Publications

Displaying 101 - 200 of 1234
  • Bowerman, M. (1994). From universal to language-specific in early grammatical development. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 346, 34-45. doi:10.1098/rstb.1994.0126.

    Abstract

    Attempts to explain children's grammatical development often assume a close initial match between units of meaning and units of form; for example, agents are said to map to sentence-subjects and actions to verbs. The meanings themselves, according to this view, are not influenced by language, but reflect children's universal non-linguistic way of understanding the world. This paper argues that, contrary to this position, meaning as it is expressed in children's early sentences is, from the beginning, organized on the basis of experience with the grammar and lexicon of a particular language. As a case in point, children learning English and Korean are shown to express meanings having to do with direct motion according to language-specific principles of semantic and grammatical structuring from the earliest stages of word combination
  • Boyle, W., Lindell, A. K., & Kidd, E. (2013). Investigating the role of verbal working memory in young children's sentence comprehension. Language Learning, 63(2), 211-242. doi:10.1111/lang.12003.

    Abstract

    This study considers the role of verbal working memory in sentence comprehension in typically developing English-speaking children. Fifty-six (N = 56) children aged 4;0–6;6 completed a test of language comprehension that contained sentences which varied in complexity, standardized tests of vocabulary and nonverbal intelligence, and three tests of memory that measured the three verbal components of Baddeley's model of Working Memory (WM): the phonological loop, the episodic buffer, and the central executive. The results showed that children experienced most difficulty comprehending sentences that contained noncanonical word order (passives and object relative clauses). A series of linear mixed effects models were run to analyze the contribution of each component of WM to sentence comprehension. In contrast to most previous studies, the measure of the central executive did not predict comprehension accuracy. A canonicity by episodic buffer interaction showed that the episodic buffer measure was positively associated with better performance on the noncanonical sentences. The results are discussed with reference to capacity-limit and experience-dependent approaches to language comprehension.
  • Brandler, W. M., Morris, A. P., Evans, D. M., Scerri, T. S., Kemp, J. P., Timpson, N. J., St Pourcain, B., Davey Smith, G., Ring, S. M., Stein, J., Monaco, A. P., Talcott, J. B., Fisher, S. E., Webber, C., & Paracchini, S. (2013). Common variants in left/right asymmetry genes and pathways are associated with relative hand skill. PLoS Genetics, 9(9): e1003751. doi:10.1371/journal.pgen.1003751.

    Abstract

    Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10−9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development.
  • Brandmeyer, A., Sadakata, M., Spyrou, L., McQueen, J. M., & Desain, P. (2013). Decoding of single-trial auditory mismatch responses for online perceptual monitoring and neurofeedback. Frontiers in Neuroscience, 7: 265. doi:10.3389/fnins.2013.00265.

    Abstract

    Multivariate pattern classification methods are increasingly applied to neuroimaging data in the context of both fundamental research and in brain-computer interfacing approaches. Such methods provide a framework for interpreting measurements made at the single-trial level with respect to a set of two or more distinct mental states. Here, we define an approach in which the output of a binary classifier trained on data from an auditory mismatch paradigm can be used for online tracking of perception and as a neurofeedback signal. The auditory mismatch paradigm is known to induce distinct perceptual states related to the presentation of high- and low-probability stimuli, which are reflected in event-related potential (ERP) components such as the mismatch negativity (MMN). The first part of this paper illustrates how pattern classification methods can be applied to data collected in an MMN paradigm, including discussion of the optimization of preprocessing steps, the interpretation of features and how the performance of these methods generalizes across individual participants and measurement sessions. We then go on to show that the output of these decoding methods can be used in online settings as a continuous index of single-trial brain activation underlying perceptual discrimination. We conclude by discussing several potential domains of application, including neurofeedback, cognitive monitoring and passive brain-computer interfaces

    Additional information

    Brandmeyer_etal_2013a.pdf
  • Brandmeyer, A., Farquhar, J., McQueen, J. M., & Desain, P. (2013). Decoding speech perception by native and non-native speakers using single-trial electrophysiological data. PLoS One, 8: e68261. doi:10.1371/journal.pone.0068261.

    Abstract

    Brain-computer interfaces (BCIs) are systems that use real-time analysis of neuroimaging data to determine the mental state of their user for purposes such as providing neurofeedback. Here, we investigate the feasibility of a BCI based on speech perception. Multivariate pattern classification methods were applied to single-trial EEG data collected during speech perception by native and non-native speakers. Two principal questions were asked: 1) Can differences in the perceived categories of pairs of phonemes be decoded at the single-trial level? 2) Can these same categorical differences be decoded across participants, within or between native-language groups? Results indicated that classification performance progressively increased with respect to the categorical status (within, boundary or across) of the stimulus contrast, and was also influenced by the native language of individual participants. Classifier performance showed strong relationships with traditional event-related potential measures and behavioral responses. The results of the cross-participant analysis indicated an overall increase in average classifier performance when trained on data from all participants (native and non-native). A second cross-participant classifier trained only on data from native speakers led to an overall improvement in performance for native speakers, but a reduction in performance for non-native speakers. We also found that the native language of a given participant could be decoded on the basis of EEG data with accuracy above 80%. These results indicate that electrophysiological responses underlying speech perception can be decoded at the single-trial level, and that decoding performance systematically reflects graded changes in the responses related to the phonological status of the stimuli. This approach could be used in extensions of the BCI paradigm to support perceptual learning during second language acquisition
  • Brascamp, J., Klink, P., & Levelt, W. J. M. (2015). The ‘laws’ of binocular rivalry: 50 years of Levelt’s propositions. Vision Research, 109, 20-37. doi:10.1016/j.visres.2015.02.019.

    Abstract

    It has been fifty years since Levelt’s monograph On Binocular Rivalry (1965) was published, but its four propositions that describe the relation between stimulus strength and the phenomenology of binocular rivalry remain a benchmark for theorists and experimentalists even today. In this review, we will revisit the original conception of the four propositions and the scientific landscape in which this happened. We will also provide a brief update concerning distributions of dominance durations, another aspect of Levelt’s monograph that has maintained a prominent presence in the field. In a critical evaluation of Levelt’s propositions against current knowledge of binocular rivalry we will then demonstrate that the original propositions are not completely compatible with what is known today, but that they can, in a straightforward way, be modified to encapsulate the progress that has been made over the past fifty years. The resulting modified, propositions are shown to apply to a broad range of bistable perceptual phenomena, not just binocular rivalry, and they allow important inferences about the underlying neural systems. We argue that these inferences reflect canonical neural properties that play a role in visual perception in general, and we discuss ways in which future research can build on the work reviewed here to attain a better understanding of these properties
  • Brehm, L., Taschenberger, L., & Meyer, A. S. (2019). Mental representations of partner task cause interference in picture naming. Acta Psychologica, 199: 102888. doi:10.1016/j.actpsy.2019.102888.

    Abstract

    Interference in picture naming occurs from representing a partner's preparations to speak (Gambi, van de Cavey, & Pickering, 2015). We tested the origins of this interference using a simple non-communicative joint naming task based on Gambi et al. (2015), where response latencies indexed interference from partner task and partner speech content, and eye fixations to partner objects indexed overt attention. Experiment 1 contrasted a partner-present condition with a control partner-absent condition to establish the role of the partner in eliciting interference. For latencies, we observed interference from the partner's task and speech content, with interference increasing due to partner task in the partner-present condition. Eye-tracking measures showed that interference in naming was not due to overt attention to partner stimuli but to broad expectations about likely utterances. Experiment 2 examined whether an equivalent non-verbal task also elicited interference, as predicted from a language as joint action framework. We replicated the finding of interference due to partner task and again found no relationship between overt attention and interference. These results support Gambi et al. (2015). Individuals co-represent a partner's task while speaking, and doing so does not require overt attention to partner stimuli.
  • Brehm, L., Jackson, C. N., & Miller, K. L. (2019). Speaker-specific processing of anomalous utterances. Quarterly Journal of Experimental Psychology, 72(4), 764-778. doi:10.1177/1747021818765547.

    Abstract

    Existing work shows that readers often interpret grammatical errors (e.g., The key to the cabinets *were shiny) and sentence-level blends (“without-blend”: Claudia left without her headphones *off) in a non-literal fashion, inferring that a more frequent or more canonical utterance was intended instead. This work examines how interlocutor identity affects the processing and interpretation of anomalous sentences. We presented anomalies in the context of “emails” attributed to various writers in a self-paced reading paradigm and used comprehension questions to probe how sentence interpretation changed based upon properties of the item and properties of the “speaker.” Experiment 1 compared standardised American English speakers to L2 English speakers; Experiment 2 compared the same standardised English speakers to speakers of a non-Standardised American English dialect. Agreement errors and without-blends both led to more non-literal responses than comparable canonical items. For agreement errors, more non-literal interpretations also occurred when sentences were attributed to speakers of Standardised American English than either non-Standardised group. These data suggest that understanding sentences relies on expectations and heuristics about which utterances are likely. These are based upon experience with language, with speaker-specific differences, and upon more general cognitive biases.

    Additional information

    Supplementary material
  • Brehm, L., & Bock, K. (2013). What counts in grammatical number agreement? Cognition, 128(2), 149-169. doi:10.1016/j.cognition.2013.03.009.

    Abstract

    Both notional and grammatical number affect agreement during language production. To explore their workings, we investigated how semantic integration, a type of conceptual relatedness, produces variations in agreement (Solomon & Pearlmutter, 2004). These agreement variations are open to competing notional and lexical–grammatical number accounts. The notional hypothesis is that changes in number agreement reflect differences in referential coherence: More coherence yields more singularity. The lexical–grammatical hypothesis is that changes in agreement arise from competition between nouns differing in grammatical number: More competition yields more plurality. These hypotheses make opposing predictions about semantic integration. On the notional hypothesis, semantic integration promotes singular agreement. On the lexical–grammatical hypothesis, semantic integration promotes plural agreement. We tested these hypotheses with agreement elicitation tasks in two experiments. Both experiments supported the notional hypothesis, with semantic integration creating faster and more frequent singular agreement. This implies that referential coherence mediates the effect of semantic integration on number agreement.
  • Brennan, J. R., & Martin, A. E. (2019). Phase synchronization varies systematically with linguistic structure composition. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences, 375(1791): 20190305. doi:10.1098/rstb.2019.0305.

    Abstract

    Computation in neuronal assemblies is putatively reflected in the excitatory and inhibitory cycles of activation distributed throughout the brain. In speech and language processing, coordination of these cycles resulting in phase synchronization has been argued to reflect the integration of information on different timescales (e.g. segmenting acoustics signals to phonemic and syllabic representations; (Giraud and Poeppel 2012 Nat. Neurosci.15, 511 (doi:10.1038/nn.3063)). A natural extension of this claim is that phase synchronization functions similarly to support the inference of more abstract higher-level linguistic structures (Martin 2016 Front. Psychol.7, 120; Martin and Doumas 2017 PLoS Biol. 15, e2000663 (doi:10.1371/journal.pbio.2000663); Martin and Doumas. 2019 Curr. Opin. Behav. Sci.29, 77–83 (doi:10.1016/j.cobeha.2019.04.008)). Hale et al. (Hale et al. 2018 Finding syntax in human encephalography with beam search. arXiv 1806.04127 (http://arxiv.org/abs/1806.04127)) showed that syntactically driven parsing decisions predict electroencephalography (EEG) responses in the time domain; here we ask whether phase synchronization in the form of either inter-trial phrase coherence or cross-frequency coupling (CFC) between high-frequency (i.e. gamma) bursts and lower-frequency carrier signals (i.e. delta, theta), changes as the linguistic structures of compositional meaning (viz., bracket completions, as denoted by the onset of words that complete phrases) accrue. We use a naturalistic story-listening EEG dataset from Hale et al. to assess the relationship between linguistic structure and phase alignment. We observe increased phase synchronization as a function of phrase counts in the delta, theta, and gamma bands, especially for function words. A more complex pattern emerged for CFC as phrase count changed, possibly related to the lack of a one-to-one mapping between ‘size’ of linguistic structure and frequency band—an assumption that is tacit in recent frameworks. These results emphasize the important role that phase synchronization, desynchronization, and thus, inhibition, play in the construction of compositional meaning by distributed neural networks in the brain.
  • Broeder, D., & Lannom, L. (2014). Data Type Registries: A Research Data Alliance Working Group. D-Lib Magazine, 20, 1. doi:10.1045/january2014-broeder.

    Abstract

    Automated processing of large amounts of scientific data, especially across domains, requires that the data can be selected and parsed without human intervention. Precise characterization of that data, as in typing, is needed once the processing goes beyond the realm of domain specific or local research group assumptions. The Research Data Alliance (RDA) Data Type Registries Working Group (DTR-WG) was assembled to address this issue through the creation of a Data Type Registry methodology, data model, and prototype. The WG was approved by the RDA Council during March of 2013 and will complete its work in mid-2014, in between the third and fourth RDA Plenaries.
  • Brouwer, S., & Bradlow, A. R. (2014). Contextual variability during speech-in-speech recognition. The Journal of the Acoustical Society of America, 136(1), EL26-EL32. doi:10.1121/1.4881322.

