Publications

Abstract

A theoretical debate in artificial grammar learning (AGL) regards the learnability of hierarchical structures. Recent studies using an AnBn grammar draw conflicting conclusions (Bahlmann and Friederici, 2006, De Vries et al., 2008). We argue that 2 conditions crucially affect learning AnBn structures: sufficient exposure to zero-level-of-embedding (0-LoE) exemplars and a staged-input. In 2 AGL experiments, learning was observed only when the training set was staged and contained 0-LoE exemplars. Our results might help understanding how natural complex structures are learned from exemplars.

Abstract

We present a coding system combined with an annotation tool for the analysis of gestural behavior. The NEUROGES coding system consists of three modules that progress from gesture kinetics to gesture function. Grounded on empirical neuropsychological and psychological studies, the theoretical assumption behind NEUROGES is that its main kinetic and functional movement categories are differentially associated with specific cognitive, emotional, and interactive functions. ELAN is a free, multimodal annotation tool for digital audio and video media. It supports multileveled transcription and complies with such standards as XML and Unicode. ELAN allows gesture categories to be stored with associated vocabularies that are reusable by means of template files. The combination of the NEUROGES coding system and the annotation tool ELAN creates an effective tool for empirical research on gestural behavior.

Abstract

Force-distance measurements have been used to examine differences in the interaction of the dendritic cell glycan-binding receptor DC-SIGN and the closely related endothelial cell receptor DC-SIGNR (L-SIGN) with membranes bearing glycan ligands. The results demonstrate that upon binding to membrane-anchored ligand, DC-SIGNR undergoes a conformational change similar to that previously observed for DC-SIGN. The results also validate a model for the extracellular domain of DC-SIGNR derived from crystallographic studies. Force measurements were performed with DC-SIGNR variants that differ in the length of the neck that result from genetic polymorphisms, which encode different numbers of the 23-amino acid repeat sequences that constitute the neck. The findings are consistent with an elongated, relatively rigid structure of the neck repeat observed in crystals. In addition, differences in the lengths of DC-SIGN and DC-SIGNR extracellular domains with equivalent numbers of neck repeats support a model in which the different dispositions of the carbohydrate-recognition domains in DC-SIGN and DC-SIGNR result from variations in the sequences of the necks.

Abstract

This paper presents a new approach to functional magnetic resonance imaging (FMRI) data analysis. The main difference lies in the view of what comprises an observation. Here we treat the data from one scanning session (comprising t volumes, say) as one observation. This is contrary to the conventional way of looking at the data where each session is treated as t different observations. Thus instead of viewing the v voxels comprising the 3D volume of the brain as the variables, we suggest the usage of the vt hypervoxels comprising the 4D volume of the brain-over-session as the variables. A linear model is fitted to the 4D volumes originating from different sessions. Parameter estimation and hypothesis testing in this model can be performed with standard techniques. The hypothesis testing generates 4D statistical images (SIs) to which any relevant test statistic can be applied. In this paper we describe two test statistics, one voxel based and one cluster based, that can be used to test a range of hypotheses. There are several benefits in treating the data from each session as one observation, two of which are: (i) the temporal characteristics of the signal can be investigated without an explicit model for the blood oxygenation level dependent (BOLD) contrast response function, and (ii) the observations (sessions) can be assumed to be independent and hence inference on the 4D SI can be made by nonparametric or Monte Carlo methods. The suggested 4D approach is applied to FMRI data and is shown to accurately detect the expected signal

Abstract

A core operation in speech production is the preparation of words from a semantic base. The theory of lexical access reviewed in this article covers a sequence of processing stages beginning with the speaker’s focusing on a target concept and ending with the initiation of articulation. The initial stages of preparation are concerned with lexical selection, which is zooming in on the appropriate lexical item in the mental lexicon. The following stages concern form encoding, i.e., retrieving a word’s morphemic phonological codes, syllabifying the word, and accessing the corresponding articulatory gestures. The theory is based on chronometric measurements of spoken word production, obtained, for instance, in picture-naming tasks. The theory is largely computationally implemented. It provides a handle on the analysis of multiword utterance production as well as a guide to the analysis and design of neuroimaging studies of spoken utterance production.

Abstract

Speakers tend to repeat materials from previous talk. This tendency is experimentally established and manipulated in various question-answering situations. It is shown that a question's surface form can affect the format of the answer given, even if this form has little semantic or conversational consequence, as in the pair Q: (At) what time do you close. A: “(At)five o'clock.” Answerers tend to match the utterance to the prepositional (nonprepositional) form of the question. This “correspondence effect” may diminish or disappear when, following the question, additional verbal material is presented to the answerer. The experiments show that neither the articulatory buffer nor long-term memory is normally involved in this retention of recent speech. Retaining recent speech in working memory may fulfill a variety of functions for speaker and listener, among them the correct production and interpretation of surface anaphora. Reusing recent materials may, moreover, be more economical than regenerating speech anew from a semantic base, and thus contribute to fluency. But the realization of this strategy requires a production system in which linguistic formulation can take place relatively independent of, and parallel to, conceptual planning.

Abstract

Comment on Sperber and Wilson

Abstract

This short report draws attention to an interesting kind of configuration in the lexicon that seems to have escaped theoretical or systematic descriptive attention. These configurations, which we dub SEMPLATES, consist of an abstract structure or template, which is recurrently instantiated in a number of lexical sets, typically of different form classes. A number of examples from different language families are adduced, and generalizations made about the nature of semplates, which are contrasted to other, perhaps similar, phenomena

Abstract

Polish translation of Levinson, S. C. (1998). Studying spatial conceptualization across cultures: Anthropology and cognitive science. Ethos, 26(1), 7-24. doi:10.1525/eth.1998.26.1.7

Abstract

This paper is one in a series that develops a pragmatic framework in loose confederation with Jay Atlas and Larry Horn: thus they may or may not be responsible for the ideas contained herein. Jay Atlas provided many comments which I have utilized or perverted as the case may be. The Australian data to which this framework is applied was collected with the financial and personal assistance of many people and agencies acknowledged separately below; but I must single out for special thanks John Haviland, who recommended the study of Guugu Yimidhirr anaphora to me and upon whose grammatical work on Guugu Yimidhirr this paper is but a minor (and perhaps flawed) elaboration. A grant from the British Academy allowed me to visit Haviland in September 1986 to discuss many aspects of Guugu Yimidhirr with him, and I am most grateful to the Academy for funding this trip and to Haviland for generously making available his time, his texts (from which I have drawn many examples, not always with specific acknowledgement) and most especially his expertise. Where I have diverged from his opinion I may well learn to regret it. I must also thank Nigel Vincent for putting me in touch with a number of recent relevant developments in syntax (only some of which I have been able to address) and for suggestions for numerous improvements. In addition, I have benefited immensely for comments on a distinct but related paper (Levinson, 1987) kindly provided by Jay Atlas, John Haviland, John Heritage, Phil Johnson-Laird, John Lyons, Tanya Reinhart, Emanuel Schegloff and an anonymous referee; and from comments on this paper by participants in the Cambridge Linguistics Department seminar where it was first presented (especial thanks to John Lyons and Huang Yan for further comments, and Mary Smith for a counter-example). Despite all this help, there are sure to be errors of data and analysis that I have persisted in. Aid in gathering the Australian data is acknowledged separately below.

Abstract

1. Introduction We claim that making sense of the typological diversity of languages demands a historical/evolutionary approach.We are pleased that the target paper (Dunn et al. 2011a) has served to bring discussion of this claim into prominence, and are grateful that leading typologists have taken the time to respond (commentaries denoted by boldface). It is unfortunate though that a number of the commentaries in this issue of LT show significant misunderstandings of our paper. Donohue thinks we were out to show the stability of typological features, but that was not our target at all (although related methods can be used to do that: see, e.g., Greenhill et al. 2010a, Dediu 2011a). Plank seems to think we were arguing against universals of any type, but our target was in fact just the implicational universals of word order that have been the bread and butter of typology. He also seems to think we ignore diachrony, whereas in fact the method introduces diachrony centrally into typological reasoning, thereby potentially revolutionising typology (see Cysouw’s commentary). Levy & Daumé think we were testing for lineage-specificity, whereas that was in fact an outcome (the main finding) of our testing for correlated evolution. Dryer thinks we must account for the distribution of language types around the world, but that was not our aim: our aim was to test the causal connection between linguistic variables by taking the perspective of language evolution (diversification and change). Longobardi & Roberts seem to think we set out to extract family trees from syntactic features, but our goal was in fact to use trees based on lexical cognates and hang reconstructed syntactic states on each node of these trees, thereby reconstructing the processes of language change.

Abstract

Most neuroimaging studies are performed using one imaging method only, either functional magnetic resonance imaging (fMRI), electroencephalography (EEG), or magnetoencephalography (MEG). Information on both location and timing has been sought by recording fMRI and EEG, simultaneously, or MEG and fMRI in separate sessions. Such approaches assume similar active areas whether detected via hemodynamic or electrophysiological signatures. Direct comparisons, after independent analysis of data from each imaging modality, have been conducted primarily on low-level sensory processing. Here, we report MEG (timing and location) and fMRI (location) results in 11 subjects when they named pictures that depicted an action or an object. The experimental design was exactly the same for the two imaging modalities. The MEG data were analyzed with two standard approaches: a set of equivalent current dipoles and a distributed minimum norm estimate. The fMRI blood-oxygenlevel dependent (BOLD) data were subjected to the usual random-effect contrast analysis. At the group level, MEG and fMRI data showed fairly good convergence, with both overall activation patterns and task effects localizing to comparable cortical regions. There were some systematic discrepancies, however, and the correspondence was less compelling in the individual subjects. The present analysis should be helpful in reconciling results of fMRI and MEG studies on high-level cognitive functions

Abstract

Educational tools claiming to use “right-brain techniques” are increasingly shaping school curricula. By implying a strong scientific basis, such approaches appeal to educators who rightly believe that knowledge of the brain should guide curriculum development. However, the notion of hemisphericity (idea that people are “left-brained” or “right-brained”) is a neuromyth that was debunked in the scientific literature 25 years ago. This article challenges the validity of “right-brain” teaching, highlighting the fact that neuroscientific research does not support its claims. Providing teachers with a basic understanding of neuroscience research as part of teacher training would enable more effective evaluation of brain-based claims and facilitate the adoption of tools validated by rigorous independent research rather than programs based on pseudoscience.

