Publications

Abstract

Nyelv és/vagy evolúció: Lehetséges-e a nyelv evolúciós magyarázata? [Derek Bickerton: Nyelv és evolúció] (Magyari Lilla); Történelmi olvasókönyv az agyról [Charles G. Gross: Agy, látás, emlékezet. Mesék az idegtudomány történetéből] (Garab Edit Anna); Művészet vagy tudomány [Margitay Tihamér: Az érvelés mestersége. Érvelések elemzése, értékelése és kritikája] (Zemplén Gábor); Tényleg ésszerűek vagyunk? [Herbert Simon: Az ésszerűség szerepe az emberi életben] (Kardos Péter); Nemi különbségek a megismerésben [Doreen Kimura: Női agy, férfi agy]. (Hahn Noémi);

Abstract

Frames of reference are coordinate systems used to compute and specify the location of objects with respect to other objects. These have long been thought of as innate concepts, built into our neurocognition. However, recent work shows that the use of such frames in language, cognition and gesture varies crossculturally, and that children can acquire different systems with comparable ease. We argue that language can play a significant role in structuring, or restructuring, a domain as fundamental as spatial cognition. This suggests we need to rethink the relation between the neurocognitive underpinnings of spatial cognition and the concepts we use in everyday thinking, and, more generally, to work out how to account for cross-cultural cognitive diversity in core cognitive domains.

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

Several models of spoken word recognition postulate that recognition is achieved via a process of competition between lexical hypotheses. Competition not only provides a mechanism for isolated word recognition, it also assists in continuous speech recognition, since it offers a means of segmenting continuous input into individual words. We present statistics on the pattern of occurrence of words embedded in the polysyllabic words of the English vocabulary, showing that an overwhelming majority (84%) of polysyllables have shorter words embedded within them. Positional analyses show that these embeddings are most common at the onsets of the longer word. Although both phonological and syntactic constraints could rule out some embedded words, they do not remove the problem. Lexical competition provides a means of dealing with lexical embedding. It is also supported by a growing body of experimental evidence. We present results which indicate that competition operates both between word candidates that begin at the same point in the input and candidates that begin at different points (McQueen, Norris, & Cutler, 1994, Noms, McQueen, & Cutler, in press). We conclude that lexical competition is an essential component in models of continuous speech recognition.

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

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

This study investigates how speakers of Dutch compute and produce relative time expressions. Naming digital clocks (e.g., 2:45, say ‘‘quarter to three’’) requires conceptual operations on the minute and hour information for the correct relative time expression. The interplay of these conceptual operations was investigated using a repetition priming paradigm. Participants named analog clocks (the primes) directly before naming digital clocks (the targets). The targets referred to the hour (e.g., 2:00), half past the hour (e.g., 2:30), or the coming hour (e.g., 2:45). The primes differed from the target in one or two hour and in five or ten minutes. Digital clock naming latencies were shorter with a five- than with a ten-min difference between prime and target, but the difference in hour had no effect. Moreover, the distance in minutes had only an effect for half past the hour and the coming hour, but not for the hour. These findings suggest that conceptual facilitation occurs when conceptual transformations are shared between prime and target in telling time.

Abstract

This paper aims to determine whether iconic tracing gestures produced while speaking constitute part of the speaker’s communicative intention. We used a picture description task in which speakers must communicate the spatial and color information of each picture to an interlocutor. By establishing the necessary minimal content of an intended message, we determined whether speech produced with concurrent gestures is less explicit than speech without gestures. We argue that a gesture must be communicatively intended if it expresses necessary information that was nevertheless omitted from speech. We found that speakers who produced iconic gestures representing spatial relations omitted more required spatial information from their descriptions than speakers who did not gesture. These results provide evidence that speakers intend these gestures to communicate. The results have implications for the cognitive architectures that underlie the production of gesture and speech.

