Publications

Displaying 1001 - 1046 of 1046
  • Warner, N., Otake, T., & Arai, A. (2010). Intonational structure as a word-boundary cue in Tokyo Japanese. Language and Speech, 53, 107-131. doi:10.1177/0023830909351235.

    Abstract

    While listeners are recognizing words from the connected speech stream, they are also parsing information from the intonational contour. This contour may contain cues to word boundaries, particularly if a language has boundary tones that occur at a large proportion of word onsets. We investigate how useful the pitch rise at the beginning of an accentual phrase (APR) would be as a potential word-boundary cue for Japanese listeners. A corpus study shows that it should allow listeners to locate approximately 40–60% of word onsets, while causing less than 1% false positives. We then present a word-spotting study which shows that Japanese listeners can, indeed, use accentual phrase boundary cues during segmentation. This work shows that the prosodic patterns that have been found in the production of Japanese also impact listeners’ processing.
  • Watson, L. M., Wong, M. M. K., Vowles, J., Cowley, S. A., & Becker, E. B. E. (2018). A simplified method for generating purkinje cells from human-induced pluripotent stem cells. The Cerebellum, 17(4), 419-427. doi:10.1007/s12311-017-0913-2.

    Abstract

    The establishment of a reliable model for the study of Purkinje cells in vitro is of particular importance, given their central role in cerebellar function and pathology. Recent advances in induced pluripotent stem cell (iPSC) technology offer the opportunity to generate multiple neuronal subtypes for study in vitro. However, to date, only a handful of studies have generated Purkinje cells from human pluripotent stem cells, with most of these protocols proving challenging to reproduce. Here, we describe a simplified method for the reproducible generation of Purkinje cells from human iPSCs. After 21 days of treatment with factors selected to mimic the self-inductive properties of the isthmic organiser—insulin, fibroblast growth factor 2 (FGF2), and the transforming growth factor β (TGFβ)-receptor blocker SB431542—hiPSCs could be induced to form En1-positive cerebellar progenitors at efficiencies of up to 90%. By day 35 of differentiation, subpopulations of cells representative of the two cerebellar germinal zones, the rhombic lip (Atoh1-positive) and ventricular zone (Ptf1a-positive), could be identified, with the latter giving rise to cells positive for Purkinje cell progenitor-specific markers, including Lhx5, Kirrel2, Olig2 and Skor2. Further maturation was observed following dissociation and co-culture of these cerebellar progenitors with mouse cerebellar cells, with 10% of human cells staining positive for the Purkinje cell marker calbindin by day 70 of differentiation. This protocol, which incorporates modifications designed to enhance cell survival and maturation and improve the ease of handling, should serve to make existing models more accessible, in order to enable future advances in the field.

    Additional information

    12311_2017_913_MOESM1_ESM.docx
  • Weber, A., Crocker, M., & Knoeferle, P. (2010). Conflicting constraints in resource-adaptive language comprehension. In M. W. Crocker, & J. Siekmann (Eds.), Resource-adaptive cognitive processes (pp. 119-141). New York: Springer.

    Abstract

    The primary goal of psycholinguistic research is to understand the architectures and mechanisms that underlie human language comprehension and production. This entails an understanding of how linguistic knowledge is represented and organized in the brain and a theory of how that knowledge is accessed when we use language. Research has traditionally emphasized purely linguistic aspects of on-line comprehension, such as the influence of lexical, syntactic, semantic and discourse constraints, and their tim -course. It has become increasingly clear, however, that nonlinguistic information, such as the visual environment, are also actively exploited by situated language comprehenders.
  • Weber, K., & Lavric, A. (2008). Syntactic anomaly elicits a lexico-semantic (N400) ERP effect in the second but not in the first language. Psychophysiology, 45(6), 920-925. doi:10.1111/j.1469-8986.2008.00691.x.

