Publications

Abstract

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

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

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

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

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

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

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

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

Abstract

Research suggests that during conversation, interlocutors coordinate their utterances by predicting the speaker’s forthcoming utterance and its end. In two experiments, we used a button-pressing task, in which participants pressed a button when they thought a speaker reached the end of their utterance, to investigate what role the wider discourse plays in turn-end prediction. Participants heard two-utterance sequences, in which the content of the second utterance was or was not constrained by the content of the first. In both experiments, participants responded earlier, but not more precisely, when the first utterance was constraining rather than unconstraining. Response times and precision were unaffected by whether they listened to dialogues or monologues (Experiment 1) and by whether they read the first utterance out loud or silently (Experiment 2), providing no indication that activation of production mechanisms facilitates prediction. We suggest that content predictions aid comprehension but not turn-end prediction.

Abstract

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

Abstract

Past events like fluctuations in population size and post-glacial colonization processes may influence the relative importance of genetic drift, migration and selection when determining the present day patterns of genetic variation. We disentangle how drift, selection and migration shape neutral and adaptive genetic variation in 12 moor frog populations along a 1700 km latitudinal gradient. We studied genetic differentiation and variation at a MHC exon II locus and a set of 18 microsatellites.
Results

Using outlier analyses, we identified the MHC II exon 2 (corresponding to the β-2 domain) locus and one microsatellite locus (RCO8640) to be subject to diversifying selection, while five microsatellite loci showed signals of stabilizing selection among populations. STRUCTURE and DAPC analyses on the neutral microsatellites assigned populations to a northern and a southern cluster, reflecting two different post-glacial colonization routes found in previous studies. Genetic variation overall was lower in the northern cluster. The signature of selection on MHC exon II was weaker in the northern cluster, possibly as a consequence of smaller and more fragmented populations.
Conclusion

Our results show that historical demographic processes combined with selection and drift have led to a complex pattern of differentiation along the gradient where some loci are more divergent among populations than predicted from drift expectations due to diversifying selection, while other loci are more uniform among populations due to stabilizing selection. Importantly, both overall and MHC genetic variation are lower at northern latitudes. Due to lower evolutionary potential, the low genetic variation in northern populations may increase the risk of extinction when confronted with emerging pathogens and climate change.

Abstract

The issue addressed in this study is whether propositional integration and world-knowledge inference can be distinguished as separate processes during the comprehension of Dutch omdat (because) sentences. “Propositional integration” refers to the process by which the reader establishes the type of relation between two clauses or sentences. “World-knowledge inference” refers to the process of deriving the general causal relation and checking it against the reader's world knowledge. An eye-tracking experiment showed that the presence of the conjunction speeds up the processing of the words immediately following the conjunction, and slows down the processing of the sentence final words in comparison to the absence of the conjunction. A second, subject-paced reading experiment replicated the reading time findings, and the results of a verification task confirmed that the effect at the end of the sentence was due to inferential processing. The findings evidence integrative processing and inferential processing, respectively.

Abstract

Several theoretical accounts have been proposed with respect to the issue how quickly the implicit causality verb bias affects the understanding of sentences such as “John beat Pete at the tennis match, because he had played very well”. They can be considered as instances of two viewpoints: the focusing and the integration account. The focusing account claims that the bias should be manifest soon after the verb has been processed, whereas the integration account claims that the interpretation is deferred until disambiguating information is encountered. Up to now, this issue has remained unresolved because materials or methods have failed to address it conclusively. We conducted two experiments that exploited the visual world paradigm and ambiguous pronouns in subordinate because clauses. The first experiment presented implicit causality sentences with the task to resolve the ambiguous pronoun. To exclude strategic processing, in the second experiment, the task was to answer simple comprehension questions and only a minority of the sentences contained implicit causality verbs. In both experiments, the implicit causality of the verb had an effect before the disambiguating information was available. This result supported the focusing account.

Abstract

In this study we test the hypothesis that symbolic play represents a fertile context for language acquisition because its inherent ambiguity elicits communicative behaviours that positively influence development. Infant-caregiver dyads (N = 54) participated in two 20-minute play sessions six months apart (Time 1 = 18 months, Time 2 = 24 months). During each session the dyads played with two sets of toys that elicited either symbolic or functional play. The sessions were transcribed and coded for several features of dyadic interaction and speech; infants’ linguistic proficiency was measured via parental report. The two play contexts resulted in different communicative and linguistic behaviour. Notably, the symbolic play condition resulted in significantly greater conversational turn-taking than functional play, and also resulted in the greater use of questions and mimetics in infant-directed speech (IDS). In contrast, caregivers used more imperative clauses in functional play. Regression analyses showed that unique properties of symbolic play (i.e., turn-taking, yes-no questions, mimetics) positively predicted children’s language proficiency, whereas unique features of functional play (i.e., imperatives in IDS) negatively predicted proficiency. The results provide evidence in support of the hypothesis that symbolic play is a fertile context for language development, driven by the need to negotiate meaning.

Abstract

Recent constituent priming experiments show that Dutch and German prefixed verbs prime their stem, regardless of semantic transparency (e.g. Smolka et al. [(2014). ‘Verstehen’ (‘understand’) primes ‘stehen’ (‘stand’): Morphological structure overrides semantic compositionality in the lexical representation of German complex verbs. Journal of Memory and Language, 72, 16–36. https://doi.org/10.1016/j.jml.2013.12.002]). We examine whether the processing of opaque verbs (e.g. herhalen “repeat”) involves the retrieval of only the whole-word meaning, or whether the lexical-semantic meaning of the stem (halen as “take/get”) is retrieved as well. We report the results of an auditory semantic priming experiment with Dutch prefixed verbs, testing whether the recognition of a semantic associate to the stem (BRENGEN “bring”) is facilitated by the presentation of an opaque prefixed verb. In contrast to prior visual studies, significant facilitation after semantically opaque primes is found, which suggests that the lexical-semantic meaning of stems in opaque words is retrieved. We examine the implications that these findings have for auditory word recognition, and for the way in which different types of meanings are represented and processed.

