Publications

Abstract

Impaired facial affect recognition is common after traumatic brain injury (TBI) and linked to poor social outcomes. We explored whether perception of emotions depicted by emoji is also impaired after TBI. Fifty participants with TBI and 50 non-injured peers generated free-text labels to describe emotions depicted by emoji and rated their levels of valence and arousal on nine-point rating scales. We compared how the two groups’ valence and arousal ratings were clustered and examined agreement in the words participants used to describe emoji. Hierarchical clustering of affect ratings produced four emoji clusters in the non-injured group and three emoji clusters in the TBI group. Whereas the non-injured group had a strongly positive and a moderately positive cluster, the TBI group had a single positive valence cluster, undifferentiated by arousal. Despite differences in cluster numbers, hierarchical structures of the two groups’ emoji ratings were significantly correlated. Most emoji had high agreement in the words participants with and without TBI used to describe them. Participants with TBI perceived emoji similarly to non-injured peers, used similar words to describe emoji, and rated emoji similarly on the valence dimension. Individuals with TBI showed small differences in perceived arousal for a minority of emoji. Overall, results suggest that basic recognition processes do not explain challenges in computer-mediated communication reported by adults with TBI. Examining perception of emoji in context by people with TBI is an essential next step for advancing our understanding of functional communication in computer-mediated contexts after brain injury.

Abstract

Previous research has shown significant effects of race and accent on children’s developing social preferences. Accounts of the primacy of accent biases in the evolution and ontogeny of discriminant cooperation have been proposed, but lack systematic cross-cultural investigation. We report three controlled studies conducted with 5−10 year old children across four towns in the Brazilian Amazon, selected for their variation in racial and accent homogeneity/heterogeneity. Study 1 investigated participants’ (N = 289) decisions about friendship and sharing across color-contrasted pairs of target individuals: Black-White, Black-Pardo (Brown), Pardo-White. Study 2 (N = 283) investigated effects of both color and accent (Local vs Non-Local) on friendship and sharing decisions. Overall, there was a significant bias toward the lighter colored individual. A significant preference for local accent mitigates but does not override the color bias, except in the site characterized by both racial and accent heterogeneity. Results also vary by participant age and color. Study 3 (N = 235) reports results of an accent discrimination task that shows an overall increase in accuracy with age. The research suggests that cooperative preferences based on accent and race develop differently in response to locally relevant parameters of racial and linguistic variation.

Abstract

Contemporary methods of computational cognitive modeling have recently been criticized by Addyman and French (2012) on the grounds that they have not kept up with developments in computer technology and human–computer interaction. They present a manifesto for change according to which, it is argued, modelers should devote more effort to making their models accessible, both to non-modelers (with an appropriate easy-to-use user interface) and modelers alike. We agree that models, like data, should be freely available according to the normal standards of science, but caution against confusing implementations with specifications. Models may embody theories, but they generally also include implementation assumptions. Cognitive modeling methodology needs to be sensitive to this. We argue that specification, replication and experimentation are methodological approaches that can address this issue.

Abstract

In this study, we compared the performance of a long short-term memory (LSTM) neural network to the behavior of human participants on a language task that requires hierarchically structured knowledge. We show that humans interpret ambiguous noun phrases, such as second blue ball, in line with their hierarchical constituent structure. LSTMs, instead, only do
so after unambiguous training, and they do not systematically generalize to novel items. Overall, the results of our simulations indicate that a model can behave hierarchically without relying on hierarchical constituent structure.

Abstract

Previous electroencephalography studies have yielded evidence for automatic processing of syntax and lexical stress. However, these studies looked at both effects in isolation, limiting their generalizability to everyday language comprehension. In the current study, we investigated automatic processing of grammatical agreement in the face of variation in lexical stress. Using an oddball paradigm, we measured the Mismatch Negativity (MMN) in Dutch-speaking participants while they listened to Dutch subject–verb sequences (linguistic context) or acoustically similar sequences in which the subject was replaced by filtered noise (nonlinguistic context). The verb forms differed in the inflectional suffix, rendering the subject–verb sequences grammatically correct or incorrect, and leading to a difference in the stress pattern of the verb forms. We found that the MMNs were modulated in both the linguistic and nonlinguistic condition, suggesting that the processing load induced by variation in lexical stress can hinder early automatic processing of grammatical agreement. However, as the morphological differences between the verb forms correlated with differences in number of syllables, an interpretation in terms of the prosodic structure of the sequences cannot be ruled out. Future research is needed to determine which of these factors (i.e., lexical stress, syllabic structure) most strongly modulate early syntactic processing.

Abstract

Since the cognitive revolution, language and action have been compared as cognitive systems, with cross-domain convergent views recently gaining renewed interest in biology, neuroscience, and cognitive science. Language and action are both combinatorial systems whose mode of combination has been argued to be hierarchical, combining elements into constituents of increasingly larger size. This structural similarity has led to the suggestion that they rely on shared cognitive and neural resources. In this article, we compare the conceptual and formal properties of hierarchy in language and action using set theory. We show that the strong compositionality of language requires a particular formalism, a magma, to describe the algebraic structure corresponding to the set of hierarchical structures underlying sentences. When this formalism is applied to actions, it appears to be both too strong and too weak. To overcome these limitations, which are related to the weak compositionality and sequential nature of action structures, we formalize the algebraic structure corresponding to the set of actions as a trace monoid. We aim to capture the different system properties of language and action in terms of the distinction between hierarchical sets and hierarchical sequences and discuss the implications for the way both systems could be represented in the brain.