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

Spatial memory deficits are core features of aging-related changes in cognitive abilities. The neural correlates of these deficits are largely unknown. In the present study, we investigated the neural underpinnings of age-related differences in spatial memory by functional MRI using a navigational memory task with route encoding and route recognition conditions. We investigated 20 healthy young (18 - 29 years old) and 20 healthy old adults (53 - 78 years old) in a random effects analysis. Old subjects showed slightly poorer performance than young subjects. Compared to the control condition, route encoding and route recognition showed activation of the dorsal and ventral visual processing streams and the frontal eye fields in both groups of subjects. Compared to old adults, young subjects showed during route encoding stronger activations in the dorsal and the ventral visual processing stream (supramarginal gyrus and posterior fusiform/parahippocampal areas). In addition, young subjects showed weaker anterior parahippocampal activity during route recognition compared to the old group. In contrast, old compared to young subjects showed less suppressed activity in the left perisylvian region and the anterior cingulate cortex during route encoding. Our findings suggest that agerelated navigational memory deficits might be caused by less effective route encoding based on reduced posterior fusiform/parahippocampal and parietal functionality combined with diminished inhibition of perisylvian and anterior cingulate cortices correlated with less effective suppression of task-irrelevant information. In contrast, age differences in neural correlates of route recognition seem to be rather subtle. Old subjects might show a diminished familiarity signal during route recognition in the anterior parahippocampal region.

Abstract

Earlier work has shown that speakers naming several objects usually look at each of them before naming them (e.g., Meyer, Sleiderink, & Levelt, 1998). In the present study, participants saw pictures and described them in utterances such as "The chair next to the cross is brown", where the colour of the first object was mentioned after another object had been mentioned. In Experiment 1, we examined whether the speakers would look at the first object (the chair) only once, before naming the object, or twice (before naming the object and before naming its colour). In Experiment 2, we examined whether speakers about to name the colour of the object would look at the object region again when the colour or the entire object had been removed while they were looking elsewhere. We found that speakers usually looked at the target object again before naming its colour, even when the colour was not displayed any more. Speakers were much less likely to fixate upon the target region when the object had been removed from view. We propose that the object contours may serve as a memory cue supporting the retrieval of the associated colour information. The results show that a speaker's eye movements in a picture description task, far from being random, depend on the available visual information and the content and structure of the planned utterance.

Abstract

A comparison of Merge, a model of comprehension, and WEAVER, a model of production, raises five issues: (1) merging models of comprehension and production necessarily creates feedback; (2) neither model is a comprehensive account of word processing; (3) the models are incomplete in different ways; (4) the models differ in their handling of competition; (5) as opposed to WEAVER, Merge is a model of metalinguistic behavior.

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

In this study we introduce an information-theoretical formulation of the emergence of type- and token-based effects in morphological processing. We describe a probabilistic measure of the informational complexity of a word, its information residual, which encompasses the combined influences of the amount of information contained by the target word and the amount of information carried by its nested morphological paradigms. By means of re-analyses of previously published data on Dutch words we show that the information residual outperforms the combination of traditional token- and type-based counts in predicting response latencies in visual lexical decision, and at the same time provides a parsimonious account of inflectional, derivational, and compounding processes.

Abstract

In this paper, we show that both token and type-based effects in lexical processing can result from a single, token-based, system, and therefore, do not necessarily reflect different levels of processing. We report three Simple Recurrent Networks modeling Dutch past-tense formation. These networks show token-based frequency effects and type-based analogical effects closely matching the behavior of human participants when producing past-tense forms for both existing verbs and pseudo-verbs. The third network covers the full vocabulary of Dutch, without imposing predefined linguistic structure on the input or output words.

Abstract

Finnish has a very productive morphology in which a stem can give rise to several thousand words. This study presents a visual lexical decision experiment addressing the processing consequences of the huge productivity of Finnish morphology. The authors observed that in Finnish words with larger morphological families elicited shorter response latencies. However, in contrast to Dutch and Hebrew, it is not the complete morphological family of a complex Finnish word that codetermines response latencies but only the subset of words directly derived from the complex word itself. Comparisons with parallel experiments using translation equivalents in Dutch and Hebrew showed substantial cross-language predictivity of family size between Finnish and Dutch but not between Finnish and Hebrew, reflecting the different ways in which the Hebrew and Finnish morphological systems contribute to the semantic organization of concepts in the mental lexicon.