Abstract

Little is known about the origins of the pointing gesture. We sought to gain insight into its emergence by investigating individual differences in the pointing of 12-month-old infants in two ways. First, we looked at differences in the communicative and interactional uses of pointing and asked how different hand shapes relate to point frequency, accompanying vocalizations, and mothers’ pointing. Second, we looked at differences in social-cognitive skills of point comprehension and imitation and tested whether these were related to infants’ own pointing. Infants’ and mothers’ spontaneous pointing correlated with one another, as did infants’ point production and comprehension. In particular, infants’ index-finger pointing had a profile different from simple whole-hand pointing. It was more frequent, it was more often accompanied by vocalizations, and it correlated more strongly with comprehension of pointing (especially to occluded referents). We conclude that whole-hand and index-finger pointing differ qualitatively and suggest that it is index-finger pointing that first embodies infants’ understanding of communicative intentions.

Abstract

One of the defining features of human language is displacement, the ability to make reference to absent entities. Here we show that prelinguistic, 12-month-old infants already can use a nonverbal pointing gesture to make reference to absent entities. We also show that chimpanzees—who can point for things they want humans to give them—do not point to refer to absent entities in the same way. These results demonstrate that the ability to communicate about absent but mutually known entities depends not on language, but rather on deeper social-cognitive skills that make acts of linguistic reference possible in the first place. These nonlinguistic skills for displaced reference emerged apparently only after humans' divergence from great apes some 6 million years ago.

Abstract

Sociocultural theories of development posit that higher cognitive functions emerge through socially mediated processes, in particular through language. However, theories of human communication posit that language itself is based on higher social cognitive skills and cooperative motivations. Prelinguistic communication is a test case to this puzzle. In the current review, I first present recent and new findings of a research program on prelinguistic infants’ ommunication skills. This research provides empirical evidence for a rich social cognitive and motivational basis of human communication before language. Next, I discuss the emergence of these foundational skills. By considering all three lines of development, and by drawing on new findings from phylogenetic and cross-cultural comparisons, this article discusses the possibility that the cognitive foundations of prelinguistic communication are, in turn, mediated by social interactional input and shared experiences.

Abstract

A growing body of theoretical and empirical research has examined cultural transmission and adaptive cultural behaviour at the individual, within-group level. However, relatively few studies have tried to examine proximate transmission or test ultimate adaptive hypotheses about behavioural or cultural diversity at a between-societies macro-level. In both the history of anthropology and in present-day work, a common approach to examining adaptive behaviour at the macro-level has been through correlating various cultural traits with features of ecology. We discuss some difficulties with simple ecological associations, and then review cultural phylogenetic studies that have attempted to go beyond correlations to understand the underlying cultural evolutionary processes. We conclude with an example of a phylogenetically controlled approach to understanding proximate transmission pathways in Austronesian cultural diversity.

Abstract

Multiple social science disciplines have converged on the senses in recent years, where formerly the domain of perception was the preserve of psychology. Linguistics, or Language, however, seems to have an ambivalent role in this undertaking. On the one hand, Language with a capital L (language as a general human capacity) is part of the problem. It was the prior focus on language (text) that led to the disregard of the senses. On the other hand, it is language (with a small "l", a particular tongue) that offers key insights into how other peoples onceptualize the senses. In this article, we argue that a systematic cross-cultural approach can reveal fundamental truths about the precise connections between language and the senses. Recurring failures to adequately describe the sensorium across specific languages reveal the intrinsic limits of Language. But the converse does not hold. Failures of expressibility in one language need not hold any implications for the Language faculty per se, and indeed can enlighten us about the possible experiential worlds available to human experience.

Abstract

Cultures are built on social exchange. Most languages have dedicated grammatical machinery for expressing this. To demonstrate that statistical methods can also be applied to grammatical meaning, we here ask whether the underlying meanings of these grammatical constructions are based on shared common concepts. To explore this, we designed video stimuli of reciprocated actions (e.g. ‘giving to each other’) and symmetrical states (e.g. ‘sitting next to each other’), and with the help of a team of linguists collected responses from 20 languages around the world. Statistical analyses revealed that many languages do, in fact, share a common conceptual core for reciprocal meanings but that this is not a universally expressed concept. The recurrent pattern of conceptual packaging found across languages is compatible with the view that there is a shared non-linguistic understanding of reciprocation. But, nevertheless, there are considerable differences between languages in the exact extensional patterns, highlighting that even in the domain of grammar semantics is highly language-specific.

Abstract

Language comprehension requires recovering meaning from linguistic form, even when the mapping between the two is indirect. A canonical example is ellipsis, the omission of information that is subsequently understood without being overtly pronounced. Comprehension of ellipsis requires retrieval of an antecedent from memory, without prior prediction, a property which enables the study of retrieval in situ ( Martin and McElree, 2008 and Martin and McElree, 2009). Sluicing, or inflectional-phrase ellipsis, in the presence of a conjunction, presents a test case where a competing antecedent position is syntactically licensed, in contrast with most cases of nonadjacent dependency, including verb–phrase ellipsis. We present speed–accuracy tradeoff and eye-movement data inconsistent with the hypothesis that retrieval is accomplished via a syntactically guided search, a particular variant of search not examined in past research. The observed timecourse profiles are consistent with the hypothesis that antecedents are retrieved via a cue-dependent direct-access mechanism susceptible to general memory variables.

Abstract

Comprehension of verb-phrase ellipsis (VPE) requires reevaluation of recently processed constituents, which often necessitates retrieval of information about the elided constituent from memory. A. E. Martin and B. McElree (2008) argued that representations formed during comprehension are content addressable and that VPE antecedents are retrieved from memory via a cue-dependent direct-access pointer rather than via a search process. This hypothesis was further tested by manipulating the location of interfering material—either before the onset of the antecedent (proactive interference; PI) or intervening between antecedent and ellipsis site (retroactive interference; RI). The speed–accuracy tradeoff procedure was used to measure the time course of VPE processing. The location of the interfering material affected VPE comprehension accuracy: RI conditions engendered lower accuracy than PI conditions. Crucially, location did not affect the speed of processing VPE, which is inconsistent with both forward and backward search mechanisms. The observed time-course profiles are consistent with the hypothesis that VPE antecedents are retrieved via a cue-dependent direct-access operation. (PsycINFO Database Record (c) 2016 APA, all rights reserved)

Abstract

Understanding the lyrics of many contemporary songs is difficult, and an earlier study [Hidalgo-Barnes, M., Massaro, D.W., 2007. Read my lips: an animated face helps communicate musical lyrics. Psychomusicology 19, 3–12] showed a benefit for lyrics recognition when seeing a computer-animated talking head (Baldi) mouthing the lyrics along with hearing the singer. However, the contribution of visual information was relatively small compared to what is usually found for speech. In the current experiments, our goal was to determine why the face appears to contribute less when aligned with sung lyrics than when aligned with normal speech presented in noise. The first experiment compared the contribution of the talking head with the originally sung lyrics versus the case when it was aligned with the Festival text-to-speech synthesis (TtS) spoken at the original duration of the song’s lyrics. A small and similar influence of the face was found in both conditions. In the three experiments, we compared the presence of the face when the durations of the TtS were equated with the duration of the original musical lyrics to the case when the lyrics were read with typical TtS durations and this speech embedded in noise. The results indicated that the unusual temporally distorted durations of musical lyrics decreases the contribution of the visible speech from the face.

Abstract

Abstract Background: Archaeologists and anthropologists have long recognized that different cultural complexes may have distinct descent histories, but they have lacked analytical techniques capable of easily identifying such incongruence. Here, we show how Bayesian phylogenetic analysis can be used to identify incongruent cultural histories. We employ the approach to investigate Iranian tribal textile traditions. Methods: We used Bayes factor comparisons in a phylogenetic framework to test two models of cultural evolution: the hierarchically integrated system hypothesis and the multiple coherent units hypothesis. In the hierarchically integrated system hypothesis, a core tradition of characters evolves through descent with modification and characters peripheral to the core are exchanged among contemporaneous populations. In the multiple coherent units hypothesis, a core tradition does not exist. Rather, there are several cultural units consisting of sets of characters that have different histories of descent. Results: For the Iranian textiles, the Bayesian phylogenetic analyses supported the multiple coherent units hypothesis over the hierarchically integrated system hypothesis. Our analyses suggest that pile-weave designs represent a distinct cultural unit that has a different phylogenetic history compared to other textile characters. Conclusions: The results from the Iranian textiles are consistent with the available ethnographic evidence, which suggests that the commercial rug market has influenced pile-rug designs but not the techniques or designs incorporated in the other textiles produced by the tribes. We anticipate that Bayesian phylogenetic tests for inferring cultural units will be of great value for researchers interested in studying the evolution of cultural traits including language, behavior, and material culture.