Abstract

Individual alpha frequency (IAF) is a promising electrophysiological marker of interindividual differences in cognitive function. IAF has been linked with trait-like differences in information processing and general intelligence, and provides an empirical basis for the definition of individualized frequency bands. Despite its widespread application, however, there is little consensus on the optimal method for estimating IAF, and many common approaches are prone to bias and inconsistency. Here, we describe an automated strategy for deriving two of the most prevalent IAF estimators in the literature: peak alpha frequency (PAF) and center of gravity (CoG). These indices are calculated from resting-state power spectra that have been smoothed using a Savitzky-Golay filter (SGF). We evaluate the performance characteristics of this analysis procedure in both empirical and simulated EEG data sets. Applying the SGF technique to resting-state data from n = 63 healthy adults furnished 61 PAF and 62 CoG estimates. The statistical properties of these estimates were consistent with previous reports. Simulation analyses revealed that the SGF routine was able to reliably extract target alpha components, even under relatively noisy spectral conditions. The routine consistently outperformed a simpler method of automated peak detection that did not involve spectral smoothing. The SGF technique is fast, open source, and available in two popular programming languages (MATLAB, Python), and thus can easily be integrated within the most popular M/EEG toolsets (EEGLAB, FieldTrip, MNE-Python). As such, it affords a convenient tool for improving the reliability and replicability of future IAF-related research.

Abstract

Comprehenders predict what a speaker is likely to say when listening to non-native (L2) and native (L1) utterances. But what are the characteristics of L2 prediction, and how does it relate to L1 prediction? We addressed this question in a visual-world eye-tracking experiment, which tested when L2 English comprehenders integrated perspective into their predictions. Male and female participants listened to male and female speakers producing sentences (e.g., I would like to wear the nice…) about stereotypically masculine (target: tie; distractor: drill) and feminine (target: dress; distractor: hairdryer) objects. Participants predicted associatively, fixating objects semantically associated with critical verbs (here, the tie and the dress). They also predicted stereotypically consistent objects (e.g., the tie rather than the dress, given the male speaker). Consistent predictions were made later than associative predictions, and were delayed for L2 speakers relative to L1 speakers. These findings suggest prediction involves both automatic and non-automatic stages.

Abstract

During conversation, interlocutors rapidly switch between speaker and listener
roles and take turns at talk. How do they achieve such fine coordination?
Most research has concentrated on the role of prediction, but listeners
must also prepare a response in advance (assuming they wish to respond)
and articulate this response at the appropriate moment. Such mechanisms
may overlap with the processes of comprehending the speaker’s incoming
turn and predicting its end. However, little is known about the stages of
response preparation and production. We discuss three questions pertaining
to such stages: (1) Do listeners prepare their own response in advance?,
(2) Can listeners buffer their prepared response?, and (3) Does buffering
lead to interference with concurrent comprehension? We argue that fine
coordination requires more than just an accurate prediction of the interlocutor’s
incoming turn: Listeners must also simultaneously prepare their own
response.

Abstract

During conversation, there is often little gap between interlocutors’ utterances. In two pairs of experiments, we manipulated the content predictability of yes/no questions to investigate whether listeners achieve such coordination by (i) preparing a response as early as possible or (ii) predicting the end of the speaker’s turn. To assess these two mechanisms, we varied the participants’ task: They either pressed a button when they thought the question was about to end (Experiments 1a and 2a), or verbally answered the questions with either yes or no (Experiments 1b and 2b). Predictability effects were present when participants had to prepare a verbal response, but not when they had to predict the turn-end. These findings suggest content prediction facilitates turn-taking because it allows listeners to prepare their own response early, rather than because it helps them predict when the speaker will reach the end of their turn.

Abstract

During dialog, interlocutors take turns at speaking with little gap or overlap between their contributions. But language production in monolog is comparatively slow. Theories of dialog tend to agree that interlocutors manage these timing demands by planning a response early, before the current speaker reaches the end of their turn. In the first half of this chapter, I review experimental research supporting these theories. But this research also suggests that planning a response early, while simultaneously comprehending, is difficult. Does response planning need to be this difficult during dialog? In other words, is early-planning always necessary? In the second half of this chapter, I discuss research that suggests the answer to this question is no. In particular, corpora of natural conversation demonstrate that speakers do not directly respond to the immediately preceding utterance of their partner—instead, they continue an utterance they produced earlier. This parallel talk likely occurs because speakers are highly incremental and plan only part of their utterance before speaking, leading to pauses, hesitations, and disfluencies. As a result, speakers do not need to engage in extensive advance planning. Thus, laboratory studies do not provide a full picture of language production in dialog, and further research using naturalistic tasks is needed.