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 describe the phenomenon of schwa-deletion in Hindi and how it is handled in the pronunciation component of a multilingual concatenative text-to-speech system. Each of the consonants in written Hindi is associated with an “inherent” schwa vowel which is not represented in the orthography. For instance, the Hindi word pronounced as [namak] (’salt’) is represented in the orthography using the consonantal characters for [n], [m], and [k]. Two main factors complicate the issue of schwa pronunciation in Hindi. First, not every schwa following a consonant is pronounced within the word. Second, in multimorphemic words, the presence of a morpheme boundary can block schwa deletion where it might otherwise occur. We propose a model for schwa-deletion which combines a general purpose schwa-deletion rule proposed in the linguistics literature (Ohala, 1983), with additional morphological analysis necessitated by the high frequency of compounds in our database. The system is implemented in the framework of finite-state transducer technology.

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

Specific language impairment (SLI) is defined as an unexplained failure to acquire normal language skills despite adequate intelligence and opportunity. We have reported elsewhere a full-genome scan in 98 nuclear families affected by this disorder, with the use of three quantitative traits of language ability (the expressive and receptive tests of the Clinical Evaluation of Language Fundamentals and a test of nonsense word repetition). This screen implicated two quantitative trait loci, one on chromosome 16q (SLI1) and a second on chromosome 19q (SLI2). However, a second independent genome screen performed by another group, with the use of parametric linkage analyses in extended pedigrees, found little evidence for the involvement of either of these regions in SLI. To investigate these loci further, we have collected a second sample, consisting of 86 families (367 individuals, 174 independent sib pairs), all with probands whose language skills are ⩾1.5 SD below the mean for their age. Haseman-Elston linkage analysis resulted in a maximum LOD score (MLS) of 2.84 on chromosome 16 and an MLS of 2.31 on chromosome 19, both of which represent significant linkage at the 2% level. Amalgamation of the wave 2 sample with the cohort used for the genome screen generated a total of 184 families (840 individuals, 393 independent sib pairs). Analysis of linkage within this pooled group strengthened the evidence for linkage at SLI1 and yielded a highly significant LOD score (MLS = 7.46, interval empirical P<.0004). Furthermore, linkage at the same locus was also demonstrated to three reading-related measures (basic reading [MLS = 1.49], spelling [MLS = 2.67], and reading comprehension [MLS = 1.99] subtests of the Wechsler Objectives Reading Dimensions).

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

Spoken utterances contain few reliable cues to word boundaries, but listeners nonetheless experience little difficulty identifying words in continuous speech. The authors present data and simulations that suggest that this ability is best accounted for by a model of spoken-word recognition combining competition between alternative lexical candidates and sensitivity to prosodic structure. In a word-spotting experiment, stress pattern effects emerged most clearly when there were many competing lexical candidates for part of the input. Thus, competition between simultaneously active word candidates can modulate the size of prosodic effects, which suggests that spoken-word recognition must be sensitive both to prosodic structure and to the effects of competition. A version of the Shortlist model ( D. G. Norris, 1994b) incorporating the Metrical Segmentation Strategy ( A. Cutler & D. Norris, 1988) accurately simulates the results using a lexicon of more than 25,000 words.

Abstract

The central thesis of the target article was that feedback is never necessary in spoken word recognition. The commentaries present no new data and no new theoretical arguments which lead us to revise this position. In this response we begin by clarifying some terminological issues which have lead to a number of significant misunderstandings. We provide some new arguments to support our case that the feedforward model Merge is indeed more parsimonious than the interactive alternatives, and that it provides a more convincing account of the data than alternative models. Finally, we extend the arguments to deal with new issues raised by the commentators such as infant speech perception and neural architecture.