    Abstract

    This study examined the influence of background language variation on speech recognition. English listeners performed an English sentence recognition task in either “pure” background conditions in which all trials had either English or Dutch background babble or in mixed background conditions in which the background language varied across trials (i.e., a mix of English and Dutch or one of these background languages mixed with quiet trials). This design allowed the authors to compare performance on identical trials across pure and mixed conditions. The data reveal that speech-in-speech recognition is sensitive to contextual variation in terms of the target-background language (mis)match depending on the relative ease/difficulty of the test trials in relation to the surrounding trials.
  • Brouwer, S. (2013). Continuous recognition memory for spoken words in noise. Proceedings of Meetings on Acoustics, 19: 060117. doi:10.1121/1.4798781.

    Abstract

    Previous research has shown that talker variability affects recognition memory for spoken words (Palmeri et al., 1993). This study examines whether additive noise is similarly retained in memory for spoken words. In a continuous recognition memory task, participants listened to a list of spoken words mixed with noise consisting of a pure tone or of high-pass filtered white noise. The noise and speech were in non-overlapping frequency bands. In Experiment 1, listeners indicated whether each spoken word in the list was OLD (heard before in the list) or NEW. Results showed that listeners were as accurate and as fast at recognizing a word as old if it was repeated with the same or different noise. In Experiment 2, listeners also indicated whether words judged as OLD were repeated with the same or with a different type of noise. Results showed that listeners benefitted from hearing words presented with the same versus different noise. These data suggest that spoken words and temporally-overlapping but spectrally non-overlapping noise are retained or reconstructed together for explicit, but not for implicit recognition memory. This indicates that the extent to which noise variability is retained seems to depend on the depth of processing
  • Brouwer, S., Mitterer, H., & Huettig, F. (2013). Discourse context and the recognition of reduced and canonical spoken words. Applied Psycholinguistics, 34, 519-539. doi:10.1017/S0142716411000853.

    Abstract

    In two eye-tracking experiments we examined whether wider discourse information helps
    the recognition of reduced pronunciations (e.g., 'puter') more than the recognition of
    canonical pronunciations of spoken words (e.g., 'computer'). Dutch participants listened to
    sentences from a casual speech corpus containing canonical and reduced target words. Target
    word recognition was assessed by measuring eye fixation proportions to four printed words
    on a visual display: the target, a "reduced form" competitor, a "canonical form" competitor
    and an unrelated distractor. Target sentences were presented in isolation or with a wider
    discourse context. Experiment 1 revealed that target recognition was facilitated by wider
    discourse information. Importantly, the recognition of reduced forms improved significantly
    when preceded by strongly rather than by weakly supportive discourse contexts. This was not
    the case for canonical forms: listeners' target word recognition was not dependent on the
    degree of supportive context. Experiment 2 showed that the differential context effects in
    Experiment 1 were not due to an additional amount of speaker information. Thus, these data
    suggest that in natural settings a strongly supportive discourse context is more important for
    the recognition of reduced forms than the recognition of canonical forms.
  • Brouwer, S., & Bradlow, A. R. (2015). The temporal dynamics of spoken word recognition in adverse listening conditions. Journal of Psycholinguistic Research. Advanced online publication. doi:10.1007/s10936-015-9396-9.

    Abstract

    This study examined the temporal dynamics of spoken word recognition in noise and background speech. In two visual-world experiments, English participants listened to target words while looking at four pictures on the screen: a target (e.g. candle), an onset competitor (e.g. candy), a rhyme competitor (e.g. sandal), and an unrelated distractor (e.g. lemon). Target words were presented in quiet, mixed with broadband noise, or mixed with background speech. Results showed that lexical competition changes throughout the observation window as a function of what is presented in the background. These findings suggest that, rather than being strictly sequential, stream segregation and lexical competition interact during spoken word recognition
  • Brown, C. M., Van Berkum, J. J. A., & Hagoort, P. (2000). Discourse before gender: An event-related brain potential study on the interplay of semantic and syntactic information during spoken language understanding. Journal of Psycholinguistic Research, 29(1), 53-68. doi:10.1023/A:1005172406969.

    Abstract

    A study is presented on the effects of discourse–semantic and lexical–syntactic information during spoken sentence processing. Event-related brain potentials (ERPs) were registered while subjects listened to discourses that ended in a sentence with a temporary syntactic ambiguity. The prior discourse–semantic information biased toward one analysis of the temporary ambiguity, whereas the lexical-syntactic information allowed only for the alternative analysis. The ERP results show that discourse–semantic information can momentarily take precedence over syntactic information, even if this violates grammatical gender agreement rules.
  • Brown, C. M., Hagoort, P., & Chwilla, D. J. (2000). An event-related brain potential analysis of visual word priming effects. Brain and Language, 72, 158-190. doi:10.1006/brln.1999.2284.

    Abstract

    Two experiments are reported that provide evidence on task-induced effects during
    visual lexical processing in a primetarget semantic priming paradigm. The research focuses on target expectancy effects by manipulating the proportion of semantically related and unrelated word pairs. In Experiment 1, a lexical decision task was used and reaction times (RTs) and event-related brain potentials (ERPs) were obtained. In Experiment 2, subjects silently read the stimuli, without any additional task demands, and ERPs were recorded. The RT and ERP results of Experiment 1 demonstrate that an expectancy mechanism contributed to the priming effect when a high proportion of related word pairs was presented. The ERP results of Experiment 2 show that in the absence of extraneous task requirements, an expectancy mechanism is not active. However, a standard ERP semantic priming effect was obtained in Experiment 2. The combined results show that priming effects due to relatedness proportion are induced by task demands and are not a standard aspect of online lexical processing.
  • Brown, A., & Gullberg, M. (2013). L1–L2 convergence in clausal packaging in Japanese and English. Bilingualism: Language and Cognition, 16, 477-494. doi:10.1017/S1366728912000491.

    Abstract

    This research received technical and financial support from Syracuse University, the Max Planck Institute for Psycholinguistics, and the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO; MPI 56-384, The Dynamics of Multilingual Processing, awarded to Marianne Gullberg and Peter Indefrey).
  • Brown, P. (1994). The INs and ONs of Tzeltal locative expressions: The semantics of static descriptions of location. Linguistics, 32, 743-790.

    Abstract

    This paper explores how static topological spatial relations such as contiguity, contact, containment, and support are expressed in the Mayan language Tzeltal. Three distinct Tzeltal systems for describing spatial relationships - geographically anchored (place names, geographical coordinates), viewer-centered (deictic), and object-centered (body parts, relational nouns, and dispositional adjectives) - are presented, but the focus here is on the object-centered system of dispositional adjectives in static locative expressions. Tzeltal encodes shape/position/configuration gestalts in verb roots; predicates formed from these are an essential element in locative descriptions. Specificity of shape in the predicate allows spatial reltaions between figure and ground objects to be understood by implication. Tzeltal illustrates an alternative stragegy to that of prepositional languages like English: rather than elaborating shape distinctions in the nouns and minimizing them in the locatives, Tzeltal encodes shape and configuration very precisely in verb roots, leaving many object nouns unspecified for shape. The Tzeltal case thus presents a direct challenge to cognitive science claims that, in both languge and cognition, WHAT is kept distinct from WHERE.
  • Brown-Schmidt, S., & Konopka, A. E. (2015). Processes of incremental message planning during conversation. Psychonomic Bulletin & Review, 22, 833-843. doi:10.3758/s13423-014-0714-2.

    Abstract

    Speaking begins with the formulation of an intended preverbal message and linguistic encoding of this information. The transition from thought to speech occurs incrementally, with cascading planning at subsequent levels of production. In this article, we aim to specify the mechanisms that support incremental message preparation. We contrast two hypotheses about the mechanisms responsible for incorporating message-level information into a linguistic plan. According to the Initial Preparation view, messages can be encoded as fluent utterances if all information is ready before speaking begins. By contrast, on the Continuous Incrementality view, messages can be continually prepared and updated throughout the production process, allowing for fluent production even if new information is added to the message while speaking is underway. Testing these hypotheses, eye-tracked speakers in two experiments produced unscripted, conjoined noun phrases with modifiers. Both experiments showed that new message elements can be incrementally incorporated into the utterance even after articulation begins, consistent with a Continuous Incrementality view of message planning, in which messages percolate to linguistic encoding immediately as that information becomes available in the mind of the speaker. We conclude by discussing the functional role of incremental message planning in conversational speech and the situations in which this continuous incremental planning would be most likely to be observed
  • Brucato, N., Guadalupe, T., Franke, B., Fisher, S. E., & Francks, C. (2015). A schizophrenia-associated HLA locus affects thalamus volume and asymmetry. Brain, Behavior, and Immunity, 46, 311-318. doi:10.1016/j.bbi.2015.02.021.

    Abstract

    Genes of the Major Histocompatibility Complex (MHC) have recently been shown to have neuronal functions in the thalamus and hippocampus. Common genetic variants in the Human Leukocyte Antigens (HLA) region, human homologue of the MHC locus, are associated with small effects on susceptibility to schizophrenia, while volumetric changes of the thalamus and hippocampus have also been linked to schizophrenia. We therefore investigated whether common variants of the HLA would affect volumetric variation of the thalamus and hippocampus. We analyzed thalamus and hippocampus volumes, as measured using structural magnetic resonance imaging, in 1.265 healthy participants. These participants had also been genotyped using genome-wide single nucleotide polymorphism (SNP) arrays. We imputed genotypes for single nucleotide polymorphisms at high density across the HLA locus, as well as HLA allotypes and HLA amino acids, by use of a reference population dataset that was specifically targeted to the HLA region. We detected a significant association of the SNP rs17194174 with thalamus volume (nominal P=0.0000017, corrected P=0.0039), as well as additional SNPs within the same region of linkage disequilibrium. This effect was largely lateralized to the left thalamus and is localized within a genomic region previously associated with schizophrenia. The associated SNPs are also clustered within a potential regulatory element, and a region of linkage disequilibrium that spans genes expressed in the thalamus, including HLA-A. Our data indicate that genetic variation within the HLA region influences the volume and asymmetry of the human thalamus. The molecular mechanisms underlying this association may relate to HLA influences on susceptibility to schizophrenia
  • Brucato, N., DeLisi, L. E., Fisher, S. E., & Francks, C. (2014). Hypomethylation of the paternally inherited LRRTM1 promoter linked to schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 165(7), 555-563. doi:10.1002/ajmg.b.32258.

    Abstract

    Epigenetic effects on psychiatric traits remain relatively under-studied, and it remains unclear what the sizes of individual epigenetic effects may be, or how they vary between different clinical populations. The gene LRRTM1 (chromosome 2p12) has previously been linked and associated with schizophrenia in a parent-of-origin manner in a set of affected siblings (LOD = 4.72), indirectly suggesting a disruption of paternal imprinting at this locus in these families. From the same set of siblings that originally showed strong linkage at this locus, we analyzed 99 individuals using 454-bisulfite sequencing, from whole blood DNA, to measure the level of DNA methylation in the promoter region of LRRTM1. We also assessed seven additional loci that would be informative to compare. Paternal identity-by-descent sharing at LRRTM1, within sibling pairs, was linked to their similarity of methylation at the gene's promoter. Reduced methylation at the promoter showed a significant association with schizophrenia. Sibling pairs concordant for schizophrenia showed more similar methylation levels at the LRRTM1 promoter than diagnostically discordant pairs. The alleles of common SNPs spanning the locus did not explain this epigenetic linkage, which can therefore be considered as largely independent of DNA sequence variation and would not be detected in standard genetic association analysis. Our data suggest that hypomethylation at the LRRTM1 promoter, particularly of the paternally inherited allele, was a risk factor for the development of schizophrenia in this set of siblings affected with familial schizophrenia, and that had previously showed linkage at this locus in an affected-sib-pair context.
  • Buetti, S., Tamietto, M., Hervais-Adelman, A., Kerzel, D., de Gelder, B., & Pegna, A. J. (2013). Dissociation between goal-directed and discrete response localization in a patient with bilateral cortical blindness. Journal of Cognitive Neuroscience, 25(10), 1769-1775. doi:10.1162/jocn_a_00404.

    Abstract

    We investigated localization performance of simple targets in patient TN, who suffered bilateral damage of his primary visual cortex and shows complete cortical blindness. Using a two-alternative forced-choice paradigm, TN was asked to guess the position of left-right targets with goal-directed and discrete manual responses. The results indicate a clear dissociation between goal-directed and discrete responses. TN pointed toward the correct target location in approximately 75% of the trials but was at chance level with discrete responses. This indicates that the residual ability to localize an unseen stimulus depends critically on the possibility to translate a visual signal into a goal-directed motor output at least in certain forms of blindsight.
  • Bull, L. E., Oliver, C., Callaghan, E., & Woodcock, K. A. (2015). Increased Exposure to Rigid Routines can Lead to Increased Challenging Behavior Following Changes to Those Routines. Journal of Autism and Developmental Disorders, 45(6), 1569-1578. doi:10.1007/s10803-014-2308-2.