Abstract

Word frequency plays a key role in theories of lexical access, which assume that the word frequency effect (WFE, faster access to high-frequency than low-frequency words) occurs as a result of differences in the representation and processing of the words. In a seminal paper, Jescheniak and Levelt (1994) proposed that the WFE arises during the retrieval of word forms, rather than the retrieval of their syntactic representations (their lemmas) or articulatory commands. An important part of Jescheniak and Levelt's argument was that they found a stable WFE in a picture naming task, which requires complete lexical access, but not in a gender decision task, which only requires access to the words' lemmas and not their word forms. We report two attempts to replicate this pattern, one with new materials, and one with Jescheniak and Levelt's orginal pictures. In both studies we found a strong WFE when the pictures were shown for the first time, but much weaker effects on their second and third presentation. Importantly these patterns were seen in both the picture naming and the gender decision tasks, suggesting that either word frequency does not exclusively affect word form retrieval, or that the gender decision task does not exclusively tap lemma access.

Abstract

Although previous research has demonstrated that language comprehension can be egocentric, there is little evidence for egocentricity during prediction. In particular, comprehenders do not appear to predict egocentrically when the context makes it clear what the speaker is likely to refer to. But do comprehenders predict egocentrically when the context does not make it clear? We tested this hypothesis using a visual-world eye-tracking paradigm, in which participants heard sentences containing the gender-neutral pronoun They (e.g. They would like to wear…) while viewing four objects (e.g. tie, dress, drill, hairdryer). Two of these objects were plausible targets of the verb (tie and dress), and one was stereotypically compatible with the participant's gender (tie if the participant was male; dress if the participant was female). Participants rapidly fixated targets more than distractors, but there was no evidence that participants ever predicted egocentrically, fixating objects stereotypically compatible with their own gender. These findings suggest that participants do not fall back on their own egocentric perspective when predicting, even when they know that context does not make it clear what the speaker is likely to refer to.

Abstract

The ABCA4 gene is the most frequently mutated Mendelian retinopathy-associated gene. Biallelic variants lead to a variety of phenotypes, however, for thousands of cases the underlying variants remain unknown. Here, we aim to shed further light on the missing heritability of ABCA4-associated retinopathy by analyzing a large cohort of macular dystrophy probands. A total of 858 probands were collected from 26 centers, of whom 722 carried no or one pathogenic ABCA4 variant while 136 cases carried two ABCA4 alleles, one of which was a frequent mild variant, suggesting that deep-intronic variants (DIVs) or other cis-modifiers might have been missed. After single molecule molecular inversion probes (smMIPs)-based sequencing of the complete 128-kb ABCA4 locus, the effect of putative splice variants was assessed in vitro by midigene splice assays in HEK293T cells. The breakpoints of copy number variants (CNVs) were determined by junction PCR and Sanger sequencing. ABCA4 sequence analysis solved 207/520 (39.8%) naïve or unsolved cases and 70/202 (34.7%) monoallelic cases, while additional causal variants were identified in 54/136 (39.7%) of probands carrying two variants. Seven novel DIVs and six novel non-canonical splice site variants were detected in a total of 35 alleles and characterized, including the c.6283-321C>G variant leading to a complex splicing defect. Additionally, four novel CNVs were identified and characterized in five alleles. These results confirm that smMIPs-based sequencing of the complete ABCA4 gene provides a cost-effective method to genetically solve retinopathy cases and that several rare structural and splice altering defects remain undiscovered in STGD1 cases.

Abstract

Single nucleotide polymorphisms (SNPs) within the MIR137, TCF4, and ZNF804A genes show genome-wide association to schizophrenia. However, the biological basis for the associations is unknown. Here, we tested the effects of these genes on brain structure in 1300 healthy adults. Using volumetry and voxel-based morphometry, neither gene-wide effects—including the combined effect of the genes—nor single SNP effects—including specific psychosis risk SNPs—were found on total brain volume, grey matter, white matter, or hippocampal volume. These results suggest that the associations between these risk genes and schizophrenia are unlikely to be mediated via effects on macroscopic brain structure.

Abstract

The extent to which languages share properties reflecting the non-linguistic constraints of the speakers who speak them is key to the debate regarding the relationship between language and cognition. A critical case is spatial communication, where it has been argued that semantic universals should exist, if anywhere. Here, using an experimental paradigm able to separate variation within a language from variation between languages, we tested the use of spatial demonstratives—the most fundamental and frequent spatial terms across languages. In n = 874 speakers across 29 languages, we show that speakers of all tested languages use spatial demonstratives as a function of being able to reach or act on an object being referred to. In some languages, the position of the addressee is also relevant in selecting between demonstrative forms. Commonalities and differences across languages in spatial communication can be understood in terms of universal constraints on action shaping spatial language and cognition.

Abstract

When speaking to infants, adults often produce speech that differs systematically from that directed to other adults. In order to quantify the acoustic properties of this speech style across a wide variety of languages and cultures, we extracted results from empirical studies on the acoustic features of infant-directed speech (IDS). We analyzed data from 88 unique studies (734 effect sizes) on the following five acoustic parameters that have been systematically examined in the literature: i) fundamental frequency (fo), ii) fo variability, iii) vowel space area, iv) articulation rate, and v) vowel duration. Moderator analyses were conducted in hierarchical Bayesian robust regression models in order to examine how these features change with infant age and differ across languages, experimental tasks and recording environments. The moderator analyses indicated that fo, articulation rate, and vowel duration became more similar to adult-directed speech (ADS) over time, whereas fo variability and vowel space area exhibited stability throughout development. These results point the way for future research to disentangle different accounts of the functions and learnability of IDS by conducting theory-driven comparisons among different languages and using computational models to formulate testable predictions.

