

Abstract

Pointing gestures are recognised to be a primary manifestation of human social cognition and communicative capacity. The goal of this task is to collect empirical descriptions of pointing practices in different cultural settings.

Abstract

Although generally studied in isolation, language and action often co-occur in everyday life. Here we investigated one particular form of simultaneous language and action, namely speech and gestures that speakers use in everyday communication. In a functional magnetic resonance imaging study, we identified the neural networks involved in the integration of semantic information from speech and gestures. Verbal and/or gestural content could be integrated easily or less easily with the content of the preceding part of speech. Premotor areas involved in action observation (Brodmann area [BA] 6) were found to be specifically modulated by action information "mismatching" to a language context. Importantly, an increase in integration load of both verbal and gestural information into prior speech context activated Broca's area and adjacent cortex (BA 45/47). A classical language area, Broca's area, is not only recruited for language-internal processing but also when action observation is integrated with speech. These findings provide direct evidence that action and language processing share a high-level neural integration system.

Abstract

Does language comprehension depend, in part, on neural systems for action? In previous studies, motor areas of the brain were activated when people read or listened to action verbs, but it remains unclear whether such activation is functionally relevant for comprehension. In the experiments reported here, we used off-line theta-burst transcranial magnetic stimulation to investigate whether a causal relationship exists between activity in premotor cortex and action-language understanding. Right-handed participants completed a lexical decision task, in which they read verbs describing manual actions typically performed with the dominant hand (e.g., “to throw,” “to write”) and verbs describing nonmanual actions (e.g., “to earn,” “to wander”). Responses to manual-action verbs (but not to nonmanual-action verbs) were faster after stimulation of the hand area in left premotor cortex than after stimulation of the hand area in right premotor cortex. These results suggest that premotor cortex has a functional role in action-language understanding.

Abstract

We investigated how visual and linguistic information interact in the perception of emotion. We borrowed a phenomenon from film theory which states that presentation of an as such neutral visual scene intensifies the percept of fear or suspense induced by a different channel of information, such as language. Our main aim was to investigate how neutral visual scenes can enhance responses to fearful language content in parts of the brain involved in the perception of emotion. Healthy participants’ brain activity was measured (using functional magnetic resonance imaging) while they read fearful and less fearful sentences presented with or without a neutral visual scene. The main idea is that the visual scenes intensify the fearful content of the language by subtly implying and concretizing what is described in the sentence. Activation levels in the right anterior temporal pole were selectively increased when a neutral visual scene was paired with a fearful sentence, compared to reading the sentence alone, as well as to reading of non-fearful sentences presented with the same neutral scene. We conclude that the right anterior temporal pole serves a binding function of emotional information across domains such as visual and linguistic information.

Abstract

A debated issue in the relationship between language and thought is how our linguistic abilities are involved in understanding the intentions of others (‘mentalizing’). The results of both theoretical and empirical work have been used to argue that linguistic, and more specifically, grammatical, abilities are crucial in representing the mental states of others. Here we contribute to this debate by investigating how damage to the language system influences the generation and understanding of intentional communicative behaviors. Four patients with pervasive language difficulties (severe global or agrammatic aphasia) engaged in an experimentally controlled non-verbal communication paradigm, which required signaling and understanding a communicative message. Despite their profound language problems they were able to engage in recipient design as well as intention recognition, showing similar indicators of mentalizing as have been observed in the neurologically healthy population. Our results show that aspects of the ability to communicate remain present even when core capacities of the language system are dysfunctional

Abstract

Co-speech gestures embody a form of manual action that is tightly coupled to the language system. As such, the co-occurrence of speech and co-speech gestures is an excellent example of the interplay between language and action. There are, however, other ways in which language and action can be thought of as closely related. In this paper we will give an overview of studies in cognitive neuroscience that examine the neural underpinnings of links between language and action. Topics include neurocognitive studies of motor representations of speech sounds, action-related language, sign language and co-speech gestures. It will be concluded that there is strong evidence on the interaction between speech and gestures in the brain. This interaction however shares general properties with other domains in which there is interplay between language and action.