Abstract

In the previous decade, dozens of studies involving thousands of children across several research disciplines have made use of a combined daylong audio-recorder and automated algorithmic analysis called the LENAⓇ system, which aims to assess children’s language environment. While the system’s prevalence in the language acquisition domain is steadily growing, there are only scattered validation efforts on only some of its key characteristics. Here, we assess the LENAⓇ system’s accuracy across all of its key measures: speaker classification, Child Vocalization Counts (CVC), Conversational Turn Counts (CTC), and Adult Word Counts (AWC). Our assessment is based on manual annotation of clips that have been randomly or periodically sampled out of daylong recordings, collected from (a) populations similar to the system’s original training data (North American English-learning children aged 3-36 months), (b) children learning another dialect of English (UK), and (c) slightly older children growing up in a different linguistic and socio-cultural setting (Tsimane’ learners in rural Bolivia). We find reasonably high accuracy in some measures (AWC, CVC), with more problematic levels of performance in others (CTC, precision of male adults and other children). Statistical analyses do not support the view that performance is worse for children who are dissimilar from the LENAⓇ original training set. Whether LENAⓇ results are accurate enough for a given research, educational, or clinical application depends largely on the specifics at hand. We therefore conclude with a set of recommendations to help researchers make this determination for their goals.

Abstract

A current theoretical view proposes that infants converge on the speech categories of their native language by attending to frequency distributions that occur in the acoustic input. To date, the only empirical support for this statistical learning hypothesis comes from studies where a single, salient dimension was manipulated. Additional evidence is sought here, by introducing a less salient pair of categories supported by multiple cues. We exposed English-learning infants to a multi-cue bidimensional grid ranging between retroflex and alveolopalatal sibilants in prevocalic position. This contrast is substantially more difficult according to previous cross-linguistic and perceptual research, and its perception is driven by cues in both the consonantal and the following vowel portions. Infants heard one of two distributions (flat, or with two peaks), and were tested with sounds varying along only one dimension. Infants' responses differed depending on the familiarization distribution, and their performance was equally good for the vocalic and the frication dimension, lending some support to the statistical hypothesis even in this harder learning situation. However, learning was restricted to the retroflex category, and a control experiment showed that lack of learning for the alveolopalatal category was not due to the presence of a competing category. Thus, these results contribute fundamental evidence on the extent and limitations of the statistical hypothesis as an explanation for infants' perceptual tuning.

Abstract

Within the debate on the mechanisms underlying infants’ perceptual acquisition, one hypothesis proposes that infants’ perception is directly affected by the acoustic implementation of sound categories in the speech they hear. In consonance with this view, the present study shows that individual variation in fine-grained, subphonemic aspects of the acoustic realization of /s/ in caregivers’ speech predicts infants’ discrimination of this sound from the highly similar /∫/, suggesting that learning based on acoustic cue distributions may indeed drive natural phonological acquisition.

Abstract

Adults' phonotactic learning is affected by perceptual biases. One such bias concerns learning of constraints affecting groups of sounds: all else being equal, learning constraints affecting a natural class (a set of sounds sharing some phonetic characteristic) is easier than learning a constraint affecting an arbitrary set of sounds. This perceptual bias could be a given, for example, the result of innately guided learning; alternatively, it could be due to human learners’ experience with sounds. Using artificial grammars, we investigated whether such a bias arises in development, or whether it is present as soon as infants can learn phonotactics. Seven-month-old English-learning infants fail to generalize a phonotactic pattern involving fricatives and nasals, which does not form a coherent phonetic group, but succeed with the natural class of oral and nasal stops. In this paper, we report an experiment that explored whether those results also follow in a cohort of 4-month-olds. Unlike the older infants, 4-month-olds were able to generalize both groups, suggesting that the perceptual bias that makes phonotactic constraints on natural classes easier to learn is likely the effect of experience.

Abstract

Features serve two main functions in the phonology of languages: they encode the distinction between pairs of contrastive phonemes (distinctive function); and they delimit sets of sounds that participate in phonological processes and patterns (classificatory function). We summarize evidence from a variety of experimental paradigms bearing on the functional relevance of phonological features. This research shows that while young infants may use abstract phonological features to learn sound patterns, this ability becomes more constrained with development and experience. Furthermore, given the lack of overlap between the ability to learn a pair of words differing in a single feature and the ability to learn sound patterns based on features, we argue for the separation of the distinctive and the classificatory function.

Abstract

When we imagine objects or events, we often engage in multisensory mental imagery. Yet, investigations of mental imagery have typically focused on only one sensory modality — vision. One reason for this is that the most common tool for the measurement of imagery, the questionnaire, has been restricted to unimodal ratings of the object. We present a new mental imagery questionnaire that measures multisensory imagery. Specifically, the newly developed Vividness of Wine Imagery Questionnaire (VWIQ) measures mental imagery of wine in the visual, olfactory, and gustatory modalities. Wine is an ideal domain to explore multisensory imagery because wine drinking is a multisensory experience, it involves the neglected chemical senses (smell and taste), and provides the opportunity to explore the effect of experience and expertise on imagery (from wine novices to experts). The VWIQ questionnaire showed high internal consistency and reliability, and correlated with other validated measures of imagery. Overall, the VWIQ may serve as a useful tool to explore mental imagery for researchers, as well as individuals in the wine industry during sommelier training and evaluation of wine professionals.

Abstract

The mother-offspring bond is one of the strongest and most essential social bonds. Following is a detailed behavioral report of a female chimpanzee two days after her 16-month-old infant died, on the first day that the mother is observed to create distance between her and the corpse. A series of repeated approaches and retreats to and from the body are documented, along with detailed accounts of behaviors directed toward the dead infant by the mother and other group members. The behavior of the mother toward her dead infant not only highlights the maternal contribution to the mother-infant relationship but also elucidates the opportunities chimpanzees have to learn about the sensory cues associated with death, and the implications of death for the social environment.