Abstract

This paper discusses some improvements in recent and planned versions of the multimodal annotation tool ELAN, which are targeted at improving the usability of annotated files. Increased support for multilingual documents is provided, by allowing for multilingual vocabularies and by specifying a language per document, annotation layer (tier) or annotation. In addition, improvements in the search possibilities and the display of the results have been implemented, which are especially relevant in the interpretation of the results of complex multi-tier searches.

Abstract

Collocations generated by concordancers are a standard instrument in the exploitation of text corpora for the analysis of language use. Multimodal corpora show similar types of patterns, activities that frequently occur together, but there is no tool that offers facilities for visualising such patterns. Examples include timing of eye contact with respect to speech, and the alignment of activities of the two hands in signed languages. This paper describes recent enhancements to the standard CLARIN tools ELAN and TROVA for multimodal annotation to address these needs: first of all the query and concordancing functions were improved, and secondly the tools now generate visualisations of multilayer collocations that allow for intuitive explorations and analyses of multimodal data. This will provide a boost to the linguistic fields of gesture and sign language studies, as it will improve the exploitation of multimodal corpora.

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

Most psycholinguistic studies on morphological processing have examined the role of morphological structure in the visual modality. This chapter discusses morphological processing in the auditory modality, which is an area of research that has only recently received more attention. It first discusses why results in the visual modality cannot straightforwardly be applied to the processing of spoken words, stressing the importance of acknowledging potential modality effects. It then gives a brief overview of the existing research on the role of morphology in the auditory modality, for which an increasing number of studies report that listeners show sensitivity to morphological structure. Finally, the chapter highlights insights gained by looking at morphological processing not only in reading, but also in listening, and it discusses directions for future research

Abstract

A recent debate in the morphological literature concerns the status of derivational affixes. While some linguists (Marantz 1997, 2001; Marvin 2003) consider derivational affixes a type of functional morpheme that realizes a categorial head, others (Lowenstamm 2015; De Belder 2011) argue that derivational affixes are roots. Our proposal, which finds its empirical basis in a study of Dutch derivational affixes, takes a middle position. We argue that there are two types of derivational affixes: some that are roots (i.e. lexical morphemes) and others that are categorial heads (i.e. functional morphemes). Affixes that are roots show ‘flexible’ categorial behavior, are subject to ‘lexical’ phonological rules, and may trigger idiosyncratic meanings. Affixes that realize categorial heads, on the other hand, are categorially rigid, do not trigger ‘lexical’ phonological rules nor allow for idiosyncrasies in their interpretation.

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

The present study investigated the neural correlates of infant discrimination of very similar linguistic varieties (Quebecois and Parisian French) using functional Near InfraRed Spectroscopy. In line with previous behavioral and electrophysiological data, there was no evidence that 3-month-olds discriminated the two regional accents, whereas 5-month-olds did, with the locus of discrimination in left anterior perisylvian regions. These neuroimaging results suggest that a developing language network relying crucially on left perisylvian cortices sustains infants' discrimination of similar linguistic varieties within this early period of infancy.

Abstract

Speaker diarization (answering 'who spoke when') is a widely researched subject within speech technology. Numerous experiments have been run on datasets built from broadcast news, meeting data, and call centers—the task sometimes appears close to being solved. Much less work has begun to tackle the hardest diarization task of all: spontaneous conversations in real-world settings. Such diarization would be particularly useful for studies of language acquisition, where researchers investigate the speech children produce and hear in their daily lives. In this paper, we study audio gathered with a recorder worn by small children as they went about their normal days. As a result, each child was exposed to different acoustic environments with a multitude of background noises and a varying number of adults and peers. The inconsistency of speech and noise within and across samples poses a challenging task for speaker diarization systems, which we tackled via retraining and data augmentation techniques. We further studied sources of structured variation across raw audio files, including the impact of speaker type distribution, proportion of speech from children, and child age on diarization performance. We discuss the extent to which these findings might generalize to other samples of speech in the wild.

Abstract

There are increasing reports that individual variation in behavioral and neurophysiological measures of infant speech processing predicts later language outcomes, and specifically concurrent or subsequent vocabulary size. If such findings are held up under scrutiny, they could both illuminate theoretical models of language development and contribute to the prediction of communicative disorders. A qualitative, systematic review of this emergent literature illustrated the variety of approaches that have been used and highlighted some conceptual problems regarding the measurements. A quantitative analysis of the same data established that the bivariate relation was significant, with correlations of similar strength to those found for well-established nonlinguistic predictors of language. Further exploration of infant speech perception predictors, particularly from a methodological perspective, is recommended.

Abstract

Typically, the point vowels [i,ɑ,u] are acoustically more peripheral in infant-directed speech (IDS) compared to adult-directed speech (ADS). If caregivers seek to highlight lexically relevant contrasts in IDS, then two sounds that are contrastive should become more distinct, whereas two sounds that are surface realizations of the same underlying sound category should not. To test this prediction, vowels that are phonemically contrastive ([i-ɪ] and [eɪ-ε]), vowels that map onto the same underlying category ([æ- ] and [ε- ]), and the point vowels [i,ɑ,u] were elicited in IDS and ADS by American English mothers of two age groups of infants (four- and eleven-month-olds). As in other work, point vowels were produced in more peripheral positions in IDS compared to ADS. However, there was little evidence of hyperarticulation per se (e.g. [i-ɪ] was hypoarticulated). We suggest that across-the-board lexically based hyperarticulation is not a necessary feature of IDS.

