Publications

Displaying 301 - 400 of 571
  • Levinson, S. C., & Meira, S. (2003). 'Natural concepts' in the spatial topological domain - adpositional meanings in crosslinguistic perspective: An exercise in semantic typology. Language, 79(3), 485-516.

    Abstract

    Most approaches to spatial language have assumed that the simplest spatial notions are (after Piaget) topological and universal (containment, contiguity, proximity, support, represented as semantic primitives suchas IN, ON, UNDER, etc.). These concepts would be coded directly in language, above all in small closed classes suchas adpositions—thus providing a striking example of semantic categories as language-specific projections of universal conceptual notions. This idea, if correct, should have as a consequence that the semantic categories instantiated in spatial adpositions should be essentially uniform crosslinguistically. This article attempts to verify this possibility by comparing the semantics of spatial adpositions in nine unrelated languages, with the help of a standard elicitation procedure, thus producing a preliminary semantic typology of spatial adpositional systems. The differences between the languages turn out to be so significant as to be incompatible withstronger versions of the UNIVERSAL CONCEPTUAL CATEGORIES hypothesis. Rather, the language-specific spatial adposition meanings seem to emerge as compact subsets of an underlying semantic space, withcertain areas being statistical ATTRACTORS or FOCI. Moreover, a comparison of systems withdifferent degrees of complexity suggests the possibility of positing implicational hierarchies for spatial adpositions. But such hierarchies need to be treated as successive divisions of semantic space, as in recent treatments of basic color terms. This type of analysis appears to be a promising approachfor future work in semantic typology.
  • Levinson, S. C., & Senft, G. (1991). Forschungsgruppe für Kognitive Anthropologie - Eine neue Forschungsgruppe in der Max-Planck-Gesellschaft. Linguistische Berichte, 133, 244-246.
  • Levinson, S. C. (1992). Primer for the field investigation of spatial description and conception. Pragmatics, 2(1), 5-47.
  • Levinson, S. C., & Senft, G. (1991). Research group for cognitive anthropology - A new research group of the Max Planck Society. Cognitive Linguistics, 2, 311-312.
  • Levinson, S. C., & Burenhult, N. (2009). Semplates: A new concept in lexical semantics? Language, 85, 153-174. doi:10.1353/lan.0.0090.

    Abstract

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

    Philosophers, psychologists, and linguists have argued that spatial conception is pivotal to cognition in general, providing a general, egocentric, and universal framework for cognition as well as metaphors for conceptualizing many other domains. But in an aboriginal community in Northern Queensland, a system of cardinal directions informs not only language, but also memory for arbitrary spatial arrays and directions. This work suggests that fundamental cognitive parameters, like the system of coding spatial locations, can vary cross-culturally, in line with the language spoken by a community. This opens up the prospect of a fruitful dialogue between anthropology and the cognitive sciences on the complex interaction between cultural and universal factors in the constitution of mind.
  • Levinson, S. C. (1991). Pragmatic reduction of the Binding Conditions revisited. Journal of Linguistics, 27, 107-161. doi:10.1017/S0022226700012433.

    Abstract

    In an earlier article (Levinson, 1987b), I raised the possibility that a Gricean theory of implicature might provide a systematic partial reduction of the Binding Conditions; the briefest of outlines is given in Section 2.1 below but the argumentation will be found in the earlier article. In this article I want, first, to show how that account might be further justified and extended, but then to introduce a radical alternative. This alternative uses the same pragmatic framework, but gives an account better adjusted to some languages. Finally, I shall attempt to show that both accounts can be combined by taking a diachronic perspective. The attraction of the combined account is that, suddenly, many facts about long-range reflexives and their associated logophoricity fall into place.
  • Liljeström, M., Hulten, A., Parkkonen, L., & Salmelin, R. (2009). Comparing MEG and fMRI views to naming actions and objects. Human Brain Mapping, 30, 1845-1856. doi:10.1002/hbm.20785.

    Abstract

    Most neuroimaging studies are performed using one imaging method only, either functional magnetic resonance imaging (fMRI), electroencephalography (EEG), or magnetoencephalography (MEG). Information on both location and timing has been sought by recording fMRI and EEG, simultaneously, or MEG and fMRI in separate sessions. Such approaches assume similar active areas whether detected via hemodynamic or electrophysiological signatures. Direct comparisons, after independent analysis of data from each imaging modality, have been conducted primarily on low-level sensory processing. Here, we report MEG (timing and location) and fMRI (location) results in 11 subjects when they named pictures that depicted an action or an object. The experimental design was exactly the same for the two imaging modalities. The MEG data were analyzed with two standard approaches: a set of equivalent current dipoles and a distributed minimum norm estimate. The fMRI blood-oxygenlevel dependent (BOLD) data were subjected to the usual random-effect contrast analysis. At the group level, MEG and fMRI data showed fairly good convergence, with both overall activation patterns and task effects localizing to comparable cortical regions. There were some systematic discrepancies, however, and the correspondence was less compelling in the individual subjects. The present analysis should be helpful in reconciling results of fMRI and MEG studies on high-level cognitive functions
  • Liszkowski, U., Schäfer, M., Carpenter, M., & Tomasello, M. (2009). Prelinguistic infants, but not chimpanzees, communicate about absent entities. Psychological Science, 20, 654-660.

    Abstract

    One of the defining features of human language is displacement, the ability to make reference to absent entities. Here we show that prelinguistic, 12-month-old infants already can use a nonverbal pointing gesture to make reference to absent entities. We also show that chimpanzees—who can point for things they want humans to give them—do not point to refer to absent entities in the same way. These results demonstrate that the ability to communicate about absent but mutually known entities depends not on language, but rather on deeper social-cognitive skills that make acts of linguistic reference possible in the first place. These nonlinguistic skills for displaced reference emerged apparently only after humans' divergence from great apes some 6 million years ago.
  • Liszkowski, U., Carpenter, M., Henning, A., Striano, T., & Tomasello, M. (2004). Twelve-month-olds point to share attention and interest. Developmental Science, 7(3), 297-307. doi:10.1111/j.1467-7687.2004.00349.x.

    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.
  • Loo, S. K., Fisher, S. E., Francks, C., Ogdie, M. N., MacPhie, I. L., Yang, M., McCracken, J. T., McGough, J. J., Nelson, S. F., Monaco, A. P., & Smalley, S. L. (2004). Genome-wide scan of reading ability in affected sibling pairs with attention-deficit/hyperactivity disorder: Unique and shared genetic effects. Molecular Psychiatry, 9, 485-493. doi:10.1038/sj.mp.4001450.

    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.
  • Lundstrom, B. N., Petersson, K. M., Andersson, J., Johansson, M., Fransson, P., & Ingvar, M. (2003). Isolating the retrieval of imagined pictures during episodic memory: Activation of the left precuneus and left prefrontal cortex. Neuroimage, 20, 1934-1943. doi:10.1016/j.neuroimage.2003.07.017.

    Abstract

    The posterior medial parietal cortex and the left prefrontal cortex have both been implicated in the recollection of past episodes. In order to clarify their functional significance, we performed this functional magnetic resonance imaging study, which employed event-related source memory and item recognition retrieval of words paired with corresponding imagined or viewed pictures. Our results suggest that episodic source memory is related to a functional network including the posterior precuneus and the left lateral prefrontal cortex. This network is activated during explicit retrieval of imagined pictures and results from the retrieval of item-context associations. This suggests that previously imagined pictures provide a context with which encoded words can be more strongly associated.
  • Mace, R., Jordan, F., & Holden, C. (2003). Testing evolutionary hypotheses about human biological adaptation using cross-cultural comparison. Comparative Biochemistry and Physiology A-Molecular & Integrative Physiology, 136(1), 85-94. doi:10.1016/S1095-6433(03)00019-9.

    Abstract

    Physiological data from a range of human populations living in different environments can provide valuable information for testing evolutionary hypotheses about human adaptation. By taking into account the effects of population history, phylogenetic comparative methods can help us determine whether variation results from selection due to particular environmental variables. These selective forces could even be due to cultural traits-which means that gene-culture co-evolution may be occurring. In this paper, we outline two examples of the use of these approaches to test adaptive hypotheses that explain global variation in two physiological traits: the first is lactose digestion capacity in adults, and the second is population sex-ratio at birth. We show that lower than average sex ratio at birth is associated with high fertility, and argue that global variation in sex ratio at birth has evolved as a response to the high physiological costs of producing boys in high fertility populations.
  • Magnuson, J. S., Tanenhaus, M. K., Aslin, R. N., & Dahan, D. (2003). The time course of spoken word learning and recognition: Studies with artificial lexicons. Journal of Experimental Psychology: General, 132(2), 202-227. doi:10.1037/0096-3445.132.2.202.

    Abstract

    The time course of spoken word recognition depends largely on the frequencies of a word and its competitors, or neighbors (similar-sounding words). However, variability in natural lexicons makes systematic analysis of frequency and neighbor similarity difficult. Artificial lexicons were used to achieve precise control over word frequency and phonological similarity. Eye tracking provided time course measures of lexical activation and competition (during spoken instructions to perform visually guided tasks) both during and after word learning, as a function of word frequency, neighbor type, and neighbor frequency. Apparent shifts from holistic to incremental competitor effects were observed in adults and neural network simulations, suggesting such shifts reflect general properties of learning rather than changes in the nature of lexical representations.
  • Magyari, L. (2003). Mit ne gondoljunk az állatokról? [What not to think about animals?] [Review of the book Wild Minds: What animals really think by M. Hauser]. Magyar Pszichológiai Szemle (Hungarian Psychological Review), 58(3), 417-424. doi:10.1556/MPSzle.58.2003.3.5.
  • Magyari, L. (2004). Nyelv és/vagy evolúció? [Book review]. Magyar Pszichológiai Szemle, 59(4), 591-607. doi:10.1556/MPSzle.59.2004.4.7.