Abstract

This study investigated links between working memory and speech processing systems. We used delayed pseudoword repetition in fMRI to investigate the neural correlates of sublexical structure in phonological working memory (pWM). We orthogonally varied the number of syllables and consonant clusters in auditory pseudowords and measured the neural responses to these manipulations under conditions of covert rehearsal (Experiment 1). A left-dominant network of temporal and motor cortex showed increased activity for longer items, with motor cortex only showing greater activity concomitant with adding consonant clusters. An individual-differences analysis revealed a significant positive relationship between activity in the angular gyrus and the hippocampus, and accuracy on pseudoword repetition. As models of pWM stipulate that its neural correlates should be activated during both perception and production/rehearsal [Buchsbaum, B. R., & D'Esposito, M. The search for the phonological store: From loop to convolution. Journal of Cognitive Neuroscience, 20, 762-778, 2008; Jacquemot, C., & Scott, S. K. What is the relationship between phonological short-term memory and speech processing? Trends in Cognitive Sciences, 10, 480-486, 2006; Baddeley, A. D., & Hitch, G. Working memory. In G. H. Bower (Ed.), The psychology of learning and motivation: Advances in research and theory (Vol. 8, pp. 47-89). New York: Academic Press, 1974], we further assessed the effects of the two factors in a separate passive listening experiment (Experiment 2). In this experiment, the effect of the number of syllables was concentrated in posterior-medial regions of the supratemporal plane bilaterally, although there was no evidence of a significant response to added clusters. Taken together, the results identify the planum temporale as a key region in pWM; within this region, representations are likely to take the form of auditory or audiomotor -templates- or -chunks- at the level of the syllable [Papoutsi, M., de Zwart, J. A., Jansma, J. M., Pickering, M. J., Bednar, J. A., & Horwitz, B. From phonemes to articulatory codes: an fMRI study of the role of Broca's area in speech production. Cerebral Cortex, 19, 2156-2165, 2009; Warren, J. E., Wise, R. J. S., & Warren, J. D. Sounds do-able: auditory-motor transformations and the posterior temporal plane. Trends in Neurosciences, 28, 636-643, 2005; Griffiths, T. D., & Warren, J. D. The planum temporale as a computational hub. Trends in Neurosciences, 25, 348-353, 2002], whereas more lateral structures on the STG may deal with phonetic analysis of the auditory input [Hickok, G. The functional neuroanatomy of language. Physics of Life Reviews, 6, 121-143, 2009].

Abstract

The strongest support for feedback in speech perception comes from evidence of apparent lexical influence on prelexical fricative-stop compensation for coarticulation. Lexical knowledge (e.g., that the ambiguous final fricative of Christma? should be [s]) apparently influences perception of following stops. We argue that all such previous demonstrations can be explained without invoking lexical feedback. In particular, we show that one demonstration [Magnuson, J. S., McMurray, B., Tanenhaus, M. K., & Aslin, R. N. (2003). Lexical effects on compensation for coarticulation: The ghost of Christmash past. Cognitive Science, 27, 285–298] involved experimentally-induced biases (from 16 practice trials) rather than feedback. We found that the direction of the compensation effect depended on whether practice stimuli were words or nonwords. When both were used, there was no lexically-mediated compensation. Across experiments, however, there were lexical effects on fricative identification. This dissociation (lexical involvement in the fricative decisions but not in the following stop decisions made on the same trials) challenges interactive models in which feedback should cause both effects. We conclude that the prelexical level is sensitive to experimentally-induced phoneme-sequence biases, but that there is no feedback during speech perception.

Abstract

We introduce the papers in this special issue by summarising the current major issues in spoken word recognition. We argue that a full understanding of the process of lexical access during speech comprehension will depend on resolving several key representational issues: what is the form of the representations used for lexical access; how is phonological information coded in the mental lexicon; and how is the morphological and semantic information about each word stored? We then discuss a number of distinct access processes: competition between lexical hypotheses; the computation of goodness-of-fit between the signal and stored lexical knowledge; segmentation of continuous speech; whether the lexicon influences prelexical processing through feedback; and the relationship of form-based processing to the processes responsible for deriving an interpretation of a complete utterance. We conclude that further progress may well be made by swapping ideas among the different sub-domains of the discipline.

Abstract

In two word-spotting experiments, Japanese listeners detected Japanese words faster in vowel contexts (e.g., agura, to sit cross-legged, in oagura) than in consonant contexts (e.g., tagura). In the same experiments, however, listeners spotted words in vowel contexts (e.g., saru, monkey, in sarua) no faster than in moraic nasal contexts (e.g., saruN). In a third word-spotting experiment, words like uni, sea urchin, followed contexts consisting of a consonant-consonant-vowel mora (e.g., gya) plus either a moraic nasal (gyaNuni), a vowel (gyaouni) or a consonant (gyabuni). Listeners spotted words as easily in the first as in the second context (where in each case the target words were aligned with mora boundaries), but found it almost impossible to spot words in the third (where there was a single consonant, such as the [b] in gyabuni, between the beginning of the word and the nearest preceding mora boundary). Three control experiments confirmed that these effects reflected the relative ease of segmentation of the words from their contexts.We argue that the listeners showed sensitivity to the viability of sound sequences as possible Japanese words in the way that they parsed the speech into words. Since single consonants are not possible Japanese words, the listeners avoided lexical parses including single consonants and thus had difficulty recognizing words in the consonant contexts. Even though moraic nasals are also impossible words, they were not difficult segmentation contexts because, as with the vowel contexts, the mora boundaries between the contexts and the target words signaled likely word boundaries. Moraic rhythm appears to provide Japanese listeners with important segmentation cues.

Abstract

BACKGROUND: Human and animal prion diseases are under genetic control, but apart from PRNP (the gene that encodes the prion protein), we understand little about human susceptibility to bovine spongiform encephalopathy (BSE) prions, the causal agent of variant Creutzfeldt-Jakob disease (vCJD).METHODS: We did a genome-wide association study of the risk of vCJD and tested for replication of our findings in samples from many categories of human prion disease (929 samples) and control samples from the UK and Papua New Guinea (4254 samples), including controls in the UK who were genotyped by the Wellcome Trust Case Control Consortium. We also did follow-up analyses of the genetic control of the clinical phenotype of prion disease and analysed candidate gene expression in a mouse cellular model of prion infection. FINDINGS: The PRNP locus was strongly associated with risk across several markers and all categories of prion disease (best single SNP [single nucleotide polymorphism] association in vCJD p=2.5 x 10(-17); best haplotypic association in vCJD p=1 x 10(-24)). Although the main contribution to disease risk was conferred by PRNP polymorphic codon 129, another nearby SNP conferred increased risk of vCJD. In addition to PRNP, one technically validated SNP association upstream of RARB (the gene that encodes retinoic acid receptor beta) had nominal genome-wide significance (p=1.9 x 10(-7)). A similar association was found in a small sample of patients with iatrogenic CJD (p=0.030) but not in patients with sporadic CJD (sCJD) or kuru. In cultured cells, retinoic acid regulates the expression of the prion protein. We found an association with acquired prion disease, including vCJD (p=5.6 x 10(-5)), kuru incubation time (p=0.017), and resistance to kuru (p=2.5 x 10(-4)), in a region upstream of STMN2 (the gene that encodes SCG10). The risk genotype was not associated with sCJD but conferred an earlier age of onset. Furthermore, expression of Stmn2 was reduced 30-fold post-infection in a mouse cellular model of prion disease. INTERPRETATION: The polymorphic codon 129 of PRNP was the main genetic risk factor for vCJD; however, additional candidate loci have been identified, which justifies functional analyses of these biological pathways in prion disease.

Abstract

Whether the brain’s speech-production system is also involved in speech comprehension is a topic of much debate. Research has focused on whether motor areas are involved in listening, but overlap between speaking and listening might occur not only at primary sensory and motor levels, but also at linguistic levels (where semantic, lexical, and syntactic processes occur). Using functional MRI adaptation during speech comprehension and production, we found that the brain areas involved in semantic, lexical, and syntactic processing are mostly the same for speaking and for listening. Effects of primary processing load (indicative of sensory and motor processes) overlapped in auditory cortex and left inferior frontal cortex, but not in motor cortex, where processing load affected activity only in speaking. These results indicate that the linguistic parts of the language system are used for both speaking and listening, but that the motor system does not seem to provide a crucial contribution to listening.

Abstract

Both local discourse and world knowledge are known to influence sentence processing. We investigated how these two sources of information conspire in language comprehension. Two types of critical sentences, correct and world knowledge anomalies, were preceded by either a neutral or a local context. The latter made the world knowledge anomalies more acceptable or plausible. We predicted that the effect of world knowledge anomalies would be weaker for the local context. World knowledge effects have previously been observed in the left inferior frontal region (Brodmann's area 45/47). In the current study, an effect of world knowledge was present in this region in the neutral context. We also observed an effect in the right inferior frontal gyrus, which was more sensitive to the discourse manipulation than the left inferior frontal gyrus. In addition, the left angular gyrus reacted strongly to the degree of discourse coherence between the context and critical sentence. Overall, both world knowledge and the discourse context affect the process of meaning unification, but do so by recruiting partly different sets of brain areas.