    Abstract

    Recent brain potential research into first versus second language (L1 vs. L2) processing revealed striking responses to morphosyntactic features absent in the mother tongue. The aim of the present study was to establish whether the presence of comparable morphosyntactic features in L1 leads to more similar electrophysiological L1 and L2 profiles. ERPs were acquired while German-English bilinguals and native speakers of English read sentences. Some sentences were meaningful and well formed, whereas others contained morphosyntactic or semantic violations in the final word. In addition to the expected P600 component, morphosyntactic violations in L2 but not L1 led to an enhanced N400. This effect may suggest either that resolution of morphosyntactic anomalies in L2 relies on the lexico-semantic system or that the weaker/slower morphological mechanisms in L2 lead to greater sentence wrap-up difficulties known to result in N400 enhancement.
  • Weber, A. (2008). What eye movements can tell us about spoken-language processing: A psycholinguistic survey. In C. M. Riehl (Ed.), Was ist linguistische Evidenz: Kolloquium des Zentrums Sprachenvielfalt und Mehrsprachigkeit, November 2006 (pp. 57-68). Aachen: Shaker.
  • Weekes, B. S., Abutalebi, J., Mak, H.-K.-F., Borsa, V., Soares, S. M. P., Chiu, P. W., & Zhang, L. (2018). Effect of monolingualism and bilingualism in the anterior cingulate cortex: a proton magnetic resonance spectroscopy study in two centers. Letras de Hoje, 53(1), 5-12. doi:10.15448/1984-7726.2018.1.30954.

    Abstract

    Reports of an advantage of bilingualism on brain structure in young adult participants
    are inconsistent. Abutalebi et al. (2012) reported more efficient monitoring of conflict during the
    Flanker task in young bilinguals compared to young monolingual speakers. The present study
    compared young adult (mean age = 24) Cantonese-English bilinguals in Hong Kong and young
    adult monolingual speakers. We expected (a) differences in metabolites in neural tissue to result
    from bilingual experience, as measured by 1H-MRS at 3T, (b) correlations between metabolic
    levels and Flanker conflict and interference effects (c) different associations in bilingual and
    monolingual speakers. We found evidence of metabolic differences in the ACC due to bilingualism,
    specifically in metabolites Cho, Cr, Glx and NAA. However, we found no significant correlations
    between metabolic levels and conflict and interference effects and no significant evidence of
    differential relationships between bilingual and monolingual speakers. Furthermore, we found no
    evidence of significant differences in the mean size of conflict and interference effects between
    groups i.e. no bilingual advantage. Lower levels of Cho, Cr, Glx and NAA in bilingual adults
    compared to monolingual adults suggest that the brains of bilinguals develop greater adaptive
    control during conflict monitoring because of their extensive bilingual experience.
  • De Weert, C., & Levelt, W. J. M. (1974). Binocular brightness combinations: Additive and nonadditive aspects. Perception and Psychophysics, 15, 551-562.
  • Widlok, T., Rapold, C. J., & Hoymann, G. (2008). Multimedia analysis in documentation projects: Kinship, interrogatives and reciprocals in ǂAkhoe Haiǁom. In K. D. Harrison, D. S. Rood, & A. Dwyer (Eds.), Lessons from documented endangered languages (pp. 355-370). Amsterdam: Benjamins.

    Abstract

    This contribution emphasizes the role of multimedia data not only for archiving languages but also for creating opportunities for innovative analyses. In the case at hand, video material was collected as part of the documentation of Akhoe Haiom, a Khoisan language spoken in northern Namibia. The multimedia documentation project brought together linguistic and anthropological work to highlight connections between specialized domains, namely kinship terminology, interrogatives and reciprocals. These connections would have gone unnoticed or undocumented in more conventional modes of language description. It is suggested that such an approach may be particularly appropriate for the documentation of endangered languages since it directs the focus of attention away from isolated traits of languages towards more complex practices of communication that are also frequently threatened with extinction.
  • Widlok, T. (2008). Landscape unbounded: Space, place, and orientation in ≠Akhoe Hai// om and beyond. Language Sciences, 30(2/3), 362-380. doi:10.1016/j.langsci.2006.12.002.

    Abstract

    Even before it became a common place to assume that “the Eskimo have a hundred words for snow” the languages of hunting and gathering people have played an important role in debates about linguistic relativity concerning geographical ontologies. Evidence from languages of hunter-gatherers has been used in radical relativist challenges to the overall notion of a comparative typology of generic natural forms and landscapes as terms of reference. It has been invoked to emphasize a personalized relationship between humans and the non-human world. It is against this background that this contribution discusses the landscape terminology of ≠Akhoe Hai//om, a Khoisan language spoken by “Bushmen” in Namibia. Landscape vocabulary is ubiquitous in ≠Akhoe Hai//om due to the fact that the landscape plays a critical role in directionals and other forms of “topographical gossip” and due to merges between landscape and group terminology. This system of landscape-cum-group terminology is outlined and related to the use of place names in the area.
  • Widlok, T. (2008). The dilemmas of walking: A comparative view. In T. Ingold, & J. L. Vergunst (Eds.), Ways of walking: Ethnography and practice on foot (pp. 51-66). Aldershot: Ashgate.
  • Willems, R. M., Ozyurek, A., & Hagoort, P. (2008). Seeing and hearing meaning: ERP and fMRI evidence of word versus picture integration into a sentence context. Journal of Cognitive Neuroscience, 20, 1235-1249. doi:10.1162/jocn.2008.20085.