Abstract

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10−8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.

Abstract

We report associations between vowel sounds, graphemes, and colours collected online from over 1000 Dutch speakers. We provide open materials including a Python implementation of the structure measure, and code for a single page web application to run simple cross-modal tasks. We also provide a full dataset of colour-vowel associations from 1164 participants, including over 200 synaesthetes identified using consistency measures. Our analysis reveals salient patterns in cross-modal associations, and introduces a novel measure of isomorphism in cross-modal mappings. We find that while acoustic features of vowels significantly predict certain mappings (replicating prior work), both vowel phoneme category and grapheme category are even better predictors of colour choice. Phoneme category is the best predictor of colour choice overall, pointing to the importance of phonological representations in addition to acoustic cues. Generally, high/front vowels are lighter, more green, and more yellow than low/back vowels. Synaesthetes respond more strongly on some dimensions, choosing lighter and more yellow colours for high and mid front vowels than non-synaesthetes. We also present a novel measure of cross-modal mappings adapted from ecology, which uses a simulated distribution of mappings to measure the extent to which participants' actual mappings are structured isomorphically across modalities. Synaesthetes have mappings that tend to be more structured than non-synaesthetes, and more consistent colour choices across trials correlate with higher structure scores. Nevertheless, the large majority (~70%) of participants produce structured mappings, indicating that the capacity to make isomorphically structured mappings across distinct modalities is shared to a large extent, even if the exact nature of mappings varies across individuals. Overall, this novel structure measure suggests a distribution of structured cross-modal association in the population, with synaesthetes on one extreme and participants with unstructured associations on the other.

Abstract

Language-specific differences in the size and distribution of the phonemic repertoire can have implications for the task facing listeners in recognising spoken words. A language with more phonemes will allow shorter words and reduced embedding of short words within longer ones, decreasing the potential for spurious lexical competitors to be activated by speech signals. We demonstrate that this is the case via comparative analyses of the vocabularies of English and Spanish. A language which uses suprasegmental as well as segmental contrasts, however, can substantially reduce the extent of spurious embedding.

Abstract

Native American English and non-native(Dutch)listeners identified either the consonant or the vowel in all possible American English CV and VC syllables. The syllables were embedded in multispeaker babble at three signal-to-noise ratios(0, 8, and 16 dB). The phoneme identification
performance of the non-native listeners was less accurate than that of the native listeners. All listeners were adversely affected by noise. With these isolated syllables, initial segments were harder to identify than final segments. Crucially, the effects of language background and noise did not interact; the performance asymmetry between the native and non-native groups was not significantly different across signal-to-noise ratios. It is concluded that the frequently reported disproportionate difficulty of non-native listening under disadvantageous conditions is not due to a disproportionate increase in phoneme misidentifications.

Abstract

The retiring academic may look back upon, inter alia, years of conference attendance. Speech error researchers are uniquely fortunate because they can collect data in any situation involving communication; accordingly, the retiring speech error researcher will have collected data at those conferences. We here address the issue of whether error data collected in situations involving conviviality (such as at conferences) is representative of error data in general. Our approach involved a comparison, across three levels of linguistic processing, between a specially constructed Conviviality Sample and the largest existing source of speech error data, the newly available Fromkin Speech Error Database. The results indicate that there are grounds for regarding the data in the Conviviality Sample as a better than average reflection of the true population of all errors committed. These findings encourage us to recommend further data collection in collaboration with like-minded colleagues.

Abstract

Part of the remarkable efficiency of listening is
accommodation to unfamiliar talkers’ specific
pronunciations by retuning of phonemic intercategory
boundaries. Such retuning occurs in second
(L2) as well as first language (L1); however, recent
research with emigrés revealed successful adaptation
in the environmental L2 but, unprecedentedly, not in
L1 despite continuing L1 use. A possible explanation
involving relative exposure to novel talkers is here
tested in heritage language users with Mandarin as
family L1 and English as environmental language. In
English, exposure to an ambiguous sound in
disambiguating word contexts prompted the expected
adjustment of phonemic boundaries in subsequent
categorisation. However, no adjustment occurred in
Mandarin, again despite regular use. Participants
reported highly asymmetric interlocutor counts in the
two languages. We conclude that successful retuning
ability requires regular exposure to novel talkers in
the language in question, a criterion not met for the
emigrés’ or for these heritage users’ L1.

Abstract

The lexicon, considered as a component of the process of recognizing speech, is a device that accepts a sound image as input and outputs meaning. Lexical access is the process of formulating an appropriate input and mapping it onto an entry in the lexicon's store of sound images matched with their meanings. This chapter addresses the problems of auditory lexical access from continuous speech. The central argument to be proposed is that utterance prosody plays a crucial role in the access process. Continuous listening faces problems that are not present in visual recognition (reading) or in noncontinuous recognition (understanding isolated words). Aspects of utterance prosody offer a solution to these particular problems.

Abstract

A distinction between strong and weak vowels can be drawn on the basis of vowel quality, of stress, or of both factors. An experiment was conducted in which sets of contextually matched word-intial vowels ranging from clearly strong to clearly weak were cross-spliced, and the naturalness of the resulting words was rated by listeners. The ratings showed that in general cross-spliced words were only significantly less acceptable than unspliced words when schwa was not involved; this supports a categorical distinction based on vowel quality.

Abstract

The perceptual processing of speech is a constant interplay of multiple competing albeit convergent processes: acoustic input vs. higher-level representations, universal mechanisms vs. language-specific, veridical traces of speech experience vs. construction and activation of abstract representations. The present summary concerns the third of these issues. The ability to generalise across experience and to deal with resulting abstractions is the hallmark of human cognition, visible even in early infancy. In speech processing, abstract representations play a necessary role in both production and perception. New sorts of evidence are now informing our understanding of the breadth of this role.