    Abstract

    Several neurodevelopmental disorders are associated with preference for routine and challenging behavior following changes to routines. We examine individuals with Prader–Willi syndrome, who show elevated levels of this behavior, to better understand how previous experience of a routine can affect challenging behavior elicited by disruption to that routine. Play based challenges exposed 16 participants to routines, which were either adhered to or changed. Temper outburst behaviors, heart rate and movement were measured. As participants were exposed to routines for longer before a change (between 10 and 80 min; within participants), more temper outburst behaviors were elicited by changes. Increased emotional arousal was also elicited, which was indexed by heart rate increases not driven by movement. Further study will be important to understand whether current intervention approaches that limit exposure to changes, may benefit from the structured integration of flexibility to ensure that the opportunity for routine establishment is also limited.

    Additional information

    10803_2014_2308_MOESM1_ESM.docx
  • Burra, N., Hervais-Adelman, A., Kerzel, D., Tamietto, M., de Gelder, B., & Pegna, A. J. (2013). Amygdala Activation for Eye Contact Despite Complete Cortical Blindness. The Journal of Neuroscience, 33(25), 10483-10489. doi:10.1523/jneurosci.3994-12.2013.

    Abstract

    Cortical blindness refers to the loss of vision that occurs after destruction of the primary visual cortex. Although there is no sensory cortex and hence no conscious vision, some cortically blind patients show amygdala activation in response to facial or bodily expressions of emotion. Here we investigated whether direction of gaze could also be processed in the absence of any functional visual cortex. A well-known patient with bilateral destruction of his visual cortex and subsequent cortical blindness was investigated in an fMRI paradigm during which blocks of faces were presented either with their gaze directed toward or away from the viewer. Increased right amygdala activation was found in response to directed compared with averted gaze. Activity in this region was further found to be functionally connected to a larger network associated with face and gaze processing. The present study demonstrates that, in human subjects, the amygdala response to eye contact does not require an intact primary visual cortex.
  • Burra, N., Hervais-Adelman, A., Celeghin, A., de Gelder, B., & Pegna, A. J. (2019). Affective blindsight relies on low spatial frequencies. Neuropsychologia, 128, 44-49. doi:10.1016/j.neuropsychologia.2017.10.009.

    Abstract

    The human brain can process facial expressions of emotions rapidly and without awareness. Several studies in patients with damage to their primary visual cortices have shown that they may be able to guess the emotional expression on a face despite their cortical blindness. This non-conscious processing, called affective blindsight, may arise through an intact subcortical visual route that leads from the superior colliculus to the pulvinar, and thence to the amygdala. This pathway is thought to process the crude visual information conveyed by the low spatial frequencies of the stimuli.

    In order to investigate whether this is the case, we studied a patient (TN) with bilateral cortical blindness and affective blindsight. An fMRI paradigm was performed in which fearful and neutral expressions were presented using faces that were either unfiltered, or filtered to remove high or low spatial frequencies. Unfiltered fearful faces produced right amygdala activation although the patient was unaware of the presence of the stimuli. More importantly, the low spatial frequency components of fearful faces continued to produce right amygdala activity while the high spatial frequency components did not. Our findings thus confirm that the visual information present in the low spatial frequencies is sufficient to produce affective blindsight, further suggesting that its existence could rely on the subcortical colliculo-pulvino-amygdalar pathway.
  • Cai, D., Fonteijn, H. M., Guadalupe, T., Zwiers, M., Wittfeld, K., Teumer, A., Hoogman, M., Arias Vásquez, A., Yang, Y., Buitelaar, J., Fernández, G., Brunner, H. G., Van Bokhoven, H., Franke, B., Hegenscheid, K., Homuth, G., Fisher, S. E., Grabe, H. J., Francks, C., & Hagoort, P. (2014). A genome wide search for quantitative trait loci affecting the cortical surface area and thickness of Heschl's gyrus. Genes, Brain and Behavior, 13, 675-685. doi:10.1111/gbb.12157.

    Abstract

    Heschl's gyrus (HG) is a core region of the auditory cortex whose morphology is highly variable across individuals. This variability has been linked to sound perception ability in both speech and music domains. Previous studies show that variations in morphological features of HG, such as cortical surface area and thickness, are heritable. To identify genetic variants that affect HG morphology, we conducted a genome-wide association scan (GWAS) meta-analysis in 3054 healthy individuals using HG surface area and thickness as quantitative traits. None of the single nucleotide polymorphisms (SNPs) showed association P values that would survive correction for multiple testing over the genome. The most significant association was found between right HG area and SNP rs72932726 close to gene DCBLD2 (3q12.1; P=2.77x10(-7)). This SNP was also associated with other regions involved in speech processing. The SNP rs333332 within gene KALRN (3q21.2; P=2.27x10(-6)) and rs143000161 near gene COBLL1 (2q24.3; P=2.40x10(-6)) were associated with the area and thickness of left HG, respectively. Both genes are involved in the development of the nervous system. The SNP rs7062395 close to the X-linked deafness gene POU3F4 was associated with right HG thickness (Xq21.1; P=2.38x10(-6)). This is the first molecular genetic analysis of variability in HG morphology
  • Cai, Z. G., Conell, L., & Holler, J. (2013). Time does not flow without language: Spatial distance affects temporal duration regardless of movement or direction. Psychonomic Bulletin & Review, 20(5), 973-980. doi:10.3758/s13423-013-0414-3.

    Abstract

    Much evidence has suggested that people conceive of time as flowing directionally in transverse space (e.g., from left to right for English speakers). However, this phenomenon has never been tested in a fully nonlinguistic paradigm where neither stimuli nor task use linguistic labels, which raises the possibility that time is directional only when reading/writing direction has been evoked. In the present study, English-speaking participants viewed a video where an actor sang a note while gesturing and reproduced the duration of the sung note by pressing a button. Results showed that the perceived duration of the note was increased by a long-distance gesture, relative to a short-distance gesture. This effect was equally strong for gestures moving from left to right and from right to left and was not dependent on gestures depicting movement through space; a weaker version of the effect emerged with static gestures depicting spatial distance. Since both our gesture stimuli and temporal reproduction task were nonlinguistic, we conclude that the spatial representation of time is nondirectional: Movement contributes, but is not necessary, to the representation of temporal information in a transverse timeline.
  • Calandruccio, L., Brouwer, S., Van Engen, K. J., Dhar, S., & Bradlow, A. R. (2013). Masking release due to linguistic and phonetic dissimilarity between the target and masker speech. American Journal of Audiology, 22, 157-164. doi:10.1044/1059-0889(2013/12-0072.

    Abstract

    Purpose: To investigate masking release for speech maskers for linguistically and phonetically close (English and Dutch) and distant (English and Mandarin) language pairs. Method: Thirty-two monolingual speakers of English with normal audiometric thresholds participated in the study. Data are reported for an English sentence recognition task in English and for Dutch and Mandarin competing speech maskers (Experiment 1) and noise maskers (Experiment 2) that were matched either to the long-term average speech spectra or to the temporal modulations of the speech maskers from Experiment 1. Results: Listener performance increased as the target-tomasker linguistic distance increased (English-in-English < English-in-Dutch < English-in-Mandarin). Conclusion: Spectral differences between maskers can account for some, but not all, of the variation in performance between maskers; however, temporal differences did not seem to play a significant role.
  • Caldwell-Harris, C. L., Lancaster, A., Ladd, D. R., Dediu, D., & Christiansen, M. H. (2015). Factors influencing sensitivity to lexical tone in an artificial language: Implications for second language learning. Studies in Second Language Acquisition, 37(2), 335-357. doi:10.1017/S0272263114000849.

    Abstract

    This study examined whether musical training, ethnicity, and experience with a natural tone language influenced sensitivity to tone while listening to an artificial tone language. The language was designed with three tones, modeled after level-tone African languages. Participants listened to a 15-min random concatenation of six 3-syllable words. Sensitivity to tone was assessed using minimal pairs differing only in one syllable (nonword task: e.g., to-kà-su compared to ca-fí-to) or only in tone (tone task: e.g., to-kà-su compared to to-ká-su). Proficiency in an East Asian heritage language was the strongest predictor of success on the tone task. Asians without tone language experience were no better than other ethnic groups. We conclude by considering implications for research on second language learning, especially as approached through artificial language learning.
  • Calkoen, F., Vervat, C., van Pel, M., de Haas, V., Vijfhuizen, L., Eising, E., Kroes, W., Hoen, P., van den Heuvel-Eibrink, M., Egeler, R., Van Tol, M., & Ball, L. (2015). Despite differential gene expression profiles pediatric MDS derived mesenchymal stromal cells display functionality in vitro. Stem Cell Research, 14(2), 198-210. doi:10.1016/j.scr.2015.01.006.

    Abstract

    Pediatric myelodysplastic syndrome (MDS) is a heterogeneous disease covering a spectrum ranging from aplasia (RCC) to myeloproliferation (RAEB(t)). In adult-type MDS there is increasing evidence for abnormal function of the bone-marrow microenvironment. Here, we extensively studied the mesenchymal stromal cells (MSCs) derived from children with MDS. MSCs were expanded from the bone-marrow of 17 MDS patients (RCC: n = 10 and advanced MDS: n = 7) and pediatric controls (n = 10). No differences were observed with respect to phenotype, differentiation capacity, immunomodulatory capacity or hematopoietic support. mRNA expression analysis by Deep-SAGE revealed increased IL-6 expression in RCC- and RAEB(t)-MDS. RCC-MDS MSC expressed increased levels of DKK3, a protein associated with decreased apoptosis. RAEB(t)-MDS revealed increased CRLF1 and decreased DAPK1 expressions. This pattern has been associated with transformation in hematopoietic malignancies. Genes reported to be differentially expressed in adult MDS-MSC did not differ between MSC of pediatric MDS and controls. An altered mRNA expression profile, associated with cell survival and malignant transformation, of MSC derived from children with MDS strengthens the hypothesis that the micro-environment is of importance in this disease. Our data support the understanding that pediatric and adult MDS are two different diseases. Further evaluation of the pathways involved might reveal additional therapy targets.
  • Calkoen, F. G., Vervat, C., Eising, E., Vijfhuizen, L. S., 't Hoen, P.-B.-A., van den Heuvel-Eibrink, M. M., & Egeler, R. M. (2015). Gene-expression and in vitro function of mesenchymal stromal cells are affected in juvenile myelomonocytic leukemia. Haematologica, 100(11), 1434-1441. doi:10.3324/haematol.2015.126938.

    Abstract

    An aberrant interaction between hematopoietic stem cells and mesenchymal stromal cells has been linked to disease and shown to contribute to the pathophysiology of hematologic malignancies in murine models. Juvenile myelomonocytic leukemia is an aggressive malignant disease affecting young infants. Here we investigated the impact of juvenile myelomonocytic leukemia on mesenchymal stromal cells. Mesenchymal stromal cells were expanded from bone marrow samples of patients at diagnosis (n=9) and after hematopoietic stem cell transplantation (n=7; from 5 patients) and from healthy children (n=10). Cells were characterized by phenotyping, differentiation, gene expression analysis (of controls and samples obtained at diagnosis) and in vitro functional studies assessing immunomodulation and hematopoietic support. Mesenchymal stromal cells from patients did not differ from controls in differentiation capacity nor did they differ in their capacity to support in vitro hematopoiesis. Deep-SAGE sequencing revealed differential mRNA expression in patient-derived samples, including genes encoding proteins involved in immunomodulation and cell-cell interaction. Selected gene expression normalized during remission after successful hematopoietic stem cell transplantation. Whereas natural killer cell activation and peripheral blood mononuclear cell proliferation were not differentially affected, the suppressive effect on monocyte to dendritic cell differentiation was increased by mesenchymal stromal cells obtained at diagnosis, but not at time of remission. This study shows that active juvenile myelomonocytic leukemia affects the immune response-related gene expression and function of mesenchymal stromal cells. In contrast, the differential gene expression of hematopoiesis-related genes could not be supported by functional data. Decreased immune surveillance might contribute to the therapy resistance and progression in juvenile myelomonocytic leukemia.
  • Campisi, E., & Ozyurek, A. (2013). Iconicity as a communicative strategy: Recipient design in multimodal demonstrations for adults and children. Journal of Pragmatics, 47, 14-27. doi:10.1016/j.pragma.2012.12.007.