    Abstract

    Understanding language always occurs within a situational context and, therefore, often implies combining streams of information from different domains and modalities. One such combination is that of spoken language and visual information, which are perceived together in a variety of ways during everyday communication. Here we investigate whether and how words and pictures differ in terms of their neural correlates when they are integrated into a previously built-up sentence context. This is assessed in two experiments looking at the time course (measuring event-related potentials, ERPs) and the locus (using functional magnetic resonance imaging, fMRI) of this integration process. We manipulated the ease of semantic integration of word and/or picture to a previous sentence context to increase the semantic load of processing. In the ERP study, an increased semantic load led to an N400 effect which was similar for pictures and words in terms of latency and amplitude. In the fMRI study, we found overlapping activations to both picture and word integration in the left inferior frontal cortex. Specific activations for the integration of a word were observed in the left superior temporal cortex. We conclude that despite obvious differences in representational format, semantic information coming from pictures and words is integrated into a sentence context in similar ways in the brain. This study adds to the growing insight that the language system incorporates (semantic) information coming from linguistic and extralinguistic domains with the same neural time course and by recruitment of overlapping brain areas.
  • Willems, R. M., Hagoort, P., & Casasanto, D. (2010). Body-specific representations of action verbs: Neural evidence from right- and left-handers. Psychological Science, 21, 67-74. doi:10.1177/0956797609354072.

    Abstract

    According to theories of embodied cognition, understanding a verb like throw involves unconsciously simulating the action of throwing, using areas of the brain that support motor planning. If understanding action words involves mentally simulating one’s own actions, then the neurocognitive representation of word meanings should differ for people with different kinds of bodies, who perform actions in systematically different ways. In a test of the body-specificity hypothesis, we used functional magnetic resonance imaging to compare premotor activity correlated with action verb understanding in right- and left-handers. Righthanders preferentially activated the left premotor cortex during lexical decisions on manual-action verbs (compared with nonmanual-action verbs), whereas left-handers preferentially activated right premotor areas. This finding helps refine theories of embodied semantics, suggesting that implicit mental simulation during language processing is body specific: Right- and lefthanders, who perform actions differently, use correspondingly different areas of the brain for representing action verb meanings.
  • Willems, R. M., Peelen, M. V., & Hagoort, P. (2010). Cerebral lateralization of face-selective and body-selective visual areas depends on handedness. Cerebral Cortex, 20, 1719-1725. doi:10.1093/cercor/bhp234.

    Abstract

    The left-hemisphere dominance for language is a core example of the functional specialization of the cerebral hemispheres. The degree of left-hemisphere dominance for language depends on hand preference: Whereas the majority of right-handers show left-hemispheric language lateralization, this number is reduced in left-handers. Here, we assessed whether handedness analogously has an influence upon lateralization in the visual system. Using functional magnetic resonance imaging, we localized 4 more or less specialized extrastriate areas in left- and right-handers, namely fusiform face area (FFA), extrastriate body area (EBA), fusiform body area (FBA), and human motion area (human middle temporal [hMT]). We found that lateralization of FFA and EBA depends on handedness: These areas were right lateralized in right-handers but not in left-handers. A similar tendency was observed in FBA but not in hMT. We conclude that the relationship between handedness and hemispheric lateralization extends to functionally lateralized parts of visual cortex, indicating a general coupling between cerebral lateralization and handedness. Our findings indicate that hemispheric specialization is not fixed but can vary considerably across individuals even in areas engaged relatively early in the visual system.
  • Willems, R. M., De Boer, M., De Ruiter, J. P., Noordzij, M. L., Hagoort, P., & Toni, I. (2010). A dissociation between linguistic and communicative abilities in the human brain. Psychological Science, 21, 8-14. doi:10.1177/0956797609355563.

    Abstract

    Although language is an effective vehicle for communication, it is unclear how linguistic and communicative abilities relate to each other. Some researchers have argued that communicative message generation involves perspective taking (mentalizing), and—crucially—that mentalizing depends on language. We employed a verbal communication paradigm to directly test whether the generation of a communicative action relies on mentalizing and whether the cerebral bases of communicative message generation are distinct from parts of cortex sensitive to linguistic variables. We found that dorsomedial prefrontal cortex, a brain area consistently associated with mentalizing, was sensitive to the communicative intent of utterances, irrespective of linguistic difficulty. In contrast, left inferior frontal cortex, an area known to be involved in language, was sensitive to the linguistic demands of utterances, but not to communicative intent. These findings show that communicative and linguistic abilities rely on cerebrally (and computationally) distinct mechanisms
  • Willems, R. M., & Hagoort, P. (2010). Cortical motor contributions to language understanding. In L. Hermer (Ed.), Reciprocal interactions among early sensory and motor areas and higher cognitive networks (pp. 51-72). Kerala, India: Research Signpost Press.