Abstract

The dendritic cell receptor DC-SIGN mediates pathogen recognition by binding to glycans characteristic of pathogen surfaces, including those found on HIV. Clustering of carbohydrate-binding sites in the receptor tetramer is believed to be critical for targeting of pathogen glycans, but the arrangement of these sites remains poorly understood. Surface force measurements between apposed lipid bilayers displaying the extracellular domain of DC-SIGN and a neoglycolipid bearing an oligosaccharide ligand provide evidence that the receptor is in an extended conformation and that glycan docking is associated with a conformational change that repositions the carbohydrate-recognition domains during ligand binding. The results further show that the lateral mobility of membrane-bound ligands enhances the engagement of multiple carbohydrate-recognition domains in the receptor oligomer with appropriately spaced ligands. These studies highlight differences between pathogen targeting by DC-SIGN and receptors in which binding sites at fixed spacing bind to simple molecular patterns

Abstract

PTEN Hamartoma Tumour Syndrome (PHTS) includes Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), and other conditions resulting from germline mutation of the PTEN tumour suppressor gene. Although macrocephaly, presumably due to megencephaly, is found in both CS and BRRS, the prevalence and degree have not been formally assessed in PHTS. We evaluated head size in a prospective nested series of 181 patients found to have pathogenic germline PTEN mutations. Clinical data including occipital-frontal circumference (OFC) measurement were requested for all participants. Macrocephaly was present in 94% of 161 evaluable PHTS individuals. In patients ≤18 years, mean OFC was +4.89 standard deviations (SD) above the population mean with no difference between genders (P=0.7). Among patients >18 years, average OFC was 60.0 cm in females and 62.8 cm in males (P<0.0001). To systematically determine whether macrocephaly was due to megencephaly, we examined PtenM3M4 missense mutant mice generated and maintained on mixed backgrounds. Mice were killed at various ages, brains were dissected out and weighed. Average brain weight for PtenM3M4 homozygous mice (N=15) was 1.02 g compared with 0.57 g for heterozygous mice (N=29) and 0.49 g for wild-type littermates (N=24) (P<0.0001). Macrocephaly, secondary to megencephaly, is an important component of PHTS and more prevalent than previously appreciated. Patients with PHTS have increased risks for breast and thyroid cancers, and early diagnosis is key to initiating timely screening to reduce patient morbidity and mortality. Clinicians should consider germline PTEN testing at an early point in the diagnostic work-up for patients with extreme macrocephaly.

Abstract

Past studies have found that, in adults, the acoustic properties of sound signals (such as fast versus slow temporal features) differentially activate the left and right hemispheres, and some have hypothesized that left-lateralization for speech processing may follow from left-lateralization to rapidly changing signals. Here, we tested whether newborns’ brains show some evidence of signal-specific lateralization responses using near-infrared spectroscopy (NIRS) and auditory stimuli that elicits lateralized responses in adults, composed of segments that vary in duration and spectral diversity. We found significantly greater bilateral responses of oxygenated hemoglobin (oxy-Hb) in the temporal areas for stimuli with a minimum segment duration of 21 ms, than stimuli with a minimum segment duration of 667 ms. However, we found no evidence for hemispheric asymmetries dependent on the stimulus characteristics. We hypothesize that acoustic-based functional brain asymmetries may develop throughout early infancy, and discuss their possible relationship with brain asymmetries for language.

Abstract

During the past ten years, research using Near-infrared Spectroscopy (NIRS) to study the developing brain has provided groundbreaking evidence of brain functions in infants. This paper presents a theoretically oriented review of this wealth of evidence, summarizing recent NIRS data on language processing, without neglecting other neuroimaging or behavioral studies in infancy and adulthood. We review three competing classes of hypotheses (i.e. signal-driven, domain-driven, and learning biases hypotheses) regarding the causes of hemispheric specialization for speech processing. We assess the fit between each of these hypotheses and neuroimaging evidence in speech perception and show that none of the three hypotheses can account for the entire set of observations on its own. However, we argue that they provide a good fit when combined within a developmental perspective. According to our proposed scenario, lateralization for language emerges out of the interaction between pre-existing left–right biases in generic auditory processing (signal-driven hypothesis), and a left-hemisphere predominance of particular learning mechanisms (learning-biases hypothesis). As a result of this completed developmental process, the native language is represented in the left hemisphere predominantly. The integrated scenario enables to link infant and adult data, and points to many empirical avenues that need to be explored more systematically.

Abstract

Understanding foreign speech is difficult, in part because of unusual mappings between sounds and words. It is known that listeners in their native language can use lexical knowledge (about how words ought to sound) to learn how to interpret unusual speech-sounds. We therefore investigated whether subtitles, which provide lexical information, support perceptual learning about foreign speech. Dutch participants, unfamiliar with Scottish and Australian regional accents of English, watched Scottish or Australian English videos with Dutch, English or no subtitles, and then repeated audio fragments of both accents. Repetition of novel fragments was worse after Dutch-subtitle exposure but better after English-subtitle exposure. Native-language subtitles appear to create lexical interference, but foreign-language subtitles assist speech learning by indicating which words (and hence sounds) are being spoken.

Abstract

There is a growing consensus that the mental lexicon contains both abstract and word-specific acoustic information. To investigate their relative importance for word recognition, we tested to what extent perceptual learning is word specific or generalizable to other words. In an exposure phase, participants were divided into two groups; each group was semantically biased to interpret an ambiguous Mandarin tone contour as either tone1 or tone2. In a subsequent test phase, the perception of ambiguous contours was dependent on the exposure phase: Participants who heard ambiguous contours as tone1 during exposure were more likely to perceive ambiguous contours as tone1 than participants who heard ambiguous contours as tone2 during exposure. This learning effect was only slightly larger for previously encountered than for not previously encountered words. The results speak for an architecture with prelexical analysis of phonological categories to achieve both lexical access and episodic storage of exemplars.

Abstract

Two experiments examined how Dutch listeners deal with the effects of connected-speech processes, specifically those arising from word-final /t/ reduction (e.g., whether Dutch [tas] is tas, bag, or a reduced-/t/ version of tast, touch). Eye movements of Dutch participants were tracked as they looked at arrays containing 4 printed words, each associated with a geometrical shape. Minimal pairs (e.g., tas/tast) were either both above (boven) or both next to (naast) different shapes. Spoken instructions (e.g., “Klik op het woordje tas boven de ster,” [Click on the word bag above the star]) thus became unambiguous only on their final words. Prior to disambiguation, listeners' fixations were drawn to /t/-final words more when boven than when naast followed the ambiguous sequences. This behavior reflects Dutch speech-production data: /t/ is reduced more before /b/ than before /n/. We thus argue that probabilistic knowledge about the effect of following context in speech production is used prelexically in perception to help resolve lexical ambiguities caused by continuous-speech processes.

Abstract

Recognizing phonetically reduced forms is a huge challenge for spoken-word recognition. Phonetic reductions not only occur often, but also come in a variety of forms. The paper investigates how two similar forms of reductions – /t/-reduction and nasal place assimilation in Dutch – can eventually be recognized, focusing on the role of following phonological context. Previous research indicated that listeners take the following phonological context into account when compensating for /t/-reduction and nasal place assimilation. The current paper shows that these context effects arise in early perceptual processes for the perception of assimilated forms, but at a later stage of processing for the perception of /t/-reduced forms. This shows first that the recognition of apparently similarly reduced words may rely on different processing mechanisms and, second, that searching for dissociations over tasks is a promising research strategy to investigate how reduced forms are recognized.

Abstract

World knowledge influences how we perceive the world. This study shows that this influence is at least partly mediated by declarative memory. Dutch and German participants categorized hues from a yellow-to-orange continuum on stimuli that were prototypically orange or yellow and that were also associated with these color labels. Both groups gave more “yellow” responses if an ambiguous hue occurred on a prototypically yellow stimulus. The language groups were also tested on a stimulus (traffic light) that is associated with the label orange in Dutch and with the label yellow in German, even though the objective color is the same for both populations. Dutch observers categorized this stimulus as orange more often than German observers, in line with the assumption that declarative knowledge mediates the influence of world knowledge on color categorization.

Abstract

Four visual-world experiments, in which listeners heard spoken words and saw printed words, compared an optimal-perception account with the theory of phonological underspecification. This theory argues that default phonological features are not specified in the mental lexicon, leading to asymmetric lexical matching: Mismatching input ("pin") activates lexical entries with underspecified coronal stops ('tin'), but lexical entries with specified labial stops ('pin') are not activated by mismatching input ("tin"). The eye-tracking data failed to show such a pattern. Although words that were phonologically similar to the spoken target attracted more looks than unrelated distractors, this effect was symmetric in Experiment 1 with minimal pairs ("tin"- "pin") and in Experiments 2 and 3 with words with an onset overlap ("peacock" - "teacake"). Experiment 4 revealed that /t/-initial words were looked at more frequently if the spoken input mismatched only in terms of place than if it mismatched in place and voice, contrary to the assumption that /t/ is unspecified for place and voice. These results show that speech perception uses signal-driven information to the fullest, as predicted by an optimal perception account.

Abstract

This study assessed, in a sample of 98 adult native speakers of Dutch, how their lexical skills and their speaking proficiency varied as a function of their age and level of education and profession (EP). Participants, categorized in terms of their age (18–35, 36–50, and 51–76 years old) and the level of their EP (low versus high), were tested on their lexical knowledge, lexical fluency, and lexical memory, and they performed four speaking tasks, differing in genre and formality. Speaking performance was rated in terms of communicative adequacy and in terms of number of words, number of T-units, words per T-unit, content words per T-unit, hesitations per T-unit, and grammatical errors per T-unit. Increasing age affected lexical knowledge positively but lexical fluency and memory negatively. High EP positively affected lexical knowledge and memory but EP did not affect lexical fluency. Communicative adequacy of the responses in the speaking tasks was positively affected by high EP but was not affected by age. It is concluded that, given the large variability in native speakers’ language knowledge and skills, studies investigating the question of whether second-language learners can reach native levels of proficiency, should take native-speaker variability into account.