    Abstract

    Humans are the only species that uses communication to teach new knowledge to novices, usually to children (Tomasello, 1999 and Csibra and Gergely, 2006). This context of communication can employ “demonstrations” and it takes place with or without the help of objects (Clark, 1996). Previous research has focused on understanding the nature of demonstrations for very young children and with objects involved. However, little is known about the strategies used in demonstrating an action to an older child in comparison to another adult and without the use of objects, i.e., with gestures only. We tested if during demonstration of an action speakers use different degrees of iconicity in gestures for a child compared to an adult. 18 Italian subjects described to a camera how to make coffee imagining the listener as a 12-year-old child, a novice or an expert adult. While speech was found more informative both for the novice adult and for the child compared to the expert adult, the rate of iconic gestures increased and they were more informative and bigger only for the child compared to both of the adult conditions. Iconicity in gestures can be a powerful communicative strategy in teaching new knowledge to children in demonstrations and this is in line with claims that it can be used as a scaffolding device in grounding knowledge in experience (Perniss et al., 2010).
  • Capilla, A., Schoffelen, J.-M., Paterson, G., Thut, G., & Gross, J. (2014). Dissociated α-band modulations in the dorsal and ventral visual pathways in visuospatial attention and perception. Cerebral Cortex., 24(2), 550-561. doi:10.1093/cercor/bhs343.

    Abstract

    Modulations of occipito-parietal α-band (8–14 Hz) power that are opposite in direction (α-enhancement vs. α-suppression) and origin of generation (ipsilateral vs. contralateral to the locus of attention) are a robust correlate of anticipatory visuospatial attention. Yet, the neural generators of these α-band modulations, their interdependence across homotopic areas, and their respective contribution to subsequent perception remain unclear. To shed light on these questions, we employed magnetoencephalography, while human volunteers performed a spatially cued detection task. Replicating previous findings, we found α-power enhancement ipsilateral to the attended hemifield and contralateral α-suppression over occipitoparietal sensors. Source localization (beamforming) analysis showed that α-enhancement and suppression were generated in 2 distinct brain regions, located in the dorsal and ventral visual streams, respectively. Moreover, α-enhancement and suppression showed different dynamics and contribution to perception. In contrast to the initial and transient dorsal α-enhancement, α-suppression in ventro-lateral occipital cortex was sustained and influenced subsequent target detection. This anticipatory biasing of ventrolateral extrastriate α-activity probably reflects increased receptivity in the brain region specialized in processing upcoming target features. Our results add to current models on the role of α-oscillations in attention orienting by showing that α-enhancement and suppression can be dissociated in time, space, and perceptual relevance.

    Additional information

    Capilla_Suppl_Data.pdf
  • Cappuccio, M. L., Chu, M., & Kita, S. (2013). Pointing as an instrumental gesture: Gaze representation through indication. Humana.Mente: Journal of Philosophical Studies, 24, 125-149.

    Abstract

    We call those gestures “instrumental” that can enhance certain thinking processes of an agent by offering him representational models of his actions in a virtual space of imaginary performative possibilities. We argue that pointing is an instrumental gesture in that it represents geometrical information on one’s own gaze direction (i.e., a spatial model for attentional/ocular fixation/orientation), and provides a ritualized template for initiating gaze coordination and joint attention. We counter two possible objections, asserting respectively that the representational content of pointing is not constitutive, but derived from language, and that pointing directly solicits gaze coordination, without representing it. We consider two studies suggesting that attention and spatial perception are actively modified by one’s own pointing activity: the first study shows that pointing gestures help children link sets of objects to their corresponding number words; the second, that adults are faster and more accurate in counting when they point.
  • Capredon, M., Brucato, N., Tonasso, L., Choesmel-Cadamuro, V., Ricaut, F.-X., Razafindrazaka, H., Ratolojanahary, M. A., Randriamarolaza, L.-P., Champion, B., & Dugoujon, J.-M. (2013). Tracing Arab-Islamic Inheritance in Madagascar: Study of the Y-chromosome and Mitochondrial DNA in the Antemoro. PLoS One, 8(11): e80932. doi:10.1371/journal.pone.0080932.

    Abstract

    Madagascar is located at the crossroads of the Asian and African worlds and is therefore of particular interest for studies on human population migration. Within the large human diversity of the Great Island, we focused our study on a particular ethnic group, the Antemoro. Their culture presents an important Arab-Islamic influence, but the question of an Arab biological inheritance remains unresolved. We analyzed paternal (n=129) and maternal (n=135) lineages of this ethnic group. Although the majority of Antemoro genetic ancestry comes from sub-Saharan African and Southeast Asian gene pools, we observed in their paternal lineages two specific haplogroups (J1 and T1) linked to Middle Eastern origins. This inheritance was restricted to some Antemoro sub-groups. Statistical analyses tended to confirm significant Middle Eastern genetic contribution. This study gives a new perspective to the large human genetic diversity in Madagascar
  • Carlsson, K., Petrovic, P., Skare, S., Petersson, K. M., & Ingvar, M. (2000). Tickling expectations: Neural processing in anticipation of a sensory stimulus. Journal of Cognitive Neuroscience, 12(4), 691-703. doi:10.1162/089892900562318.
  • Carrion Castillo, A., Van der Haegen, L., Tzourio-Mazoyer, N., Kavaklioglu, T., Badillo, S., Chavent, M., Saracco, J., Brysbaert, M., Fisher, S. E., Mazoyer, B., & Francks, C. (2019). Genome sequencing for rightward hemispheric language dominance. Genes, Brain and Behavior, 18(5): e12572. doi:10.1111/gbb.12572.

    Abstract

    Most people have left‐hemisphere dominance for various aspects of language processing, but only roughly 1% of the adult population has atypically reversed, rightward hemispheric language dominance (RHLD). The genetic‐developmental program that underlies leftward language laterality is unknown, as are the causes of atypical variation. We performed an exploratory whole‐genome‐sequencing study, with the hypothesis that strongly penetrant, rare genetic mutations might sometimes be involved in RHLD. This was by analogy with situs inversus of the visceral organs (left‐right mirror reversal of the heart, lungs and so on), which is sometimes due to monogenic mutations. The genomes of 33 subjects with RHLD were sequenced and analyzed with reference to large population‐genetic data sets, as well as 34 subjects (14 left‐handed) with typical language laterality. The sample was powered to detect rare, highly penetrant, monogenic effects if they would be present in at least 10 of the 33 RHLD cases and no controls, but no individual genes had mutations in more than five RHLD cases while being un‐mutated in controls. A hypothesis derived from invertebrate mechanisms of left‐right axis formation led to the detection of an increased mutation load, in RHLD subjects, within genes involved with the actin cytoskeleton. The latter finding offers a first, tentative insight into molecular genetic influences on hemispheric language dominance.

    Additional information

    gbb12572-sup-0001-AppendixS1.docx
  • Carrion Castillo, A., Franke, B., & Fisher, S. E. (2013). Molecular genetics of dyslexia: An overview. Dyslexia, 19(4), 214-240. doi:10.1002/dys.1464.

    Abstract

    Dyslexia is a highly heritable learning disorder with a complex underlying genetic architecture. Over the past decade, researchers have pinpointed a number of candidate genes that may contribute to dyslexia susceptibility. Here, we provide an overview of the state of the art, describing how studies have moved from mapping potential risk loci, through identification of associated gene variants, to characterization of gene function in cellular and animal model systems. Work thus far has highlighted some intriguing mechanistic pathways, such as neuronal migration, axon guidance, and ciliary biology, but it is clear that we still have much to learn about the molecular networks that are involved. We end the review by highlighting the past, present, and future contributions of the Dutch Dyslexia Programme to studies of genetic factors. In particular, we emphasize the importance of relating genetic information to intermediate neurobiological measures, as well as the value of incorporating longitudinal and developmental data into molecular designs
  • Casillas, M., & Cristia, A. (2019). A step-by-step guide to collecting and analyzing long-format speech environment (LFSE) recordings. Collabra, 5(1): 24. doi:10.1525/collabra.209.

    Abstract

    Recent years have seen rapid technological development of devices that can record communicative behavior as participants go about daily life. This paper is intended as an end-to-end methodological guidebook for potential users of these technologies, including researchers who want to study children’s or adults’ communicative behavior in everyday contexts. We explain how long-format speech environment (LFSE) recordings provide a unique view on language use and how they can be used to complement other measures at the individual and group level. We aim to help potential users of these technologies make informed decisions regarding research design, hardware, software, and archiving. We also provide information regarding ethics and implementation, issues that are difficult to navigate for those new to this technology, and on which little or no resources are available. This guidebook offers a concise summary of information for new users and points to sources of more detailed information for more advanced users. Links to discussion groups and community-augmented databases are also provided to help readers stay up-to-date on the latest developments.
  • Casillas, M., Rafiee, A., & Majid, A. (2019). Iranian herbalists, but not cooks, are better at naming odors than laypeople. Cognitive Science, 43(6): e12763. doi:10.1111/cogs.12763.

    Abstract

    Odor naming is enhanced in communities where communication about odors is a central part of daily life (e.g., wine experts, flavorists, and some hunter‐gatherer groups). In this study, we investigated how expert knowledge and daily experience affect the ability to name odors in a group of experts that has not previously been investigated in this context—Iranian herbalists; also called attars—as well as cooks and laypeople. We assessed naming accuracy and consistency for 16 herb and spice odors, collected judgments of odor perception, and evaluated participants' odor meta‐awareness. Participants' responses were overall more consistent and accurate for more frequent and familiar odors. Moreover, attars were more accurate than both cooks and laypeople at naming odors, although cooks did not perform significantly better than laypeople. Attars' perceptual ratings of odors and their overall odor meta‐awareness suggest they are also more attuned to odors than the other two groups. To conclude, Iranian attars—but not cooks—are better odor namers than laypeople. They also have greater meta‐awareness and differential perceptual responses to odors. These findings further highlight the critical role that expertise and type of experience have on olfactory functions.

    Additional information

    Supplementary Materials
  • Castells-Nobau, A., Eidhof, I., Fenckova, M., Brenman-Suttner, D. B., Scheffer-de Gooyert, J. M., Christine, S., Schellevis, R. L., Van der Laan, K., Quentin, C., Van Ninhuijs, L., Hofmann, F., Ejsmont, R., Fisher, S. E., Kramer, J. M., Sigrist, S. J., Simon, A. F., & Schenck, A. (2019). Conserved regulation of neurodevelopmental processes and behavior by FoxP in Drosophila. PLoS One, 14(2): e211652. doi:10.1371/journal.pone.0211652.

    Abstract

    FOXP proteins form a subfamily of evolutionarily conserved transcription factors involved in the development and functioning of several tissues, including the central nervous system. In humans, mutations in FOXP1 and FOXP2 have been implicated in cognitive deficits including intellectual disability and speech disorders. Drosophila exhibits a single ortholog, called FoxP, but due to a lack of characterized mutants, our understanding of the gene remains poor. Here we show that the dimerization property required for mammalian FOXP function is conserved in Drosophila. In flies, FoxP is enriched in the adult brain, showing strong expression in ~1000 neurons of cholinergic, glutamatergic and GABAergic nature. We generate Drosophila loss-of-function mutants and UAS-FoxP transgenic lines for ectopic expression, and use them to characterize FoxP function in the nervous system. At the cellular level, we demonstrate that Drosophila FoxP is required in larvae for synaptic morphogenesis at axonal terminals of the neuromuscular junction and for dendrite development of dorsal multidendritic sensory neurons. In the developing brain, we find that FoxP plays important roles in α-lobe mushroom body formation. Finally, at a behavioral level, we show that Drosophila FoxP is important for locomotion, habituation learning and social space behavior of adult flies. Our work shows that Drosophila FoxP is important for regulating several neurodevelopmental processes and behaviors that are related to human disease or vertebrate disease model phenotypes. This suggests a high degree of functional conservation with vertebrate FOXP orthologues and established flies as a model system for understanding FOXP related pathologies.
  • Cathomas, F., Azzinnari, D., Bergamini, G., Sigrist, H., Buerge, M., Hoop, V., Wicki, B., Goetze, L., Soares, S. M. P., Kukelova, D., Seifritz, E., Goebbels, S., Nave, K.-A., Ghandour, M. S., Seoighe, C., Hildebrandt, T., Leparc, G., Klein, H., Stupka, E., Hengerer, B. and 1 moreCathomas, F., Azzinnari, D., Bergamini, G., Sigrist, H., Buerge, M., Hoop, V., Wicki, B., Goetze, L., Soares, S. M. P., Kukelova, D., Seifritz, E., Goebbels, S., Nave, K.-A., Ghandour, M. S., Seoighe, C., Hildebrandt, T., Leparc, G., Klein, H., Stupka, E., Hengerer, B., & Pryce, C. R. (2019). Oligodendrocyte gene expression is reduced by and influences effects of chronic social stress in mice. Genes, Brain and Behavior, 18(1): e12475. doi:10.1111/gbb.12475.