Abstract

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

Abstract

In English and Dutch, listeners entrain to prosodic contours to predict where focus will fall in an utterance. However, is this strategy universally available, even in languages with different phonological systems? In a phoneme detection experiment, we examined whether prosodic entrainment is also found in Mandarin Chinese, a tone language, where in principle the use of pitch for lexical identity may take precedence over the use of pitch cues to salience. Consistent with the results from Germanic languages, response times were facilitated when preceding intonation predicted accent on the target-bearing word. Acoustic analyses revealed greater F0 range in the preceding intonation of the predicted-accent sentences. These findings have implications for how universal and language-specific mechanisms interact in the processing of salience.

Abstract

Listeners process spoken language in ways which are adapted to the phonological structure of their native language. As a consequence, non-native speakers do not listen to a language in the same way as native speakers; moreover, listeners may use their native language listening procedures inappropriately with foreign input. With sufficient experience, however, it may be possible to inhibit this latter (counter-productive) behavior.

Abstract

Listeners performed speeded two-alternative choice between two unfamiliar and relatively similar voices or between two phonetically close segments, in VC syllables. For each decision type (segment, voice), the non-target dimension (voice, segment) either was constant, or varied across four alternatives. Responses were always slower when a non-target dimension varied than when it did not, but the effect of phonetic variation on voice identity decision was stronger than that of voice variation on phonetic identity decision. Cues to voice and segment identity in speech are processed inter-dependently, but hard categorization decisions about voices draw on, and are hence sensitive to, segmental information.

Abstract

The recent claim by Black and Byng (1986) that lexical access in reading is subject to prosodic constraints is examined and found to be unsupported. The evidence from impaired reading which Black and Byng report is based on poorly controlled stimulus materials and is inadequately analysed and reported. An alternative explanation of their findings is proposed, and new data are reported for which this alternative explanation can account but their model cannot. Finally, their proposal is shown to be theoretically unmotivated and in conflict with evidence from normal reading.

Abstract

The recognition of speech involves the segmentation of continuous utterances into their component words. Cross-linguistic evidence is briefly reviewed which suggests that although there are language-specific solutions to this segmentation problem, they have one thing in common: they are all based on language rhythm. In English, segmentation is stress-based: strong syllables are postulated to be the onsets of words. Segmentation, however, can also be achieved by a process of competition between activated lexical hypotheses, as in the Shortlist model. A series of experiments is summarised showing that segmentation of continuous speech depends on both lexical competition and a metrically-guided procedure. In the final section, the implementation of metrical segmentation in the Shortlist model is described: the activation of lexical hypotheses matching strong syllables in the input is boosted and that of hypotheses mismatching strong syllables in the input is penalised.

Abstract

Japanese listeners detect speech sound targets which correspond precisely to a mora (a phonological unit which is the unit of rhythm in Japanese) more easily than targets which do not. English listeners detect medial vowel targets more slowly than consonants. Six phoneme detection experiments investigated these effects in both subject populations, presented with native- and foreign-language input. Japanese listeners produced faster and more accurate responses to moraic than to nonmoraic targets both in Japanese and, where possible, in English; English listeners responded differently. The detection disadvantage for medial vowels appeared with English listeners both in English and in Japanese; again, Japanese listeners responded differently. Some processing operations which listeners apply to speech input are language-specific; these language-specific procedures, appropriate for listening to input in the native language, may be applied to foreign-language input irrespective of whether they remain appropriate.

Abstract

English and French listeners performed two tasks - click location and speeded click detection - with both English and French sentences, closely matched for syntactic and phonological structure. Clicks were located more accurately in open- than in closed-class words in both English and French; they were detected more rapidly in open- than in closed-class words in English, but not in French. The two listener groups produced the same pattern of responses, suggesting that higher-level linguistic processing was not involved in these tasks.

Abstract

One of a listener's major tasks in understanding continuous speech is segmenting the speech signal into separate words. When listening conditions are difficult, speakers can help listeners by deliberately speaking more clearly. In three experiments, we examined how word boundaries are produced in deliberately clear speech. We found that speakers do indeed attempt to mark word boundaries; moreover, they differentiate between word boundaries in a way which suggests they are sensitive to listener needs. Application of heuristic segmentation strategies makes word boundaries before strong syllables easiest for listeners to perceive; but under difficult listening conditions speakers pay more attention to marking word boundaries before weak syllables, i.e. they mark those boundaries which are otherwise particularly hard to perceive.

Abstract

Speakers and listeners have a shared goal: to communicate. The processes of speech perception and of speech production interact in many ways under the constraints of this communicative goal; such interaction is as characteristic of prosodic processing as of the processing of other aspects of linguistic structure. Two of the major uses of prosodic information in situations of communication are to encode salience and segmentation, and these themes unite the contributions to the symposium introduced by the present review.

Abstract

The performance of automatic speech recognition systems is usually assessed in terms of error rate. Human speech recognition produces few errors, but relative difficulty of processing can be assessed via response time techniques. We report the construction of a measure analogous to response time in a machine recognition system. This measure may be compared directly with human response times. We conducted a trial comparison of this type at the phoneme level, including both tense and lax vowels and a variety of consonant classes. The results suggested similarities between human and machine processing in the case of consonants, but differences in the case of vowels.

Abstract

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

Abstract

Word blends combine fragments from two words, either in speech errors or when a new word is created. Previous work has demonstrated that in Japanese, such blends preserve moraic structure; in English they do not. A similar effect of moraic structure is observed in perceptual research on segmentation of continuous speech in Japanese; English listeners, by contrast, exploit stress units in segmentation, suggesting that a general rhythmic constraint may underlie both findings. The present study examined whether mis parallel would also hold for word blends. In spontaneous English polysyllabic blends, the source words were significantly more likely to be split before a strong than before a weak (unstressed) syllable, i.e. to be split at a stress unit boundary. In an experiment in which listeners were asked to identify the source words of blends, significantly more correct detections resulted when splits had been made before strong syllables. Word blending, like speech segmentation, appears to be constrained by language rhythm.