    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);
  • Majid, A. (2004). Out of context. The Psychologist, 17(6), 330-330.
  • Majid, A. (2003). Towards behavioural genomics. The Psychologist, 16(6), 298-298.
  • Majid, A. (2004). Data elicitation methods. Language Archive Newsletter, 1(2), 6-6.
  • Majid, A. (2004). Developing clinical understanding. The Psychologist, 17, 386-387.
  • Majid, A. (2004). Coned to perfection. The Psychologist, 17(7), 386-386.
  • Majid, A., Bowerman, M., Kita, S., Haun, D. B. M., & Levinson, S. C. (2004). Can language restructure cognition? The case for space. Trends in Cognitive Sciences, 8(3), 108-114. doi:10.1016/j.tics.2004.01.003.

    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.
  • Majid, A. (2004). An integrated view of cognition [Review of the book Rethinking implicit memory ed. by J. S. Bowers and C. J. Marsolek]. The Psychologist, 17(3), 148-149.
  • Majid, A. (2004). [Review of the book The new handbook of language and social psychology ed. by W. Peter Robinson and Howard Giles]. Language and Society, 33(3), 429-433.
  • Majid, A. (2003). Into the deep. The Psychologist, 16(6), 300-300.
  • Mangione-Smith, R., Elliott, M. N., Stivers, T., McDonald, L., Heritage, J., & McGlynn, E. A. (2004). Racial/ethnic variation in parent expectations for antibiotics: Implications for public health campaigns. Pediatrics, 113(5), 385-394.
  • Mangione-Smith, R., Stivers, T., Elliott, M. N., McDonald, L., & Heritage, J. (2003). Online commentary during the physical examination: A communication tool for avoiding inappropriate antibiotic prescribing? Social Science and Medicine, 56(2), 313-320.
  • Marcus, G. F., & Fisher, S. E. (2003). FOXP2 in focus: What can genes tell us about speech and language? Trends in Cognitive Sciences, 7, 257-262. doi:10.1016/S1364-6613(03)00104-9.

    Abstract

    The human capacity for acquiring speech and language must derive, at least in part, from the genome. In 2001, a study described the first case of a gene, FOXP2, which is thought to be implicated in our ability to acquire spoken language. In the present article, we discuss how this gene was discovered, what it might do, how it relates to other genes, and what it could tell us about the nature of speech and language development. We explain how FOXP2 could, without being specific to the brain or to our own species, still provide an invaluable entry-point into understanding the genetic cascades and neural pathways that contribute to our capacity for speech and language.
  • Marlow, A. J., Fisher, S. E., Francks, C., MacPhie, I. L., Cherny, S. S., Richardson, A. J., Talcott, J. B., Stein, J. F., Monaco, A. P., & Cardon, L. R. (2003). Use of multivariate linkage analysis for dissection of a complex cognitive trait. American Journal of Human Genetics, 72(3), 561-570. doi:10.1086/368201.

    Abstract

    Replication of linkage results for complex traits has been exceedingly difficult, owing in part to the inability to measure the precise underlying phenotype, small sample sizes, genetic heterogeneity, and statistical methods employed in analysis. Often, in any particular study, multiple correlated traits have been collected, yet these have been analyzed independently or, at most, in bivariate analyses. Theoretical arguments suggest that full multivariate analysis of all available traits should offer more power to detect linkage; however, this has not yet been evaluated on a genomewide scale. Here, we conduct multivariate genomewide analyses of quantitative-trait loci that influence reading- and language-related measures in families affected with developmental dyslexia. The results of these analyses are substantially clearer than those of previous univariate analyses of the same data set, helping to resolve a number of key issues. These outcomes highlight the relevance of multivariate analysis for complex disorders for dissection of linkage results in correlated traits. The approach employed here may aid positional cloning of susceptibility genes in a wide spectrum of complex traits.
  • Martin, A. E., & McElree, B. (2009). Memory operations that support language comprehension: Evidence from verb-phrase ellipsis. Journal of Experimental Psychology: Learning, Memory, and Cognition, 35(5), 1231-1239. doi:10.1037/a0016271.

    Abstract

    Comprehension of verb-phrase ellipsis (VPE) requires reevaluation of recently processed constituents, which often necessitates retrieval of information about the elided constituent from memory. A. E. Martin and B. McElree (2008) argued that representations formed during comprehension are content addressable and that VPE antecedents are retrieved from memory via a cue-dependent direct-access pointer rather than via a search process. This hypothesis was further tested by manipulating the location of interfering material—either before the onset of the antecedent (proactive interference; PI) or intervening between antecedent and ellipsis site (retroactive interference; RI). The speed–accuracy tradeoff procedure was used to measure the time course of VPE processing. The location of the interfering material affected VPE comprehension accuracy: RI conditions engendered lower accuracy than PI conditions. Crucially, location did not affect the speed of processing VPE, which is inconsistent with both forward and backward search mechanisms. The observed time-course profiles are consistent with the hypothesis that VPE antecedents are retrieved via a cue-dependent direct-access operation. (PsycINFO Database Record (c) 2016 APA, all rights reserved)
  • Massaro, D. W., & Jesse, A. (2009). Read my lips: Speech distortions in musical lyrics can be overcome (slightly) by facial information. Speech Communication, 51(7), 604-621. doi:10.1016/j.specom.2008.05.013.

    Abstract

    Understanding the lyrics of many contemporary songs is difficult, and an earlier study [Hidalgo-Barnes, M., Massaro, D.W., 2007. Read my lips: an animated face helps communicate musical lyrics. Psychomusicology 19, 3–12] showed a benefit for lyrics recognition when seeing a computer-animated talking head (Baldi) mouthing the lyrics along with hearing the singer. However, the contribution of visual information was relatively small compared to what is usually found for speech. In the current experiments, our goal was to determine why the face appears to contribute less when aligned with sung lyrics than when aligned with normal speech presented in noise. The first experiment compared the contribution of the talking head with the originally sung lyrics versus the case when it was aligned with the Festival text-to-speech synthesis (TtS) spoken at the original duration of the song’s lyrics. A small and similar influence of the face was found in both conditions. In the three experiments, we compared the presence of the face when the durations of the TtS were equated with the duration of the original musical lyrics to the case when the lyrics were read with typical TtS durations and this speech embedded in noise. The results indicated that the unusual temporally distorted durations of musical lyrics decreases the contribution of the visible speech from the face.
  • McQueen, J. M. (2003). The ghost of Christmas future: Didn't Scrooge learn to be good? Commentary on Magnuson, McMurray, Tanenhaus and Aslin (2003). Cognitive Science, 27(5), 795-799. doi:10.1207/s15516709cog2705_6.

    Abstract

    Magnuson, McMurray, Tanenhaus, and Aslin [Cogn. Sci. 27 (2003) 285] suggest that they have evidence of lexical feedback in speech perception, and that this evidence thus challenges the purely feedforward Merge model [Behav. Brain Sci. 23 (2000) 299]. This evidence is open to an alternative explanation, however, one which preserves the assumption in Merge that there is no lexical-prelexical feedback during on-line speech processing. This explanation invokes the distinction between perceptual processing that occurs in the short term, as an utterance is heard, and processing that occurs over the longer term, for perceptual learning.
  • McQueen, J. M., Cutler, A., & Norris, D. (2003). Flow of information in the spoken word recognition system. Speech Communication, 41(1), 257-270. doi:10.1016/S0167-6393(02)00108-5.

    Abstract

    Spoken word recognition consists of two major component processes. First, at the prelexical stage, an abstract description of the utterance is generated from the information in the speech signal. Second, at the lexical stage, this description is used to activate all the words stored in the mental lexicon which match the input. These multiple candidate words then compete with each other. We review evidence which suggests that positive (match) and negative (mismatch) information of both a segmental and a suprasegmental nature is used to constrain this activation and competition process. We then ask whether, in addition to the necessary influence of the prelexical stage on the lexical stage, there is also feedback from the lexicon to the prelexical level. In two phonetic categorization experiments, Dutch listeners were asked to label both syllable-initial and syllable-final ambiguous fricatives (e.g., sounds ranging from [f] to [s]) in the word–nonword series maf–mas, and the nonword–word series jaf–jas. They tended to label the sounds in a lexically consistent manner (i.e., consistent with the word endpoints of the series). These lexical effects became smaller in listeners’ slower responses, even when the listeners were put under pressure to respond as fast as possible. Our results challenge models of spoken word recognition in which feedback modulates the prelexical analysis of the component sounds of a word whenever that word is heard
  • McQueen, J. M., Jesse, A., & Norris, D. (2009). No lexical–prelexical feedback during speech perception or: Is it time to stop playing those Christmas tapes? Journal of Memory and Language, 61, 1-18. doi:10.1016/j.jml.2009.03.002.

    Abstract

    The strongest support for feedback in speech perception comes from evidence of apparent lexical influence on prelexical fricative-stop compensation for coarticulation. Lexical knowledge (e.g., that the ambiguous final fricative of Christma? should be [s]) apparently influences perception of following stops. We argue that all such previous demonstrations can be explained without invoking lexical feedback. In particular, we show that one demonstration [Magnuson, J. S., McMurray, B., Tanenhaus, M. K., & Aslin, R. N. (2003). Lexical effects on compensation for coarticulation: The ghost of Christmash past. Cognitive Science, 27, 285–298] involved experimentally-induced biases (from 16 practice trials) rather than feedback. We found that the direction of the compensation effect depended on whether practice stimuli were words or nonwords. When both were used, there was no lexically-mediated compensation. Across experiments, however, there were lexical effects on fricative identification. This dissociation (lexical involvement in the fricative decisions but not in the following stop decisions made on the same trials) challenges interactive models in which feedback should cause both effects. We conclude that the prelexical level is sensitive to experimentally-induced phoneme-sequence biases, but that there is no feedback during speech perception.
  • Mead, S., Poulter, M., Uphill, J., Beck, J., Whitfield, J., Webb, T. E., Campbell, T., Adamson, G., Deriziotis, P., Tabrizi, S. J., Hummerich, H., Verzilli, C., Alpers, M. P., Whittaker, J. C., & Collinge, J. (2009). Genetic risk factors for variant Creutzfeldt-Jakob disease: A genome-wide association study. Lancet Neurology, 8(1), 57-66. doi:10.1016/S1474-4422(08)70265-5.