Abstract

INTRODUCTION: Smoking behaviors, including heaviness of smoking and smoking cessation, are known to be under a degree of genetic influence. The enzyme catechol O-methyltransferase (COMT) is of relevance in studies of smoking behavior and smoking cessation due to its presence in dopaminergic brain regions. While the COMT gene is therefore one of the more promising candidate genes for smoking behavior, some inconsistencies have begun to emerge. METHODS: We explored whether the rs4680 A (Met) allele of the COMT gene predicts increased heaviness of smoking and reduced likelihood of smoking cessation in a large population-based cohort of pregnant women. We further conducted a meta-analysis of published data from community samples investigating the association of this polymorphism with heaviness of smoking and smoking status. RESULTS: In our primary sample, the A (Met) allele was associated with increased heaviness of smoking before pregnancy but not with the odds of continuing to smoke in pregnancy either in the first trimester or in the third trimester. Meta-analysis also indicated modest evidence of association of the A (Met) allele with increased heaviness of smoking but not with persistent smoking. CONCLUSIONS: Our data suggest a weak association between COMT genotype and heaviness of smoking, which is supported by our meta-analysis. However, it should be noted that the strength of evidence for this association was modest. Neither our primary data nor our meta-analysis support an association between COMT genotype and smoking cessation. Therefore, COMT remains a plausible candidate gene for smoking behavior phenotypes, in particular, heaviness of smoking.

Abstract

We investigate how Tamil- and Dutch-speaking adults and 4- to 5-year-old children use caused posture verbs (‘lay/stand a bottle on a table’) to label placement events in which objects are oriented vertically or horizontally. Tamil caused posture verbs consist of morphemes that individually label the causal and result subevents (nikka veyyii ‘make stand’; paDka veyyii ‘make lie’), occurring in situational and discourse contexts where object orientation is at issue. Dutch caused posture verbs are less semantically transparent: they are monomorphemic (zetten ‘set/stand’; leggen ‘lay’), often occurring in contexts where factors other than object orientation determine use. Caused posture verbs occur rarely in corpora of Tamil input, whereas in Dutch input, they are used frequently. Elicited production data reveal that Tamil four-year-olds use infrequent placement verbs appropriately whereas Dutch children use high-frequency placement verbs inappropriately even at age five. Semantic transparency exerts a stronger influence than input frequency in constraining children’s verb meaning acquisition.

Abstract

We report a genome-wide assessment of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) in schizophrenia. We investigated SNPs using 871 patients and 863 controls, following up the top hits in four independent cohorts comprising 1,460 patients and 12,995 controls, all of European origin. We found no genome-wide significant associations, nor could we provide support for any previously reported candidate gene or genome-wide associations. We went on to examine CNVs using a subset of 1,013 cases and 1,084 controls of European ancestry, and a further set of 60 cases and 64 controls of African ancestry. We found that eight cases and zero controls carried deletions greater than 2 Mb, of which two, at 8p22 and 16p13.11-p12.4, are newly reported here. A further evaluation of 1,378 controls identified no deletions greater than 2 Mb, suggesting a high prior probability of disease involvement when such deletions are observed in cases. We also provide further evidence for some smaller, previously reported, schizophrenia-associated CNVs, such as those in NRXN1 and APBA2. We could not provide strong support for the hypothesis that schizophrenia patients have a significantly greater “load” of large (>100 kb), rare CNVs, nor could we find common CNVs that associate with schizophrenia. Finally, we did not provide support for the suggestion that schizophrenia-associated CNVs may preferentially disrupt genes in neurodevelopmental pathways. Collectively, these analyses provide the first integrated study of SNPs and CNVs in schizophrenia and support the emerging view that rare deleterious variants may be more important in schizophrenia predisposition than common polymorphisms. While our analyses do not suggest that implicated CNVs impinge on particular key pathways, we do support the contribution of specific genomic regions in schizophrenia, presumably due to recurrent mutation. On balance, these data suggest that very few schizophrenia patients share identical genomic causation, potentially complicating efforts to personalize treatment regimens.

Abstract

Specific language impairment (SLI) is a common developmental disorder haracterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.

Abstract

The ability to design tailored messages for specific listeners is an important aspect of
human communication. The present study investigates whether a mere belief about an
addressee’s identity influences the generation and production of a communicative message in
a novel, non-verbal communication task. Participants were made to believe they were playing a game with a child or an adult partner, while a confederate acted as both child
and adult partners with matched performance and response times. The participants’ belief
influenced their behavior, spending longer when interacting with the presumed child
addressee, but only during communicative portions of the game, i.e. using time as a tool
to place emphasis on target information. This communicative adaptation attenuated with
experience, and it was related to personality traits, namely Empathy and Need for Cognition
measures. Overall, these findings indicate that novel nonverbal communicative interactions
are selected according to a socio-centric perspective, and they are strongly
influenced by participants’ traits.

Abstract

The present study discusses psycholinguistic evidence for a difference between paradigmatic and extraparadigmatic morphology by investigating the processing of Finnish inflected and cliticized words. The data are derived from three sources of Finnish: from single-word reading performance in an agrammatic deep dyslectic speaker, as well as from visual lexical decision and wordness/learnability ratings of cliticized vs. inflected items by normal Finnish speakers. The agrammatic speaker showed awareness of the suffixes in multimorphemic words, including clitics, since he attempted to fill in this slot with morphological material. However, he never produced a clitic — either as the correct response or as an error — in any morphological configuration (simplex, derived, inflected, compound). Moreover, he produced more nominative singular errors for case-inflected nouns than he did for the cliticized words, a pattern that is expected if case-inflected forms were closely associated with their lexical heads, i.e., if they were paradigmatic and cliticized words were not. Furthermore, a visual lexical decision task with normal speakers of Finnish, showed an additional processing cost (longer latencies and more errors on cliticized than on case-inflected noun forms). Finally, a rating task indicated no difference in relative wordness between these two types of words. However, the same cliticized words were judged harder to learn as L2 items than the inflected words, most probably due to their conceptual/semantic properties, in other words due to their lack of word-level translation equivalents in SAVE languages. Taken together, the present results suggest that the distinction between paradigmatic and extraparadigmatic morphology is psychologically real.

Abstract

Research using the intermodal preferential looking paradigm (IPLP) has consistently shown that English-learning children aged 2 can associate transitive argument structure with causal events. However, studies using the same methodology investigating 2-year-old children’s knowledge of the conjoined agent intransitive and semantic role assignment have reported inconsistent findings. The aim of the present study was to establish at what age English-learning children have verb-general knowledge of both transitive and intransitive argument structure using a new method: the forced-choice pointing paradigm. The results suggest that young 2-year-olds can associate transitive structures with causal (or externally caused) events and can use transitive structure to assign agent and patient roles correctly. However, the children were unable to associate the conjoined agent intransitive with noncausal events until aged 3;4. The results confirm the pattern from previous IPLP studies and indicate that children may develop the ability to comprehend different aspects of argument structure at different ages. The implications for theories of language acquisition and the nature of the language acquisition mechanism are discussed.

Abstract

Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”). However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender) and recognizing the communicative intention of the same actions (by a receiver) relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus). The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

Abstract

Two word-spotting experiments are reported that examine whether the Possible-Word Constraint (PWC) is a language-specific or language-universal strategy for the segmentation of continuous speech. The PWC disfavours parses which leave an impossible residue between the end of a candidate word and any likely location of a word boundary, as cued in the speech signal. The experiments examined cases where the residue was either a CVC syllable with a schwa, or a CV syllable with a lax vowel. Although neither of these syllable contexts is a possible lexical word in English, word-spotting in both contexts was easier than in a context consisting of a single consonant. Two control lexical-decision experiments showed that the word-spotting results reflected the relative segmentation difficulty of the words in different contexts. The PWC appears to be language-universal rather than language-specific.

Abstract

Recent functional brain imaging studies have shown that sensory-specific brain regions that are activated during perception/encoding of sensory-specific information are reactivated during memory retrieval of the same information. Here we used PET to examine whether verbal retrieval of action phrases is associated with reactivation of motor brain regions if the actions were overtly or covertly performed during encoding. Compared to a verbal condition, encoding by means of overt as well as covert activity was associated with differential activity in regions in contralateral somatosensory and motor cortex. Several of these regions were reactivated during retrieval. Common to both the overt and covert conditions was reactivation of regions in left ventral motor cortex and left inferior parietal cortex. A direct comparison of the overt and covert activity conditions showed that activation and reactivation of left dorsal parietal cortex and right cerebellum was specific to the overt condition. These results support the reactivation hypothesis by showing that verbal-explicit memory of actions involves areas that are engaged during overt and covert motor activity.

Abstract

Speech perception requires the decoding of complex acoustic patterns. According to most cognitive models of spoken word recognition, this complexity is dealt with before lexical access via a process of abstraction from the acoustic signal to pre-lexical categories. It is currently unclear how these categories are implemented in the auditory cortex. Recent advances in animal neurophysiology and human functional imaging have made it possible to investigate the processing of speech in terms of probabilistic cortical maps rather than simple cognitive subtraction, which will enable us to relate neurometric data more directly to behavioural studies. We suggest that integration of insights from cognitive science, neurophysiology and functional imaging is necessary for furthering our understanding of pre-lexical abstraction in the cortex.

Abstract

The acoustic realisation of a speech sound varies, often showing allophonic variation triggered by surrounding sounds. Listeners recognise words and sounds well despite such variation, and even make use of allophonic variability in processing. This study reports five experiments on processing of the reduced/unreduced allophonic alternation of Japanese high vowels. The results show that listeners use phonological knowledge of their native language during phoneme processing and word recognition. However, interactions of the phonological and acoustic effects differ in these two processes. A facilitatory phonological effect and an inhibitory acoustic effect cancel one another out in phoneme processing; while in word recognition, the facilitatory phonological effect overrides the inhibitory acoustic effect. Four potential models of the processing of allophonic variation are discussed. The results can be accommodated in two of them, but require additional assumptions or modifications to the models, and primarily support lexical specification of allophonic variability.