    Abstract

    Here we review evidence from cognitive neuroscience for a tight relation between language and action in the brain. We focus on two types of relation between language and action. First, we investigate whether the perception of speech and speech sounds leads to activation of parts of the cortical motor system also involved in speech production. Second, we evaluate whether understanding action-related language involves the activation of parts of the motor system. We conclude that whereas there is considerable evidence that understanding language can involve parts of our motor cortex, this relation is best thought of as inherently flexible. As we explain, the exact nature of the input as well as the intention with which language is perceived influences whether and how motor cortex plays a role in language processing.
  • Willems, R. M., Oostenveld, R., & Hagoort, P. (2008). Early decreases in alpha and gamma band power distinguish linguistic from visual information during spoken sentence comprehension. Brain Research, 1219, 78-90. doi:10.1016/j.brainres.2008.04.065.

    Abstract

    Language is often perceived together with visual information. This raises the question on how the brain integrates information conveyed in visual and/or linguistic format during spoken language comprehension. In this study we investigated the dynamics of semantic integration of visual and linguistic information by means of time-frequency analysis of the EEG signal. A modified version of the N400 paradigm with either a word or a picture of an object being semantically incongruous with respect to the preceding sentence context was employed. Event-Related Potential (ERP) analysis showed qualitatively similar N400 effects for integration of either word or picture. Time-frequency analysis revealed early specific decreases in alpha and gamma band power for linguistic and visual information respectively. We argue that these reflect a rapid context-based analysis of acoustic (word) or visual (picture) form information. We conclude that although full semantic integration of linguistic and visual information occurs through a common mechanism, early differences in oscillations in specific frequency bands reflect the format of the incoming information and, importantly, an early context-based detection of its congruity with respect to the preceding language context
  • Willems, R. M., & Cristia, A. (2018). Hemodynamic methods: fMRI and fNIRS. In A. M. B. De Groot, & P. Hagoort (Eds.), Research methods in psycholinguistics and the neurobiology of language: A practical guide (pp. 266-287). Hoboken: Wiley.
  • Willems, R. M., Toni, I., Hagoort, P., & Casasanto, D. (2010). Neural dissociations between action verb understanding and motor imagery. Journal of Cognitive Neuroscience, 22(10), 2387-2400. doi:10.1162/jocn.2009.21386.

    Abstract

    According to embodied theories of language, people understand a verb like throw, at least in part, by mentally simulating throwing. This implicit simulation is often assumed to be similar or identical to motor imagery. Here we used fMRI totest whether implicit simulations of actions during language understanding involve the same cortical motor regions as explicit motor imagery Healthy participants were presented with verbs related to hand actions (e.g., to throw) and nonmanual actions (e.g., to kneel). They either read these verbs (lexical decision task) or actively imagined performing the actions named by the verbs (imagery task). Primary motor cortex showd effector-specific activation during imagery, but not during lexical decision. Parts of premotor cortex distinguished manual from nonmanual actions during both lexical decision and imagery, but there was no overlap or correlation between regions activated during the two tasks. These dissociations suggest that implicit simulation and explicit imagery cued by action verbs may involve different types of motor representations and that the construct of “mental simulation” should be distinguished from “mental imagery” in embodied theories of language.
  • Willems, R. M., & Varley, R. (2010). Neural insights into the relation between language and communication. Frontiers in Human Neuroscience, 4, 203. doi:10.3389/fnhum.2010.00203.

    Abstract

    The human capacity to communicate has been hypothesized to be causally dependent upon language. Intuitively this seems plausible since most communication relies on language. Moreover, intention recognition abilities (as a necessary prerequisite for communication) and language development seem to co-develop. Here we review evidence from neuroimaging as well as from neuropsychology to evaluate the relationship between communicative and linguistic abilities. Our review indicates that communicative abilities are best considered as neurally distinct from language abilities. This conclusion is based upon evidence showing that humans rely on different cortical systems when designing a communicative message for someone else as compared to when performing core linguistic tasks, as well as upon observations of individuals with severe language loss after extensive lesions to the language system, who are still able to perform tasks involving intention understanding
  • Willems, R. M., & Van Gerven, M. (2018). New fMRI methods for the study of language. In S.-A. Rueschemeyer, & M. G. Gaskell (Eds.), The Oxford Handbook of Psycholinguistics (2nd ed., pp. 975-991). Oxford: Oxford University Press.
  • Williams, N. M., Williams, H., Majounie, E., Norton, N., Glaser, B., Morris, H. R., Owen, M. J., & O'Donovan, M. C. (2008). Analysis of copy number variation using quantitative interspecies competitive PCR. Nucleic Acids Research, 36(17): e112. doi:10.1093/nar/gkn495.

