Publications

Abstract

Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS. We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups. Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error. Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.

Abstract

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

Abstract

How can one conceive of the neuronal implementation of the processing model we proposed in our target article? In his commentary (Pulvermüller 1999, reprinted here in this issue), Pulvermüller makes various proposals concerning the underlying neural mechanisms and their potential localizations in the brain. These proposals demonstrate the compatibility of our processing model and current neuroscience. We add further evidence on details of localization based on a recent meta-analysis of neuroimaging studies of word production (Indefrey & Levelt 2000). We also express some minor disagreements with respect to Pulvermüller’s interpretation of the “lemma” notion, and concerning his neural modeling of phonological code retrieval. Branigan & Pickering discuss important aspects of syntactic encoding, which was not the topic of the target article. We discuss their well-taken proposal that multiple syntactic frames for a single verb lemma are represented as independent nodes, which can be shared with other verbs, such as accounting for syntactic priming in speech production. We also discuss how, in principle, the alternative multiple-frame-multiplelemma account can be tested empirically. The available evidence does not seem to support that account.

Abstract

During the second half of the 19th century, the psychology of language was invented as a discipline for the sole purpose of explaining the evolution of spoken language. These efforts culminated in Wilhelm Wundt’s monumental Die Sprache of 1900, which outlined the psychological mechanisms involved in producing utterances and considered how these mechanisms could have evolved. Wundt assumes that articulatory movements were originally rather arbitrary concomitants of larger, meaningful expressive bodily gestures. The sounds such articulations happened to produce slowly acquired the meaning of the gesture as a whole, ultimately making the gesture superfluous. Over a century later, gestural theories of language origins still abound. I argue that such theories are unlikely and wasteful, given the biological, neurological and genetic evidence.

Abstract

The first, theoretical part of this paper sketches a framework for phonological encoding in which the speaker successively generates phonological syllables in connected speech. The final stage of this process, phonetic encoding, consists of accessing articulatory gestural scores for each of these syllables in a "mental syllabary". The second, experimental part studies various predictions derived from this theory. The main finding is a syllable frequency effect: words ending in a high-frequent syllable are named faster than words ending in a low-frequent syllable. As predicted, this syllable frequency effect is independent of and additive to the effect of word frequency on naming latency. The effect, moreover, is not due to the complexity of the word-final syllable. In the General Discussion, the syllabary model is further elaborated with respect to phonological underspecification and activation spreading. Alternative accounts of the empirical findings in terms of core syllables and demisyllables are considered.

Abstract

In recent decades, psychologists have become increasingly interested in our ability to speak. This paper sketches the present theoretical perspective on this most complex skill of homo sapiens. The generation of fluent speech is based on the interaction of various processing components. These mechanisms are highly specialized, dedicated to performing specific subroutines, such as retrieving appropriate words, generating morpho-syntactic structure, computing the phonological target shape of syllables, words, phrases and whole utterances, and creating and executing articulatory programmes. As in any complex skill, there is a self-monitoring mechanism that checks the output. These component processes are targets of increasingly sophisticated experimental research, of which this paper presents a few salient examples.

Abstract

This paper confronts Kant’s (1768) view of human conceptions of space as fundamentally divided along the three planes of the human body with an empirical case study in the Mayan community of Tenejapa in southern Mexico, whose inhabitants do not use left/right distinctions to project regions in space. Tenejapans have names for the left hand and the right hand, and also a term for hand/arm in general, but they do not generalize the distinction to spatial regions -- there is no linguistic expression glossing as 'to the left' or 'on the left-hand side', for example. Tenejapans also show a remarkable indifference to incongruous counterparts. Nor is there any system of value associations with the left and the right. The Tenejapan evidence that speaks to these Kantian themes points in two directions: (a) Kant was wrong to think that the structure of spatial regions founded on the human frame, and in particular the distinctions based on left and right, are in some sense essential human intuitions; (b) Kant may have been right to think that the left/right opposition, the perception of enantiomorphs, clockwiseness, East-West dichotomies, etc., are intimately connected to an overall system of spatial conception.

Abstract

This article explores the relation between language and cognition by examining the case of "absolute" (cardinal direction) spatial description in the Australian aboriginal language Guugu Yimithirr. This kind of spatial description is incongruent with the "relative" (e.g., left/right/front/back) spatial description familiar in European languages. Building on Haviland's 1993 analysis of Guugu Yimithirr directionals in speech and gesture, a series of informal experiments were developed. It is shown that Guugu Yimithirr speakers predominantly code for nonverbal memory in "absolute" concepts congruent with their language, while a comparative sample of Dutch speakers do so in "relative" concepts. Much anecdotal evidence also supports this. The conclusion is that Whorfian effects may in fact be demonstrable in the spatial domain.