    Abstract

    BACKGROUND: Human and animal prion diseases are under genetic control, but apart from PRNP (the gene that encodes the prion protein), we understand little about human susceptibility to bovine spongiform encephalopathy (BSE) prions, the causal agent of variant Creutzfeldt-Jakob disease (vCJD).METHODS: We did a genome-wide association study of the risk of vCJD and tested for replication of our findings in samples from many categories of human prion disease (929 samples) and control samples from the UK and Papua New Guinea (4254 samples), including controls in the UK who were genotyped by the Wellcome Trust Case Control Consortium. We also did follow-up analyses of the genetic control of the clinical phenotype of prion disease and analysed candidate gene expression in a mouse cellular model of prion infection. FINDINGS: The PRNP locus was strongly associated with risk across several markers and all categories of prion disease (best single SNP [single nucleotide polymorphism] association in vCJD p=2.5 x 10(-17); best haplotypic association in vCJD p=1 x 10(-24)). Although the main contribution to disease risk was conferred by PRNP polymorphic codon 129, another nearby SNP conferred increased risk of vCJD. In addition to PRNP, one technically validated SNP association upstream of RARB (the gene that encodes retinoic acid receptor beta) had nominal genome-wide significance (p=1.9 x 10(-7)). A similar association was found in a small sample of patients with iatrogenic CJD (p=0.030) but not in patients with sporadic CJD (sCJD) or kuru. In cultured cells, retinoic acid regulates the expression of the prion protein. We found an association with acquired prion disease, including vCJD (p=5.6 x 10(-5)), kuru incubation time (p=0.017), and resistance to kuru (p=2.5 x 10(-4)), in a region upstream of STMN2 (the gene that encodes SCG10). The risk genotype was not associated with sCJD but conferred an earlier age of onset. Furthermore, expression of Stmn2 was reduced 30-fold post-infection in a mouse cellular model of prion disease. INTERPRETATION: The polymorphic codon 129 of PRNP was the main genetic risk factor for vCJD; however, additional candidate loci have been identified, which justifies functional analyses of these biological pathways in prion disease.
  • Meeuwissen, M., Roelofs, A., & Levelt, W. J. M. (2003). Planning levels in naming and reading complex numerals. Memory & Cognition, 31(8), 1238-1249.

    Abstract

    On the basis of evidence from studies of the naming and reading of numerals, Ferrand (1999) argued that the naming of objects is slower than reading their names, due to a greater response uncertainty in naming than in reading, rather than to an obligatory conceptual preparation for naming, but not for reading. We manipulated the need for conceptual preparation, while keeping response uncertainty constant in the naming and reading of complex numerals. In Experiment 1, participants named three-digit Arabic numerals either as house numbers or clock times. House number naming latencies were determined mostly by morphophonological factors, such as morpheme frequency and the number of phonemes, whereas clock time naming latencies revealed an additional conceptual involvement. In Experiment 2, the numerals were presented in alphabetic format and had to be read aloud. Reading latencies were determined mostly by morphophonological factors in both modes. These results suggest that conceptual preparation, rather than response uncertainty, is responsible for the difference between naming and reading latencies.
  • Meeuwissen, M., Roelofs, A., & Levelt, W. J. M. (2004). Naming analog clocks conceptually facilitates naming digital clocks. Brain and Language, 90(1-3), 434-440. doi:10.1016/S0093-934X(03)00454-1.

    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.
  • Melinger, A., & Levelt, W. J. M. (2004). Gesture and the communicative intention of the speaker. Gesture, 4(2), 119-141.

    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.
  • Menenti, L., Petersson, K. M., Scheeringa, R., & Hagoort, P. (2009). When elephants fly: Differential sensitivity of right and left inferior frontal gyri to discourse and world knowledge. Journal of Cognitive Neuroscience, 21, 2358-2368. doi:10.1162/jocn.2008.21163.

    Abstract

    Both local discourse and world knowledge are known to influence sentence processing. We investigated how these two sources of information conspire in language comprehension. Two types of critical sentences, correct and world knowledge anomalies, were preceded by either a neutral or a local context. The latter made the world knowledge anomalies more acceptable or plausible. We predicted that the effect of world knowledge anomalies would be weaker for the local context. World knowledge effects have previously been observed in the left inferior frontal region (Brodmann's area 45/47). In the current study, an effect of world knowledge was present in this region in the neutral context. We also observed an effect in the right inferior frontal gyrus, which was more sensitive to the discourse manipulation than the left inferior frontal gyrus. In addition, the left angular gyrus reacted strongly to the degree of discourse coherence between the context and critical sentence. Overall, both world knowledge and the discourse context affect the process of meaning unification, but do so by recruiting partly different sets of brain areas.
  • Menon, S., Rosenberg, K., Graham, S. A., Ward, E. M., Taylor, M. E., Drickamer, K., & Leckband, D. E. (2009). Binding-site geometry and flexibility in DC-SIGN demonstrated with surface force measurements. PNAS, 106, 11524-11529. doi:10.1073/pnas.0901783106.

    Abstract

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

    Additional information

    Menon_2009_Supporting_Information.pdf
  • Meulenbroek, O., Petersson, K. M., Voermans, N., Weber, B., & Fernández, G. (2004). Age differences in neural correlates of route encoding and route recognition. Neuroimage, 22, 1503-1514. doi:10.1016/j.neuroimage.2004.04.007.

    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.
  • Meyer, A. S., Roelofs, A., & Levelt, W. J. M. (2003). Word length effects in object naming: The role of a response criterion. Journal of Memory and Language, 48(1), 131-147. doi:10.1016/S0749-596X(02)00509-0.

    Abstract

    According to Levelt, Roelofs, and Meyer (1999) speakers generate the phonological and phonetic representations of successive syllables of a word in sequence and only begin to speak after having fully planned at least one complete phonological word. Therefore, speech onset latencies should be longer for long than for short words. We tested this prediction in four experiments in which Dutch participants named or categorized objects with monosyllabic or disyllabic names. Experiment 1 yielded a length effect on production latencies when objects with long and short names were tested in separate blocks, but not when they were mixed. Experiment 2 showed that the length effect was not due to a difference in the ease of object recognition. Experiment 3 replicated the results of Experiment 1 using a within-participants design. In Experiment 4, the long and short target words appeared in a phrasal context. In addition to the speech onset latencies, we obtained the viewing times for the target objects, which have been shown to depend on the time necessary to plan the form of the target names. We found word length effects for both dependent variables, but only when objects with short and long names were presented in separate blocks. We argue that in pure and mixed blocks speakers used different response deadlines, which they tried to meet by either generating the motor programs for one syllable or for all syllables of the word before speech onset. Computer simulations using WEAVER++ support this view.
  • Meyer, A. S., Van der Meulen, F. F., & Brooks, A. (2004). Eye movements during speech planning: Talking about present and remembered objects. Visual Cognition, 11, 553-576. doi:10.1080/13506280344000248.

    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.
  • Meyer, A. S. (1992). Investigation of phonological encoding through speech error analyses: Achievements, limitations, and alternatives. Cognition, 42, 181-211. doi:10.1016/0010-0277(92)90043-H.

    Abstract

    Phonological encoding in language production can be defined as a set of processes generating utterance forms on the basis of semantic and syntactic information. Most evidence about these processes stems from analyses of sound errors. In section 1 of this paper, certain important results of these analyses are reviewed. Two prominent models of phonological encoding, which are mainly based on speech error evidence, are discussed in section 2. In section 3, limitations of speech error analyses are discussed, and it is argued that detailed and comprehensive models of phonological encoding cannot be derived solely on the basis of error analyses. As is argued in section 4, a new research strategy is required. Instead of using the properties of errors to draw inferences about the generation of correct word forms, future research should directly investigate the normal process of phonological encoding.
  • Meyer, A. S., & Schriefers, H. (1991). Phonological facilitation in picture-word interference experiments: Effects of stimulus onset asynchrony and types of interfering stimuli. Journal of Experimental Psychology: Learning, Memory, and Cognition, 17, 1146-1160. doi:10.1037/0278-7393.17.6.1146.

    Abstract

    Subjects named pictures while hearing distractor words that shared word-initial or word-final segments with the picture names or were unrelated to the picture names. The relative timing of distractor and picture presentation was varied. Compared with unrelated distractors, both types of related distractors facilitated picture naming under certain timing conditions. Begin-related distractors facilitated the naming responses if the shared segments began 150 ms before, at, or 150 ms after picture onset. By contrast, end-related distractors only facilitated the responses if the shared segments began at or 150 ms after picture onset. The results suggest that the phonological encoding of the beginning of a word is initiated before the encoding of its end.
  • Meyer, A. S. (1991). The time course of phonological encoding in language production: Phonological encoding inside a syllable. Journal of Memory and Language, 30, 69-69. doi:10.1016/0749-596X(91)90011-8.

    Abstract

    Eight experiments were carried out investigating whether different parts of a syllable must be phonologically encoded in a specific order or whether they can be encoded in any order. A speech production task was used in which the subjects in each test trial had to utter one out of three or five response words as quickly as possible. In the so-called homogeneous condition these words were related in form, while in the heterogeneous condition they were unrelated in form. For monosyllabic response words shorter reaction times were obtained in the homogeneous than in the heterogeneous condition when the words had the same onset, but not when they had the same rhyme. Similarly, for disyllabic response words, the reaction times were shorter in the homogeneous than in the heterogeneous condition when the words shared only the onset of the first syllable, but not when they shared only its rhyme. Furthermore, a stronger facilitatory effect was observed when the words had the entire first syllable in common than when they only shared the onset, or the onset and the nucleus, but not the coda of the first syllable. These results suggest that syllables are phonologically encoded in two ordered steps, the first of which is dedicated to the onset and the second to the rhyme.
  • Meyer, A. S., & Bock, K. (1992). The tip-of-the-tongue phenomenon: Blocking or partial activation? Memory and Cognition, 20, 181-211.