Abstract

Despite growing clinical and neurobiological interest in the brain mechanisms that process emotion in music, these mechanisms remain incompletely understood. Patients with frontotemporal lobar degeneration (FTLD) frequently exhibit clinical syndromes that illustrate the effects of breakdown in emotional and social functioning. Here we investigated the neuroanatomical substrate for recognition of musical emotion in a cohort of 26 patients with FTLD (16 with behavioural variant frontotemporal dementia, bvFTD, 10 with semantic dementia, SemD) using voxel-based morphometry. On neuropsychological evaluation, patients with FTLD showed deficient recognition of canonical emotions (happiness, sadness, anger and fear) from music as well as faces and voices compared with healthy control subjects. Impaired recognition of emotions from music was specifically associated with grey matter loss in a distributed cerebral network including insula, orbitofrontal cortex, anterior cingulate and medial prefrontal cortex, anterior temporal and more posterior temporal and parietal cortices, amygdala and the subcortical mesolimbic system. This network constitutes an essential brain substrate for recognition of musical emotion that overlaps with brain regions previously implicated in coding emotional value, behavioural context, conceptual knowledge and theory of mind. Musical emotion recognition may probe the interface of these processes, delineating a profile of brain damage that is essential for the abstraction of complex social emotions.

Abstract

This paper describes FieldTrip, an open source software package that we developed for the analysis of MEG, EEG, and other electrophysiological data. The software is implemented as a MATLAB toolbox and includes a complete set of consistent and user-friendly high-level functions that allow experimental neuroscientists to analyze experimental data. It includes algorithms for simple and advanced analysis, such as time-frequency analysis using multitapers, source reconstruction using dipoles, distributed sources and beamformers, connectivity analysis, and nonparametric statistical permutation tests at the channel and source level. The implementation as toolbox allows the user to perform elaborate and structured analyses of large data sets using the MATLAB command line and batch scripting. Furthermore, users and developers can easily extend the functionality and implement new algorithms. The modular design facilitates the reuse in other software packages.

Abstract

Do all components of a sign contribute equally to its recognition? In the present study, misperceptions in the sign-spotting task (based on the word-spotting task; Cutler & Norris, 1988) were analyzed to address this question. Three groups of deaf signers of British Sign Language (BSL) with different ages of acquisition (AoA) saw BSL signs combined with nonsense signs, along with combinations of two nonsense signs. They were asked to spot real signs and report what they had spotted. We will present an analysis of false alarms to the nonsense-sign combinations—that is, misperceptions of nonsense signs as real signs (cf. van Ooijen, 1996). Participants modified the movement and handshape parameters more than the location parameter. Within this pattern, however, there were differences as a function of AoA. These results show that the theoretical distinctions between form-based parameters in sign-language models have consequences for online processing. Vowels and consonants have different roles in speech recognition; similarly, it appears that movement, handshape, and location parameters contribute differentially to sign recognition.

Abstract

Evidence for the etiology of autism spectrum disorders (ASDs) has consistently pointed to a strong genetic component complicated by substantial locus heterogeneity1, 2. We sequenced the exomes of 20 individuals with sporadic ASD (cases) and their parents, reasoning that these families would be enriched for de novo mutations of major effect. We identified 21 de novo mutations, 11 of which were protein altering. Protein-altering mutations were significantly enriched for changes at highly conserved residues. We identified potentially causative de novo events in 4 out of 20 probands, particularly among more severely affected individuals, in FOXP1, GRIN2B, SCN1A and LAMC3. In the FOXP1 mutation carrier, we also observed a rare inherited CNTNAP2 missense variant, and we provide functional support for a multi-hit model for disease risk3. Our results show that trio-based exome sequencing is a powerful approach for identifying new candidate genes for ASDs and suggest that de novo mutations may contribute substantially to the genetic etiology of ASDs.

Abstract

Prior research has indicated that readers and listeners can use information in the prior discourse to rapidly predict specific upcoming words, as the text is unfolding. Here we used event-related potentials to explore whether the ability to make rapid online predictions depends on a reader's working memory capacity (WMC). Readers with low WMC were hypothesized to differ from high WMC readers either in their overall capability to make predictions (because of their lack of cognitive resources). High and low WMC participants read highly constraining stories that supported the prediction of a specific noun, mixed with coherent but essentially unpredictive ‘prime control’ control stories that contained the same content words as the predictive stories. To test whether readers were anticipating upcoming words, critical nouns were preceded by a determiner whose gender agreed or disagreed with the gender of the expected noun. In predictive stories, both high and low WMC readers displayed an early negative deflection (300–600 ms) to unexpected determiners, which was not present in prime control stories. Only the low WMC participants displayed an additional later negativity (900–1500 ms) to unexpected determiners. This pattern of results suggests that WMC does not influence the ability to anticipate upcoming words per se, but does change the way in which readers deal with information that disconfirms the generated prediction.

Abstract

The archaeological site of Sagalassos is located in Southwest Turkey, in the western part of the Taurus mountain range. Human occupation of its territory is attested from the late 12th millennium BP up to the 13th century AD. By analysing the mtDNA variation in 85 skeletons from Sagalassos dated to the 11th–13th century AD, this study attempts to reconstruct the genetic signature potentially left in this region of Anatolia by the many civilizations, which succeeded one another over the centuries until the mid-Byzantine period (13th century BC). Authentic ancient DNA data were determined from the control region and some SNPs in the coding region of the mtDNA in 53 individuals. Comparative analyses with up to 157 modern populations allowed us to reconstruct the origin of the mid-Byzantine people still dwelling in dispersed hamlets in Sagalassos, and to detect the maternal contribution of their potential ancestors. By integrating the genetic data with historical and archaeological information, we were able to attest in Sagalassos a significant maternal genetic signature of Balkan/Greek populations, as well as ancient Persians and populations from the Italian peninsula. Some contribution from the Levant has been also detected, whereas no contribution from Central Asian population could be ascertained.

Abstract

Background Thirty-two common variants associated with body mass index (BMI) have been identified in genome-wide association studies, explaining ∼1.45% of BMI variation in general population cohorts. We performed a genome-wide association study in a sample of young adults enriched for extremely overweight individuals. We aimed to identify new loci associated with BMI and to ascertain whether using an extreme sampling design would identify the variants known to be associated with BMI in general populations. Methodology/Principal Findings From two large Danish cohorts we selected all extremely overweight young men and women (n = 2,633), and equal numbers of population-based controls (n = 2,740, drawn randomly from the same populations as the extremes, representing ∼212,000 individuals). We followed up novel (at the time of the study) association signals (p<}0.001) from the discovery cohort in a genome-wide study of 5,846 Europeans, before attempting to replicate the most strongly associated 28 SNPs in an independent sample of Danish individuals (n = 20,917) and a population-based cohort of 15-year-old British adolescents (n = 2,418). Our discovery analysis identified SNPs at three loci known to be associated with BMI with genome-wide confidence (P{<}5×10−8; FTO, MC4R and FAIM2). We also found strong evidence of association at the known TMEM18, GNPDA2, SEC16B, TFAP2B, SH2B1 and KCTD15 loci (p{<}0.001), and nominal association (p{<0.05) at a further 8 loci known to be associated with BMI. However, meta-analyses of our discovery and replication cohorts identified no novel associations. Significance Our results indicate that the detectable genetic variation associated with extreme overweight is very similar to that previously found for general BMI. This suggests that population-based study designs with enriched sampling of individuals with the extreme phenotype may be an efficient method for identifying common variants that influence quantitative traits and a valid alternative to genotyping all individuals in large population-based studies, which may require tens of thousands of subjects to achieve similar power.

Abstract

The study of illiterate subjects, which for specific socio-cultural reasons did not have the opportunity to acquire basic reading and writing skills, represents one approach to study the interaction between neurobiological and cultural factors in cognitive development and the functional organization of the human brain. In addition the naturally occurring illiteracy may serve as a model for studying the influence of alphabetic orthography on auditory-verbal language. In this paper we have reviewed some recent behavioral and functional neuroimaging data indicating that learning an alphabetic written language modulates the auditory-verbal language system in a non-trivial way and provided support for the hypothesis that the functional architecture of the brain is modulated by literacy. We have also indicated that the effects of literacy and formal schooling is not limited to language related skills but appears to affect also other cognitive domains. In particular, we indicate that formal schooling influences 2D but not 3D visual naming skills. We have also pointed to the importance of using ecologically relevant tasks when comparing literate and illiterate subjects. We also demonstrate the applicability of a network approach in elucidating differences in the functional organization of the brain between groups. The strength of such an approach is the ability to study patterns of interactions between functionally specialized brain regions and the possibility to compare such patterns of brain interactions between groups or functional states. This complements the more commonly used activation approach to functional neuroimaging data, which characterize functionally specialized regions, and provides important data characterizing the functional interactions between these regions.

Abstract

Background

Noncoding RNA (ncRNA) has been recognized as an important regulator of gene expression networks in Bacteria and Eucaryota. Little is known about ncRNA in thermococcal archaea except for the eukaryotic-like C/D and H/ACA modification guide RNAs.
Results

Using a combination of in silico and experimental approaches, we identified and characterized novel P. abyssi ncRNAs transcribed from 12 intergenic regions, ten of which are conserved throughout the Thermococcales. Several of them accumulate in the late-exponential phase of growth. Analysis of the genomic context and sequence conservation amongst related thermococcal species revealed two novel P. abyssi ncRNA families. The CRISPR family is comprised of crRNAs expressed from two of the four P. abyssi CRISPR cassettes. The 5'UTR derived family includes four conserved ncRNAs, two of which have features similar to known bacterial riboswitches. Several of the novel ncRNAs have sequence similarities to orphan OrfB transposase elements. Based on RNA secondary structure predictions and experimental results, we show that three of the twelve ncRNAs include Kink-turn RNA motifs, arguing for a biological role of these ncRNAs in the cell. Furthermore, our results show that several of the ncRNAs are subjected to processing events by enzymes that remain to be identified and characterized.
Conclusions

This work proposes a revised annotation of CRISPR loci in P. abyssi and expands our knowledge of ncRNAs in the Thermococcales, thus providing a starting point for studies needed to elucidate their biological function.