Abstract

Do people use sensori-motor cortices to understand language? Here we review neurocognitive studies of language comprehension in healthy adults and evaluate their possible contributions to theories of language in the brain. We start by sketching the minimal predictions that an embodied theory of language understanding makes for empirical research, and then survey studies that have been offered as evidence for embodied semantic representations. We explore four debated issues: first, does activation of sensori-motor cortices during action language understanding imply that action semantics relies on mirror neurons? Second, what is the evidence that activity in sensori-motor cortices plays a functional role in understanding language? Third, to what extent do responses in perceptual and motor areas depend on the linguistic and extra-linguistic context? And finally, can embodied theories accommodate language about abstract concepts? Based on the available evidence, we conclude that sensori-motor cortices are activated during a variety of language comprehension tasks, for both concrete and abstract language. Yet, this activity depends on the context in which perception and action words are encountered. Although modality-specific cortical activity is not a sine qua non of language processing even for language about perception and action, sensori-motor regions of the brain appear to make functional contributions to the construction of meaning, and should therefore be incorporated into models of the neurocognitive architecture of language.

Abstract

Marr and Poggio’s levels of description are one of the most well-known theoretical constructs of twentieth century cognitive science. It entails that behavior can and should be considered at three different levels: computation, algorithm, and implementation. In this contribution focus is on the computational level of description, the level that describes the “why” of cognition. I argue that the computational level should be taken as a starting point in devising experiments in cognitive (neuro)science. Instead, the starting point in empirical practice often is a focus on the stimulus or on some capacity of the cognitive system. The “why” of cognition tends to be ignored when designing research, and is not considered in subsequent inference from experimental results. The overall aim of this manuscript is to show how re-appreciation of the computational level of description as a starting point for experiments can lead to more informative experimentation.

Abstract

Background

The biological mechanisms of headache chronification are poorly understood. We aimed to identify changes in DNA methylation associated with the transformation from episodic to chronic headache.
Methods

Participants were recruited from the population-based Norwegian HUNT Study. Thirty-six female headache patients who transformed from episodic to chronic headache between baseline and follow-up 11 years later were matched against 35 controls with episodic headache. DNA methylation was quantified at 485,000 CpG sites, and changes in methylation level at these sites were compared between cases and controls by linear regression analysis. Data were analyzed in two stages (Stages 1 and 2) and in a combined meta-analysis.
Results

None of the top 20 CpG sites identified in Stage 1 replicated in Stage 2 after multiple testing correction. In the combined meta-analysis the strongest associated CpG sites were related to SH2D5 and NPTX2, two brain-expressed genes involved in the regulation of synaptic plasticity. Functional enrichment analysis pointed to processes including calcium ion binding and estrogen receptor pathways.
Conclusion

In this first genome-wide study of DNA methylation in headache chronification several potentially implicated loci and processes were identified. The study exemplifies the use of prospectively collected population cohorts to search for epigenetic mechanisms of disease

Abstract

Researchers have suggested that the vocabularies of languages are oriented towards the communicative needs of language users. Here, we provide evidence demonstrating that the higher frequency of visual words in a large variety of English corpora is reflected in greater lexical differentiation—a greater number of unique words—for the visual domain in the English lexicon. In comparison, sensory modalities that are less frequently talked about, particularly taste and smell, show less lexical differentiation. In addition, we show that even though sensory language can be expected to change across historical time and between contexts of use (e.g., spoken language versus fiction), the pattern of visual dominance is a stable property of the English language. Thus, we show that across the board, precisely those semantic domains that are more frequently talked about are also more lexically differentiated, for perceptual experiences. This correlation between type and token frequencies suggests that the sensory lexicon of English is geared towards communicative efficiency.