Abstract

In the wild, chimpanzees (Pan troglodytes) are often faced with clumped food resources that they may know how to access but abstain from doing so due to social pressures. To better understand how social settings influence resource acquisition, we tested fifteen semi-wild chimpanzees from two social groups alone and in the presence of others. We investigated how resource acquisition was affected by relative social dominance, whether collaborative problem solving or (active or passive) sharing occurred amongst any of the dyads, and whether these outcomes were related to relationship quality as determined from six months of observational data. Results indicated that chimpanzees, regardless of rank, obtained fewer rewards when tested in the presence of others compared to when they were tested alone. Chimpanzees demonstrated behavioral inhibition; chimpanzees who showed proficient skill when alone often abstained from solving the task when in the presence of others. Finally, individuals with close social relationships spent more time together in the problem solving space, but collaboration and sharing were infrequent and sessions in which collaboration or sharing did occur contained more instances of aggression. Group living provides benefits and imposes costs, and these findings highlight that one cost of group living may be diminishing productive individual behaviors.

Abstract

Recent debates have questioned the extent to which culturally-transmitted norms drive behavioral variation in resource sharing across human populations. We shed new light on this discussion by examining the group-level variation in the social dynamics and resource sharing of chimpanzees, a species that is highly social and forms long-term community associations but differs from humans in the extent to which cultural norms are adopted and enforced. We rely on theory developed in primate socioecology to guide our investigation in four neighboring chimpanzee groups at a sanctuary in Zambia. We used a combination of experimental and observational approaches to assess the distribution of resource holding potential in each group. In the first assessment, we measured the proportion of the population that gathered in a resource-rich zone, in the second we assessed naturally occurring social spacing via social network analysis, and in the third we assessed the degree to which benefits were equally distributed within the group. We report significant, stable group-level variation across these multiple measures, indicating that group-level variation in resource sharing and social tolerance is not necessarily reliant upon human-like cultural norms.

Abstract

A large amount of variability exists across human brains; revealed initially on a small scale by postmortem studies and,
more recently, on a larger scale with the advent of neuroimaging. Here we compared structural variability between human
and macaque monkey brains using grey and white matter magnetic resonance imaging measures. The monkey brain was
overall structurally as variable as the human brain, but variability had a distinct distribution pattern, with some key areas
showing high variability. We also report the first evidence of a relationship between anatomical variability and evolutionary
expansion in the primate brain. This suggests a relationship between variability and stability, where areas of low variability
may have evolved less recently and have more stability, while areas of high variability may have evolved more recently and
be less similar across individuals. We showed specific differences between the species in key areas, including the amount of
hemispheric asymmetry in variability, which was left-lateralized in the human brain across several phylogenetically recent
regions. This suggests that cerebral variability may be another useful measure for comparison between species and may add
another dimension to our understanding of evolutionary mechanisms.

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

In two experiments, Mandarin listeners resolved potential syntactic ambiguities in spoken utterances in (a) their native language (L1) and (b) English which they had learned as a second language (L2). A new disambiguation task was used, requiring speeded responses to select the correct meaning for structurally ambiguous sentences. Importantly, the ambiguities used in the study are identical in Mandarin and in English, and production data show that prosodic disambiguation of this type of ambiguity is also realised very similarly in the two languages. The perceptual results here showed however that listeners’ response patterns differed for L1 and L2, although there was a significant increase in similarity between the two response patterns with increasing exposure to the L2. Thus identical ambiguity and comparable disambiguation patterns in L1 and L2 do not lead to immediate application of the appropriate L1 listening strategy to L2; instead, it appears that such a strategy may have to be learned anew for the L2.

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

Using a phoneme detection task, the present series of
experiments examines whether listeners can entrain to
different combinations of prosodic cues to predict where focus
will fall in an utterance. The stimuli were recorded by four
female native speakers of Australian English who happened to
have used different prosodic cues to produce sentences with
prosodic focus: a combination of duration cues, mean and
maximum F0, F0 range, and longer pre-target interval before
the focused word onset, only mean F0 cues, only pre-target
interval, and only duration cues. Results revealed that listeners
can entrain in almost every condition except for where
duration was the only reliable cue. Our findings suggest that
listeners are flexible in the cues they use for focus processing.

Abstract

Listeners adapt rapidly to previously unheard talkers by
adjusting phoneme categories using lexical knowledge, in a
process termed lexically-guided perceptual learning. Although
this is firmly established for listening in the native language
(L1), perceptual flexibility in second languages (L2) is as yet
less well understood. We report two experiments examining L1
and L2 perceptual learning, the first in Mandarin-English late
bilinguals, the second in Australian learners of Mandarin. Both
studies showed stronger learning in L1; in L2, however,
learning appeared for the English-L1 group but not for the
Mandarin-L1 group. Phonological mapping differences from
the L1 to the L2 are suggested as the reason for this result.

Abstract

Speech signals originate as a sequence of linguistic units selected by speakers, but these units are necessarily realised in the suprasegmental dimensions of time, frequency and amplitude. For this reason prosodic structure has been viewed as a mandatory target of language processing by both speakers and listeners. In apparent contradiction, however, prosody has also been argued to be ancillary rather than core linguistic structure, making processing of prosodic structure essentially optional. In the present tribute to one of the luminaries of prosodic research for the past quarter century, we review evidence from studies of the processing of lexical stress and focal accent which reconciles these views and shows that both claims are, each in their own way, fully true.