    Abstract

    Oligodendrocyte gene expression is downregulated in stress-related neuropsychiatric disorders,
    including depression. In mice, chronic social stress (CSS) leads to depression-relevant changes
    in brain and emotional behavior, and the present study shows the involvement of oligodendrocytes in this model. In C57BL/6 (BL/6) mice, RNA-sequencing (RNA-Seq) was conducted with
    prefrontal cortex, amygdala and hippocampus from CSS and controls; a gene enrichment database for neurons, astrocytes and oligodendrocytes was used to identify cell origin of deregulated genes, and cell deconvolution was applied. To assess the potential causal contribution of
    reduced oligodendrocyte gene expression to CSS effects, mice heterozygous for the oligodendrocyte gene cyclic nucleotide phosphodiesterase (Cnp1) on a BL/6 background were studied;
    a 2 genotype (wildtype, Cnp1+/−
    ) × 2 environment (control, CSS) design was used to investigate
    effects on emotional behavior and amygdala microglia. In BL/6 mice, in prefrontal cortex and
    amygdala tissue comprising gray and white matter, CSS downregulated expression of multiple
    oligodendroycte genes encoding myelin and myelin-axon-integrity proteins, and cell deconvolution identified a lower proportion of oligodendrocytes in amygdala. Quantification of oligodendrocyte proteins in amygdala gray matter did not yield evidence for reduced translation,
    suggesting that CSS impacts primarily on white matter oligodendrocytes or the myelin transcriptome. In Cnp1 mice, social interaction was reduced by CSS in Cnp1+/− mice specifically;
    using ionized calcium-binding adaptor molecule 1 (IBA1) expression, microglia activity was
    increased additively by Cnp1+/− and CSS in amygdala gray and white matter. This study provides back-translational evidence that oligodendrocyte changes are relevant to the pathophysiology and potentially the treatment of stress-related neuropsychiatric disorders.
  • Cattani, A., Floccia, C., Kidd, E., Pettenati, P., Onofrio, D., & Volterra, V. (2019). Gestures and words in naming: Evidence from crosslinguistic and crosscultural comparison. Language Learning, 69(3), 709-746. doi:10.1111/lang.12346.

    Abstract

    We report on an analysis of spontaneous gesture production in 2‐year‐old children who come from three countries (Italy, United Kingdom, Australia) and who speak two languages (Italian, English), in an attempt to tease apart the influence of language and culture when comparing children from different cultural and linguistic environments. Eighty‐seven monolingual children aged 24–30 months completed an experimental task measuring their comprehension and production of nouns and predicates. The Italian children scored significantly higher than the other groups on all lexical measures. With regard to gestures, British children produced significantly fewer pointing and speech combinations compared to Italian and Australian children, who did not differ from each other. In contrast, Italian children produced significantly more representational gestures than the other two groups. We conclude that spoken language development is primarily influenced by the input language over gesture production, whereas the combination of cultural and language environments affects gesture production.
  • Ceroni, F., Simpson, N. H., Francks, C., Baird, G., Conti-Ramsden, G., Clark, A., Bolton, P. F., Hennessy, E. R., Donnelly, P., Bentley, D. R., Martin, H., IMGSAC, SLI Consortium, WGS500 Consortium, Parr, J., Pagnamenta, A. T., Maestrini, E., Bacchelli, E., Fisher, S. E., & Newbury, D. F. (2014). Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment. European Journal of Human Genetics, 22, 1165-1171. doi:10.1038/ejhg.2014.4.

    Abstract

    Specific language impairment (SLI), an unexpected failure to develop appropriate language skills despite adequate non-verbal intelligence, is a heterogeneous multifactorial disorder with a complex genetic basis. We identified a homozygous microdeletion of 21,379 bp in the ZNF277 gene (NM_021994.2), encompassing exon 5, in an individual with severe receptive and expressive language impairment. The microdeletion was not found in the proband’s affected sister or her brother who had mild language impairment. However, it was inherited from both parents, each of whom carries a heterozygous microdeletion and has a history of language problems. The microdeletion falls within the AUTS1 locus, a region linked to autistic spectrum disorders (ASDs). Moreover, ZNF277 is adjacent to the DOCK4 and IMMP2L genes, which have been implicated in ASD. We screened for the presence of ZNF277 microdeletions in cohorts of children with SLI or ASD and panels of control subjects. ZNF277 microdeletions were at an increased allelic frequency in SLI probands (1.1%) compared with both ASD family members (0.3%) and independent controls (0.4%). We performed quantitative RT-PCR analyses of the expression of IMMP2L, DOCK4 and ZNF277 in individuals carrying either an IMMP2L_DOCK4 microdeletion or a ZNF277 microdeletion. Although ZNF277 microdeletions reduce the expression of ZNF277, they do not alter the levels of DOCK4 or IMMP2L transcripts. Conversely, IMMP2L_DOCK4 microdeletions do not affect the expression levels of ZNF277. We postulate that ZNF277 microdeletions may contribute to the risk of language impairments in a manner that is independent of the autism risk loci previously described in this region.
  • Ceroni, F., Simpson, N. H., Francks, C., Baird, G., Conti-Ramsden, G., Clark, A., Bolton, P. F., Hennessy, E. R., Donnelly, P., Bentley, D. R., Martin, H., IMGSAC, SLI Consortium, WGS500 Consortium, Parr, J., Pagnamenta, A. T., Maestrini, E., Bacchelli, E., Fisher, S. E., & Newbury, D. F. (2015). Reply to Pembrey et al: ‘ZNF277 microdeletions, specific language impairment and the meiotic mismatch methylation (3M) hypothesis’. European Journal of Human Genetics, 23, 1113-1115. doi:10.1038/ejhg.2014.275.
  • Chang, Y.-N., Monaghan, P., & Welbourne, S. (2019). A computational model of reading across development: Effects of literacy onset on language processing. Journal of Memory and Language, 108: 104025. doi:10.1016/j.jml.2019.05.003.

    Abstract

    Cognitive development is shaped by interactions between cognitive architecture and environmental experiences
    of the growing brain. We examined the extent to which this interaction during development could be observed in
    language processing. We focused on age of acquisition (AoA) effects in reading, where early-learned words tend
    to be processed more quickly and accurately relative to later-learned words. We implemented a computational
    model including representations of print, sound and meaning of words, with training based on children’s gradual
    exposure to language. The model produced AoA effects in reading and lexical decision, replicating the larger
    effects of AoA when semantic representations are involved. Further, the model predicted that AoA would relate
    to differing use of the reading system, with words acquired before versus after literacy onset with distinctive
    accessing of meaning and sound representations. An analysis of behaviour from the English Lexicon project was
    consistent with the predictions: Words acquired before literacy are more likely to access meaning via sound,
    showing a suppressed AoA effect, whereas words acquired after literacy rely more on direct print to meaning
    mappings, showing an exaggerated AoA effect. The reading system reveals vestigial traces of acquisition reflected
    in differing use of word representations during reading.
  • Chang, F., Bauman, M., Pappert, S., & Fitz, H. (2015). Do lemmas speak German?: A verb position effect in German structural priming. Cognitive Science, 39(5), 1113-1130. doi:10.1111/cogs.12184.

    Abstract

    Lexicalized theories of syntax often assume that verb-structure regularities are mediated by lemmas, which abstract over variation in verb tense and aspect. German syntax seems to challenge this assumption, because verb position depends on tense and aspect. To examine how German speakers link these elements, a structural priming study was performed which varied syntactic structure, verb position (encoded by tense and aspect), and verb overlap. Abstract structural priming was found, both within and across verb position, but priming was larger when the verb position was the same between prime and target. Priming was boosted by verb overlap, but there was no interaction with verb position. The results can be explained by a lemma model where tense and aspect are linked to structural choices in German. Since the architecture of this lemma model is not consistent with results from English, a connectionist model was developed which could explain the cross-linguistic variation in the production system. Together, these findings support the view that language learning plays an important role in determining the nature of structural priming in different languages
  • Chang, Y.-N., & Monaghan, P. (2019). Quantity and diversity of preliteracy language exposure both affect literacy development: Evidence from a computational model of reading. Scientific Studies of Reading, 23(3), 235-253. doi:10.1080/10888438.2018.1529177.

    Abstract

    Diversity of vocabulary knowledge and quantity of language exposure prior to literacy are key predictors of reading development. However, diversity and quantity of exposure are difficult to distinguish in behavioural studies, and so the causal relations with literacy are not well known. We tested these relations by training a connectionist triangle model of reading that learned to map between semantic; phonological; and, later, orthographic forms of words. The model first learned to map between phonology and semantics, where we manipulated the quantity and diversity of this preliterate language experience. Then the model learned to read. Both diversity and quantity of exposure had unique effects on reading performance, with larger effects for written word comprehension than for reading fluency. The results further showed that quantity of preliteracy language exposure was beneficial only when this was to a varied vocabulary and could be an impediment when exposed to a limited vocabulary.
  • Chang, F., Kidd, E., & Rowland, C. F. (2013). Prediction in processing is a by-product of language learning [Commentary on Pickering & Garrod: An integrated theory of language production and comprehension]. Behavioral and Brain Sciences, 36(4), 350-351. doi:10.1017/S0140525X12001495.

    Abstract

    Both children and adults predict the content of upcoming language, suggesting that prediction is useful for learning as well as processing. We present an alternative model which can explain prediction behaviour as a by-product of language learning. We suggest that a consideration of language acquisition places important constraints on Pickering & Garrod's (P&G's) theory.
  • Chen, J., Calhoun, V. D., Arias-Vasquez, A., Zwiers, M. P., Van Hulzen, K., Fernández, G., Fisher, S. E., Franke, B., Turner, J. A., & Liu, J. (2015). G-Protein genomic association with normal variation in gray matter density. Human Brain Mapping, 36(11), 4272-4286. doi:10.1002/hbm.22916.

    Abstract

    While detecting genetic variations underlying brain structures helps reveal mechanisms of neural disorders, high data dimensionality poses a major challenge for imaging genomic association studies. In this work, we present the application of a recently proposed approach, parallel independent component analysis with reference (pICA-R), to investigate genomic factors potentially regulating gray matter variation in a healthy population. This approach simultaneously assesses many variables for an aggregate effect and helps to elicit particular features in the data. We applied pICA-R to analyze gray matter density (GMD) images (274,131 voxels) in conjunction with single nucleotide polymorphism (SNP) data (666,019 markers) collected from 1,256 healthy individuals of the Brain Imaging Genetics (BIG) study. Guided by a genetic reference derived from the gene GNA14, pICA-R identified a significant SNP-GMD association (r = −0.16, P = 2.34 × 10−8), implying that subjects with specific genotypes have lower localized GMD. The identified components were then projected to an independent dataset from the Mind Clinical Imaging Consortium (MCIC) including 89 healthy individuals, and the obtained loadings again yielded a significant SNP-GMD association (r = −0.25, P = 0.02). The imaging component reflected GMD variations in frontal, precuneus, and cingulate regions. The SNP component was enriched in genes with neuronal functions, including synaptic plasticity, axon guidance, molecular signal transduction via PKA and CREB, highlighting the GRM1, PRKCH, GNA12, and CAMK2B genes. Collectively, our findings suggest that GNA12 and GNA14 play a key role in the genetic architecture underlying normal GMD variation in frontal and parietal regions
  • Christoffels, I. K., Ganushchak, L. Y., & Koester, D. (2013). Language conflict in translation; An ERP study of translation production. Journal of Cognitive Psychology, 25, 646-664. doi:10.1080/20445911.2013.821127.

    Abstract

    Although most bilinguals can translate with relative ease, the underlying neuro-cognitive processes are poorly understood. Using event-related brain potentials (ERPs) we investigated the temporal course of word translation. Participants translated words from and to their first (L1, Dutch) and second (L2, English) language while ERPs were recorded. Interlingual homographs (IHs) were included to introduce language conflict. IHs share orthographic form but have different meanings in L1 and L2 (e.g., room in Dutch refers to cream). Results showed that the brain distinguished between translation directions as early as 200 ms after word presentation: the P2 amplitudes were more positive in the L1L2 translation direction. The N400 was also modulated by translation direction, with more negative amplitudes in the L2L1 translation direction. Furthermore, the IHs were translated more slowly, induced more errors, and elicited more negative N400 amplitudes than control words. In a naming experiment, participants read aloud the same words in L1 or L2 while ERPs were recorded. Results showed no effect of either IHs or language, suggesting that task schemas may be crucially related to language control in translation. Furthermore, translation appears to involve conceptual processing in both translation directions, and the task goal appears to influence how words are processed.

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  • Chu, M., Meyer, A. S., Foulkes, L., & Kita, S. (2014). Individual differences in frequency and saliency of speech-accompanying gestures: The role of cognitive abilities and empathy. Journal of Experimental Psychology: General, 143, 694-709. doi:10.1037/a0033861.

    Abstract

    The present study concerns individual differences in gesture production. We used correlational and multiple regression analyses to examine the relationship between individuals’ cognitive abilities and empathy levels and their gesture frequency and saliency. We chose predictor variables according to experimental evidence of the functions of gesture in speech production and communication. We examined 3 types of gestures: representational gestures, conduit gestures, and palm-revealing gestures. Higher frequency of representational gestures was related to poorer visual and spatial working memory, spatial transformation ability, and conceptualization ability; higher frequency of conduit gestures was related to poorer visual working memory, conceptualization ability, and higher levels of empathy; and higher frequency of palm-revealing gestures was related to higher levels of empathy. The saliency of all gestures was positively related to level of empathy. These results demonstrate that cognitive abilities and empathy levels are related to individual differences in gesture frequency and saliency
  • Chu, M., & Hagoort, P. (2014). Synchronization of speech and gesture: Evidence for interaction in action. Journal of Experimental Psychology: General, 143(4), 1726-1741. doi:10.1037/a0036281.