Abstract

Top-down feedback does not benefit speech recognition; on the contrary, it can hinder it. No experimental data imply that feedback loops are required for speech recognition. Feedback is accordingly unnecessary and spoken word recognition is modular. To defend this thesis, we analyse lexical involvement in phonemic decision making. TRACE (McClelland & Elman 1986), a model with feedback from the lexicon to prelexical processes, is unable to account for all the available data on phonemic decision making. The modular Race model (Cutler & Norris 1979) is likewise challenged by some recent results, however. We therefore present a new modular model of phonemic decision making, the Merge model. In Merge, information flows from prelexical processes to the lexicon without feedback. Because phonemic decisions are based on the merging of prelexical and lexical information, Merge correctly predicts lexical involvement in phonemic decisions in both words and nonwords. Computer simulations show how Merge is able to account for the data through a process of competition between lexical hypotheses. We discuss the issue of feedback in other areas of language processing and conclude that modular models are particularly well suited to the problems and constraints of speech recognition.

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

We completed fine mapping of nine positional candidate regions for attention-deficit/hyperactivity disorder (ADHD) in an extended population sample of 308 affected sibling pairs (ASPs), constituting the largest linkage sample of families with ADHD published to date. The candidate chromosomal regions were selected from all three published genomewide scans for ADHD, and fine mapping was done to comprehensively validate these positional candidate regions in our sample. Multipoint maximum LOD score (MLS) analysis yielded significant evidence of linkage on 6q12 (MLS 3.30; empiric P=.024) and 17p11 (MLS 3.63; empiric P=.015), as well as suggestive evidence on 5p13 (MLS 2.55; empiric P=.091). In conjunction with the previously reported significant linkage on the basis of fine mapping 16p13 in the same sample as this report, the analyses presented here indicate that four chromosomal regions—5p13, 6q12, 16p13, and 17p11—are likely to harbor susceptibility genes for ADHD. The refinement of linkage within each of these regions lays the foundation for subsequent investigations using association methods to detect risk genes of moderate effect size.

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

In the present study, using event-related functional magnetic resonance imaging, we investigated a group of participants on a grammaticality classification task after they had been exposed to well-formed consonant strings generated from an artificial regular grammar.We used an implicit acquisition paradigm in which the participants were exposed to positive examples. The objective of this studywas to investigate whether brain regions related to language processing overlap with the brain regions activated by the grammaticality classification task used in the present study. Recent meta-analyses of functional neuroimaging studies indicate that syntactic processing is related to the left inferior frontal gyrus (Brodmann's areas 44 and 45) or Broca's region. In the present study, we observed that artificial grammaticality violations activated Broca's region in all participants. This observation lends some support to the suggestions that artificial grammar learning represents a model for investigating aspects of language learning in infants.

Abstract

The autonomic responses to acute pain exposure usually habituate rapidly while the subjective ratings of pain remain high for more extended periods of time. Thus, systems involved in the autonomic response to painful stimulation, for example the hypothalamus and the brainstem, would be expected to attenuate the response to pain during prolonged stimulation. This suggestion is in line with the hypothesis that the brainstem is specifically involved in the initial response to pain. To probe this hypothesis, we performed a positron emission tomography (PET) study where we scanned subjects during the first and second minute of a prolonged tonic painful cold stimulation (cold pressor test) and nonpainful cold stimulation. Galvanic skin response (GSR) was recorded during the PET scanning as an index of autonomic sympathetic response. In the main effect of pain, we observed increased activity in the thalamus bilaterally, in the contralateral insula and in the contralateral anterior cingulate cortex but no significant increases in activity in the primary or secondary somatosensory cortex. The autonomic response (GSR) decreased with stimulus duration. Concomitant with the autonomic response, increased activity was observed in brainstem and hypothalamus areas during the initial vs. the late stimulation. This effect was significantly stronger for the painful than for the cold stimulation. Activity in the brainstem showed pain-specific covariation with areas involved in pain processing, indicating an interaction between the brainstem and cortical pain networks. The findings indicate that areas in the brainstem are involved in the initial response to noxious stimulation, which is also characterized by an increased sympathetic response.