Abstract

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

Abstract

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

Abstract

We propose that the choice between the auxiliaries hebben 'have' and zijn 'be' in Dutch is determined by a particular semantic feature of verbs. In particular we propose a feature of meaning [IEPS] for 'inferable eventual position or state' that characterizes whether the action denoted by the verb allows us to determine the eventual position or state of the verb's highest argument. It is argued that only verbs which exhibit the feature [+IEPS] or which obtain the feature compositionally in the syntax select zijn as their auxiliary. Our analysis is then compared to a number of other analyses of auxiliary selection in Dutch.

Abstract

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

Abstract

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

Abstract

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

Abstract

Infants point for various motives. Classically, one such motive is declarative, to share attention and interest with adults to events. Recently, some researchers have questioned whether infants have this motivation. In the current study, an adult reacted to 12-month-olds' pointing in different ways, and infants' responses were observed. Results showed that when the adult shared attention and interest (i.e. alternated gaze and emoted), infants pointed more frequently across trials and tended to prolong each point – presumably to prolong the satisfying interaction. However, when the adult emoted to the infant alone or looked only to the event, infants pointed less across trials and repeated points more within trials – presumably in an attempt to establish joint attention. Results suggest that 12-month-olds point declaratively and understand that others have psychological states that can be directed and shared.

Abstract

Mutations of the renal-specific chloride channel (CLCN5) gene, which is located on chromosome Xp11.22, are associated with hypercalciuric nephrolithiasis (kidney stones) in the Northern European and Japanese populations. CLCN5 encodes a 746 amino acid channel (CLC-5) that has approximately 12 transmembrane domains, and heterologous expression of wild-type CLC-5 in Xenopus oocytes has yielded outwardly rectifying chloride currents that were markedly reduced or abolished by these mutations. In order to assess further the structural and functional relationships of this recently cloned chloride channel, additional CLCN5 mutations have been identified in five unrelated families with this disorder. Three of these mutations were missense (G57V, G512R and E527D), one was a nonsense (R648Stop) and one was an insertion (30:H insertion). In addition, two of the mutations (30:H insertion and E527D) were demonstrated to be de novo, and the G57V and E527D mutations were identified in families of Afro-American and Indian origin, respectively. The G57V and 30:H insertion mutations represent the first CLCN5 mutations to be identified in the N-terminus region, and the R648Stop mutation, which has been observed previously in an unrelated family, suggests that this codon may be particularly prone to mutations. Heterologous expression of the mutations resulted in a marked reduction or abolition of the chloride currents, thereby establishing their functional importance. These results help to elucidate further the structure-function relationships of this renal chloride channel.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) and reading disability (RD) are common highly heritable disorders of childhood, which frequently co-occur. Data from twin and family studies suggest that this overlap is, in part, due to shared genetic underpinnings. Here, we report the first genome-wide linkage analysis of measures of reading ability in children with ADHD, using a sample of 233 affected sibling pairs who previously participated in a genome-wide scan for susceptibility loci in ADHD. Quantitative trait locus (QTL) analysis of a composite reading factor defined from three highly correlated reading measures identified suggestive linkage (multipoint maximum lod score, MLS>2.2) in four chromosomal regions. Two regions (16p, 17q) overlap those implicated by our previous genome-wide scan for ADHD in the same sample: one region (2p) provides replication for an RD susceptibility locus, and one region (10q) falls approximately 35 cM from a modestly highlighted region in an independent genome-wide scan of siblings with ADHD. Investigation of an individual reading measure of Reading Recognition supported linkage to putative RD susceptibility regions on chromosome 8p (MLS=2.4) and 15q (MLS=1.38). Thus, the data support the existence of genetic factors that have pleiotropic effects on ADHD and reading ability--as suggested by shared linkages on 16p, 17q and possibly 10q--but also those that appear to be unique to reading--as indicated by linkages on 2p, 8p and 15q that coincide with those previously found in studies of RD. Our study also suggests that reading measures may represent useful phenotypes in ADHD research. The eventual identification of genes underlying these unique and shared linkages may increase our understanding of ADHD, RD and the relationship between the two.