    Abstract

    Tip-of-the-tongue states may represent the momentary unavailability of an otherwise accessible word or the weak activation of an otherwise inaccessible word. In three experiments designed to address these alternative views, subjects attempted to retrieve rare target words from their definitions. The definitions were followed by cues that were related to the targets in sound, by cues that were related in meaning, and by cues that were not related to the targets. Experiment 1 found that compared with unrelated cues, related cue words that were presented immediately after target definitions helped rather than hindered lexical retrieval, and that sound cues were more effective retrieval aids than meaning cues. Experiment 2 replicated these results when cues were presented after an initial target-retrieval attempt. These findings reverse a previous one (Jones, 1989) that was reproduced in Experiment 3 and shown to stem from a small group of unusually difficult target definitions.
  • Meyer, A. S., Sleiderink, A. M., & Levelt, W. J. M. (1998). Viewing and naming objects: Eye movements during noun phrase production. Cognition, 66(2), B25-B33. doi:10.1016/S0010-0277(98)00009-2.

    Abstract

    Eye movements have been shown to reflect word recognition and language comprehension processes occurring during reading and auditory language comprehension. The present study examines whether the eye movements speakers make during object naming similarly reflect speech planning processes. In Experiment 1, speakers named object pairs saying, for instance, 'scooter and hat'. The objects were presented as ordinary line drawings or with partly dele:ed contours and had high or low frequency names. Contour type and frequency both significantly affected the mean naming latencies and the mean time spent looking at the objects. The frequency effects disappeared in Experiment 2, in which the participants categorized the objects instead of naming them. This suggests that the frequency effects of Experiment 1 arose during lexical retrieval. We conclude that eye movements during object naming indeed reflect linguistic planning processes and that the speakers' decision to move their eyes from one object to the next is contingent upon the retrieval of the phonological form of the object names.
  • Mitterer, H., & McQueen, J. M. (2009). Foreign subtitles help but native-language subtitles harm foreign speech perception. PLoS ONE, 4(11), e7785. doi:10.1371/journal.pone.0007785.

    Abstract

    Understanding foreign speech is difficult, in part because of unusual mappings between sounds and words. It is known that listeners in their native language can use lexical knowledge (about how words ought to sound) to learn how to interpret unusual speech-sounds. We therefore investigated whether subtitles, which provide lexical information, support perceptual learning about foreign speech. Dutch participants, unfamiliar with Scottish and Australian regional accents of English, watched Scottish or Australian English videos with Dutch, English or no subtitles, and then repeated audio fragments of both accents. Repetition of novel fragments was worse after Dutch-subtitle exposure but better after English-subtitle exposure. Native-language subtitles appear to create lexical interference, but foreign-language subtitles assist speech learning by indicating which words (and hence sounds) are being spoken.
  • Mitterer, H., & McQueen, J. M. (2009). Processing reduced word-forms in speech perception using probabilistic knowledge about speech production. Journal of Experimental Psychology: Human Perception and Performance, 35(1), 244-263. doi:10.1037/a0012730.

    Abstract

    Two experiments examined how Dutch listeners deal with the effects of connected-speech processes, specifically those arising from word-final /t/ reduction (e.g., whether Dutch [tas] is tas, bag, or a reduced-/t/ version of tast, touch). Eye movements of Dutch participants were tracked as they looked at arrays containing 4 printed words, each associated with a geometrical shape. Minimal pairs (e.g., tas/tast) were either both above (boven) or both next to (naast) different shapes. Spoken instructions (e.g., “Klik op het woordje tas boven de ster,” [Click on the word bag above the star]) thus became unambiguous only on their final words. Prior to disambiguation, listeners' fixations were drawn to /t/-final words more when boven than when naast followed the ambiguous sequences. This behavior reflects Dutch speech-production data: /t/ is reduced more before /b/ than before /n/. We thus argue that probabilistic knowledge about the effect of following context in speech production is used prelexically in perception to help resolve lexical ambiguities caused by continuous-speech processes.
  • Mitterer, H., Horschig, J. M., Müsseler, J., & Majid, A. (2009). The influence of memory on perception: It's not what things look like, it's what you call them. Journal of Experimental Psychology: Learning, Memory, and Cognition, 35(6), 1557-1562. doi:10.1037/a0017019.

    Abstract

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

    Files private

    Request files
  • Moscoso del Prado Martín, F., Kostic, A., & Baayen, R. H. (2004). Putting the bits together: An information theoretical perspective on morphological processing. Cognition, 94(1), 1-18. doi:10.1016/j.cognition.2003.10.015.

    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.
  • Moscoso del Prado Martín, F., Ernestus, M., & Baayen, R. H. (2004). Do type and token effects reflect different mechanisms? Connectionist modeling of Dutch past-tense formation and final devoicing. Brain and Language, 90(1-3), 287-298. doi:10.1016/j.bandl.2003.12.002.

    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.
  • Moscoso del Prado Martín, F., Bertram, R., Haikio, T., Schreuder, R., & Baayen, R. H. (2004). Morphological family size in a morphologically rich language: The case of Finnish compared to Dutch and Hebrew. Journal of Experimental Psychology: Learning, Memory and Cognition, 30(6), 1271-1278. doi:10.1037/0278-7393.30.6.1271.

    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.
  • Narasimhan, B., Sproat, R., & Kiraz, G. (2004). Schwa-deletion in Hindi text-to-speech synthesis. International Journal of Speech Technology, 7(4), 319-333. doi:10.1023/B:IJST.0000037075.71599.62.

    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.
  • Narasimhan, B. (2003). Motion events and the lexicon: The case of Hindi. Lingua, 113(2), 123-160. doi:10.1016/S0024-3841(02)00068-2.

    Abstract

    English, and a variety of Germanic languages, allow constructions such as the bottle floated into the cave , whereas languages such as Spanish, French, and Hindi are highly restricted in allowing manner of motion verbs to occur with path phrases. This typological observation has been accounted for in terms of the conflation of complex meaning in basic or derived verbs [Talmy, L., 1985. Lexicalization patterns: semantic structure in lexical forms. In: Shopen, T. (Ed.), Language Typology and Syntactic Description 3: Grammatical Categories and the Lexicon. Cambridge University Press, Cambridge, pp. 57–149; Levin, B., Rappaport-Hovav, M., 1995. Unaccusativity: At the Syntax–Lexical Semantics Interface. MIT Press, Cambridge, MA], or the presence of path “satellites” with special grammatical properties in the lexicon of languages such as English, which allow such phrasal combinations [cf. Talmy, L., 1985. Lexicalization patterns: semantic structure in lexical forms. In: Shopen, T. (Ed.), Language Typology and Syntactic Description 3: Grammatical Categories and the Lexicon. Cambridge University Press, Cambridge, pp. 57–149; Talmy, L., 1991. Path to realisation: via aspect and result. In: Proceedings of the Seventeenth Annual Meeting of the Berkeley Linguistics Society. Berkeley Linguistics Society, Berkeley, pp. 480–520]. I use data from Hindi to show that there is little empirical support for the claim that the constraint on the phrasal combination is correlated with differences in verb meaning or the presence of satellites in the lexicon of a language. However, proposals which eschew lexicalization accounts for more general aspectual constraints on the manner verb + path phrase combination in Spanish-type languages (Aske, J., 1989. Path Predicates in English and Spanish: A Closer look. In: Proceedings of the Fifteenth Annual Meeting of the Berkeley Linguistics Society. Berkeley Linguistics Society, Berkeley, pp. 1–14) cannot account for the full range of data in Hindi either. On the basis of these facts, I argue that an empirically adequate account can be formulated in terms of a general mapping constraint, formulated in terms of whether the lexical requirements of the verb strictly or weakly constrain its syntactic privileges of occurrence. In Hindi, path phrases can combine with manner of motion verbs only to the degree that they are compatible with the semantic profile of the verb. Path phrases in English, on the other hand, can extend the verb's “semantic profile” subject to certain constraints. I suggest that path phrases are licensed in English by the semantic requirements of the “construction” in which they appear rather than by the selectional requirements of the verb (Fillmore, C., Kay, P., O'Connor, M.C., 1988, Regularity and idiomaticity in grammatical constructions. Language 64, 501–538; Jackendoff, 1990, Semantic Structures. MIT Press, Cambridge, MA; Goldberg, 1995, Constructions: A Construction Grammar Approach to Argument Structure. University of Chicago Press, Chicago and London).
  • Need, A. C., Ge, D., Weale, M. E., Maia, J., Feng, S., Heinzen, E. L., Shianna, K. V., Yoon, W., Kasperavičiūtė, D., Gennarelli, M., Strittmatter, W. J., Bonvicini, C., Rossi, G., Jayathilake, K., Cola, P. A., McEvoy, J. P., Keefe, R. S. E., Fisher, E. M. C., St. Jean, P. L., Giegling, I. and 13 moreNeed, A. C., Ge, D., Weale, M. E., Maia, J., Feng, S., Heinzen, E. L., Shianna, K. V., Yoon, W., Kasperavičiūtė, D., Gennarelli, M., Strittmatter, W. J., Bonvicini, C., Rossi, G., Jayathilake, K., Cola, P. A., McEvoy, J. P., Keefe, R. S. E., Fisher, E. M. C., St. Jean, P. L., Giegling, I., Hartmann, A. M., Möller, H.-J., Ruppert, A., Fraser, G., Crombie, C., Middleton, L. T., St. Clair, D., Roses, A. D., Muglia, P., Francks, C., Rujescu, D., Meltzer, H. Y., & Goldstein, D. B. (2009). A genome-wide investigation of SNPs and CNVs in schizophrenia. PLoS Genetics, 5(2), e1000373. doi:10.1371/journal.pgen.1000373.