Abstract

The amygdala has been implicated in fundamental functions for the survival of the organism, such as fear and pain. In accord with this, several studies have shown increased amygdala activity during fear conditioning and the processing of fear-relevant material in human subjects. In contrast, functional neuroimaging studies of pain have shown a decreased amygdala activity. It has previously been proposed that the observed deactivations of the amygdala in these studies indicate a cognitive strategy to adapt to a distressful but in the experimental setting unavoidable painful event. In this positron emission tomography study, we show that a simple contextual manipulation, immediately preceding a painful stimulation, that increases the anticipated duration of the painful event leads to a decrease in amygdala activity and modulates the autonomic response during the noxious stimulation. On a behavioral level, 7 of the 10 subjects reported that they used coping strategies more intensely in this context. We suggest that the altered activity in the amygdala may be part of a mechanism to attenuate pain-related stress responses in a context that is perceived as being more aversive. The study also showed an increased activity in the rostral part of anterior cingulate cortex in the same context in which the amygdala activity decreased, further supporting the idea that this part of the cingulate cortex is involved in the modulation of emotional and pain networks

Abstract

It has previously been suggested that the activity in sensory regions of the brain can be modulated by attentional mechanisms during parallel cognitive processing. To investigate whether such attention-related modulations are present in the processing of pain, the regional cerebral blood ¯ow was measured using [15O]butanol and positron emission tomography in conditions involving both pain and parallel cognitive demands. The painful stimulus consisted of the standard cold pressor test and the cognitive task was a computerised perceptual maze test. The activations during the maze test reproduced findings in previous studies of the same cognitive task. The cold pressor test evoked signi®cant activity in the contralateral S1, and bilaterally in the somatosensory association areas (including S2), the ACC and the mid-insula. The activity in the somatosensory association areas and periaqueductal gray/midbrain were significantly modified, i.e. relatively decreased, when the subjects also were performing the maze task. The altered activity was accompanied with significantly lower ratings of pain during the cognitive task. In contrast, lateral orbitofrontal regions showed a relative increase of activity during pain combined with the maze task as compared to only pain, which suggests the possibility of the involvement of frontal cortex in modulation of regions processing pain

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

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

In this paper hypothesis‐testing behaviour is compared to risk‐taking behaviour. It is proposed that choosing a suitable test for a given hypothesis requires making a preposterior analysis of two aspects of such a test: the probability of obtaining supporting evidence and the evidential value of this evidence. This consideration resembles the one a gambler makes when choosing among bets, each having a probability of winning and an amount to be won. A confirmatory testing strategy can be defined within this framework as a strategy directed at maximizing either the probability or the value of a confirming outcome. Previous theories on testing behaviour have focused on the human tendency to maximize the probability of a confirming outcome. In this paper, two experiments are presented in which participants tend to maximize the confirming value of the test outcome. Motivational factors enhance this tendency dependent on the context of the testing situation. Both this result and the framework are discussed in relation to other studies in the field of testing behaviour.

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

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.

Abstract

A series of eye-tracking and categorization experiments investigated the use of speaking-rate information in the segmentation of Dutch ambiguous-word sequences. Juncture phonemes with ambiguous durations (e.g., [s] in 'eens (s)peer,' “once (s)pear,” [t] in 'nooit (t)rap,' “never staircase/quick”) were perceived as longer and hence more often as word-initial when following a fast than a slow context sentence. Listeners used speaking-rate information as soon as it became available. Rate information from a context proximal to the juncture phoneme and from a more distal context was used during on-line word recognition, as reflected in listeners' eye movements. Stronger effects of distal context, however, were observed in the categorization task, which measures the off-line results of the word-recognition process. In categorization, the amount of rate context had the greatest influence on the use of rate information, but in eye tracking, the rate information's proximal location was the most important. These findings constrain accounts of how speaking rate modulates the interpretation of durational cues during word recognition by suggesting that rate estimates are used to evaluate upcoming phonetic information continuously during prelexical speech processing.