Abstract

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

Abstract

In languages with variable stress placement, lexical stress patterns can convey information about word identity. The experiments reported here address the question of whether lexical stress information can be used in word recognition. The results allow the following conclusions: 1. Prior information as to the number of syllables and lexical stress patterns of words and nonwords does not facilitate lexical decision responses (Experiment 1). 2. The strong correspondences between grammatical category membership and stress pattern in bisyllabic English words (strong-weak stress being associated primarily with nouns, weak-strong with verbs) are not exploited in the recognition of isolated words (Experiment 2). 3. When a change in lexical stress also involves a change in vowel quality, i.e., a segmental as well as a suprasegmental alteration, effects on word recognition are greater when no segmental correlates of suprasegmental changes are involved (Experiments 2 and 3). 4. Despite the above finding, when all other factors are controlled, lexical stress information per se can indeed be shown to play a part in word-recognition process (Experiment 3).

Abstract

One of a listener's major tasks in understanding continuous speech is segmenting the speech signal into separate words. When listening conditions are difficult, speakers can help listeners by deliberately speaking more clearly. In four experiments, we examined how word boundaries are produced in deliberately clear speech. In an earlier report we showed that speakers do indeed mark word boundaries in clear speech, by pausing at the boundary and lengthening pre-boundary syllables; moreover, these effects are applied particularly to boundaries preceding weak syllables. In English, listeners use segmentation procedures which make word boundaries before strong syllables easier to perceive; thus marking word boundaries before weak syllables in clear speech will make clear precisely those boundaries which are otherwise hard to perceive. The present report presents supplementary data, namely prosodic analyses of the syllable following a critical word boundary. More lengthening and greater increases in intensity were applied in clear speech to weak syllables than to strong. Mean F0 was also increased to a greater extent on weak syllables than on strong. Pitch movement, however, increased to a greater extent on strong syllables than on weak. The effects were, however, very small in comparison to the durational effects we observed earlier for syllables preceding the boundary and for pauses at the boundary.

Abstract

In a 50,000-word corpus of spoken British English the occurrence of words embedded within other words is reported. Within-word embedding in this real speech sample is common, and analogous to the extent of embedding observed in the vocabulary. Imposition of a syllable boundary matching constraint reduces but by no means eliminates spurious embedding. Embedded words are most likely to overlap with the beginning of matrix words, and thus may pose serious problems for speech recognisers.

Abstract

This study evaluates whether early vocalizations develop in similar ways in children across diverse cultural contexts. We analyze data from daylong audio recordings of 49 children (1–36 months) from five different language/cultural backgrounds. Citizen scientists annotated these recordings to determine if child vocalizations contained canonical transitions or not (e.g., “ba” vs. “ee”). Results revealed that the proportion of clips reported to contain canonical transitions increased with age. Furthermore, this proportion exceeded 0.15 by around 7 months, replicating and extending previous findings on canonical vocalization development but using data from the natural environments of a culturally and linguistically diverse sample. This work explores how crowdsourcing can be used to annotate corpora, helping establish developmental milestones relevant to multiple languages and cultures. Lower inter‐annotator reliability on the crowdsourcing platform, relative to more traditional in‐lab expert annotators, means that a larger number of unique annotators and/or annotations are required, and that crowdsourcing may not be a suitable method for more fine‐grained annotation decisions. Audio clips used for this project are compiled into a large‐scale infant vocalization corpus that is available for other researchers to use in future work.

Abstract

The authors used 2 “visual-world” eye-tracking experiments to examine lexical access using Dutch constructions in which the verb did or did not place semantic constraints on its subsequent subject noun phrase. In Experiment 1, fixations to the picture of a cohort competitor (overlapping with the onset of the referent’s name, the subject) did not differ from fixations to a distractor in the constraining-verb condition. In Experiment 2, cross-splicing introduced phonetic information that temporarily biased the input toward the cohort competitor. Fixations to the cohort competitor temporarily increased in both the neutral and constraining conditions. These results favor models in which mapping from the input onto meaning is continuous over models in which contextual effects follow access of an initial form-based competitor set.

Abstract

Speech-in-speech perception can be challenging because the processing of competing acoustic and linguistic information leads to informational masking. Here, a method is proposed to isolate the linguistic component of informational masking while keeping the distractor's acoustic information unchanged. Participants performed a dichotic listening cocktail-party task before and after training on 4-band noise-vocoded sentences that became intelligible through the training. Distracting noise-vocoded speech interfered more with target speech comprehension after training (i.e., when intelligible) than before training (i.e., when unintelligible) at −3 dB SNR. These findings confirm that linguistic and acoustic information have distinct masking effects during speech-in‐speech comprehension

Abstract

The Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA) is a new tool for the systematic assessment of perceptual and sensorimotor timing skills. It spans a broad range of timing skills aimed at differentiating individual timing profiles. BAASTA consists of sensitive time perception and production tasks. Perceptual tasks include duration discrimination, anisochrony detection (with tones and music), and a version of the Beat Alignment Task. Perceptual thresholds for duration discrimination and anisochrony detection are estimated with a maximum likelihood procedure (MLP) algorithm. Production tasks use finger tapping and include unpaced and paced tapping (with tones and music), synchronization-continuation, and adaptive tapping to a sequence with a tempo change. BAASTA was tested in a proof-of-concept study with 20 non-musicians (Experiment 1). To validate the results of the MLP procedure, less widespread than standard staircase methods, three perceptual tasks of the battery (duration discrimination, anisochrony detection with tones, and with music) were further tested in a second group of non-musicians using 2 down / 1 up and 3 down / 1 up staircase paradigms (n = 24) (Experiment 2). The results show that the timing profiles provided by BAASTA allow to detect cases of timing/rhythm disorders. In addition, perceptual thresholds yielded by the MLP algorithm, although generally comparable to the results provided by standard staircase, tend to be slightly lower. In sum, BAASTA provides a comprehensive battery to test perceptual and sensorimotor timing skills, and to detect timing/rhythm deficits.