Abstract

Understanding speech usually seems easy, but it can become noticeably harder when the speaker has a foreign accent. This is because foreign accents add considerable variation to speech. Research on foreign-accented speech shows that participants are able to adapt quickly to this type of variation. Less is known, however, about longer-term maintenance of adaptation. The current study focused on long-term adaptation by exposing native listeners to foreign-accented speech on Day 1, and testing them on comprehension of the accent one day later. Comprehension was thus not tested immediately, but only after a 24 hour period. On Day 1, native Dutch listeners listened to the speech of a Hebrew learner of Dutch while performing a phoneme monitoring task that did not depend on the talker’s accent. In particular, shortening of the long vowel /i/ into /ɪ/ (e.g., lief [li:f], ‘sweet’, pronounced as [lɪf]) was examined. These mispronunciations did not create lexical ambiguities in Dutch. On Day 2, listeners participated in a cross-modal priming task to test their comprehension of the accent. The results will be contrasted with results from an experiment without delayed testing and related to accounts of how listeners maintain adaptation to foreign-accented speech.

Abstract

Foreign-accented speech is often perceived as more difficult to understand than native speech. What causes this potential difficulty, however, remains unknown. In the present study, we compared acoustic similarity and accent ratings of American-accented Dutch with a cross-modal priming task designed to measure online speech processing. We focused on two Dutch diphthongs: ui and ij. Though both diphthongs deviated from standard Dutch to varying degrees and perceptually varied in accent strength, native Dutch listeners recognized words containing the diphthongs easily. Thus, not all foreign-accented speech hinders comprehension, and acoustic similarity and perceived accentedness are not always predictive of processing difficulties.

Abstract

Utilization of computer tools in linguistic research has gained importance with the maturation of media frameworks for the handling of digital audio and video. The increased use of these tools in gesture, sign language and multimodal interaction studies has led to stronger requirements on the flexibility, the efficiency and in particular the time accuracy of annotation tools. This paper describes the efforts made to make ELAN a tool that meets these requirements, with special attention to the developments in the area of time accuracy. In subsequent sections an overview will be given of other enhancements in the latest versions of ELAN, that make it a useful tool in multimodality research.

Abstract

A number of serious reasons will convince an increasing amount of researchers to store their relevant material in centers which we will call "language resource archives". They combine the duty of taking care of long-term preservation as well as the task to give access to their material to different user groups. Access here is meant in the sense that an active interaction with the data will be made possible to support the integration of new data, new versions or commentaries of all sort. Modern Language Resource Archives will have to adhere to a number of basic principles to fulfill all requirements and they will have to be involved in federations to create joint language resource domains making it even more simple for the researchers to access the data. This paper makes an attempt to formulate the essential pillars language resource archives have to adhere to.

Abstract

Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions.

Abstract

Spinocerebellar ataxia type 14 (SCA14) is a subtype of the autosomal dominant cerebellar ataxias that is characterized by slowly progressive cerebellar dysfunction and neurodegeneration. SCA14 is caused by mutations in the PRKCG gene, encoding protein kinase C gamma (PKCγ). Despite the identification of 40 distinct disease-causing mutations in PRKCG, the pathological mechanisms underlying SCA14 remain poorly understood. Here we report the molecular neuropathology of SCA14 in post-mortem cerebellum and in human patient-derived induced pluripotent stem cells (iPSCs) carrying two distinct SCA14 mutations in the C1 domain of PKCγ, H36R and H101Q. We show that endogenous expression of these mutations results in the cytoplasmic mislocalization and aggregation of PKCγ in both patient iPSCs and cerebellum. PKCγ aggregates were not efficiently targeted for degradation. Moreover, mutant PKCγ was found to be hyper-activated, resulting in increased substrate phosphorylation. Together, our findings demonstrate that a combination of both, loss-of-function and gain-of-function mechanisms are likely to underlie the pathogenesis of SCA14, caused by mutations in the C1 domain of PKCγ. Importantly, SCA14 patient iPSCs were found to accurately recapitulate pathological features observed in post-mortem SCA14 cerebellum, underscoring their potential as relevant disease models and their promise as future drug discovery tools.