    Abstract

    We report a genome-wide assessment of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) in schizophrenia. We investigated SNPs using 871 patients and 863 controls, following up the top hits in four independent cohorts comprising 1,460 patients and 12,995 controls, all of European origin. We found no genome-wide significant associations, nor could we provide support for any previously reported candidate gene or genome-wide associations. We went on to examine CNVs using a subset of 1,013 cases and 1,084 controls of European ancestry, and a further set of 60 cases and 64 controls of African ancestry. We found that eight cases and zero controls carried deletions greater than 2 Mb, of which two, at 8p22 and 16p13.11-p12.4, are newly reported here. A further evaluation of 1,378 controls identified no deletions greater than 2 Mb, suggesting a high prior probability of disease involvement when such deletions are observed in cases. We also provide further evidence for some smaller, previously reported, schizophrenia-associated CNVs, such as those in NRXN1 and APBA2. We could not provide strong support for the hypothesis that schizophrenia patients have a significantly greater “load” of large (>100 kb), rare CNVs, nor could we find common CNVs that associate with schizophrenia. Finally, we did not provide support for the suggestion that schizophrenia-associated CNVs may preferentially disrupt genes in neurodevelopmental pathways. Collectively, these analyses provide the first integrated study of SNPs and CNVs in schizophrenia and support the emerging view that rare deleterious variants may be more important in schizophrenia predisposition than common polymorphisms. While our analyses do not suggest that implicated CNVs impinge on particular key pathways, we do support the contribution of specific genomic regions in schizophrenia, presumably due to recurrent mutation. On balance, these data suggest that very few schizophrenia patients share identical genomic causation, potentially complicating efforts to personalize treatment regimens.
  • Newbury, D. F., Winchester, L., Addis, L., Paracchini, S., Buckingham, L.-L., Clark, A., Cohen, W., Cowie, H., Dworzynski, K., Everitt, A., Goodyer, I. M., Hennessy, E., Kindley, A. D., Miller, L. L., Nasir, J., O'Hare, A., Shaw, D., Simkin, Z., Simonoff, E., Slonims, V. and 11 moreNewbury, D. F., Winchester, L., Addis, L., Paracchini, S., Buckingham, L.-L., Clark, A., Cohen, W., Cowie, H., Dworzynski, K., Everitt, A., Goodyer, I. M., Hennessy, E., Kindley, A. D., Miller, L. L., Nasir, J., O'Hare, A., Shaw, D., Simkin, Z., Simonoff, E., Slonims, V., Watson, J., Ragoussis, J., Fisher, S. E., Seckl, J. R., Helms, P. J., Bolton, P. F., Pickles, A., Conti-Ramsden, G., Baird, G., Bishop, D. V., & Monaco, A. P. (2009). CMIP and ATP2C2 modulate phonological short-term memory in language impairment. American Journal of Human Genetics, 85(2), 264-272. doi:10.1016/j.ajhg.2009.07.004.

    Abstract

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

    Additional information

    mmc1.pdf
  • Newbury, D. F., Cleak, J. D., Banfield, E., Marlow, A. J., Fisher, S. E., Monaco, A. P., Stott, C. M., Merricks, M. J., Goodyer, I. M., Slonims, V., Baird, G., Bolton, P., Everitt, A., Hennessy, E., Main, M., Helms, P., Kindley, A. D., Hodson, A., Watson, J., O’Hare, A. and 9 moreNewbury, D. F., Cleak, J. D., Banfield, E., Marlow, A. J., Fisher, S. E., Monaco, A. P., Stott, C. M., Merricks, M. J., Goodyer, I. M., Slonims, V., Baird, G., Bolton, P., Everitt, A., Hennessy, E., Main, M., Helms, P., Kindley, A. D., Hodson, A., Watson, J., O’Hare, A., Cohen, W., Cowie, H., Steel, J., MacLean, A., Seckl, J., Bishop, D. V. M., Simkin, Z., Conti-Ramsden, G., & Pickles, A. (2004). Highly significant linkage to the SLI1 Locus in an expanded sample of Individuals affected by specific language impairment. American Journal of Human Genetics, 74(6), 1225-1238. doi:10.1086/421529.

    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).
  • Newman-Norlund, S. E., Noordzij, M. L., Newman-Norlund, R. D., Volman, I. A., De Ruiter, J. P., Hagoort, P., & Toni, I. (2009). Recipient design in tacit communication. Cognition, 111, 46-54. doi:10.1016/j.cognition.2008.12.004.

    Abstract

    The ability to design tailored messages for specific listeners is an important aspect of
    human communication. The present study investigates whether a mere belief about an
    addressee’s identity influences the generation and production of a communicative message in
    a novel, non-verbal communication task. Participants were made to believe they were playing a game with a child or an adult partner, while a confederate acted as both child
    and adult partners with matched performance and response times. The participants’ belief
    influenced their behavior, spending longer when interacting with the presumed child
    addressee, but only during communicative portions of the game, i.e. using time as a tool
    to place emphasis on target information. This communicative adaptation attenuated with
    experience, and it was related to personality traits, namely Empathy and Need for Cognition
    measures. Overall, these findings indicate that novel nonverbal communicative interactions
    are selected according to a socio-centric perspective, and they are strongly
    influenced by participants’ traits.
  • Niemi, J., Laine, M., & Järvikivi, J. (2009). Paradigmatic and extraparadigmatic morphology in the mental lexicon: Experimental evidence for a dissociation. The mental lexicon, 4(1), 26-40. doi:10.1075/ml.4.1.02nie.

    Abstract

    The present study discusses psycholinguistic evidence for a difference between paradigmatic and extraparadigmatic morphology by investigating the processing of Finnish inflected and cliticized words. The data are derived from three sources of Finnish: from single-word reading performance in an agrammatic deep dyslectic speaker, as well as from visual lexical decision and wordness/learnability ratings of cliticized vs. inflected items by normal Finnish speakers. The agrammatic speaker showed awareness of the suffixes in multimorphemic words, including clitics, since he attempted to fill in this slot with morphological material. However, he never produced a clitic — either as the correct response or as an error — in any morphological configuration (simplex, derived, inflected, compound). Moreover, he produced more nominative singular errors for case-inflected nouns than he did for the cliticized words, a pattern that is expected if case-inflected forms were closely associated with their lexical heads, i.e., if they were paradigmatic and cliticized words were not. Furthermore, a visual lexical decision task with normal speakers of Finnish, showed an additional processing cost (longer latencies and more errors on cliticized than on case-inflected noun forms). Finally, a rating task indicated no difference in relative wordness between these two types of words. However, the same cliticized words were judged harder to learn as L2 items than the inflected words, most probably due to their conceptual/semantic properties, in other words due to their lack of word-level translation equivalents in SAVE languages. Taken together, the present results suggest that the distinction between paradigmatic and extraparadigmatic morphology is psychologically real.
  • Nijland, L., & Janse, E. (Eds.). (2009). Auditory processing in speakers with acquired or developmental language disorders [Special Issue]. Clinical Linguistics and Phonetics, 23(3).
  • Noordman, L. G. M., & Vonk, W. (1998). Memory-based processing in understanding causal information. Discourse Processes, 191-212. doi:10.1080/01638539809545044.

    Abstract

    The reading process depends both on the text and on the reader. When we read a text, propositions in the current input are matched to propositions in the memory representation of the previous discourse but also to knowledge structures in long‐term memory. Therefore, memory‐based text processing refers both to the bottom‐up processing of the text and to the top‐down activation of the reader's knowledge. In this article, we focus on the role of cognitive structures in the reader's knowledge. We argue that causality is an important category in structuring human knowledge and that this property has consequences for text processing. Some research is discussed that illustrates that the more the information in the text reflects causal categories, the more easily the information is processed.
  • Noordzij, M., Newman-Norlund, S. E., De Ruiter, J. P., Hagoort, P., Levinson, S. C., & Toni, I. (2009). Brain mechanisms underlying human communication. Frontiers in Human Neuroscience, 3:14. doi:10.3389/neuro.09.014.2009.

    Abstract

    Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”). However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender) and recognizing the communicative intention of the same actions (by a receiver) relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus). The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.
  • Norris, D., McQueen, J. M., & Cutler, A. (2003). Perceptual learning in speech. Cognitive Psychology, 47(2), 204-238. doi:10.1016/S0010-0285(03)00006-9.

    Abstract

    This study demonstrates that listeners use lexical knowledge in perceptual learning of speech sounds. Dutch listeners first made lexical decisions on Dutch words and nonwords. The final fricative of 20 critical words had been replaced by an ambiguous sound, between [f] and [s]. One group of listeners heard ambiguous [f]-final words (e.g., [WI tlo?], from witlof, chicory) and unambiguous [s]-final words (e.g., naaldbos, pine forest). Another group heard the reverse (e.g., ambiguous [na:ldbo?], unambiguous witlof). Listeners who had heard [?] in [f]-final words were subsequently more likely to categorize ambiguous sounds on an [f]–[s] continuum as [f] than those who heard [?] in [s]-final words. Control conditions ruled out alternative explanations based on selective adaptation and contrast. Lexical information can thus be used to train categorization of speech. This use of lexical information differs from the on-line lexical feedback embodied in interactive models of speech perception. In contrast to on-line feedback, lexical feedback for learning is of benefit to spoken word recognition (e.g., in adapting to a newly encountered dialect).
  • Nyberg, L., Marklund, P., Persson, J., Cabeza, R., Forkstam, C., Petersson, K. M., & Ingvar, M. (2003). Common prefrontal activations during working memory, episodic memory, and semantic memory. Neuropsychologia, 41(3), 371-377. doi:10.1016/S0028-3932(02)00168-9.