Abstract

Vocabularies contain hundreds of thousands of words built from only a handful of phonemes; longer words inevitably tend to contain shorter ones. Recognising speech thus requires distinguishing intended words from accidentally present ones. Acoustic information in speech is used wherever it contributes significantly to this process; but as this review shows, its contribution differs across languages, with the consequences of this including: identical and equivalently present information distinguishing the same phonemes being used in Polish but not in German, or in English but not in Italian; identical stress cues being used in Dutch but not in English; expectations about likely embedding patterns differing across English, French, Japanese.

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

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

Abstract

Listeners' recognition of spoken language involves complex decoding processes: The continuous speech stream must be segmented into its component words, and words must be recognized despite great variability in their pronunciation (due to talker differences, or to influence of phonetic context, or to speech register) and despite competition from many spuriously present forms supported by the speech signal. L1 listeners deal more readily with all levels of this complexity than L2 listeners. Fortunately, the decoding processes necessary for competent L2 listening can be taught in the classroom. Evidence-based methodologies targeted at the development of efficient speech decoding include teaching of minimal pairs, of phonotactic constraints, and of reduction processes, as well as the use of dictation and L2 video captions.

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

An acoustically invariant one-word segment occurred in two versions of one syntactic context. In one version, the preceding intonation contour indicated that a stress would fall at the point where this word occurred. In the other version, the preceding contour predicted reduced stress at that point. Reaction time to the initial phoneme of the word was faster in the former case, despite the fact that no acoustic correlates of stress were present. It is concluded that a part of the sentence comprehension process is the prediction of upcoming sentence accents.

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

Two lexical decision studies examined the effects of single-phoneme mismatches on lexical activation in spoken-word recognition. One study was carried out in English, and involved spoken primes and visually presented lexical decision targets. The other study was carried out in Dutch, and primes and targets were both presented auditorily. Facilitation was found only for spoken targets preceded immediately by spoken primes; no facilitation occurred when targets were presented visually, or when intervening input occurred between prime and target. The effects of vowel mismatches and consonant mismatches were equivalent.

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

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 neural mechanism for selectively tuning in to a target speaker while tuning out the others in a multi-speaker situation (i.e., the cocktail-party effect) remains elusive. Here we addressed this issue by measuring brain activity simultaneously from a listener and from multiple speakers while they were involved in naturalistic conversations. Results consistently show selectively enhanced interpersonal neural synchronization (INS) between the listener and the attended speaker at left temporal–parietal junction, compared with that between the listener and the unattended speaker across different multi-speaker situations. Moreover, INS increases significantly prior to the occurrence of verbal responses, and even when the listener’s brain activity precedes that of the speaker. The INS increase is independent of brain-to-speech synchronization in both the anatomical location and frequency range. These findings suggest that INS underlies the selective process in a multi-speaker situation through neural predictions at the content level but not the sensory level of speech.

Abstract

This work was supported by grants from the French Agence Nationale de la Recherche (ANR-2010-BLAN-1901) and from French Fondation de France to Anne Christophe, from the National Institute of Child Health and Human Development (HD054448) to Cynthia Fisher, Fondation Fyssen and Ecole de Neurosciences de Paris to Alex Cristia, and a PhD fellowship from the Direction Générale de l'Armement (DGA, France) supported by the PhD program FdV (Frontières du Vivant) to Isabelle Dautriche. We thank Isabelle Brunet for the recruitment, Michel Dutat for the technical support, and Hernan Anllo for his puppet mastery skill. We are grateful to the families that participated in this study. We also thank two anonymous reviewers for their comments on an earlier draft of this manuscript.

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

This article surveys what is currently known about the complex interplay between genetics and the language sciences. It focuses not only on the genetic architecture of language and speech, but also on their interactions on the cultural and evolutionary timescales. Given the complexity of these issues and their current state of flux and high dynamism, this article surveys the main findings and topics of interest while also briefly introducing the main relevant methods, thus allowing the interested reader to fully appreciate and understand them in their proper context. Of course, not all the relevant publications and resources are mentioned, but this article aims to select the most relevant, promising, or accessible for nonspecialists.

Abstract

One of the best-known types of non-independence between languages is caused by genealogical relationships due to descent from a common ancestor. These can be represented by (more or less resolved and controversial) language family trees. In theory, one can argue that language families should be built through the strict application of the comparative method of historical linguistics, but in practice this is not always the case, and there are several proposed classifications of languages into language families, each with its own advantages and disadvantages. A major stumbling block shared by most of them is that they are relatively difficult to use with computational methods, and in particular with phylogenetics. This is due to their lack of standardization, coupled with the general non-availability of branch length information, which encapsulates the amount of evolution taking place on the family tree. In this paper I introduce a method (and its implementation in R) that converts the language classifications provided by four widely-used databases (Ethnologue, WALS, AUTOTYP and Glottolog) intothe de facto Newick standard generally used in phylogenetics, aligns the four most used conventions for unique identifiers of linguistic entities (ISO 639-3, WALS, AUTOTYP and Glottocode), and adds branch length information from a variety of sources (the tree's own topology, an externally given numeric constant, or a distance matrix). The R scripts, input data and resulting Newick trees are available under liberal open-source licenses in a GitHub repository (https://github.com/ddediu/lgfam-newick), to encourage and promote the use of phylogenetic methods to investigate linguistic diversity and its temporal dynamics.