Abstract

This auditory lexical decision study shows that cohort entropies, conditional root uniqueness points, and morphological family size all contribute to the dynamics of the auditory comprehension of prefixed words. Three entropy measures calculated for different positions in the stem of Dutch prefixed words revealed facilitation for higher entropies, except at the point of disambiguation, where we observed inhibition. Morphological family size was also facilitatory, but only for prefixed words in which the conditional root uniqueness point coincided with the conventional uniqueness point. For words with early conditional disambiguation, in contrast, only the morphologically related words that were onset-aligned with the target word facilitated lexical decision.

Abstract

Electroencephalography (EEG) provides high temporal resolution cognitive information from non-invasive recordings. However, one of the common practices-using a subset of sensors in ERP analysis is hard to provide a holistic and precise dynamic results. Selecting or grouping subsets of sensors may also be subject to selection bias, multiple comparison, and further complicated by individual differences in the group-level analysis. More importantly, changes in neural generators and variations in response magnitude from the same neural sources are difficult to separate, which limit the capacity of testing different aspects of cognitive hypotheses. We introduce EasyEEG, a toolbox that includes several multivariate analysis methods to directly test cognitive hypotheses based on topographic responses that include data from all sensors. These multivariate methods can investigate effects in the dimensions of response magnitude and topographic patterns separately using data in the sensor space, therefore enable assessing neural response dynamics. The concise workflow and the modular design provide user-friendly and programmer-friendly features. Users of all levels can benefit from the open-sourced, free EasyEEG to obtain a straightforward solution for efficient processing of EEG data and a complete pipeline from raw data to final results for publication.

Abstract

The three Olutec stories from Oluta, Veracruz, werenarrated by Antonio Asistente Maldonado. Roberto Zavala presents amorpheme-by-morpheme analysis of the texts with a sketch of the majorgrammatical and typological features of this language. Olutec is spoken bythree dozen speakers. The grammatical structure of this language has not beendescribed before. The sketch contains information on verb and noun morphology,verb dasses, clause types, inverse/direct patterns, grammaticalizationprocesses, applicatives, incorporation, word order type, and discontinuousexpressions. The stories presented here are the first Olutec texts everpublished. The motifs of the stories are well known throughout Middle America.The story of "the Rabbit who wants to be big" explains why one of the mainprotagonists of Middle American folktales acquired long ears. The story of "theDevil who is inebriated by the people of a village" explains how theinhabitants of a village discover the true identity of a man who likes to dancehuapango and decide to get rid of him. Finally the story of "theshit-sellers" presents two compadres, one who is lazy and the otherone who works hard. The hard-worker asks the lazy compadre how he surviveswithout working. The latter lies to to him that he sells shit in theneighboring village. The hard-working compadre decides to become a shit-sellerand in the process realizes that the lazy compadre deceived him. However, he islucky and meets with the Devil who offers him money in compensation for havingbeen deceived. When the lazy compadre realizes that the hard-working compadrehas become rich, he tries to do the same business but gets beaten in theprocess.

Abstract

Although sign language-using communities exist in all areas of the world, few sign languages have been documented in detail. Sign languages occur in a variety of sociocultural contexts, ranging from sign languages used in closed village communities to officially recognized national sign languages. They may be grouped into language families on historical grounds or may participate in various language contact situations. Systematic cross-linguistic comparison reveals both significant structural similarities and important typological differences between sign languages. Focusing on information from non-Western countries, this article provides an overview of the sign languages of the world.