Abstract

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

Abstract

In the present article we provide evidence for the occurrence of transfer of conceptualization patterns in narratives of two German-Turkish bilingual groups. All bilingual participants grew up in Germany, but only one group is still resident in Germany (n = 49). The other, the returnees, moved back to Turkey after having lived in Germany for thirteen years (n = 35). The study is based on the theoretical framework for conceptual transfer outlined in Jarvis and Pavlenko (2008) and on the typology of satellite-framed and verb-framed languages developed by Talmy (1985, 1991, 2000a, b) and Slobin (1987, 1996, 2003, 2004, 2005, 2006). In the present study we provide evidence for the hypothesis that language structure affects the organization of information structure at the level of the Conceptualizer, and show that bilingual speakers’ conceptualization of motion events is influenced by the dominant linguistic environment in both languages (German for the group in Germany and Turkish for the returnees). The returnees follow the Turkish blueprints for the conceptualization of motion, in both Turkish and German event construals, whereas the German-resident bilinguals follow the German blueprints, when speaking German as well as Turkish. We argue that most of the patterns found are the result of transfer of conceptualization patterns from the dominant language of the environment.

Abstract

Some major classes of RNAs (such as mRNA, rRNA, tRNA and RNase P) are ubiquitous in all living systems so are inferred to have arisen early during the origin of life. However, the situation is not so clear for the system of RNA regulatory networks that continue to be uncovered, especially in eukaryotes. It is increasingly being recognised that networks of small RNAs are important for regulation in all cells, but it is not certain whether the origin of these networks are as old as rRNAs and tRNA. Another group of ncRNAs, including snoRNAs, occurs mainly in archaea and eukaryotes and their ultimate origin is less certain, although perhaps the simplest hypothesis is that they were present in earlier stages of life and were lost from bacteria. Some RNA networks may trace back to an early stage when there was just RNA and proteins, the RNP‑world; before DNA.

Abstract

Many children with Specific Language Impairment (SLI) show impairments in discriminating auditorily presented stimuli. The present study investigates whether these discrimination problems are speech specific or of a general auditory nature. This was studied by using a linguistic and nonlinguistic contrast that were matched for acoustic complexity in an active behavioral task and a passive ERP paradigm, known to elicit the mismatch negativity (MMN). In addition, attention skills and a variety of language skills were measured. Participants were 25 five-year-old Dutch children with SLI having receptive as well as productive language problems and 25 control children with typical speechand language development. At the behavioral level, the SLI group was impaired in discriminating the linguistic contrast as compared to the control group, while both groups were unable to distinguish the non-linguistic contrast. Moreover, the SLI group tended to have impaired attention skills which correlated with performance on most of the language tests. At the neural level, the SLI group, in contrast to the control group, did not show an MMN in response to either the linguistic or nonlinguistic contrast. The MMN data are consistent with an account that relates the symptoms in children with SLI to non-speech processing difficulties.

Abstract

Cognitive control involves not only the ability to manage competing task demands, but also the ability to adapt task performance during learning. This study investigated how violation-, response-, and feedback-related electrophysiological (EEG) activity changes over time during language learning. Twenty-two Dutch learners of German classified short prepositional phrases presented serially as text. The phrases were initially presented without feedback during a pre-test phase, and then with feedback in a training phase on two separate days spaced 1 week apart. The stimuli included grammatically correct phrases, as well as grammatical violations of gender and declension. Without feedback, participants' classification was near chance and did not improve over trials. During training with feedback, behavioral classification improved and violation responses appeared to both types of violation in the form of a P600. Feedback-related negative and positive components were also present from the first day of training. The results show changes in the electrophysiological responses in concert with improving behavioral discrimination, suggesting that the activity is related to grammar learning.

Abstract

We present written naming norms from 153 young adult Dutch speakers for 1397 photographs (the BOSS set; see Brodeur, Dionne-Dostie, Montreuil, & Lepage, 2010; Brodeur, Guérard, & Bouras, 2014). From the norming study, we report the preferred (modal) name, alternative names, name agreement, and average object agreement. In addition, the data base includes Zipf frequency, word prevalence and Age of Acquisition for the modal picture names collected. Furthermore, we describe a subset of 359 photographs with very good name agreement and a subset of 35 photos with two common names. These sets may be particularly valuable for designing experiments. Though the participants typed the object names, comparisons with other datasets indicate that the collected norms are valuable for spoken naming studies as well.

Abstract

It is generally accepted that the relationship between human genes
and language is very complex and multifaceted. This has its roots in the
“regular” complexity governing the interplay among genes and between genes
and environment for most phenotypes, but with the added layer of supraontogenetic
and supra-individual processes defining culture. At the coarsest
level, focusing on the species, it is clear that human-specific—but not necessarily
faculty-specific—genetic factors subtend our capacity for language and a
currently very productive research program is aiming at uncovering them. At the
other end of the spectrum, it is uncontroversial that individual-level variations in
different aspects related to speech and language have an important genetic
component and their discovery and detailed characterization have already started
to revolutionize the way we think about human nature. However, at the
intermediate, glossogenetic/population level, the relationship becomes controversial,
partly due to deeply ingrained beliefs about language acquisition and
universality and partly because of confusions with a different type of genelanguages
correlation due to shared history. Nevertheless, conceptual, mathematical
and computational models—and, recently, experimental evidence from
artificial languages and songbirds—have repeatedly shown that genetic biases
affecting the acquisition or processing of aspects of language and speech can be
amplified by population-level intergenerational cultural processes and made
manifest either as fixed “universal” properties of language or as structured
linguistic diversity. Here, I review several such models as well as the recently
proposed case of a causal relationship between the distribution of tone languages
and two genes related to brain growth and development, ASPM and Microcephalin,
and I discuss the relevance of such genetic biasing for language
evolution, change, and diversity.