Abstract

Disagreement exists about whether lexical selection in word production is a competitive process. Competition predicts semanticinterference from distractor words in immediate but not in delayed picture naming. In contrast, Janssen, Schirm, Mahon, and Caramazza (2008) obtained semanticinterference in delayed picture naming when participants had to decide between picture naming and oral reading depending on the distractor word’s colour. We report three experiments that examined the role of such taskdecisions. In a single-task situation requiring picture naming only (Experiment 1), we obtained semanticinterference in immediate but not in delayednaming. In a task-decision situation (Experiments 2 and 3), no semantic effects were obtained in immediate and delayed picture naming and word reading using either the materials of Experiment 1 or the materials of Janssen et al. (2008). We present an attentional account in which taskdecisions may hide or reveal semanticinterference from lexical competition depending on the amount of parallelism between task-decision and picture–word processing.

Abstract

In The Netherlands, grammar teaching is an especially important subject in the curriculum of children aged 10-15 for several reasons. However, in spite of all attention and time invested, the results are poor. This article describes the problems and our attempt to overcome them by developing an intelligent computational instructional environment consisting of: a linguistic expert system, containing a module representing grammar and spelling rules and a number of modules to manipulate these rules; a didactic module; and a student interface with special facilities for grammar and spelling. Three prototypes of the functionality are discussed: BOUWSTEEN and COGO, which are programs for constructing and analyzing Dutch sentences; and TDTDT, a program for the conjugation of Dutch verbs.

Abstract

While autism is one of the most intensively researched psychiatric disorders, little is known about reasoning skills of people with autism. The focus of this study was on defeasible inferences, that is inferences that can be revised in the light of new information. We used a behavioral task to investigate (a) conditional reasoning and (b) the suppression of conditional inferences in high-functioning adults with autism. In the suppression task a possible exception was made salient which could prevent a conclusion from being drawn. We predicted that the autism group would have difficulties dealing with such exceptions because they require mental flexibility to adjust to the context, which is often impaired in autism. The findings confirm our hypothesis that high-functioning adults with autism have a specific difficulty with exception-handling during reasoning. It is suggested that defeasible reasoning is also involved in other cognitive domains. Implications for neural underpinnings of reasoning and autism are discussed.

Abstract

Defeasible inferences are inferences that can be revised in the light of new information. Although defeasible inferences are pervasive in everyday communication, little is known about how and when they are processed by the brain. This study examined the electrophysiological signature of defeasible reasoning using a modified version of the suppression task. Participants were presented with conditional inferences (of the type “if p, then q; p, therefore q”) that were preceded by a congruent or a disabling context. The disabling context contained a possible exception or precondition that prevented people from drawing the conclusion. Acceptability of the conclusion was indeed lower in the disabling condition compared to the congruent condition. Further, we found a large sustained negativity at the conclusion of the disabling condition relative to the congruent condition, which started around 250 msec and was persistent throughout the entire epoch. Possible accounts for the observed effect are discussed.

Abstract

Although people with autism spectrum disorders (ASD) often have severe problems with pragmatic aspects of language, little is known about their pragmatic reasoning. We carried out a behavioral study on highfunctioning adults with autistic disorder (n = 11) and Asperger syndrome (n = 17) and matched controls (n = 28) to investigate whether they are capable of deriving scalar implicatures, which are generally considered to be pragmatic inferences. Participants were presented with underinformative sentences like ‘‘Some sparrows are birds’’. This sentence is logically true, but pragmatically inappropriate if the scalar implicature ‘‘Not all sparrows are birds’’ is derived. The present findings indicate that the combined ASD group was just as likely as controls to derive scalar implicatures, yet there was a difference between participants with autistic disorder and Asperger syndrome, suggesting a potential differentiation between these disorders in pragmatic reasoning. Moreover, our results suggest that verbal intelligence is a constraint for task performance in autistic disorder but not in Asperger syndrome.

Abstract

Adults and children acquire knowledge of the structure of their environment on the basis of repeated exposure to samples of structured stimuli. In the study of inductive learning, a straightforward issue is how much sample information is needed to learn the structure. The present study distinguishes between two measures for the amount of information in the sample: set size and the extent to which the set of exemplars statistically covers the underlying structure. In an artificial grammar learning experiment, learning was affected by the sample’s statistical coverage of the grammar, but not by its mere size. Our result suggests an alternative explanation of the set size effects on learning found in previous studies (McAndrews & Moscovitch, 1985; Meulemans & Van der Linden, 1997), because, as we argue, set size was confounded with statistical coverage in these studies. nt]mis|This research was supported by a grant from the Netherlands Organization for Scientific Research. We thank Jarry Porsius for his help with the data analyses.

Abstract

Learning local regularities in sequentially structured materials is typically assumed to be based on encoding of the frequencies of these regularities. We explore the view that transitional probabilities between elements of chunks, rather than frequencies of chunks, may be the primary factor in artificial grammar learning (AGL). The transitional probability model (TPM) that we propose is argued to provide an adaptive and parsimonious strategy for encoding local regularities in order to induce sequential structure from an input set of exemplars of the grammar. In a variant of the AGL procedure, in which participants estimated the frequencies of bigrams occurring in a set of exemplars they had been exposed to previously, participants were shown to be more sensitive to local transitional probability information than to mere pattern frequencies.

Abstract

OBJECTIVE: There is overlap between an autistic and hyperactive-inattentive symptomatology when studied cross-sectionally. This study is the first to examine the longitudinal pattern of association between social-communication deficits and hyperactive-inattentive symptoms in the general population, from childhood through adolescence. We explored the interrelationship between trajectories of co-occurring symptoms, and sought evidence for shared prenatal/perinatal risk factors. METHOD: Study participants were 5,383 singletons of white ethnicity from the Avon Longitudinal Study of Parents and Children (ALSPAC). Multiple measurements of hyperactive-inattentive traits (Strengths and Difficulties Questionnaire) and autistic social-communication impairment (Social Communication Disorder Checklist) were obtained between 4 and 17 years. Both traits and their trajectories were modeled in parallel using latent class growth analysis (LCGA). Trajectory membership was subsequently investigated with respect to prenatal/perinatal risk factors. RESULTS: LCGA analysis revealed two distinct social-communication trajectories (persistently impaired versus low-risk) and four hyperactive-inattentive trait trajectories (persistently impaired, intermediate, childhood-limited and low-risk). Autistic symptoms were more stable than those of attention-deficit/hyperactivity disorder (ADHD) behaviors, which showed greater variability. Trajectories for both traits were strongly but not reciprocally interlinked, such that the majority of children with a persistent hyperactive-inattentive symptomatology also showed persistent social-communication deficits but not vice versa. Shared predictors, especially for trajectories of persistent impairment, were maternal smoking during the first trimester, which included familial effects, and a teenage pregnancy. CONCLUSIONS: Our longitudinal study reveals that a complex relationship exists between social-communication and hyperactive-inattentive traits. Patterns of association change over time, with corresponding implications for removing exclusivity criteria for ASD and ADHD, as proposed for DSM-5.

Abstract

GalMBP is a fragment of serum mannose-binding protein that has been modified to create a probe for galactose-containing ligands. Glycan array screening demonstrated that the carbohydrate-recognition domain of GalMBP selectively binds common groups of tumor-associated glycans, including Lewis-type structures and T antigen, suggesting that engineered glycan-binding proteins such as GalMBP represent novel tools for the characterization of glycoproteins bearing tumor-associated glycans. Blotting of cell extracts and membranes from MCF7 breast cancer cells with radiolabeled GalMBP was used to demonstrate that it binds to a selected set of high molecular weight glycoproteins that could be purified from MCF7 cells on an affinity column constructed with GalMBP. Proteomic and glycomic analysis of these glycoproteins by mass spectrometry showed that they are forms of CD98hc that bear glycans displaying heavily fucosylated termini, including Lewis(x) and Lewis(y) structures. The pool of ligands was found to include the target ligands for anti-CD15 antibodies, which are commonly used to detect Lewis(x) antigen on tumors, and for the endothelial scavenger receptor C-type lectin, which may be involved in tumor metastasis through interactions with this antigen. A survey of additional breast cancer cell lines reveals that there is wide variation in the types of glycosylation that lead to binding of GalMBP. Higher levels of binding are associated either with the presence of outer-arm fucosylated structures carried on a variety of different cell surface glycoproteins or with the presence of high levels of the mucin MUC1 bearing T antigen.

Abstract

Objective—The vascular competence of human-derived hematopoietic progenitors for postnatal vascularization is still poorly characterized. It is unclear whether, in the absence of ischemia, hematopoietic progenitors participate in neovascularization and whether they play a role in new blood vessel formation by incorporating into developing vessels or by a paracrine action. Methods and Results—In the present study, human cord blood–derived CD34+ (hCD34+) cells were transplanted into pre- and postgastrulation zebrafish embryos and in an adult vascular regeneration model induced by caudal fin amputation. When injected before gastrulation, hCD34+ cells cosegregated with the presumptive zebrafish hemangioblasts, characterized by Scl and Gata2 expression, in the anterior and posterior lateral mesoderm and were involved in early development of the embryonic vasculature. These morphogenetic events occurred without apparent lineage reprogramming, as shown by CD45 expression. When transplanted postgastrulation, hCD34+ cells were recruited into developing vessels, where they exhibited a potent paracrine proangiogenic action. Finally, hCD34+ cells rescued vascular defects induced by Vegf-c in vivo targeting and enhanced vascular repair in the zebrafish fin amputation model. Conclusion—These results indicate an unexpected developmental ability of human-derived hematopoietic progenitors and support the hypothesis of an evolutionary conservation of molecular pathways involved in endothelial progenitor differentiation in vivo.