Abstract

Here we re-evaluate our 2013 paper on the antiquity of language (Dediu and Levinson, 2013) in the light of a surge of new information on human evolution in the last half million years. Although new genetic data suggest the existence of some cognitive differences between Neanderthals and modern humans — fully expected after hundreds of thousands of years of partially separate evolution, overall our claims that Neanderthals were fully articulate beings and that language evolution was gradual are further substantiated by the wealth of new genetic, paleontological and archeological evidence briefly reviewed here.

Abstract

This paper presents the first part of a guide for documenting and describing child language, child-directed language and socialization patterns in diverse languages and cultures. The guide is intended for anyone interested in working across child language and language documentation,
including, for example, field linguists and language documenters, community language workers, child language researchers or graduate students. We assume some basic familiarity with language documentation principles and methods, and, based on this, provide step-by-step suggestions for
collecting, analyzing and presenting child data. This first part of the guide focuses on constructing a sketch corpus that consists of minimally five hours of annotated and archived data and which documents communicative practices of children between the ages of 2 and 4.

Abstract

This paper presents the second part of a guide for documenting and describing child language, child-directed language and socialization patterns in diverse languages and cultures. The guide is intended for anyone interested in working across child language and language documentation,
including, for example, field linguists and language documenters, community language workers, child language researchers or graduate students. We assume some basic familiarity with language documentation principles and methods, and, based on this, provide step-by-step suggestions for
collecting, analyzing and presenting child data. This second part of the guide focuses on developing a child language acquisition sketch. It takes the sketch corpus as its basis (which was introduced in the first part of this guide), and presents a model for analyzing and describing the corpus data.

Abstract

In this article we investigate the relation between discourse markers and turn-transition strategies in face-to-face conversations and Instant Messaging (IM), that is, unplanned, real-time, text-based, computer-mediated communication. By means of a quantitative corpus study of utterances containing a discourse marker, we show that utterance-final discourse markers are used more often in IM than in face-to-face conversations. Moreover, utterance-final discourse markers are shown to occur more often at points of turn-transition compared with points of turn-maintenance in both types of conversation. From our results we conclude that the discourse markers in utterance-final position can function as a turn-transition mechanism, signaling that the turn is over and the floor is open to the hearer. We argue that this linguistic turn-taking strategy is essentially similar in face-to-face and IM communication. Our results add to the evidence that communication in IM is more like speech than like writing.

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

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

Recurrent de novo variants in the TBR1 transcription factor are implicated in the etiology of sporadic autism spectrum disorders (ASD). Disruptions include missense variants located in the T-box DNA-binding domain and previous work has demonstrated that they disrupt TBR1 protein function. Recent screens of thousands of simplex families with sporadic ASD cases uncovered additional T-box variants in TBR1 but their etiological relevance is unclear. We performed detailed functional analyses of de novo missense TBR1 variants found in the T-box of ASD cases, assessing many aspects of protein function, including subcellular localization, transcriptional activity and protein-interactions. Only two of the three tested variants severely disrupted TBR1 protein function, despite in silico predictions that all would be deleterious. Furthermore, we characterized a putative interaction with BCL11A, a transcription factor that was recently implicated in a neurodevelopmental syndrome involving developmental delay and language deficits. Our findings enhance understanding of molecular functions of TBR1, as well as highlighting the importance of functional testing of variants that emerge from next-generation sequencing, to decipher their contributions to neurodevelopmental disorders like ASD.

Abstract

Next-generation sequencing recently revealed that recurrent disruptive mutations in a few genes may account for 1% of sporadic autism cases. Coupling these novel genetic data to empirical assays of protein function can illuminate crucial molecular networks. Here we demonstrate the power of the approach, performing the first functional analyses of TBR1 variants identified in sporadic autism. De novo truncating and missense mutations disrupt multiple aspects of TBR1 function, including subcellular localization, interactions with co-regulators and transcriptional repression. Missense mutations inherited from unaffected parents did not disturb function in our assays. We show that TBR1 homodimerizes, that it interacts with FOXP2, a transcription factor implicated in speech/language disorders, and that this interaction is disrupted by pathogenic mutations affecting either protein. These findings support the hypothesis that de novo mutations in sporadic autism have severe functional consequences. Moreover, they uncover neurogenetic mechanisms that bridge different neurodevelopmental disorders involving language deficits.

Abstract

Assays based on Bioluminescence Resonance Energy Transfer (BRET) provide a sensitive and reliable means to monitor protein-protein interactions in live cells. BRET is the non-radiative transfer of energy from a ‘donor’ luciferase enzyme to an ‘acceptor’ fluorescent protein. In the most common configuration of this assay, the donor is Renilla reniformis luciferase and the acceptor is Yellow Fluorescent Protein (YFP). Because the efficiency of energy transfer is strongly distance-dependent, observation of the BRET phenomenon requires that the donor and acceptor be in close proximity. To test for an interaction between two proteins of interest in cultured mammalian cells, one protein is expressed as a fusion with luciferase and the second as a fusion with YFP. An interaction between the two proteins of interest may bring the donor and acceptor sufficiently close for energy transfer to occur. Compared to other techniques for investigating protein-protein interactions, the BRET assay is sensitive, requires little hands-on time and few reagents, and is able to detect interactions which are weak, transient, or dependent on the biochemical environment found within a live cell. It is therefore an ideal approach for confirming putative interactions suggested by yeast two-hybrid or mass spectrometry proteomics studies, and in addition it is well-suited for mapping interacting regions, assessing the effect of post-translational modifications on protein-protein interactions, and evaluating the impact of mutations identified in patient DNA.