    Abstract

    Language and action systems are highly interlinked. A critical piece of evidence is that speech and its accompanying gestures are tightly synchronized. Five experiments were conducted to test 2 hypotheses about the synchronization of speech and gesture. According to the interactive view, there is continuous information exchange between the gesture and speech systems, during both their planning and execution phases. According to the ballistic view, information exchange occurs only during the planning phases of gesture and speech, but the 2 systems become independent once their execution has been initiated. In all experiments, participants were required to point to and/or name a light that had just lit up. Virtual reality and motion tracking technologies were used to disrupt their gesture or speech execution. Participants delayed their speech onset when their gesture was disrupted. They did so even when their gesture was disrupted at its late phase and even when they received only the kinesthetic feedback of their gesture. Also, participants prolonged their gestures when their speech was disrupted. These findings support the interactive view and add new constraints on models of speech and gesture production
  • Chwilla, D., Brown, C. M., & Hagoort, P. (1995). The N400 as a function of the level of processing. Psychophysiology, 32, 274-285. doi:10.1111/j.1469-8986.1995.tb02956.x.

    Abstract

    In a semantic priming paradigm, the effects of different levels of processing on the N400 were assessed by changing the task demands. In the lexical decision task, subjects had to discriminate between words and nonwords and in the physical task, subjects had to discriminate between uppercase and lowercase letters. The proportion of related versus unrelated word pairs differed between conditions. A lexicality test on reaction times demonstrated that the physical task was performed nonlexically. Moreover, a semantic priming reaction time effect was obtained only in the lexical decision task. The level of processing clearly affected the event-related potentials. An N400 priming effect was only observed in the lexical decision task. In contrast, in the physical task a P300 effect was observed for either related or unrelated targets, depending on their frequency of occurrence. Taken together, the results indicate that an N400 priming effect is only evoked when the task performance induces the semantic aspects of words to become part of an episodic trace of the stimulus event.
  • Cohen, E., & Haun, D. B. M. (2013). The development of tag-based cooperation via a socially acquired trait. Evolution and Human Behavior, 24, 230-235. doi:10.1016/j.evolhumbehav.2013.02.001.

    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.

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  • Comasco, E., Schijven, D., de Maeyer, H., Vrettou, M., Nylander, I., Sundström-Poromaa, I., & Olivier, J. D. A. (2019). Constitutive serotonin transporter reduction resembles maternal separation with regard to stress-related gene expression. ACS Chemical Neuroscience, 10, 3132-3142. doi:10.1021/acschemneuro.8b00595.

    Abstract

    Interactive effects between allelic variants of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) and stressors on depression symptoms have been documented, as well as questioned, by meta-analyses. Translational models of constitutive 5-htt reduction and experimentally controlled stressors often led to inconsistent behavioral and molecular findings and often did not include females. The present study sought to investigate the effect of 5-htt genotype, maternal separation, and sex on the expression of stress-related candidate genes in the rat hippocampus and frontal cortex. The mRNA expression levels of Avp, Pomc, Crh, Crhbp, Crhr1, Bdnf, Ntrk2, Maoa, Maob, and Comt were assessed in the hippocampus and frontal cortex of 5-htt ± and 5-htt +/+ male and female adult rats exposed, or not, to daily maternal separation for 180 min during the first 2 postnatal weeks. Gene- and brain region-dependent, but sex-independent, interactions between 5-htt genotype and maternal separation were found. Gene expression levels were higher in 5-htt +/+ rats not exposed to maternal separation compared with the other experimental groups. Maternal separation and 5-htt +/− genotype did not yield additive effects on gene expression. Correlative relationships, mainly positive, were observed within, but not across, brain regions in all groups except in non-maternally separated 5-htt +/+ rats. Gene expression patterns in the hippocampus and frontal cortex of rats exposed to maternal separation resembled the ones observed in rats with reduced 5-htt expression regardless of sex. These results suggest that floor effects of 5-htt reduction and maternal separation might explain inconsistent findings in humans and rodents
  • Connell, L., Cai, Z. G., & Holler, J. (2013). Do you see what I'm singing? Visuospatial movement biases pitch perception. Brain and Cognition, 81, 124-130. doi:10.1016/j.bandc.2012.09.005.

    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.
  • Cooper, R. P., & Guest, O. (2014). Implementations are not specifications: Specification, replication and experimentation in computational cognitive modeling. Cognitive Systems Research, 27, 42-49. doi:10.1016/j.cogsys.2013.05.001.

    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.
  • Cooper, A., Brouwer, S., & Bradlow, A. R. (2015). Interdependent processing and encoding of speech and concurrent background noise. Attention, Perception & Psychophysics, 77(4), 1342-1357. doi:10.3758/s13414-015-0855-z.

    Abstract

    Speech processing can often take place in adverse listening conditions that involve the mixing of speech and background noise. In this study, we investigated processing dependencies between background noise and indexical speech features, using a speeded classification paradigm (Garner, 1974; Exp. 1), and whether background noise is encoded and represented in memory for spoken words in a continuous recognition memory paradigm (Exp. 2). Whether or not the noise spectrally overlapped with the speech signal was also manipulated. The results of Experiment 1 indicated that background noise and indexical features of speech (gender, talker identity) cannot be completely segregated during processing, even when the two auditory streams are spectrally nonoverlapping. Perceptual interference was asymmetric, whereby irrelevant indexical feature variation in the speech signal slowed noise classification to a greater extent than irrelevant noise variation slowed speech classification. This asymmetry may stem from the fact that speech features have greater functional relevance to listeners, and are thus more difficult to selectively ignore than background noise. Experiment 2 revealed that a recognition cost for words embedded in different types of background noise on the first and second occurrences only emerged when the noise and the speech signal were spectrally overlapping. Together, these data suggest integral processing of speech and background noise, modulated by the level of processing and the spectral separation of the speech and noise.
  • Corps, R. E., Pickering, M. J., & Gambi, C. (2019). Predicting turn-ends in discourse context. Language, Cognition and Neuroscience, 34(5), 615-627. doi:10.1080/23273798.2018.1552008.

    Abstract

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

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    plcp_a_1552008_sm1646.pdf
  • Cousijn, H., Eissing, M., Fernández, G., Fisher, S. E., Franke, B., Zwers, M., Harrison, P. J., & Arias-Vasquez, A. (2014). No effect of schizophrenia risk genes MIR137, TCF4, and ZNF804A on macroscopic brain structure. Schizophrenia Research, 159, 329-332. doi:10.1016/j.schres.2014.08.007.

    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.
  • Cousminer, D. L., Berry, D. J., Timpson, N. J., Ang, W., Thiering, E., Byrne, E. M., Taal, H. R., Huikari, V., Bradfield, J. P., Kerkhof, M., Groen-Blokhuis, M. M., Kreiner-Møller, E., Marinelli, M., Holst, C., Leinonen, J. T., Perry, J. R. B., Surakka, I., Pietiläinen, O., Kettunen, J., Anttila, V. and 50 moreCousminer, D. L., Berry, D. J., Timpson, N. J., Ang, W., Thiering, E., Byrne, E. M., Taal, H. R., Huikari, V., Bradfield, J. P., Kerkhof, M., Groen-Blokhuis, M. M., Kreiner-Møller, E., Marinelli, M., Holst, C., Leinonen, J. T., Perry, J. R. B., Surakka, I., Pietiläinen, O., Kettunen, J., Anttila, V., Kaakinen, M., Sovio, U., Pouta, A., Das, S., Lagou, V., Power, C., Prokopenko, I., Evans, D. M., Kemp, J. P., St Pourcain, B., Ring, S., Palotie, A., Kajantie, E., Osmond, C., Lehtimäki, T., Viikari, J. S., Kähönen, M., Warrington, N. M., Lye, S. J., Palmer, L. J., Tiesler, C. M. T., Flexeder, C., Montgomery, G. W., Medland, S. E., Hofman, A., Hakonarson, H., Guxens, M., Bartels, M., Salomaa, V., Murabito, J. M., Kaprio, J., Sørensen, T. I. A., Ballester, F., Bisgaard, H., Boomsma, D. I., Koppelman, G. H., Grant, S. F. A., Jaddoe, V. W. V., Martin, N. G., Heinrich, J., Pennell, C. E., Raitakari, O. T., Eriksson, J. G., Smith, G. D., Hyppönen, E., Järvelin, M.-R., McCarthy, M. I., Ripatti, S., Widén, E., Consortium ReproGen, & Consortium Early Growth Genetics (EGG) (2013). Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. Human Molecular Genetics, 22(13), 2735-2747. doi:10.1093/hmg/ddt104.

    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.
  • Cristia, A., Dupoux, E., Hakuno, Y., Lloyd-Fox, S., Schuetze, M., Kivits, J., Bergvelt, T., Van Gelder, M., Filippin, L., Charron, S., & Minagawa-Kawai, Y. (2013). An online database of infant functional Near InfraRed Spectroscopy studies: A community-augmented systematic review. PLoS One, 8(3): e58906. doi:10.1371/journal.pone.0058906.

    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.
  • Cristia, A. (2013). Input to language: The phonetics of infant-directed speech. Language and Linguistics Compass, 7, 157-170. doi:10.1111/lnc3.12015.

    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

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    Cristia_Suppl_Material.xls
  • Cristia, A., Minagawa-Kawai, Y., Egorova, N., Gervain, J., Filippin, L., Cabrol, D., & Dupoux, E. (2014). Neural correlates of infant accent discrimination: An fNIRS study. Developmental Science, 17(4), 628-635. doi:10.1111/desc.12160.

    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.

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  • Cristia, A., Mielke, J., Daland, R., & Peperkamp, S. (2013). Similarity in the generalization of implicitly learned sound patterns. Journal of Laboratory Phonology, 4(2), 259-285.

    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.
  • Cristia, A., Seidl, A., Junge, C., Soderstrom, M., & Hagoort, P. (2014). Predicting individual variation in language from infant speech perception measures. Child development, 85(4), 1330-1345. doi:10.1111/cdev.12193.

    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.
  • Cristia, A., & Seidl, A. (2014). The hyperarticulation hypothesis of infant-directed speech. Journal of Child Language, 41(4), 913-934. doi:10.1017/S0305000912000669.

    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.

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    CORRIGENDUM
  • Croijmans, I., Speed, L., Arshamian, A., & Majid, A. (2019). Measuring the multisensory imagery of wine: The Vividness of Wine Imagery Questionnaire. Multisensory Research, 32(3), 179-195. doi:10.1163/22134808-20191340.

    Abstract

    When we imagine objects or events, we often engage in multisensory mental imagery. Yet, investigations of mental imagery have typically focused on only one sensory modality — vision. One reason for this is that the most common tool for the measurement of imagery, the questionnaire, has been restricted to unimodal ratings of the object. We present a new mental imagery questionnaire that measures multisensory imagery. Specifically, the newly developed Vividness of Wine Imagery Questionnaire (VWIQ) measures mental imagery of wine in the visual, olfactory, and gustatory modalities. Wine is an ideal domain to explore multisensory imagery because wine drinking is a multisensory experience, it involves the neglected chemical senses (smell and taste), and provides the opportunity to explore the effect of experience and expertise on imagery (from wine novices to experts). The VWIQ questionnaire showed high internal consistency and reliability, and correlated with other validated measures of imagery. Overall, the VWIQ may serve as a useful tool to explore mental imagery for researchers, as well as individuals in the wine industry during sommelier training and evaluation of wine professionals.
  • Cronin, K. A., De Groot, E., & Stevens, J. M. G. (2015). Bonobos show limited social tolerance in a group setting: A comparison with chimpanzees and a test of the Relational Model. Folia primatologica, 86, 164-177. doi:10.1159/000373886.

    Abstract

    Social tolerance is a core aspect of primate social relationships with implications for the evolution of cooperation, prosociality and social learning. We measured the social tolerance of bonobos in an experiment recently validated with chimpanzees to allow for a comparative assessment of group-level tolerance, and found that the bonobo group studied here exhibited lower social tolerance on average than chimpanzees. Furthermore, following the Relational Model [de Waal, 1996], we investigated whether bonobos responded to an increased potential for social conflict with tolerance, conflict avoidance or conflict escalation, and found that only behaviours indicative of conflict escalation differed across conditions. Taken together, these findings contribute to the current debate over the level of social tolerance of bonobos and lend support to the position that the social tolerance of bonobos may not be notably high compared with other primates.
  • Cronin, K. A. (2013). [Review of the book Chimpanzees of the Lakeshore: Natural history and culture at Mahale by Toshisada Nishida]. Animal Behaviour, 85, 685-686. doi:10.1016/j.anbehav.2013.01.001.

    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.
  • Cronin, K. A., Acheson, D. J., Hernández, P., & Sánchez, A. (2015). Hierarchy is Detrimental for Human Cooperation. Scientific Reports, 5: 18634. doi:10.1038/srep18634.