    Abstract

    Regions of the prefrontal cortex (PFC) are typically activated in many different cognitive functions. In most studies, the focus has been on the role of specific PFC regions in specific cognitive domains, but more recently similarities in PFC activations across cognitive domains have been stressed. Such similarities may suggest that a region mediates a common function across a variety of cognitive tasks. In this study, we compared the activation patterns associated with tests of working memory, semantic memory and episodic memory. The results converged on a general involvement of four regions across memory tests. These were located in left frontopolar cortex, left mid-ventrolateral PFC, left mid-dorsolateral PFC and dorsal anterior cingulate cortex. These findings provide evidence that some PFC regions are engaged during many different memory tests. The findings are discussed in relation to theories about the functional contribition of the PFC regions and the architecture of memory.
  • Nyberg, L., Sandblom, J., Jones, S., Stigsdotter Neely, A., Petersson, K. M., Ingvar, M., & Bäckman, L. (2003). Neural correlates of training-related memory improvement in adulthood and aging. Proceedings of the National Academy of Sciences of the United States of America, 100(23), 13728-13733. doi:10.1073/pnas.1735487100.

    Abstract

    Cognitive studies show that both younger and older adults can increase their memory performance after training in using a visuospatial mnemonic, although age-related memory deficits tend to be magnified rather than reduced after training. Little is known about the changes in functional brain activity that accompany training-induced memory enhancement, and whether age-related activity changes are associated with the size of training-related gains. Here, we demonstrate that younger adults show increased activity during memory encoding in occipito-parietal and frontal brain regions after learning the mnemonic. Older adults did not show increased frontal activity, and only those elderly persons who benefited from the mnemonic showed increased occipitoparietal activity. These findings suggest that age-related differences in cognitive reserve capacity may reflect both a frontal processing deficiency and a posterior production deficiency.
  • Obleser, J., & Eisner, F. (2009). Pre-lexical abstraction of speech in the auditory cortex. Trends in Cognitive Sciences, 13, 14-19. doi:10.1016/j.tics.2008.09.005.

    Abstract

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

    Files private

    Request files
  • O'Brien, D. P., & Bowerman, M. (1998). Martin D. S. Braine (1926–1996): Obituary. American Psychologist, 53, 563. doi:10.1037/0003-066X.53.5.563.

    Abstract

    Memorializes Martin D. S. Braine, whose research on child language acquisition and on both child and adult thinking and reasoning had a major influence on modern cognitive psychology. Addressing meaning as well as position, Braine argued that children start acquiring language by learning narrow-scope positional formulas that map components of meaning to positions in the utterance. These proposals were critical in starting discussions of the possible universality of the pivot-grammar stage and of the role of syntax, semantics,and pragmatics in children's early grammar and were pivotal to the rise of approaches in which cognitive development in language acquisition is stressed.
  • Ogasawara, N., & Warner, N. (2009). Processing missing vowels: Allophonic processing in Japanese. Language and Cognitive Processes, 24, 376 -411. doi:10.1080/01690960802084028.

    Abstract

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

    Files private

    Request files
  • Ogdie, M. N., Fisher, S. E., Yang, M., Ishii, J., Francks, C., Loo, S. K., Cantor, R. M., McCracken, J. T., McGough, J. J., Smalley, S. L., & Nelson, S. F. (2004). Attention Deficit Hyperactivity Disorder: Fine mapping supports linkage to 5p13, 6q12, 16p13, and 17p11. American Journal of Human Genetics, 75(4), 661-668. doi:10.1086/424387.

    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.
  • Ogdie, M. N., MacPhie, I. L., Minassian, S. L., Yang, M., Fisher, S. E., Francks, C., Cantor, R. M., McCracken, J. T., McGough, J. J., Nelson, S. F., Monaco, A. P., & Smalley, S. L. (2003). A genomewide scan for Attention-Deficit/Hyperactivity Disorder in an extended sample: Suggestive linkage on 17p11. American Journal of Human Genetics, 72(5), 1268-1279. doi:10.1086/375139.

    Abstract

    Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is a common, highly heritable neurobehavioral disorder of childhood onset, characterized by hyperactivity, impulsivity, and/or inattention. As part of an ongoing study of the genetic etiology of ADHD, we have performed a genomewide linkage scan in 204 nuclear families comprising 853 individuals and 270 affected sibling pairs (ASPs). Previously, we reported genomewide linkage analysis of a “first wave” of these families composed of 126 ASPs. A follow-up investigation of one region on 16p yielded significant linkage in an extended sample. The current study extends the original sample of 126 ASPs to 270 ASPs and provides linkage analyses of the entire sample, using polymorphic microsatellite markers that define an ∼10-cM map across the genome. Maximum LOD score (MLS) analysis identified suggestive linkage for 17p11 (MLS=2.98) and four nominal regions with MLS values >1.0, including 5p13, 6q14, 11q25, and 20q13. These data, taken together with the fine mapping on 16p13, suggest two regions as highly likely to harbor risk genes for ADHD: 16p13 and 17p11. Interestingly, both regions, as well as 5p13, have been highlighted in genomewide scans for autism.
  • Orfanidou, E., Adam, R., McQueen, J. M., & Morgan, G. (2009). Making sense of nonsense in British Sign Language (BSL): The contribution of different phonological parameters to sign recognition. Memory & Cognition, 37(3), 302-315. doi:10.3758/MC.37.3.302.

    Abstract

    Do all components of a sign contribute equally to its recognition? In the present study, misperceptions in the sign-spotting task (based on the word-spotting task; Cutler & Norris, 1988) were analyzed to address this question. Three groups of deaf signers of British Sign Language (BSL) with different ages of acquisition (AoA) saw BSL signs combined with nonsense signs, along with combinations of two nonsense signs. They were asked to spot real signs and report what they had spotted. We will present an analysis of false alarms to the nonsense-sign combinations—that is, misperceptions of nonsense signs as real signs (cf. van Ooijen, 1996). Participants modified the movement and handshape parameters more than the location parameter. Within this pattern, however, there were differences as a function of AoA. These results show that the theoretical distinctions between form-based parameters in sign-language models have consequences for online processing. Vowels and consonants have different roles in speech recognition; similarly, it appears that movement, handshape, and location parameters contribute differentially to sign recognition.
  • Otten, M., & Van Berkum, J. J. A. (2009). Does working memory capacity affect the ability to predict upcoming words in discourse? Brain Research, 1291, 92-101. doi:doi:10.1016/j.brainres.2009.07.042.

    Abstract

    Prior research has indicated that readers and listeners can use information in the prior discourse to rapidly predict specific upcoming words, as the text is unfolding. Here we used event-related potentials to explore whether the ability to make rapid online predictions depends on a reader's working memory capacity (WMC). Readers with low WMC were hypothesized to differ from high WMC readers either in their overall capability to make predictions (because of their lack of cognitive resources). High and low WMC participants read highly constraining stories that supported the prediction of a specific noun, mixed with coherent but essentially unpredictive ‘prime control’ control stories that contained the same content words as the predictive stories. To test whether readers were anticipating upcoming words, critical nouns were preceded by a determiner whose gender agreed or disagreed with the gender of the expected noun. In predictive stories, both high and low WMC readers displayed an early negative deflection (300–600 ms) to unexpected determiners, which was not present in prime control stories. Only the low WMC participants displayed an additional later negativity (900–1500 ms) to unexpected determiners. This pattern of results suggests that WMC does not influence the ability to anticipate upcoming words per se, but does change the way in which readers deal with information that disconfirms the generated prediction.
  • Paterson, K. B., Liversedge, S. P., Rowland, C. F., & Filik, R. (2003). Children's comprehension of sentences with focus particles. Cognition, 89(3), 263-294. doi:10.1016/S0010-0277(03)00126-4.

    Abstract

    We report three studies investigating children's and adults' comprehension of sentences containing the focus particle only. In Experiments 1 and 2, four groups of participants (6–7 years, 8–10 years, 11–12 years and adult) compared sentences with only in different syntactic positions against pictures that matched or mismatched events described by the sentence. Contrary to previous findings (Crain, S., Ni, W., & Conway, L. (1994). Learning, parsing and modularity. In C. Clifton, L. Frazier, & K. Rayner (Eds.), Perspectives on sentence processing. Hillsdale, NJ: Lawrence Erlbaum; Philip, W., & Lynch, E. (1999). Felicity, relevance, and acquisition of the grammar of every and only. In S. C. Howell, S. A. Fish, & T. Keith-Lucas (Eds.), Proceedings of the 24th annual Boston University conference on language development. Somerville, MA: Cascadilla Press) we found that young children predominantly made errors by failing to process contrast information rather than errors in which they failed to use syntactic information to restrict the scope of the particle. Experiment 3 replicated these findings with pre-schoolers.
  • Pederson, E., Danziger, E., Wilkins, D. G., Levinson, S. C., Kita, S., & Senft, G. (1998). Semantic typology and spatial conceptualization. Language, 74(3), 557-589. doi:10.2307/417793.
  • Perdue, C., & Klein, W. (1992). Why does the production of some learners not grammaticalize? Studies in Second Language Acquisition, 14, 259-272. doi:10.1017/S0272263100011116.

    Abstract

    In this paper we follow two beginning learners of English, Andrea and Santo, over a period of 2 years as they develop means to structure the declarative utterances they produce in various production tasks, and then we look at the following problem: In the early stages of acquisition, both learners develop a common learner variety; during these stages, we see a picture of two learner varieties developing similar regularities determined by the minimal requirements of the tasks we examine. Andrea subsequently develops further morphosyntactic means to achieve greater cohesion in his discourse. But Santo does not. Although we can identify contexts where the grammaticalization of Andrea's production allows him to go beyond the initial constraints of his variety, it is much more difficult to ascertain why Santo, faced with the same constraints in the same contexts, does not follow this path. Some lines of investigation into this problem are then suggested.
  • Petersson, K. M. (1998). Comments on a Monte Carlo approach to the analysis of functional neuroimaging data. NeuroImage, 8, 108-112.
  • Petersson, K. M., Forkstam, C., & Ingvar, M. (2004). Artificial syntactic violations activate Broca’s region. Cognitive Science, 28(3), 383-407. doi:10.1207/s15516709cog2803_4.