Abstract

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

Abstract

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

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

Although word boundaries are rarely clearly marked, listeners can rapidly recognize the individual words of spoken sentences. Some theories explain this in terms of competition between multiply activated lexical hypotheses; others invoke sensitivity to prosodic structure. We describe a connectionist model, SHORTLIST, in which recognition by activation and competition is successful with a realistically sized lexicon. Three experiments are then reported in which listeners detected real words embedded in nonsense strings, some of which were themselves the onsets of longer words. Effects both of competition between words and of prosodic structure were observed, suggesting that activation and competition alone are not sufficient to explain word recognition in continuous speech. However, the results can be accounted for by a version of SHORTLIST that is sensitive to prosodic structure.

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

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

Although spontaneous speech occurs more frequently in most listeners’ experience than read speech, laboratory studies of human speech recognition typically use carefully controlled materials read from a script. The phonological and prosodic characteristics of spontaneous and read speech differ considerably, however, which suggests that laboratory results may not generalize to the recognition of spontaneous and read speech materials, and their response time to detect word-initial target phonemes was measured. Response were, overall, equally fast in each speech mode. However analysis of effects previously reported in phoneme detection studies revealed significant differences between speech modes. In read speech but not in spontaneous speech, later targets were detected more rapidly than earlier targets, and targets preceded by long words were detected more rapidly than targets preceded by short words. In contrast, in spontaneous speech but not in read speech, targets were detected more rapidly in accented than unaccented words and in strong than in weak syllables. An explanation for this pattern is offered in terms of characteristic prosodic differences between spontaneous and read speech. The results support claim from previous work that listeners pay great attention to prosodic information in the process of recognizing speech.

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

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 series of experiments was carried out investigating the time course of phonological encoding in language production, i.e., the question of whether all parts of the phonological form of a word are created in parallel, or whether they are created in a specific order. a speech production task was used in which the subjects in each test trial had to say one out of three or five response words as quickly as possible. In one condition, information was provided about part of the forms of the words to be uttered, in another condition this was not the case. The production of disyllabic words was speeded by information about their first syllable, but not by information about their second syllable. Experiments using trisyllabic words showed that a facilitatory effect could be obtained from information about the second syllable of the words, provided that the first syllable was also known. These findings suggest that the syllables of a word must be encoded strictly sequentially, according to their order in the word.

Abstract

Recently, a new theory of timing in sentence production has been proposed by Ferreira (1993). This theory assumes that at the phonological level, each syllable of an utterance is assigned one or more abstract timing units depending on its position in the prosodic structure. The number of timing units associated with a syllable determines the time interval between its onset and the onset of the next syllable. An interesting prediction from the theory, which was confirmed in Ferreira's experiments with speakers of American English, is that the time intervals between syllable onsets should only depend on the syllables' positions in the prosodic structure, but not on their segmental content. However, in the present experiments, which were carried out in Dutch, the intervals between syllable onsets were consistently longer for phonetically long syllables than for short syllables. The implications of this result for models of timing in sentence production are discussed.

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

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

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

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

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

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

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

We propose that word recognition in continuous speech is subject to constraints on what may constitute a viable word of the language. This Possible-Word Constraint (PWC) reduces activation of candidate words if their recognition would imply word status for adjacent input which could not be a word - for instance, a single consonant. In two word-spotting experiments, listeners found it much harder to detectapple,for example, infapple(where [f] alone would be an impossible word), than invuffapple(wherevuffcould be a word of English). We demonstrate that the PWC can readily be implemented in a competition-based model of continuous speech recognition, as a constraint on the process of competition between candidate words; where a stretch of speech between a candidate word and a (known or likely) word boundary is not a possible word, activation of the candidate word is reduced. This implementation accurately simulates both the present results and data from a range of earlier studies of speech segmentation.

Abstract

Previous research comparing detection times for syllables and for phonemes has consistently found that syllables are responded to faster than phonemes. This finding poses theoretical problems for strictly hierarchical models of speech recognition, in which smaller units should be able to be identified faster than larger units. However, inspection of the characteristics of previous experiments’stimuli reveals that subjects have been able to respond to syllables on the basis of only a partial analysis of the stimulus. In the present experiment, five groups of subjects listened to identical stimulus material. Phoneme and syllable monitoring under standard conditions was compared with monitoring under conditions in which near matches of target and stimulus occurred on no-response trials. In the latter case, when subjects were forced to analyze each stimulus fully, phonemes were detected faster than syllables.