    Abstract

    Studies of animal behavior consistently demonstrate that the social environment impacts cooperation, yet the effect of social dynamics has been largely excluded from studies of human cooperation. Here, we introduce a novel approach inspired by nonhuman primate research to address how social hierarchies impact human cooperation. Participants competed to earn hierarchy positions and then could cooperate with another individual in the hierarchy by investing in a common effort. Cooperation was achieved if the combined investments exceeded a threshold, and the higher ranked individual distributed the spoils unless control was contested by the partner. Compared to a condition lacking hierarchy, cooperation declined in the presence of a hierarchy due to a decrease in investment by lower ranked individuals. Furthermore, hierarchy was detrimental to cooperation regardless of whether it was earned or arbitrary. These findings mirror results from nonhuman primates and demonstrate that hierarchies are detrimental to cooperation. However, these results deviate from nonhuman primate findings by demonstrating that human behavior is responsive to changing hierarchical structures and suggests partnership dynamics that may improve cooperation. This work introduces a controlled way to investigate the social influences on human behavior, and demonstrates the evolutionary continuity of human behavior with other primate species.
  • Cronin, K. A., Pieper, B., Van Leeuwen, E. J. C., Mundry, R., & Haun, D. B. M. (2014). Problem solving in the presence of others: How rank and relationship quality impact resource acquisition in chimpanzees (Pan troglodytes). PLoS One, 9(4): e93204. doi:10.1371/journal.pone.0093204.

    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.
  • Cronin, K. A., Van Leeuwen, E. J. C., Vreeman, V., & Haun, D. B. M. (2014). Population-level variability in the social climates of four chimpanzee societies. Evolution and Human Behavior, 35(5), 389-396. doi:10.1016/j.evolhumbehav.2014.05.004.

    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.
  • Cuskley, C., Dingemanse, M., Kirby, S., & Van Leeuwen, T. M. (2019). Cross-modal associations and synesthesia: Categorical perception and structure in vowel–color mappings in a large online sample. Behavior Research Methods, 51, 1651-1675. doi:10.3758/s13428-019-01203-7.

    Abstract

    We report associations between vowel sounds, graphemes, and colours collected online from over 1000 Dutch speakers. We provide open materials including a Python implementation of the structure measure, and code for a single page web application to run simple cross-modal tasks. We also provide a full dataset of colour-vowel associations from 1164 participants, including over 200 synaesthetes identified using consistency measures. Our analysis reveals salient patterns in cross-modal associations, and introduces a novel measure of isomorphism in cross-modal mappings. We find that while acoustic features of vowels significantly predict certain mappings (replicating prior work), both vowel phoneme category and grapheme category are even better predictors of colour choice. Phoneme category is the best predictor of colour choice overall, pointing to the importance of phonological representations in addition to acoustic cues. Generally, high/front vowels are lighter, more green, and more yellow than low/back vowels. Synaesthetes respond more strongly on some dimensions, choosing lighter and more yellow colours for high and mid front vowels than non-synaesthetes. We also present a novel measure of cross-modal mappings adapted from ecology, which uses a simulated distribution of mappings to measure the extent to which participants' actual mappings are structured isomorphically across modalities. Synaesthetes have mappings that tend to be more structured than non-synaesthetes, and more consistent colour choices across trials correlate with higher structure scores. Nevertheless, the large majority (~70%) of participants produce structured mappings, indicating that the capacity to make isomorphically structured mappings across distinct modalities is shared to a large extent, even if the exact nature of mappings varies across individuals. Overall, this novel structure measure suggests a distribution of structured cross-modal association in the population, with synaesthetes on one extreme and participants with unstructured associations on the other.
  • Cutler, A., Sebastian-Galles, N., Soler-Vilageliu, O., & Van Ooijen, B. (2000). Constraints of vowels and consonants on lexical selection: Cross-linguistic comparisons. Memory & Cognition, 28, 746-755.

    Abstract

    Languages differ in the constitution of their phonemic repertoire and in the relative distinctiveness of phonemes within the repertoire. In the present study, we asked whether such differences constrain spoken-word recognition, via two word reconstruction experiments, in which listeners turned non-words into real words by changing single sounds. The experiments were carried out in Dutch (which has a relatively balanced vowel-consonant ratio and many similar vowels) and in Spanish (which has many more consonants than vowels and high distinctiveness among the vowels). Both Dutch and Spanish listeners responded significantly faster and more accurately when required to change vowels as opposed to consonants; when allowed to change any phoneme, they more often altered vowels than consonants. Vowel information thus appears to constrain lexical selection less tightly (allow more potential candidates) than does consonant information, independent of language-specific phoneme repertoire and of relative distinctiveness of vowels.
  • Cutler, A., & Van de Weijer, J. (2000). De ontdekking van de eerste woorden. Stem-, Spraak- en Taalpathologie, 9, 245-259.

    Abstract

    Spraak is continu, er zijn geen betrouwbare signalen waardoor de luisteraar weet waar het ene woord eindigt en het volgende begint. Voor volwassen luisteraars is het segmenteren van gesproken taal in afzonderlijke woorden dus niet onproblematisch, maar voor een kind dat nog geen woordenschat bezit, vormt de continuïteit van spraak een nog grotere uitdaging. Desalniettemin produceren de meeste kinderen hun eerste herkenbare woorden rond het begin van het tweede levensjaar. Aan deze vroege spraakproducties gaat een formidabele perceptuele prestatie vooraf. Tijdens het eerste levensjaar - met name gedurende de tweede helft - ontwikkelt de spraakperceptie zich van een algemeen fonetisch discriminatievermogen tot een selectieve gevoeligheid voor de fonologische contrasten die in de moedertaal voorkomen. Recent onderzoek heeft verder aangetoond dat kinderen, lang voordat ze ook maar een enkel woord kunnen zeggen, in staat zijn woorden die kenmerkend zijn voor hun moedertaal te onderscheiden van woorden die dat niet zijn. Bovendien kunnen ze woorden die eerst in isolatie werden aangeboden herkennen in een continue spraakcontext. Het dagelijkse taalaanbod aan een kind van deze leeftijd maakt het in zekere zin niet gemakkelijk, bijvoorbeeld doordat de meeste woorden niet in isolatie voorkomen. Toch wordt het kind ook wel houvast geboden, onder andere doordat het woordgebruik beperkt is.
  • Cutler, A. (2014). In thrall to the vocabulary. Acoustics Australia, 42, 84-89.

    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.
  • Cutler, A., Norris, D., & McQueen, J. M. (1994). Modelling lexical access from continuous speech input. Dokkyo International Review, 7, 193-215.

    Abstract

    The recognition of speech involves the segmentation of continuous utterances into their component words. Cross-linguistic evidence is briefly reviewed which suggests that although there are language-specific solutions to this segmentation problem, they have one thing in common: they are all based on language rhythm. In English, segmentation is stress-based: strong syllables are postulated to be the onsets of words. Segmentation, however, can also be achieved by a process of competition between activated lexical hypotheses, as in the Shortlist model. A series of experiments is summarised showing that segmentation of continuous speech depends on both lexical competition and a metrically-guided procedure. In the final section, the implementation of metrical segmentation in the Shortlist model is described: the activation of lexical hypotheses matching strong syllables in the input is boosted and that of hypotheses mismatching strong syllables in the input is penalised.
  • Cutler, A., & Otake, T. (1994). Mora or phoneme? Further evidence for language-specific listening. Journal of Memory and Language, 33, 824-844. doi:10.1006/jmla.1994.1039.

    Abstract

    Japanese listeners detect speech sound targets which correspond precisely to a mora (a phonological unit which is the unit of rhythm in Japanese) more easily than targets which do not. English listeners detect medial vowel targets more slowly than consonants. Six phoneme detection experiments investigated these effects in both subject populations, presented with native- and foreign-language input. Japanese listeners produced faster and more accurate responses to moraic than to nonmoraic targets both in Japanese and, where possible, in English; English listeners responded differently. The detection disadvantage for medial vowels appeared with English listeners both in English and in Japanese; again, Japanese listeners responded differently. Some processing operations which listeners apply to speech input are language-specific; these language-specific procedures, appropriate for listening to input in the native language, may be applied to foreign-language input irrespective of whether they remain appropriate.
  • Cutler, A., Mehler, J., Norris, D., & Segui, J. (1988). Limits on bilingualism [Letters to Nature]. Nature, 340, 229-230. doi:10.1038/340229a0.

    Abstract

    SPEECH, in any language, is continuous; speakers provide few reliable cues to the boundaries of words, phrases, or other meaningful units. To understand speech, listeners must divide the continuous speech stream into portions that correspond to such units. This segmentation process is so basic to human language comprehension that psycholinguists long assumed that all speakers would do it in the same way. In previous research1,2, however, we reported that segmentation routines can be language-specific: speakers of French process spoken words syllable by syllable, but speakers of English do not. French has relatively clear syllable boundaries and syllable-based timing patterns, whereas English has relatively unclear syllable boundaries and stress-based timing; thus syllabic segmentation would work more efficiently in the comprehension of French than in the comprehension of English. Our present study suggests that at this level of language processing, there are limits to bilingualism: a bilingual speaker has one and only one basic language.
  • Cutler, A. (2015). Representation of second language phonology. Applied Psycholinguistics, 36(1), 115-128. doi:10.1017/S0142716414000459.

    Abstract

    Orthographies encode phonological information only at the level of words (chiefly, the information encoded concerns phonetic segments; in some cases, tonal information or default stress may be encoded). Of primary interest to second language (L2) learners is whether orthography can assist in clarifying L2 phonological distinctions that are particularly difficult to perceive (e.g., where one native-language phonemic category captures two L2 categories). A review of spoken-word recognition evidence suggests that orthographic information can install knowledge of such a distinction in lexical representations but that this does not affect learners’ ability to perceive the phonemic distinction in speech. Words containing the difficult phonemes become even harder for L2 listeners to recognize, because perception maps less accurately to lexical content.
  • Cutler, A. (1994). The perception of rhythm in language. Cognition, 50, 79-81. doi:10.1016/0010-0277(94)90021-3.
  • Cutler, A., & Norris, D. (1988). The role of strong syllables in segmentation for lexical access. Journal of Experimental Psychology: Human Perception and Performance, 14, 113-121. doi:10.1037/0096-1523.14.1.113.

    Abstract

    A model of speech segmentation in a stress language is proposed, according to which the occurrence of a strong syllable triggers segmentation of the speech signal, whereas occurrence of a weak syllable does not trigger segmentation. We report experiments in which listeners detected words embedded in nonsense bisyllables more slowly when the bisyllable had two strong syllables than when it had a strong and a weak syllable; mint was detected more slowly in mintayve than in mintesh. According to our proposed model, this result is an effect of segmentation: When the second syllable is strong, it is segmented from the first syllable, and successful detection of the embedded word therefore requires assembly of speech material across a segmentation position. Speech recognition models involving phonemic or syllabic recoding, or based on strictly left-to-right processes, do not predict this result. It is argued that segmentation at strong syllables in continuous speech recognition serves the purpose of detecting the most efficient locations at which to initiate lexical access. (C) 1988 by the American Psychological Association
  • D'Alessandra, Y., Carena, M. C., Spazzafumo, L., Martinelli, F., Bassetti, B., Devanna, P., Rubino, M., Marenzi, G., Colombo, G. I., Achilli, F., Maggiolini, S., Capogrossi, M. C., & Pompilio, G. (2013). Diagnostic Potential of Plasmatic MicroRNA Signatures in Stable and Unstable Angina. PLoS ONE, 8(11), e80345. doi:10.1371/journal.pone.0080345.

    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.
  • Dastjerdi, M., Ozker, M., Foster, B. L., Rangarajan, V., & Parvizi, J. (2013). Numerical processing in the human parietal cortex during experimental and natural conditions. Nature Communications, 4: 2528. doi:10.1038/ncomms3528.

    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.
  • Dautriche, I., Cristia, A., Brusini, P., Yuan, S., Fisher, C., & Christophe, A. (2014). Toddlers default to canonical surface-to-meaning mapping when learning verbs. Child Development, 85(3), 1168-1180. doi:10.1111/cdev.12183.

    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.
  • Davidson, D., & Martin, A. E. (2013). Modeling accuracy as a function of response time with the generalized linear mixed effects model. Acta Psychologica, 144(1), 83-96. doi:10.1016/j.actpsy.2013.04.016.

    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.
  • Debreslioska, S., Ozyurek, A., Gullberg, M., & Perniss, P. M. (2013). Gestural viewpoint signals referent accessibility. Discourse Processes, 50(7), 431-456. doi:10.1080/0163853x.2013.824286.

    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.
  • Dediu, D., & Levinson, S. C. (2013). On the antiquity of language: The reinterpretation of Neandertal linguistic capacities and its consequences. Frontiers in Language Sciences, 4: 397. doi:10.3389/fpsyg.2013.00397.

