Publications

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

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

Abstract

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

Abstract

The scavenger receptor C-type lectin (SRCL) is an endothelial receptor that is similar in organization to type A scavenger receptors for modified low density lipoproteins but contains a C-type carbohydrate-recognition domain (CRD). Fragments of the receptor consisting of the entire extracellular domain and the CRD have been expressed and characterized. The extracellular domain is a trimer held together by collagen-like and coiled-coil domains adjacent to the CRD. The amino acid sequence of the CRD is very similar to the CRD of the asialoglycoprotein receptor and other galactose-specific receptors, but SRCL binds selectively to asialo-orosomucoid rather than generally to asialoglycoproteins. Screening of a glycan array and further quantitative binding studies indicate that this selectivity results from high affinity binding to glycans bearing the Lewis(x) trisaccharide. Thus, SRCL shares with the dendritic cell receptor DC-SIGN the ability to bind the Lewis(x) epitope. However, it does so in a fundamentally different way, making a primary binding interaction with the galactose moiety of the glycan rather than the fucose residue. SRCL shares with the asialoglycoprotein receptor the ability to mediate endocytosis and degradation of glycoprotein ligands. These studies suggest that SRCL might be involved in selective clearance of specific desialylated glycoproteins from circulation and/or interaction of cells bearing Lewis(x)-type structures with the vascular endothelium.

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

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

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

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

Abstract

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

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

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

Abstract

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

Abstract

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

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

Abstract

We investigated cooperative problem solving in unrelated pairs of the cooperatively breeding cottontop tamarin, Saguinus oedipus, to assess the cognitive basis of cooperative behaviour in this species and to compare abilities with other apes and monkeys. A transparent apparatus was used that required extension of two handles at opposite ends of the apparatus for access to rewards. Resistance was applied to both handles so that two tamarins had to act simultaneously in order to receive rewards. In contrast to several previous studies of cooperation, both tamarins received rewards as a result of simultaneous pulling. The results from two experiments indicated that the cottontop tamarins (1) had a much higher success rate and efficiency of pulling than many of the other species previously studied, (2) adjusted pulling behaviour to the presence or absence of a partner, and (3) spontaneously developed sustained pulling techniques to solve the task. These findings suggest that cottontop tamarins understand the role of the partner in this cooperative task, a cognitive ability widely ascribed only to great apes. The cooperative social system of tamarins, the intuitive design of the apparatus, and the provision of rewards to both participants may explain the performance of the tamarins.

Abstract

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

Abstract

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

Three groups of listeners identified the vowel in CV and VC syllables produced by an American English talker. The listeners were (a) native speakers of American English, (b) native speakers of Australian English (different dialect), and (c) native speakers of Dutch (different language). The syllables were embedded in multispeaker babble at three signal-to-noise ratios (0 dB, 8 dB, and 16 dB). The identification performance of native listeners was significantly better than that of listeners with another language but did not significantly differ from the performance of listeners with another dialect. Dialect differences did however affect the type of perceptual confusions which listeners made; in particular, the Australian listeners’ judgements of vowel tenseness were more variable than the American listeners’ judgements, which may be ascribed to cross-dialectal differences in this vocalic feature. Although listening difficulty can result when speech input mismatches the native dialect in terms of the precise cues for and boundaries of phonetic categories, the difficulty is very much less than that which arises when speech input mismatches the native language in terms of the repertoire of phonemic categories available.

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

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

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

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

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

Because stress can occur in any position within an Eglish word, lexical prosody could serve as a minimal distinguishing feature between pairs of words. However, most pairs of English words with stress pattern opposition also differ vocalically: OBject an obJECT, CONtent and content have different vowels in their first syllables an well as different stress patters. To test whether prosodic information is made use in auditory word recognition independently of segmental phonetic information, it is necessary to examine pairs like FORbear – forBEAR of TRUSty – trusTEE, semantically unrelated words which echbit stress pattern opposition but no segmental difference. In a cross-modal priming task, such words produce the priming effects characteristic of homophones, indicating that lexical prosody is not used in the same was as segmental structure to constrain lexical access.

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

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

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

The order of some conjoined words is rigidly fixed (e.g. dribs and drabs/*drabs and dribs). Both phonetic and semantic factors can play a role in determining the fixed order. An experiment was conducted to test whether listerners’ reaction times for monitoring a predetermined phoneme are influenced by phonetic constraints on ordering. Two such constraints were investigated: monosyllable-bissyllable and high-low vowel sequences. In English, conjoined words occur in such sequences with much greater frequency than their converses, other factors being equal. Reaction times were significantly shorter for phoneme monitoring in monosyllable-bisyllable sequences than in bisyllable- monosyllable sequences. However, reaction times were not significantly different for high-low vs. low-high vowel sequences.

Abstract

Two bodies of recent research from experimental psycholinguistics are summarised, each of which is centred upon a concept from phonology: LEXICAL STRESS and the SYLLABLE. The evidence indicates that neither construct plays a role in prelexical representations during speech recog- nition. Both constructs, however, are well supported by other performance evidence. Testing phonological claims against performance evidence from psycholinguistics can be difficult, since the results of studies designed to test processing models are often of limited relevance to phonological theory.