Abstract

Indo-Pakistani Sign Language (IPSL) is the sign language used by deaf communities in a large region across India and Pakistan. This visual-gestural language has a dedicated construction for specifically expressing reciprocal relationships, which can be applied to agreement verbs and to auxiliaries. The reciprocal construction relies on a change in the movement pattern of the signs it applies to. In addition, IPSL has a number of other strategies which can have a reciprocal interpretation, and the IPSL lexicon includes a good number of inherently reciprocal signs. All reciprocal expressions can be modified in complex ways that rely on the grammatical use of the sign space. Considering grammaticalisation and lexicalisation processes linking some of these constructions is also important for a better understanding of reciprocity in IPSL.

Abstract

Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. To investigate how bilinguals monitor their speech errors and control their languages in use, we recorded event-related potentials (ERPs) in unbalanced Dutch-English bilingual speakers in a cued language-switching task. We tested the conflict-based monitoring model of Nozari and colleagues by investigating the error-related negativity (ERN) and comparing the effects of the two switching directions (i.e., to the first language, L1 vs. to the second language, L2). Results show that the speakers made more language selection errors when switching from their L2 to the L1 than vice versa. In the EEG, we observed a robust ERN effect following language selection errors compared to correct responses, reflecting monitoring of speech errors. Most interestingly, the ERN effect was enlarged when the speakers were switching to their L2 (less conflict) compared to switching to the L1 (more conflict). Our findings do not support the conflict-based monitoring model. We discuss an alternative account in terms of error prediction and reinforcement learning.

Abstract

Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. We examined the relative contribution of top-down cognitive control and bottom-up language priming to these errors. Unbalanced Dutch-English bilinguals named pictures and were cued to switch between languages under time pressure. We also manipulated the number of same-language trials before a switch (long vs. short runs). Results show that speakers made more language selection errors when switching from their second language (L2) to the first language (L1) than vice versa. Furthermore, they made more errors when switching to the L1 after a short compared to a long run of L2 trials. In the reverse switching direction (L1 to L2), run length had no effect. These findings are most compatible with an account of language selection errors that assigns a strong role to top-down processes of cognitive control.

Abstract

Genome-wide association studies using thousands to hundreds of thousands of single nucleotide polymorphism (SNP) markers and region-wide association studies using a dense panel of SNPs are already in use to identify disease susceptibility genes and to predict disease risk in individuals. Because these tasks become increasingly important, three different data sets were provided for the Genetic Analysis Workshop 15, thus allowing examination of various novel and existing data mining methods for both classification and identification of disease susceptibility genes, gene by gene or gene by environment interaction. The approach most often applied in this presentation group was random forests because of its simplicity, elegance, and robustness. It was used for prediction and for screening for interesting SNPs in a first step. The logistic tree with unbiased selection approach appeared to be an interesting alternative to efficiently select interesting SNPs. Machine learning, specifically ensemble methods, might be useful as pre-screening tools for large-scale association studies because they can be less prone to overfitting, can be less computer processor time intensive, can easily include pair-wise and higher-order interactions compared with standard statistical approaches and can also have a high capability for classification. However, improved implementations that are able to deal with hundreds of thousands of SNPs at a time are required.

Abstract

It is undisputed that presenting a rhythmic stimulus leads to a measurable brain response that follows the rhythmic structure of this stimulus. What is still debated, however, is the question whether this brain response exclusively reflects a regular repetition of evoked responses, or whether it also includes entrained oscillatory activity. Here we systematically present evidence in favor of an involvement of entrained neural oscillations in the processing of rhythmic input while critically pointing out which questions still need to be addressed before this evidence could be considered conclusive. In this context, we also explicitly discuss the potential functional role of such entrained oscillations, suggesting that these stimulus-aligned oscillations reflect, and serve as, predictive processes, an idea often only implicitly assumed in the literature.

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Review: User friendliness of the first dictionary of Sign Language of the Netherlands can be improved

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(Needed: staff for residential care home with good eye-hand coordination. Measuring NGT-skills.)

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(The Corpus NGT and the daily practice of language teaching)

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(The Corpus NGT and teacher NGT/interpreter NGT training)