Abstract

Language is a hallmark of our species and understanding linguistic diversity is an area of major interest. Genetic factors influencing the cultural transmission of language provide a powerful and elegant explanation for aspects of the present day linguistic diversity and a window into the emergence and evolution of language. In particular, it has recently been proposed that linguistic tone—the usage of voice pitch to convey lexical and grammatical meaning—is biased by two genes involved in brain growth and development, ASPM and Microcephalin. This hypothesis predicts that tone is a stable characteristic of language because of its ‘genetic anchoring’. The present paper tests this prediction using a Bayesian phylogenetic framework applied to a large set of linguistic features and language families, using multiple software implementations, data codings, stability estimations, linguistic classifications and outgroup choices. The results of these different methods and datasets show a large agreement, suggesting that this approach produces reliable estimates of the stability of linguistic data. Moreover, linguistic tone is found to be stable across methods and datasets, providing suggestive support for the hypothesis of genetic influences on its distribution.

Abstract

Language is not a purely cultural phenomenon somehow isolated from its wider environment, and we may only understand its origins and evolution by seriously considering its embedding in this environment as well as its multimodal nature. By environment here we understand other aspects of culture (such as communication technology, attitudes towards language contact, etc.), of the physical environment (ultraviolet light incidence, air humidity, etc.), and of the biological infrastructure for language and speech. We are specifically concerned in this paper with the latter, in the form of the biases, constraints and affordances that the anatomy and physiology of the vocal tract create on speech and language. In a nutshell, our argument is that (a) there is an under-appreciated amount of inter-individual variation in vocal tract (VT) anatomy and physiology, (b) variation that is non-randomly distributed across populations, and that (c) results in systematic differences in phonetics and phonology between languages. Relevant differences in VT anatomy include the overall shape of the hard palate, the shape of the alveolar ridge, the relationship between the lower and upper jaw, to mention just a few, and our data offer a new way to systematically explore such differences and their potential impact on speech. These differences generate very small biases that nevertheless can be amplified by the repeated use and transmission of language, affecting language diachrony and resulting in cross-linguistic synchronic differences. Moreover, the same type of biases and processes might have played an essential role in the emergence and evolution of language, and might allow us a glimpse into the speech and language of extinct humans by, for example, reconstructing the anatomy of parts of their vocal tract from the fossil record and extrapolating the biases we find in present-day humans.

Abstract

This paper argues that inter-individual and inter-group variation in language acquisition, perception, processing and production, rooted in our biology, may play a largely neglected role in sound change. We begin by discussing the patterning of these differences, highlighting those related to vocal tract anatomy with a foundation in genetics and development. We use our ArtiVarK database, a large multi-ethnic sample comprising 3D intraoral optical scans, as well as structural, static and real-time MRI scans of vocal tract anatomy and speech articulation, to quantify the articulatory strategies used to produce the North American English /r/ and to statistically show that anatomical factors seem to influence these articulatory strategies. Building on work showing that these alternative articulatory strategies may have indirect coarticulatory effects, we propose two models for how biases due to variation in vocal tract anatomy may affect sound change. The first involves direct overt acoustic effects of such biases that are then reinterpreted by the hearers, while the second is based on indirect coarticulatory phenomena generated by acoustically covert biases that produce overt “at-a-distance” acoustic effects. This view implies that speaker communities might be “poised” for change because they always contain pools of “standing variation” of such biased speakers, and when factors such as the frequency of the biased speakers in the community, their positions in the communicative network or the topology of the network itself change, sound change may rapidly follow as a self-reinforcing network-level phenomenon, akin to a phase transition. Thus, inter-speaker variation in structured and dynamic communicative networks may couple the initiation and actuation of sound change.

Abstract

Linguistic diversity is affected by multiple factors, but it is usually assumed that variation in the anatomy of our speech organs
plays no explanatory role. Here we use realistic computer models of the human speech organs to test whether inter-individual
and inter-group variation in the shape of the hard palate (the bony roof of the mouth) affects acoustics of speech sounds. Based
on 107 midsagittal MRI scans of the hard palate of human participants, we modelled with high accuracy the articulation of a set
of five cross-linguistically representative vowels by agents learning to produce speech sounds. We found that different hard
palate shapes result in subtle differences in the acoustics and articulatory strategies of the produced vowels, and that these
individual-level speech idiosyncrasies are amplified by the repeated transmission of language across generations. Therefore,
we suggest that, besides culture and environment, quantitative biological variation can be amplified, also influencing language.

Abstract

Understanding the mechanisms that drive variation in children’s language acquisition requires large, population-representative datasets of children’s word learning across development. Parent report measures such as the MacArthur-Bates Communicative Development Inventories (CDI) are commonly used to collect such data, but the traditional paper-based forms make the curation of large datasets logistically challenging. Many CDI datasets are thus gathered using convenience samples, often recruited from communities in proximity to major research institutions. Here, we introduce Web-CDI, a web-based tool which allows researchers to collect CDI data online. Web-CDI contains functionality to collect and manage longitudinal data, share links to test administrations, and download vocabulary scores. To date, over 3,500 valid Web-CDI administrations have been completed. General trends found in past norming studies of the CDI are present in data collected from Web-CDI: scores of children’s productive vocabulary grow with age, female children show a slightly faster rate of vocabulary growth, and participants with higher levels of educational attainment report slightly higher vocabulary production scores than those with lower levels of education attainment. We also report results from an effort to oversample non-white, lower-education participants via online recruitment (N = 241). These data showed similar demographic trends to the full sample but this effort resulted in a high exclusion rate. We conclude by discussing implications and challenges for the collection of large, population-representative datasets.

Abstract

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.

Abstract

The discovery of the FOXP2 transcription factor, and its implication in a rare severe human speech and language disorder, has led to two decades of empirical studies focused on uncovering its roles in the brain using a range of in vitro and in vivo methods. Here, we discuss what we have learned about the regulation of FOXP2, its downstream effectors, and its modes of action as a transcription factor in brain development and function, providing an integrated overview of what is currently known about the critical molecular networks.