    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.
  • Petersson, K. M., Sandblom, J., Elfgren, C., & Ingvar, M. (2003). Instruction-specific brain activations during episodic encoding: A generalized level of processing effect. Neuroimage, 20, 1795-1810. doi:10.1016/S1053-8119(03)00414-2.

    Abstract

    In a within-subject design we investigated the levels-of-processing (LOP) effect using visual material in a behavioral and a corresponding PET study. In the behavioral study we characterize a generalized LOP effect, using pleasantness and graphical quality judgments in the encoding situation, with two types of visual material, figurative and nonfigurative line drawings. In the PET study we investigate the related pattern of brain activations along these two dimensions. The behavioral results indicate that instruction and material contribute independently to the level of recognition performance. Therefore the LOP effect appears to stem both from the relative relevance of the stimuli (encoding opportunity) and an altered processing of stimuli brought about by the explicit instruction (encoding mode). In the PET study, encoding of visual material under the pleasantness (deep) instruction yielded left lateralized frontoparietal and anterior temporal activations while surface-based perceptually oriented processing (shallow instruction) yielded right lateralized frontoparietal, posterior temporal, and occipitotemporal activations. The result that deep encoding was related to the left prefrontal cortex while shallow encoding was related to the right prefrontal cortex, holding the material constant, is not consistent with the HERA model. In addition, we suggest that the anterior medial superior frontal region is related to aspects of self-referential semantic processing and that the inferior parts of the anterior cingulate as well as the medial orbitofrontal cortex is related to affective processing, in this case pleasantness evaluation of the stimuli regardless of explicit semantic content. Finally, the left medial temporal lobe appears more actively engaged by elaborate meaning-based processing and the complex response pattern observed in different subregions of the MTL lends support to the suggestion that this region is functionally segregated.
  • Petersson, K. M. (2004). The human brain, language, and implicit learning. Impuls, Tidsskrift for psykologi (Norwegian Journal of Psychology), 58(3), 62-72.
  • Petrovic, P., Petersson, K. M., Hansson, P., & Ingvar, M. (2004). Brainstem involvement in the initial response to pain. NeuroImage, 22, 995-1005. doi:10.1016/j.neuroimage.2004.01.046.

    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.
  • Petrovic, P., Carlsson, K., Petersson, K. M., Hansson, P., & Ingvar, M. (2004). Context-dependent deactivation of the amygdala during pain. Journal of Cognitive Neuroscience, 16, 1289-1301.

    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
  • Pijnacker, J., Geurts, B., Van Lambalgen, M., Kan, C. C., Buitelaar, J. K., & Hagoort, P. (2009). Defeasible reasoning in high-functioning adults with autism: Evidence for impaired exception-handling. Neuropsychologia, 47, 644-651. doi:10.1016/j.neuropsychologia.2008.11.011.

    Abstract

    While autism is one of the most intensively researched psychiatric disorders, little is known about reasoning skills of people with autism. The focus of this study was on defeasible inferences, that is inferences that can be revised in the light of new information. We used a behavioral task to investigate (a) conditional reasoning and (b) the suppression of conditional inferences in high-functioning adults with autism. In the suppression task a possible exception was made salient which could prevent a conclusion from being drawn. We predicted that the autism group would have difficulties dealing with such exceptions because they require mental flexibility to adjust to the context, which is often impaired in autism. The findings confirm our hypothesis that high-functioning adults with autism have a specific difficulty with exception-handling during reasoning. It is suggested that defeasible reasoning is also involved in other cognitive domains. Implications for neural underpinnings of reasoning and autism are discussed.
  • Pijnacker, J., Hagoort, P., Buitelaar, J., Teunisse, J.-P., & Geurts, B. (2009). Pragmatic inferences in high-functioning adults with autism and Asperger syndrome. Journal of Autism and Developmental Disorders, 39(4), 607-618. doi:10.1007/s10803-008-0661-8.

    Abstract

    Although people with autism spectrum disorders (ASD) often have severe problems with pragmatic aspects of language, little is known about their pragmatic reasoning. We carried out a behavioral study on highfunctioning adults with autistic disorder (n = 11) and Asperger syndrome (n = 17) and matched controls (n = 28) to investigate whether they are capable of deriving scalar implicatures, which are generally considered to be pragmatic inferences. Participants were presented with underinformative sentences like ‘‘Some sparrows are birds’’. This sentence is logically true, but pragmatically inappropriate if the scalar implicature ‘‘Not all sparrows are birds’’ is derived. The present findings indicate that the combined ASD group was just as likely as controls to derive scalar implicatures, yet there was a difference between participants with autistic disorder and Asperger syndrome, suggesting a potential differentiation between these disorders in pragmatic reasoning. Moreover, our results suggest that verbal intelligence is a constraint for task performance in autistic disorder but not in Asperger syndrome.
  • Pine, J. M., Lieven, E. V., & Rowland, C. F. (1998). Comparing different models of the development of the English verb category. Linguistics, 36(4), 807-830. doi:10.1515/ling.1998.36.4.807.

    Abstract

    In this study data from the first six months of 12 children s multiword speech were used to test the validity of Valian's (1991) syntactic perfor-mance-limitation account and Tomasello s (1992) verb-island account of early multiword speech with particular reference to the development of the English verb category. The results provide evidence for appropriate use of verb morphology, auxiliary verb structures, pronoun case marking, and SVO word order from quite early in development. However, they also demonstrate a great deal of lexical specificity in the children's use of these systems, evidenced by a lack of overlap in the verbs to which different morphological markers were applied, a lack of overlap in the verbs with which different auxiliary verbs were used, a disproportionate use of the first person singular nominative pronoun I, and a lack of overlap in the lexical items that served as the subjects and direct objects of transitive verbs. These findings raise problems for both a syntactic performance-limitation account and a strong verb-island account of the data and suggest the need to develop a more general lexiealist account of early multiword speech that explains why some words come to function as "islands" of organization in the child's grammar and others do not.
  • Poletiek, F. H. (1998). De geest van de jury. Psychologie en Maatschappij, 4, 376-378.
  • Poletiek, F. H., & Van Schijndel, T. J. P. (2009). Stimulus set size and statistical coverage of the grammar in artificial grammar learning. Psychonomic Bulletin & Review, 16(6), 1058-1064. doi:10.3758/PBR.16.6.1058.

    Abstract

    Adults and children acquire knowledge of the structure of their environment on the basis of repeated exposure to samples of structured stimuli. In the study of inductive learning, a straightforward issue is how much sample information is needed to learn the structure. The present study distinguishes between two measures for the amount of information in the sample: set size and the extent to which the set of exemplars statistically covers the underlying structure. In an artificial grammar learning experiment, learning was affected by the sample’s statistical coverage of the grammar, but not by its mere size. Our result suggests an alternative explanation of the set size effects on learning found in previous studies (McAndrews & Moscovitch, 1985; Meulemans & Van der Linden, 1997), because, as we argue, set size was confounded with statistical coverage in these studies. nt]mis|This research was supported by a grant from the Netherlands Organization for Scientific Research. We thank Jarry Porsius for his help with the data analyses.
  • Poletiek, F. H. (2009). Popper's Severity of Test as an intuitive probabilistic model of hypothesis testing. Behavioral and Brain Sciences, 32(1), 99-100. doi:10.1017/S0140525X09000454.
  • Poletiek, F. H., & Wolters, G. (2009). What is learned about fragments in artificial grammar learning? A transitional probabilities approach. Quarterly Journal of Experimental Psychology, 62(5), 868-876. doi:10.1080/17470210802511188.

    Abstract

    Learning local regularities in sequentially structured materials is typically assumed to be based on encoding of the frequencies of these regularities. We explore the view that transitional probabilities between elements of chunks, rather than frequencies of chunks, may be the primary factor in artificial grammar learning (AGL). The transitional probability model (TPM) that we propose is argued to provide an adaptive and parsimonious strategy for encoding local regularities in order to induce sequential structure from an input set of exemplars of the grammar. In a variant of the AGL procedure, in which participants estimated the frequencies of bigrams occurring in a set of exemplars they had been exposed to previously, participants were shown to be more sensitive to local transitional probability information than to mere pattern frequencies.
  • Powlesland, A. S., Hitchen, P. G., Parry, S., Graham, S. A., Barrio, M. M., Elola, M. T., Mordoh, J., Dell, A., Drickamer, K., & Taylor, M. E. (2009). Targeted glycoproteomic identification of cancer cell glycosylation. Glycobiology, 9, 899-909. doi:10.1093/glycob/cwp065.

    Abstract

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

    Additional information

    Powlesland_2009_Suppl_Mat.pdf
  • Praamstra, P., Stegeman, D. F., Cools, A. R., Meyer, A. S., & Horstink, M. W. I. M. (1998). Evidence for lateral premotor and parietal overactivity in Parkinson's disease during sequential and bimanual movements: A PET study. Brain, 121, 769-772. doi:10.1093/brain/121.4.769.
  • Praamstra, P., Hagoort, P., Maassen, B., & Crul, T. (1991). Word deafness and auditory cortical function: A case history and hypothesis. Brain, 114, 1197-1225. doi:10.1093/brain/114.3.1197.

    Abstract

    A patient who already had Wernick's aphasia due to a left temporal lobe lesion suffered a severe deterioration specifically of auditory language comprehension, subsequent to right temporal lobe infarction. A detailed comparison of his new condition with his language status before the second stroke revealed that the newly acquired deficit was limited to tasks related to auditory input. Further investigations demonstrated a speech perceptual disorder, which we analysed as due to deficits both at the level of general auditory processes and at the level of phonetic analysis. We discuss some arguments related to hemisphere specialization of phonetic processing and to the disconnection explanation of word deafness that support the hypothesis of word deafness being generally caused by mixed deficits.
  • Protopapas, A., & Gerakaki, S. (2009). Development of processing stress diacritics in reading Greek. Scientific Studies of Reading, 13(6), 453-483. doi:10.1080/10888430903034788.