Abstract

Four studies are reported in which young children’s response time to detect word targets was measured. Children under about six years of age did not show response time advantage for accented target words which adult listeners show. When semantic focus of the target word was manipulated independently of accent, children of about five years of age showed an adult-like response time advantage for focussed targets, but children younger than five did not. Id is argued that the processing advantage for accented words reflect the semantic role of accent as an expression of sentence focus. Processing advantages for accented words depend on the prior development of representations of sentence semantic structure, including the concept of focus. The previous literature on the development of prosodic competence shows an apparent anomaly in that young children’s productive skills appear to outstrip their receptive skills; however, this anomaly disappears if very young children’s prosody is assumed to be produced without an underlying representation of the relationship between prosody and semantics.

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

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

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

Speech segmentation procedures may differ in speakers of different languages. Earlier work based on French speakers listening to French words suggested that the syllable functions as a segmentation unit in speech processing. However, while French has relatively regular and clearly bounded syllables, other languages, such as English, do not. No trace of syllabifying segmentation was found in English listeners listening to English words, French words, or nonsense words. French listeners, however, showed evidence of syllabification even when they were listening to English words. We conclude that alternative segmentation routines are available to the human language processor. In some cases speech segmentation may involve the operation of more than one procedure

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

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

Vocabularies contain hundreds of thousands of words built from only a handful of phonemes, so that inevitably longer words tend to contain shorter ones. In many languages (but not all) such embedded words occur more often word-initially than word-finally, and this asymmetry, if present, has farreaching consequences for spoken-word recognition. Prior research had ascribed the asymmetry to suffixing or to effects of stress (in particular, final syllables containing the vowel schwa). Analyses of the standard French vocabulary here reveal an effect of suffixing, as predicted by this account, and further analyses of an artificial variety of French reveal that extensive final schwa has an independent and additive effect in promoting the embedding asymmetry.

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

Participants' eye movements to four objects displayed on a computer screen were monitored as the participants clicked on the object named in a spoken instruction. The display contained pictures of the referent (e.g., a snake), a competitor that shared features with the visual representation associated with the referent's concept (e.g., a rope), and two distractor objects (e.g., a couch and an umbrella). As the first sounds of the referent's name were heard, the participants were more likely to fixate the visual competitor than to fixate either of the distractor objects. Moreover, this effect was not modulated by the visual similarity between the referent and competitor pictures, independently estimated in a visual similarity rating task. Because the name of the visual competitor did not overlap with the phonetic input, eye movements reflected word-object matching at the level of lexically activated perceptual features and not merely at the level of preactivated sound forms.

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

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

Abstract

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

Abstract

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

Abstract

Speech comprehension is resistant to acoustic distortion in the input, reflecting listeners' ability to adjust perceptual processes to match the speech input. For noise-vocoded sentences, a manipulation that removes spectral detail from speech, listeners' reporting improved from near 0% to 70% correct over 30 sentences (Experiment 1). Learning was enhanced if listeners heard distorted sentences while they knew the identity of the undistorted target (Experiments 2 and 3). Learning was absent when listeners were trained with nonword sentences (Experiments 4 and 5), although the meaning of the training sentences did not affect learning (Experiment 5). Perceptual learning of noise-vocoded speech depends on higher level information, consistent with top-down, lexically driven learning. Similar processes may facilitate comprehension of speech in an unfamiliar accent or following cochlear implantation.

Abstract

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

Abstract

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 chapter argues that an evolutionary cultural approach to language not only has already proven fruitful, but it probably holds the key to understand many puzzling aspects of language, its change and origins. The chapter begins by highlighting several still common misconceptions about language that might seem to call into question a cultural evolutionary approach. It explores the antiquity of language and sketches a general evolutionary approach discussing the aspects of function, fi tness, replication, and selection, as well the relevant units of linguistic evolution. In this context, the chapter looks at some fundamental aspects of linguistic diversity such as the nature of the design space, the mechanisms generating it, and the shape and fabric of language. Given that biology is another evolutionary system, its complex coevolution with language needs to be understood in order to have a proper theory of language. Throughout the chapter, various challenges are identifi ed and discussed, sketching promising directions for future research. The chapter ends by listing the necessary data, methods, and theoretical developments required for a grounded evolutionary approach to language.

Abstract

The complex inter-relationships between genetics and linguistics encompass all four scales highlighted by the contributions to this book and, together with cultural transmission, the genetics of language holds the promise to offer a unitary understanding of this fascinating phenomenon. There are inter-individual differences in genetic makeup which contribute to the obvious fact that we are not identical in the way we understand and use language and, by studying them, we will be able to both better treat and enhance ourselves. There are correlations between the genetic configuration of human groups and their languages, reflecting the historical processes shaping them, and there also seem to exist genes which can influence some characteristics of language, biasing it towards or against certain states by altering the way language is transmitted across generations. Besides the joys of pure knowledge, the understanding of these three aspects of genetics relevant to language will potentially trigger advances in medicine, linguistics, psychology or the understanding of our own past and, last but not least, a profound change in the way we regard one of the emblems of being human: our capacity for language.

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

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

Abstract

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

Abstract

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.