Abstract

Whereas large-scale statistical analyses can robustly identify disease-gene relationships, they do not accurately capture genotype-phenotype correlations or disease mechanisms. We use multiple lines of independent evidence to show that different variant types in a single gene, SATB1, cause clinically overlapping but distinct neurodevelopmental disorders. Clinical evaluation of 42 individuals carrying SATB1 variants identified overt genotype-phenotype relationships, associated with different pathophysiological mechanisms, established by functional assays. Missense variants in the CUT1 and CUT2 DNA-binding domains result in stronger chromatin binding, increased transcriptional repression and a severe phenotype. Contrastingly, variants predicted to result in haploinsufficiency are associated with a milder clinical presentation. A similarly mild phenotype is observed for individuals with premature protein truncating variants that escape nonsense-mediated decay and encode truncated proteins, which are transcriptionally active but mislocalized in the cell. Our results suggest that in-depth mutation-specific genotype-phenotype studies are essential to capture full disease complexity and to explain phenotypic variability.

Abstract

* Deriziotis, P., André, R., and Smith. D.M. contributed equally to this work * - Prion diseases are associated with the conversion of cellular prion protein (PrP(C)) to toxic β-sheet isoforms (PrP(Sc)), which are reported to inhibit the ubiquitin-proteasome system (UPS). Accordingly, UPS substrates accumulate in prion-infected mouse brains, suggesting impairment of the 26S proteasome. A direct interaction between its 20S core particle and PrP isoforms was demonstrated by immunoprecipitation. β-PrP aggregates associated with the 20S particle, but did not impede binding of the PA26 complex, suggesting that the aggregates do not bind to its ends. Aggregated β-PrP reduced the 20S proteasome's basal peptidase activity, and the enhanced activity induced by C-terminal peptides from the 19S ATPases or by the 19S regulator itself, including when stimulated by polyubiquitin conjugates. However, the 20S proteasome was not inhibited when the gate in the α-ring was open due to a truncation mutation or by association with PA26/PA28. These PrP aggregates inhibit by stabilising the closed conformation of the substrate entry channel. A similar inhibition of substrate entry into the proteasome may occur in other neurodegenerative diseases where misfolded β-sheet-rich proteins accumulate.

Abstract

Investigation of the biological basis of human speech and language is being transformed by developments in molecular technologies, including high-throughput genotyping and next-generation sequencing of whole genomes. These advances are shedding new light on the genetic architecture underlying language-related disorders (speech apraxia, specific language impairment, developmental dyslexia) as well as that contributing to variation in relevant skills in the general population. We discuss how state-of-the-art methods are uncovering a range of genetic mechanisms, from rare mutations of large effect to common polymorphisms that increase risk in a subtle way, while converging on neurogenetic pathways that are shared between distinct disorders. We consider the future of the field, highlighting the unusual challenges and opportunities associated with studying genomics of language-related traits.

Abstract

This chapter discusses the genetic foundations of the human capacity for language. It reviews the molecular structure of the genome and the complex molecular mechanisms that allow genetic information to influence multiple levels of biology. It goes on to describe the active regulation of genes and their formation of complex genetic pathways that in turn control the cellular environment and function. At each of these levels, examples of genes and genetic variants that may influence the human capacity for language are given. Finally, it discusses the value of using animal models to understand the genetic underpinnings of speech and language. From this chapter will emerge the complexity of the genome in action and the multidisciplinary efforts that are currently made to bridge the gap between genetics and language.

Abstract

Background: Human fibroblasts can be directly converted to several subtypes of neurons, but cortical projection neurons have not been generated. Methods: Here we screened for transcription factor combinations that could potentially convert human fibroblasts to functional excitatory cortical neurons. The induced cortical (iCtx) cells were analyzed for cortical neuronal identity using immunocytochemistry, single-cell quantitative polymerase chain reaction (qPCR), electrophysiology, and their ability to integrate into human neural networks in vitro and ex vivo using electrophysiology and rabies virus tracing. Results: We show that a combination of three ranscription fact ors, BRN2, MYT1L, and FEZF2, have the ability to directly convert human fibroblasts to functional excitatory cortical neurons. The conversion efficiency was increased to about 16% by treatment with small molecules and microRNAs. The iCtx cells exhibited electrophysiological properties of functional neurons, had pyramidal-like cell morphology, and expressed key cortical projection neuronal markers. Single-cell analysis of iCtx cells revealed a complex gene expression profile, a subpopulation of them displaying a molecular signature closely resembling that of human fetal primary cortical neurons. The iCtx cells received synaptic inputs from co-cultured human fetal primary cortical neurons, contained spines, and expressed the postsyna ptic excitatory scaffold protein PSD95. When transplanted ex vivo to organotypic cultures of adult human cerebral cortex, the iCtx cells exhibited morphological and electrophysiological properties of mature neurons, integrated structurally into the cortical tissue, and received synaptic inputs from adult human neurons. Conclusions: Our findings indicate that functional excitatory cortical neurons, generated here for the first time by direct conversion of human somatic cells, have the capacity for synaptic integration into adult human cortex.

Abstract

Sex differences in development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants two scans, 104 three scans, age range: 16-70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. While hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and thickness and lower variability for sulcal width. Across sexes, variability decreased with age for all measures except for cortical volume and thickness. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.

Abstract

Do interlocutors adjust their conversational strategies to the specific contextual demands of a given situation? Prior studies have yielded conflicting results, making it unclear how strategies vary with demands. We combine insights from qualitative and quantitative approaches in a within-participant experimental design involving two different contexts: spontaneously occurring conversations (SOC) and task-oriented conversations (TOC). We systematically assess backchanneling, other-repair and linguistic alignment. We find that SOC exhibit a higher number of backchannels, a reduced and more generic repair format and higher rates of lexical and syntactic alignment. TOC are characterized by a high number of specific repairs and a lower rate of lexical and syntactic alignment. However, when alignment occurs, more linguistic forms are aligned. The findings show that conversational strategies adapt to specific contextual demands.