    Abstract

    In Greek orthography, stress position is marked with a diacritic. We investigated the developmental course of processing the stress diacritic in Grades 2 to 4. Ninety children read 108 pseudowords presented without or with a diacritic either in the same or in a different position relative to the source word. Half of the pseudowords resembled the words they were derived from. Results showed that lexical sources of stress assignment were active in Grade 2 and remained stronger than the diacritic through Grade 4. The effect of the diacritic increased more rapidly and approached the lexical effect with increasing grade. In a second experiment, 90 children read 54 words and 54 pseudowords. The pattern of results for words was similar to that for nonwords suggesting that findings regarding stress assignment using nonwords may generalize to word reading. Decoding of the diacritic does not appear to be the preferred option for developing readers.
  • Pylkkänen, L., Martin, A. E., McElree, B., & Smart, A. (2009). The Anterior Midline Field: Coercion or decision making? Brain and Language, 108(3), 184-190. doi:10.1016/j.bandl.2008.06.006.

    Abstract

    To study the neural bases of semantic composition in language processing without confounds from syntactic composition, recent magnetoencephalography (MEG) studies have investigated the processing of constructions that exhibit some type of syntax-semantics mismatch. The most studied case of such a mismatch is complement coercion; expressions such as the author began the book, where an entity-denoting noun phrase is coerced into an eventive meaning in order to match the semantic properties of the event-selecting verb (e.g., ‘the author began reading/writing the book’). These expressions have been found to elicit increased activity in the Anterior Midline Field (AMF), an MEG component elicited at frontomedial sensors at ∼400 ms after the onset of the coercing noun [Pylkkänen, L., & McElree, B. (2007). An MEG study of silent meaning. Journal of Cognitive Neuroscience, 19, 11]. Thus, the AMF constitutes a potential neural correlate of coercion. However, the AMF was generated in ventromedial prefrontal regions, which are heavily associated with decision-making. This raises the possibility that, instead of semantic processing, the AMF effect may have been related to the experimental task, which was a sensicality judgment. We tested this hypothesis by assessing the effect of coercion when subjects were simply reading for comprehension, without a decision-task. Additionally, we investigated coercion in an adjectival rather than a verbal environment to further generalize the findings. Our results show that an AMF effect of coercion is elicited without a decision-task and that the effect also extends to this novel syntactic environment. We conclude that in addition to its role in non-linguistic higher cognition, ventromedial prefrontal regions contribute to the resolution of syntax-semantics mismatches in language processing.
  • Qin, S., Rijpkema, M., Tendolkar, I., Piekema, C., Hermans, E. J., Binder, M., Petersson, K. M., Luo, J., & Fernández, G. (2009). Dissecting medial temporal lobe contributions to item and associative memory formation. NeuroImage, 46, 874-881. doi:10.1016/j.neuroimage.2009.02.039.

    Abstract

    A fundamental and intensively discussed question is whether medial temporal lobe (MTL) processes that lead to non-associative item memories differ in their anatomical substrate from processes underlying associative memory formation. Using event-related functional magnetic resonance imaging, we implemented a novel design to dissociate brain activity related to item and associative memory formation not only by subsequent memory performance and anatomy but also in time, because the two constituents of each pair to be memorized were presented sequentially with an intra-pair delay of several seconds. Furthermore, the design enabled us to reduce potential differences in memory strength between item and associative memory by increasing task difficulty in the item recognition memory test. Confidence ratings for correct item recognition for both constituents did not differ between trials in which only item memory was correct and trials in which item and associative memory were correct. Specific subsequent memory analyses for item and associative memory formation revealed brain activity that appears selectively related to item memory formation in the posterior inferior temporal, posterior parahippocampal, and perirhinal cortices. In contrast, hippocampal and inferior prefrontal activity predicted successful retrieval of newly formed inter-item associations. Our findings therefore suggest that different MTL subregions indeed play distinct roles in the formation of item memory and inter-item associative memory as expected by several dual process models of the MTL memory system.
  • Reesink, G., Singer, R., & Dunn, M. (2009). Explaining the linguistic diversity of Sahul using population models. PLoS Biology, 7(11), e1000241. doi:10.1371/journal.pbio.1000241.

    Abstract

    The region of the ancient Sahul continent (present day Australia and New Guinea, and surrounding islands) is home to extreme linguistic diversity. Even apart from the huge Austronesian language family, which spread into the area after the breakup of the Sahul continent in the Holocene, there are hundreds of languages from many apparently unrelated families. On each of the subcontinents, the generally accepted classification recognizes one large, widespread family and a number of unrelatable smaller families. If these language families are related to each other, it is at a depth which is inaccessible to standard linguistic methods. We have inferred the history of structural characteristics of these languages under an admixture model, using a Bayesian algorithm originally developed to discover populations on the basis of recombining genetic markers. This analysis identifies 10 ancestral language populations, some of which can be identified with clearly defined phylogenetic groups. The results also show traces of early dispersals, including hints at ancient connections between Australian languages and some Papuan groups (long hypothesized, never before demonstrated). Systematic language contact effects between members of big phylogenetic groups are also detected, which can in some cases be identified with a diffusional or substrate signal. Most interestingly, however, there remains striking evidence of a phylogenetic signal, with many languages showing negligible amounts of admixture.
  • Reis, A., Guerreiro, M., & Petersson, K. M. (2003). A sociodemographic and neuropsychological characterization of an illiterate population. Applied Neuropsychology, 10, 191-204. doi:10.1207/s15324826an1004_1.

    Abstract

    The objectives of this article are to characterize the performance and to discuss the performance differences between literate and illiterate participants in a well-defined study population.We describe the participant-selection procedure used to investigate this population. Three groups with similar sociocultural backgrounds living in a relatively homogeneous fishing community in southern Portugal were characterized in terms of socioeconomic and sociocultural background variables and compared on a simple neuropsychological test battery; specifically, a literate group with more than 4 years of education (n = 9), a literate group with 4 years of education (n = 26), and an illiterate group (n = 31) were included in this study.We compare and discuss our results with other similar studies on the effects of literacy and illiteracy. The results indicate that naming and identification of real objects, verbal fluency using ecologically relevant semantic criteria, verbal memory, and orientation are not affected by literacy or level of formal education. In contrast, verbal working memory assessed with digit span, verbal abstraction, long-term semantic memory, and calculation (i.e., multiplication) are significantly affected by the level of literacy. We indicate that it is possible, with proper participant-selection procedures, to exclude general cognitive impairment and to control important sociocultural factors that potentially could introduce bias when studying the specific effects of literacy and level of formal education on cognitive brain function.
  • Reis, A., & Petersson, K. M. (2003). Educational level, socioeconomic status and aphasia research: A comment on Connor et al. (2001)- Effect of socioeconomic status on aphasia severity and recovery. Brain and Language, 87, 449-452. doi:10.1016/S0093-934X(03)00140-8.

    Abstract

    Is there a relation between socioeconomic factors and aphasia severity and recovery? Connor, Obler, Tocco, Fitzpatrick, and Albert (2001) describe correlations between the educational level and socioeconomic status of aphasic subjects with aphasia severity and subsequent recovery. As stated in the introduction by Connor et al. (2001), studies of the influence of educational level and literacy (or illiteracy) on aphasia severity have yielded conflicting results, while no significant link between socioeconomic status and aphasia severity and recovery has been established. In this brief note, we will comment on their findings and conclusions, beginning first with a brief review of literacy and aphasia research, and complexities encountered in these fields of investigation. This serves as a general background to our specific comments on Connor et al. (2001), which will be focusing on methodological issues and the importance of taking normative values in consideration when subjects with different socio-cultural or socio-economic backgrounds are assessed.
  • Richards, J. B., Waterworth, D., O'Rahilly, S., Hivert, M.-F., Loos, R. J. F., Perry, J. R. B., Tanaka, T., Timpson, N. J., Semple, R. K., Soranzo, N., Song, K., Rocha, N., Grundberg, E., Dupuis, J., Florez, J. C., Langenberg, C., Prokopenko, I., Saxena, R., Sladek, R., Aulchenko, Y. and 47 moreRichards, J. B., Waterworth, D., O'Rahilly, S., Hivert, M.-F., Loos, R. J. F., Perry, J. R. B., Tanaka, T., Timpson, N. J., Semple, R. K., Soranzo, N., Song, K., Rocha, N., Grundberg, E., Dupuis, J., Florez, J. C., Langenberg, C., Prokopenko, I., Saxena, R., Sladek, R., Aulchenko, Y., Evans, D., Waeber, G., Erdmann, J., Burnett, M.-S., Sattar, N., Devaney, J., Willenborg, C., Hingorani, A., Witteman, J. C. M., Vollenweider, P., Glaser, B., Hengstenberg, C., Ferrucci, L., Melzer, D., Stark, K., Deanfield, J., Winogradow, J., Grassl, M., Hall, A. S., Egan, J. M., Thompson, J. R., Ricketts, S. L., König, I. R., Reinhard, W., Grundy, S., Wichmann, H.-E., Barter, P., Mahley, R., Kesaniemi, Y. A., Rader, D. J., Reilly, M. P., Epstein, S. E., Stewart, A. F. R., Van Duijn, C. M., Schunkert, H., Burling, K., Deloukas, P., Pastinen, T., Samani, N. J., McPherson, R., Davey Smith, G., Frayling, T. M., Wareham, N. J., Meigs, J. B., Mooser, V., Spector, T. D., & Consortium, G. (2009). A genome-wide association study reveals variants in ARL15 that influence adiponectin levels. PLoS Genetics, 5(12): e1000768. doi:10.1371/journal.pgen.1000768.

    Abstract

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

Share this page