    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.
  • Dediu, D., & Moisik, S. R. (2019). Pushes and pulls from below: Anatomical variation, articulation and sound change. Glossa: A Journal of General Linguistics, 4(1): 7. doi:10.5334/gjgl.646.

    Abstract

    This paper argues that inter-individual and inter-group variation in language acquisition, perception, processing and production, rooted in our biology, may play a largely neglected role in sound change. We begin by discussing the patterning of these differences, highlighting those related to vocal tract anatomy with a foundation in genetics and development. We use our ArtiVarK database, a large multi-ethnic sample comprising 3D intraoral optical scans, as well as structural, static and real-time MRI scans of vocal tract anatomy and speech articulation, to quantify the articulatory strategies used to produce the North American English /r/ and to statistically show that anatomical factors seem to influence these articulatory strategies. Building on work showing that these alternative articulatory strategies may have indirect coarticulatory effects, we propose two models for how biases due to variation in vocal tract anatomy may affect sound change. The first involves direct overt acoustic effects of such biases that are then reinterpreted by the hearers, while the second is based on indirect coarticulatory phenomena generated by acoustically covert biases that produce overt “at-a-distance” acoustic effects. This view implies that speaker communities might be “poised” for change because they always contain pools of “standing variation” of such biased speakers, and when factors such as the frequency of the biased speakers in the community, their positions in the communicative network or the topology of the network itself change, sound change may rapidly follow as a self-reinforcing network-level phenomenon, akin to a phase transition. Thus, inter-speaker variation in structured and dynamic communicative networks may couple the initiation and actuation of sound change.
  • Dediu, D., & Cysouw, M. A. (2013). Some structural aspects of language are more stable than others: A comparison of seven methods. PLoS One, 8: e55009. doi:10.1371/journal.pone.0055009.

    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.
  • Dediu, D., Janssen, R., & Moisik, S. R. (2019). Weak biases emerging from vocal tract anatomy shape the repeated transmission of vowels. Nature Human Behaviour, 3, 1107-1115. doi:10.1038/s41562-019-0663-x.

    Abstract

    Linguistic diversity is affected by multiple factors, but it is usually assumed that variation in the anatomy of our speech organs
    plays no explanatory role. Here we use realistic computer models of the human speech organs to test whether inter-individual
    and inter-group variation in the shape of the hard palate (the bony roof of the mouth) affects acoustics of speech sounds. Based
    on 107 midsagittal MRI scans of the hard palate of human participants, we modelled with high accuracy the articulation of a set
    of five cross-linguistically representative vowels by agents learning to produce speech sounds. We found that different hard
    palate shapes result in subtle differences in the acoustics and articulatory strategies of the produced vowels, and that these
    individual-level speech idiosyncrasies are amplified by the repeated transmission of language across generations. Therefore,
    we suggest that, besides culture and environment, quantitative biological variation can be amplified, also influencing language.
  • Defina, R. (2014). Arbil: Free tool for creating, editing and searching metadata. Language Documentation and Conservation, 8, 307-314.
  • Dell, G. S., Reed, K. D., Adams, D. R., & Meyer, A. S. (2000). Speech errors, phonotactic constraints, and implicit learning: A study of the role of experience in language production. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1355-1367. doi:10.1037/0278-7393.26.6.1355.

    Abstract

    Speech errors follow the phonotactics of the language being spoken. For example, in English, if [n] is mispronounced as [n] the [n] will always appear in a syllable coda. The authors created an analogue to this phenomenon by having participants recite lists of consonant-vowel-consonant syllables in 4 sessions on different days. In the first 2 experiments, some consonants were always onsets, some were always codas, and some could be both. In a third experiment, the set of possible onsets and codas depended on vowel identity. In all 3 studies, the production errors that occurred respected the "phonotactics" of the experiment. The results illustrate the implicit learning of the sequential constraints present in the stimuli and show that the language production system adapts to recent experience.
  • Demontis, D., Walters, R. K., Martin, J., Mattheisen, M., Als, T. D., Agerbo, E., Baldursson, G., Belliveau, R., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Cerrato, F., Chambert, K., Churchhouse, C., Dumont, A., Eriksson, N., Gandal, M., Goldstein, J. I., Grasby, K. L., Grove, J., Gudmundsson, O. O. and 61 moreDemontis, D., Walters, R. K., Martin, J., Mattheisen, M., Als, T. D., Agerbo, E., Baldursson, G., Belliveau, R., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Cerrato, F., Chambert, K., Churchhouse, C., Dumont, A., Eriksson, N., Gandal, M., Goldstein, J. I., Grasby, K. L., Grove, J., Gudmundsson, O. O., Hansen, C. S., Hauberg, M. E., Hollegaard, M. V., Howrigan, D. P., Huang, H., Maller, J. B., Martin, A. R., Martin, N. G., Moran, J., Pallesen, J., Palmer, D. S., Pedersen, C. B., Pedersen, M. G., Poterba, T., Poulsen, J. B., Ripke, S., Robinson, E. B., Satterstrom, F. K., Stefansson, H., Stevens, C., Turley, P., Walters, G. B., Won, H., Wright, M. J., ADHD Working Group of the Psychiatric Genomics Consortium (PGC), EArly Genetics and Lifecourse Epidemiology (EAGLE) Consortium, 23andme Research Team, Andreassen, O. A., Asherson, P., Burton, C. L., Boomsma, D. I., Cormand, B., Dalsgaard, S., Franke, B., Gelernter, J., Geschwind, D., Hakonarson, H., Haavik, J., Kranzler, H. R., Kuntsi, J., Langley, K., Lesch, K.-P., Middeldorp, C., Reif, A., Rohde, L. A., Roussos, P., Schachar, R., Sklar, P., Sonuga-Barke, E. J. S., Sullivan, P. F., Thapar, A., Tung, J. Y., Waldman, I. D., Medland, S. E., Stefansson, K., Nordentoft, M., Hougaard, D. M., Werge, T., Mors, O., Mortensen, P. B., Daly, M. J., Faraone, S. V., Børglum, A. D., & Neale, B. (2019). Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nature Genetics, 51, 63-75. doi:10.1038/s41588-018-0269-7.

    Abstract

    Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.
  • den Hoed, M., Eijgelsheim, M., Esko, T., Brundel, B. J. J. M., Peal, D. S., Evans, D. M., Nolte, I. M., Segrè, A. V., Holm, H., Handsaker, R. E., Westra, H.-J., Johnson, T., Isaacs, A., Yang, J., Lundby, A., Zhao, J. H., Kim, Y. J., Go, M. J., Almgren, P., Bochud, M. and 249 moreden Hoed, M., Eijgelsheim, M., Esko, T., Brundel, B. J. J. M., Peal, D. S., Evans, D. M., Nolte, I. M., Segrè, A. V., Holm, H., Handsaker, R. E., Westra, H.-J., Johnson, T., Isaacs, A., Yang, J., Lundby, A., Zhao, J. H., Kim, Y. J., Go, M. J., Almgren, P., Bochud, M., Boucher, G., Cornelis, M. C., Gudbjartsson, D., Hadley, D., van der Harst, P., Hayward, C., den Heijer, M., Igl, W., Jackson, A. U., Kutalik, Z., Luan, J., Kemp, J. P., Kristiansson, K., Ladenvall, C., Lorentzon, M., Montasser, M. E., Njajou, O. T., O'Reilly, P. F., Padmanabhan, S., St Pourcain, B., Rankinen, T., Salo, P., Tanaka, T., Timpson, N. J., Vitart, V., Waite, L., Wheeler, W., Zhang, W., Draisma, H. H. M., Feitosa, M. F., Kerr, K. F., Lind, P. A., Mihailov, E., Onland-Moret, N. C., Song, C., Weedon, M. N., Xie, W., Yengo, L., Absher, D., Albert, C. M., Alonso, A., Arking, D. E., de Bakker, P. I. W., Balkau, B., Barlassina, C., Benaglio, P., Bis, J. C., Bouatia-Naji, N., Brage, S., Chanock, S. J., Chines, P. S., Chung, M., Darbar, D., Dina, C., Dörr, M., Elliott, P., Felix, S. B., Fischer, K., Fuchsberger, C., de Geus, E. J. C., Goyette, P., Gudnason, V., Harris, T. B., Hartikainen, A.-L., Havulinna, A. S., Heckbert, S. R., Hicks, A. A., Hofman, A., Holewijn, S., Hoogstra-Berends, F., Hottenga, J.-J., Jensen, M. K., Johansson, A., Junttila, J., Kääb, S., Kanon, B., Ketkar, S., Khaw, K.-T., Knowles, J. W., Kooner, A. S., Kors, J. A., Kumari, M., Milani, L., Laiho, P., Lakatta, E. G., Langenberg, C., Leusink, M., Liu, Y., Luben, R. N., Lunetta, K. L., Lynch, S. N., Markus, M. R. P., Marques-Vidal, P., Mateo Leach, I., McArdle, W. L., McCarroll, S. A., Medland, S. E., Miller, K. A., Montgomery, G. W., Morrison, A. C., Müller-Nurasyid, M., Navarro, P., Nelis, M., O'Connell, J. R., O'Donnell, C. J., Ong, K. K., Newman, A. B., Peters, A., Polasek, O., Pouta, A., Pramstaller, P. P., Psaty, B. M., Rao, D. C., Ring, S. M., Rossin, E. J., Rudan, D., Sanna, S., Scott, R. A., Sehmi, J. S., Sharp, S., Shin, J. T., Singleton, A. B., Smith, A. V., Soranzo, N., Spector, T. D., Stewart, C., Stringham, H. M., Tarasov, K. V., Uitterlinden, A. G., Vandenput, L., Hwang, S.-J., Whitfield, J. B., Wijmenga, C., Wild, S. H., Willemsen, G., Wilson, J. F., Witteman, J. C. M., Wong, A., Wong, Q., Jamshidi, Y., Zitting, P., Boer, J. M. A., Boomsma, D. I., Borecki, I. B., van Duijn, C. M., Ekelund, U., Forouhi, N. G., Froguel, P., Hingorani, A., Ingelsson, E., Kivimaki, M., Kronmal, R. A., Kuh, D., Lind, L., Martin, N. G., Oostra, B. A., Pedersen, N. L., Quertermous, T., Rotter, J. I., van der Schouw, Y. T., Verschuren, W. M. M., Walker, M., Albanes, D., Arnar, D. O., Assimes, T. L., Bandinelli, S., Boehnke, M., de Boer, R. A., Bouchard, C., Caulfield, W. L. M., Chambers, J. C., Curhan, G., Cusi, D., Eriksson, J., Ferrucci, L., van Gilst, W. H., Glorioso, N., de Graaf, J., Groop, L., Gyllensten, U., Hsueh, W.-C., Hu, F. B., Huikuri, H. V., Hunter, D. J., Iribarren, C., Isomaa, B., Jarvelin, M.-R., Jula, A., Kähönen, M., Kiemeney, L. A., van der Klauw, M. M., Kooner, J. S., Kraft, P., Iacoviello, L., Lehtimäki, T., Lokki, M.-L.-L., Mitchell, B. D., Navis, G., Nieminen, M. S., Ohlsson, C., Poulter, N. R., Qi, L., Raitakari, O. T., Rimm, E. B., Rioux, J. D., Rizzi, F., Rudan, I., Salomaa, V., Sever, P. S., Shields, D. C., Shuldiner, A. R., Sinisalo, J., Stanton, A. V., Stolk, R. P., Strachan, D. P., Tardif, J.-C., Thorsteinsdottir, U., Tuomilehto, J., van Veldhuisen, D. J., Virtamo, J., Viikari, J., Vollenweider, P., Waeber, G., Widen, E., Cho, Y. S., Olsen, J. V., Visscher, P. M., Willer, C., Franke, L., Erdmann, J., Thompson, J. R., Pfeufer, A., Sotoodehnia, N., Newton-Cheh, C., Ellinor, P. T., Stricker, B. H. C., Metspalu, A., Perola, M., Beckmann, J. S., Smith, G. D., Stefansson, K., Wareham, N. J., Munroe, P. B., Sibon, O. C. M., Milan, D. J., Snieder, H., Samani, N. J., Loos, R. J. F., Global BPgen Consortium, CARDIoGRAM Consortium, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC Consortium, & CHARGE-AF Consortium (2013). Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nature Genetics, 45(6), 621-631. doi:10.1038/ng.2610.

    Abstract

    Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
  • Deriziotis, P., O'Roak, B. J., Graham, S. A., Estruch, S. B., Dimitropoulou, D., Bernier, R. A., Gerdts, J., Shendure, J., Eichler, E. E., & Fisher, S. E. (2014). De novo TBR1 mutations in sporadic autism disrupt protein functions. Nature Communications, 5: 4954. doi:10.1038/ncomms5954.

    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.
  • Deriziotis, P., Graham, S. A., Estruch, S. B., & Fisher, S. E. (2014). Investigating protein-protein interactions in live cells using Bioluminescence Resonance Energy Transfer. Journal of visualized experiments, 87: e51438. doi:10.3791/51438.

    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.

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