Abstract

In Greek orthography, stress position is marked with a diacritic. We investigated the developmental course of processing the stress diacritic in Grades 2 to 4. Ninety children read 108 pseudowords presented without or with a diacritic either in the same or in a different position relative to the source word. Half of the pseudowords resembled the words they were derived from. Results showed that lexical sources of stress assignment were active in Grade 2 and remained stronger than the diacritic through Grade 4. The effect of the diacritic increased more rapidly and approached the lexical effect with increasing grade. In a second experiment, 90 children read 54 words and 54 pseudowords. The pattern of results for words was similar to that for nonwords suggesting that findings regarding stress assignment using nonwords may generalize to word reading. Decoding of the diacritic does not appear to be the preferred option for developing readers.

Abstract

To study the neural bases of semantic composition in language processing without confounds from syntactic composition, recent magnetoencephalography (MEG) studies have investigated the processing of constructions that exhibit some type of syntax-semantics mismatch. The most studied case of such a mismatch is complement coercion; expressions such as the author began the book, where an entity-denoting noun phrase is coerced into an eventive meaning in order to match the semantic properties of the event-selecting verb (e.g., ‘the author began reading/writing the book’). These expressions have been found to elicit increased activity in the Anterior Midline Field (AMF), an MEG component elicited at frontomedial sensors at ∼400 ms after the onset of the coercing noun [Pylkkänen, L., & McElree, B. (2007). An MEG study of silent meaning. Journal of Cognitive Neuroscience, 19, 11]. Thus, the AMF constitutes a potential neural correlate of coercion. However, the AMF was generated in ventromedial prefrontal regions, which are heavily associated with decision-making. This raises the possibility that, instead of semantic processing, the AMF effect may have been related to the experimental task, which was a sensicality judgment. We tested this hypothesis by assessing the effect of coercion when subjects were simply reading for comprehension, without a decision-task. Additionally, we investigated coercion in an adjectival rather than a verbal environment to further generalize the findings. Our results show that an AMF effect of coercion is elicited without a decision-task and that the effect also extends to this novel syntactic environment. We conclude that in addition to its role in non-linguistic higher cognition, ventromedial prefrontal regions contribute to the resolution of syntax-semantics mismatches in language processing.

Abstract

A fundamental and intensively discussed question is whether medial temporal lobe (MTL) processes that lead to non-associative item memories differ in their anatomical substrate from processes underlying associative memory formation. Using event-related functional magnetic resonance imaging, we implemented a novel design to dissociate brain activity related to item and associative memory formation not only by subsequent memory performance and anatomy but also in time, because the two constituents of each pair to be memorized were presented sequentially with an intra-pair delay of several seconds. Furthermore, the design enabled us to reduce potential differences in memory strength between item and associative memory by increasing task difficulty in the item recognition memory test. Confidence ratings for correct item recognition for both constituents did not differ between trials in which only item memory was correct and trials in which item and associative memory were correct. Specific subsequent memory analyses for item and associative memory formation revealed brain activity that appears selectively related to item memory formation in the posterior inferior temporal, posterior parahippocampal, and perirhinal cortices. In contrast, hippocampal and inferior prefrontal activity predicted successful retrieval of newly formed inter-item associations. Our findings therefore suggest that different MTL subregions indeed play distinct roles in the formation of item memory and inter-item associative memory as expected by several dual process models of the MTL memory system.

Abstract

ASA conference abstract

Abstract

The current study examined the acquisition of relative clauses (RCs) in Persian-speaking children. Persian is a relatively unique data point in crosslinguistic research in acquisition because it is a head-final language with post-nominal RCs. Children (N = 51) aged 2 to 7 years completed a picture-selection task that tested their comprehension of subject-, object-, and genitive-RCs. The results showed that the children experienced greater difficulty processing object and genitive RCs when compared to subject RCs, suggesting that the children have particular difficulty processing sentences with non-canonical word order. The results are discussed with reference to a number of theoretical accounts proposed to account for sentence difficulty.

Abstract

The authors determined the effects of changes in task demands on interpersonal and intrapersonal coordination. Participants performed a joint task in which one participant held a stick to which a circle was attached at the top (holding role), while the other held a pointer through the circle without touching its borders (pointing role). Experiment 1 investigated whether interpersonal and intrapersonal coordination varied depending on task difficulty. Results showed that interpersonal and intrapersonal coordination increased in degree and stability with increments in task difficulty. Experiment 2 explored the effects of individual constraints by increasing the balance demands of the task (one or both members of the pair stood in a less stable tandem stance). Results showed that interpersonal coordination increased in degree and stability as joint task demands increased and that coupling strength varied depending on joint and individual task constraints. In all, results suggest that interpersonal and intrapersonal coordination are affected by the nature of the task performed and the constraints it places on joint and individual performance.

Abstract

Fetal akinesia refers to a broad spectrum of disorders in which the unifying feature is a reduction or lack of fetal movement. Fetal akinesias may be caused by defects at any point along the motor system pathway including the central and peripheral nervous system, the neuromuscular junction and the muscle, as well as by restrictive dermopathy or external restriction of the fetus in utero. The fetal akinesias are clinically and genetically heterogeneous, with causative mutations identified to date in a large number of genes encoding disparate parts of the motor system. However, for most patients, the molecular cause remains unidentified. One reason for this is because the tools are only now becoming available to efficiently and affordably identify mutations in a large panel of disease genes. Next-generation sequencing offers the promise, if sufficient cohorts of patients can be assembled, to identify the majority of the remaining genes on a research basis and facilitate efficient clinical molecular diagnosis. The benefits of identifying the causative mutation(s) for each individual patient or family include accurate genetic counselling and the options of prenatal diagnosis or preimplantation genetic diagnosis.

In this review, we summarise known single-gene disorders affecting the spinal cord, peripheral nerves, neuromuscular junction or skeletal muscles that result in fetal akinesia. This audit of these known molecular and pathophysiological mechanisms involved in fetal akinesia provides a basis for improved molecular diagnosis and completing disease gene discovery.

Abstract

The region of the ancient Sahul continent (present day Australia and New Guinea, and surrounding islands) is home to extreme linguistic diversity. Even apart from the huge Austronesian language family, which spread into the area after the breakup of the Sahul continent in the Holocene, there are hundreds of languages from many apparently unrelated families. On each of the subcontinents, the generally accepted classification recognizes one large, widespread family and a number of unrelatable smaller families. If these language families are related to each other, it is at a depth which is inaccessible to standard linguistic methods. We have inferred the history of structural characteristics of these languages under an admixture model, using a Bayesian algorithm originally developed to discover populations on the basis of recombining genetic markers. This analysis identifies 10 ancestral language populations, some of which can be identified with clearly defined phylogenetic groups. The results also show traces of early dispersals, including hints at ancient connections between Australian languages and some Papuan groups (long hypothesized, never before demonstrated). Systematic language contact effects between members of big phylogenetic groups are also detected, which can in some cases be identified with a diffusional or substrate signal. Most interestingly, however, there remains striking evidence of a phylogenetic signal, with many languages showing negligible amounts of admixture.

Abstract

Several linkage analyses implicated the chromosome 9q22 region in attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disease with remarkable persistence into adulthood. This locus contains the brain-expressed GTP-binding RAS-like 2 gene (DIRAS2) thought to regulate neurogenesis. As DIRAS2 is a positional and functional ADHD candidate gene, we conducted an association study in 600 patients suffering from adult ADHD (aADHD) and 420 controls. Replication samples consisted of 1035 aADHD patients and 1381 controls, as well as 166 families with a child affected from childhood ADHD. Given the high degree of co-morbidity with ADHD, we also investigated patients suffering from bipolar disorder (BD) (n=336) or personality disorders (PDs) (n=622). Twelve single-nucleotide polymorphisms (SNPs) covering the structural gene and the transcriptional control region of DIRAS2 were analyzed. Four SNPs and two haplotype blocks showed evidence of association with ADHD, with nominal p-values ranging from p=0.006 to p=0.05. In the adult replication samples, we obtained a consistent effect of rs1412005 and of a risk haplotype containing the promoter region (p=0.026). Meta-analysis resulted in a significant common OR of 1.12 (p=0.04) for rs1412005 and confirmed association with the promoter risk haplotype (OR=1.45, p=0.0003). Subsequent analysis in nuclear families with childhood ADHD again showed an association of the promoter haplotype block (p=0.02). rs1412005 also increased risk toward BD (p=0.026) and cluster B PD (p=0.031). Additional SNPs showed association with personality scores (p=0.008–0.048). Converging lines of evidence implicate genetic variance in the promoter region of DIRAS2 in the etiology of ADHD and co-morbid impulsive disorders.

Abstract

Three categorization experiments investigated whether the speaking rate of a preceding sentence influences durational cues to the perception of suprasegmental lexical-stress patterns. Dutch two-syllable word fragments had to be judged as coming from one of two longer words that matched the fragment segmentally but differed in lexical stress placement. Word pairs contrasted primary stress on either the first versus the second syllable or the first versus the third syllable. Duration of the initial or the second syllable of the fragments and rate of the preceding context (fast vs. slow) were manipulated. Listeners used speaking rate to decide about the degree of stress on initial syllables whether the syllables' absolute durations were informative about stress (Experiment 1a) or not (Experiment 1b). Rate effects on the second syllable were visible only when the initial syllable was ambiguous in duration with respect to the preceding rate context (Experiment 2). Absolute second syllable durations contributed little to stress perception (Experiment 3). These results suggest that speaking rate is used to disambiguate words and that rate-modulated stress cues are more important on initial than non-initial syllables. Speaking rate affects perception of suprasegmental information.