Abstract

Retinoic acid-related orphan receptor alpha gene (RORa) and the microRNA MIR137 have both recently been identified as novel candidate genes for neuropsychiatric disorders. RORa encodes a ligand-dependent orphan nuclear receptor that acts as a transcriptional regulator and miR-137 is a brain enriched small non-coding RNA that interacts with gene transcripts to control protein levels. Given the mounting evidence for RORa in autism spectrum disorders (ASD) and MIR137 in schizophrenia and ASD, we investigated if there was a functional biological relationship between these two genes. Herein, we demonstrate that miR-137 targets the 3'UTR of RORa in a site specific manner. We also provide further support for MIR137 as an autism candidate by showing that a large number of previously implicated autism genes are also putatively targeted by miR-137. This work supports the role of MIR137 as an ASD candidate and demonstrates a direct biological link between these previously unrelated autism candidate genes

Abstract

FOXP2 was the first gene shown to cause a Mendelian form of speech and language disorder. Although developmentally expressed in many organs, loss of a single copy of FOXP2 leads to a phenotype that is largely restricted to orofacial impairment during articulation and linguistic processing deficits. Why perturbed FOXP2 function affects specific aspects of the developing brain remains elusive. We investigated the role of FOXP2 in neuronal differentiation and found that FOXP2 drives molecular changes consistent with neuronal differentiation in a human model system. We identified a network of FOXP2 regulated genes related to retinoic acid signaling and neuronal differentiation. FOXP2 also produced phenotypic changes associated with neuronal differentiation including increased neurite outgrowth and reduced migration. Crucially, cells expressing FOXP2 displayed increased sensitivity to retinoic acid exposure. This suggests a mechanism by which FOXP2 may be able to increase the cellular differentiation response to environmental retinoic acid cues for specific subsets of neurons in the brain. These data demonstrate that FOXP2 promotes neuronal differentiation by interacting with the retinoic acid signaling pathway and regulates key processes required for normal circuit formation such as neuronal migration and neurite outgrowth. In this way, FOXP2, which is found only in specific subpopulations of neurons in the brain, may drive precise neuronal differentiation patterns and/or control localization and connectivity of these FOXP2 positive cells

Abstract

Intellectual disability (ID) is a severe neurodevelopmental disorder with genetically heterogeneous causes. Large-scale sequencing has led to the identification of many gene-disrupting mutations; however, a substantial proportion of cases lack a molecular diagnosis. As such, there remains much to uncover for a complete understanding of the genetic underpinnings of ID. Genetic variants present in non-coding regions of the genome have been highlighted as potential contributors to neurodevelopmental disorders given their role in regulating gene expression. Nevertheless the functional characterization of non-coding variants remains challenging. We describe the identification and characterization of de novo non-coding variation in 3′UTR regulatory regions within an ID cohort of 50 patients. This cohort was previously screened for structural and coding pathogenic variants via CNV, whole exome and whole genome analysis. We identified 44 high-confidence single nucleotide non-coding variants within the 3′UTR regions of these 50 genomes. Four of these variants were located within predicted miRNA binding sites and were thus hypothesised to have regulatory consequences. Functional testing showed that two of the variants interfered with miRNA-mediated regulation of their target genes, AMD1 and FAIM. Both these variants were found in the same individual and their functional consequences may point to a potential role for such variants in intellectual disability.

Abstract

Understanding the genetic factors underlying neurodevelopmental and neuropsychiatric disorders is a major challenge given their prevalence and potential severity for quality of life. While large-scale genomic screens have made major advances in this area, for many disorders the genetic underpinnings are complex and poorly understood. To date the field has focused predominantly on protein coding variation, but given the importance of tightly controlled gene expression for normal brain development and disorder, variation that affects non-coding regulatory regions of the genome is likely to play an important role in these phenotypes. Herein we show the importance of 3 prime untranslated region (3'UTR) non-coding regulatory variants across neurodevelopmental and neuropsychiatric disorders. We devised a pipeline for identifying and functionally validating putatively pathogenic variants from next generation sequencing (NGS) data. We applied this pipeline to a cohort of children with severe specific language impairment (SLI) and identified a functional, SLI-associated variant affecting gene regulation in cells and post-mortem human brain. This variant and the affected gene (ARHGEF39) represent new putative risk factors for SLI. Furthermore, we identified 3′UTR regulatory variants across autism, schizophrenia and bipolar disorder NGS cohorts demonstrating their impact on neurodevelopmental and neuropsychiatric disorders. Our findings show the importance of investigating non-coding regulatory variants when determining risk factors contributing to neurodevelopmental and neuropsychiatric disorders. In the future, integration of such regulatory variation with protein coding changes will be essential for uncovering the genetic causes of complex neurological disorders and the fundamental mechanisms underlying health and disease