Abstract

Human societies are built on collaborative activities. Already from early childhood, human children are skillful and proficient collaborators. They recognize when they need help in solving a problem and actively recruit collaborators [ [1] and 2 F. Warneken, F. Chen and M. Tomasello, Cooperative activities in young children and chimpanzees. Child Dev., 77 (2006), pp. 640–663. | View Record in Scopus | [MPG-SFX] | | Full Text via CrossRef | Cited By in Scopus (56) [2] ]. The societies of other primates are also to some degree cooperative. Chimpanzees, for example, engage in a variety of cooperative activities such as border patrols, group hunting, and intra- and intergroup coalitionary behavior [ [3] , [4] and [5] ]. Recent studies have shown that chimpanzees possess many of the cognitive prerequisites necessary for human-like collaboration. Chimpanzees have been shown to recognize when they need help in solving a problem and to actively recruit good over bad collaborators [ [6] and [7] ]. However, cognitive abilities might not be all that differs between chimpanzees and humans when it comes to cooperation. Another factor might be the motivation to engage in a cooperative activity. Here, we hypothesized that a key difference between human and chimpanzee collaboration—and so potentially a key mechanism in the evolution of human cooperation—is a simple preference for collaborating (versus acting alone) to obtain food. Our results supported this hypothesis, finding that whereas children strongly prefer to work together with another to obtain food, chimpanzees show no such preference.

Abstract

Aim and method: A comparison study of four six-year-old children attending a school with a play-based curriculum and a school with a traditionally structured classroom from low socioeconomic areas was conducted in Victoria, Australia. Children’s play, language and social skills were measured in February and again in August. At baseline assessment there was a combined sample of 31 children (mean age 5.5 years, SD 0.35 years; 13 females and 18 males). At follow-up there was a combined sample of 26 children (mean age 5.9 years, SD 0.35 years; 10 females, 16 males). Results: There was no significant difference between the school groups in play, language, social skills, age and sex at baseline assessment. Compared to norms on a standardised assessment, all the children were beginning school with delayed play ability. At follow-up assessment, children at the play-based curriculum school had made significant gains in all areas assessed (p values ranged from 0.000 to 0.05). Children at the school with the traditional structured classroom had made significant positive gains in use of symbols in play (p < 0.05) and semantic language (p < 0.05). At follow-up, there were significant differences between schools in elaborate play (p < 0.000), semantic language (p < 0.000), narrative language (p < 0.01) and social connection (p < 0.01), with children in the play-based curriculum school having significantly higher scores in play, narrative language and language and lower scores in social disconnection. Implications: Children from low SES areas begin school at risk of failure as skills in play, language and social skills are delayed. The school experience increases children’s skills, with children in the play-based curriculum showing significant improvements in all areas assessed. It is argued that a play-based curriculum meets children’s developmental and learning needs more effectively. More research is needed to replicate these results.

Abstract

The adipocyte-derived protein adiponectin is highly heritable and inversely associated with risk of type 2 diabetes mellitus (T2D) and coronary heart disease (CHD). We meta-analyzed 3 genome-wide association studies for circulating adiponectin levels (n = 8,531) and sought validation of the lead single nucleotide polymorphisms (SNPs) in 5 additional cohorts (n = 6,202). Five SNPs were genome-wide significant in their relationship with adiponectin (P<} or =5x10(-8)). We then tested whether these 5 SNPs were associated with risk of T2D and CHD using a Bonferroni-corrected threshold of P{< or =0.011 to declare statistical significance for these disease associations. SNPs at the adiponectin-encoding ADIPOQ locus demonstrated the strongest associations with adiponectin levels (P-combined = 9.2x10(-19) for lead SNP, rs266717, n = 14,733). A novel variant in the ARL15 (ADP-ribosylation factor-like 15) gene was associated with lower circulating levels of adiponectin (rs4311394-G, P-combined = 2.9x10(-8), n = 14,733). This same risk allele at ARL15 was also associated with a higher risk of CHD (odds ratio [OR] = 1.12, P = 8.5x10(-6), n = 22,421) more nominally, an increased risk of T2D (OR = 1.11, P = 3.2x10(-3), n = 10,128), and several metabolic traits. Expression studies in humans indicated that ARL15 is well-expressed in skeletal muscle. These findings identify a novel protein, ARL15, which influences circulating adiponectin levels and may impact upon CHD risk.