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

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

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

Evaluation plays a role in the telling and understanding of narratives, in communicative interaction, emotional understanding, and in psychological well-being. This article reports a study of evaluation by describing how readers monitor the concerns of characters over the course of a narrative. The main hypothesis is that readers tract the well-being via the expression of a character's internal states. Reader evaluations were revealed in think aloud protocols obtained during reading of narrative texts, one sentence at a time. Five kinds of evaluative inferences were found: appraisals (good versus bad), preferences (like versus don't like), emotions (happy versus frustrated), goals (want versus don't want), or purposes (to attain or maintain X versus to prevent or avoid X). Readers evaluated all sentences. The mean rate of evaluation per sentence was 0.55. Positive and negative evaluations over the course of the story indicated that things initially went badly for characters, improved with the formulation and execution of goal plans, declined with goal failure, and improved as characters formulated new goals and succeeded. The kind of evaluation made depended upon the episodic category of the event and the event's temporal location in the story. Evaluations also served to explain or predict events. In making evaluations, readers stayed within the frame of the story and perspectives of the character or narrator. They also moved out of the narrative frame and addressed evaluations towards the experimenter in a communicative context.

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

Understanding the role of the medial temporal lobe (MTL) in learning and memory is an important problem in cognitive neuroscience. Memory and learning processes that depend on the function of the MTL and related diencephalic structures (e.g., the anterior and mediodorsal thalamic nuclei) are defined as declarative. We have studied the MTL activity as indicated by regional cerebral blood flow with positron emission tomography and statistical parametric mapping during recall of abstract designs in a less practiced memory state as well as in a well-practiced (well-encoded) memory state. The results showed an increased activity of the MTL bilaterally (including parahippocampal gyrus extending into hippocampus proper, as well as anterior lingual and anterior fusiform gyri) during retrieval in the less practiced memory state compared to the well-practiced memory state, indicating a dynamic role of the MTL in retrieval during the learning processes. The results also showed that the activation of the MTL decreases as the subjects learn to draw abstract designs from memory, indicating a changing role of the MTL during recall in the earlier stages of acquisition compared to the well-encoded declarative memory state.

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

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

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

In this study we test a number of different claims about the nature of stylistic variation at the “single-word” stage by examining the relation between variation in early vocabulary composition, variation in early language use, and variation in the structural and functional propreties of mothers' child-directed speech. Maternal-report and observational data were collected for 26 children at 10, 50, and 100 words, These were then correlated with a variety of different measures of maternal speech at 10 words, The results show substantial variation in the percentage of common nouns and unanalyzed phrases in children's vocabularies, and singficant relations between this variation and the way in which language is used by the child. They also reveal singficant relations between the way in whch mothers use language at 10 words and the way in chich their children use language at 50 words and between certain formal properties of mothers speech at 10 words and the percentage of common nouns and unanalyzed phrases in children's early vocabularies, However, most of these relations desappear when an attempt is made to control for ossible effects of the child on the mother at Time 1. The exception is a singficant negative correlation between mothers tendency to produce speech that illustrates word boundaries and the percentage of unanalyzed phrases at 50 and 100 words. This suggests that mothers whose sprech provides the child with information about where new words begin and end tend to have children with few unanalyzed. phrases in their early vocabularies.

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

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

Two experiments examined phonological priming effects on reaction times, error rates, and event-related brain potential (ERP) measures in an auditory lexical decision task. In Experiment 1 related prime-target pairs rhymed, and in Experiment 2 they alliterated (i.e., shared the consonantal onset and vowel). Event-related potentials were recorded in a delayed response task. Reaction times and error rates were obtained both for the delayed and an immediate response task. The behavioral data of Experiment 1 provided evidence for phonological facilitation of word, but not of nonword decisions. The brain potentials were more negative to unrelated than to rhyming word-word pairs between 450 and 700 msec after target onset. This negative enhancement was not present for word-nonword pairs. Thus, the ERP results match the behavioral data. The behavioral data of Experiment 2 provided no evidence for phonological Facilitation. However, between 250 and 450 msec after target onset, i.e., considerably earlier than in Experiment 1, brain potentials were more negative for unrelated than for alliterating word and word-nonword pairs. It is argued that the ERP effects in the two experiments could be modulations of the same underlying component, possibly the N400. The difference in the timing of the effects is likely to be due to the fact that the shared segments in related stimulus pairs appeared in different word positions in the two experiments.

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

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.