    Abstract

    Over recent years small submicroscopic DNA copy-number variants (CNVs) have been highlighted as an important source of variation in the human genome, human phenotypic diversity and disease susceptibility. Consequently, there is a pressing need for the development of methods that allow the efficient, accurate and cheap measurement of genomic copy number polymorphisms in clinical cohorts. We have developed a simple competitive PCR based method to determine DNA copy number which uses the entire genome of a single chimpanzee as a competitor thus eliminating the requirement for competitive sequences to be synthesized for each assay. This results in the requirement for only a single reference sample for all assays and dramatically increases the potential for large numbers of loci to be analysed in multiplex. In this study we establish proof of concept by accurately detecting previously characterized mutations at the PARK2 locus and then demonstrating the potential of quantitative interspecies competitive PCR (qicPCR) to accurately genotype CNVs in association studies by analysing chromosome 22q11 deletions in a sample of previously characterized patients and normal controls.
  • Winsvold, B. S., Palta, P., Eising, E., Page, C. M., The International Headache Genetics Consortium, Van den Maagdenberg, A. M. J. M., Palotie, A., & Zwart, J.-A. (2018). Epigenetic DNA methylation changes associated with headache chronification: A retrospective case-control study. Cephalalgia, 38(2), 312-322. doi:10.1177/0333102417690111.

    Abstract

    Background

    The biological mechanisms of headache chronification are poorly understood. We aimed to identify changes in DNA methylation associated with the transformation from episodic to chronic headache.
    Methods

    Participants were recruited from the population-based Norwegian HUNT Study. Thirty-six female headache patients who transformed from episodic to chronic headache between baseline and follow-up 11 years later were matched against 35 controls with episodic headache. DNA methylation was quantified at 485,000 CpG sites, and changes in methylation level at these sites were compared between cases and controls by linear regression analysis. Data were analyzed in two stages (Stages 1 and 2) and in a combined meta-analysis.
    Results

    None of the top 20 CpG sites identified in Stage 1 replicated in Stage 2 after multiple testing correction. In the combined meta-analysis the strongest associated CpG sites were related to SH2D5 and NPTX2, two brain-expressed genes involved in the regulation of synaptic plasticity. Functional enrichment analysis pointed to processes including calcium ion binding and estrogen receptor pathways.
    Conclusion

    In this first genome-wide study of DNA methylation in headache chronification several potentially implicated loci and processes were identified. The study exemplifies the use of prospectively collected population cohorts to search for epigenetic mechanisms of disease
  • Winter, B., Perlman, M., & Majid, A. (2018). Vision dominates in perceptual language: English sensory vocabulary is optimized for usage. Cognition, 179, 213-220. doi:10.1016/j.cognition.2018.05.008.

    Abstract

    Researchers have suggested that the vocabularies of languages are oriented towards the communicative needs of language users. Here, we provide evidence demonstrating that the higher frequency of visual words in a large variety of English corpora is reflected in greater lexical differentiation—a greater number of unique words—for the visual domain in the English lexicon. In comparison, sensory modalities that are less frequently talked about, particularly taste and smell, show less lexical differentiation. In addition, we show that even though sensory language can be expected to change across historical time and between contexts of use (e.g., spoken language versus fiction), the pattern of visual dominance is a stable property of the English language. Thus, we show that across the board, precisely those semantic domains that are more frequently talked about are also more lexically differentiated, for perceptual experiences. This correlation between type and token frequencies suggests that the sensory lexicon of English is geared towards communicative efficiency.
  • Witteman, M. J., & Segers, E. (2010). The modality effect tested in children in a user-paced multimedia environment. Journal of Computer Assisted Learning, 26, 132-142. doi:10.1111/j.1365-2729.2009.00335.x.

    Abstract

    The modality learning effect, according to Mayer (2001), proposes that learning is enhanced when information is presented in both the visual and auditory domain (e.g., pictures and spoken information), compared to presenting information solely in the visual channel (e.g., pictures and written text). Most of the evidence for this effect comes from adults in a laboratory setting. Therefore, we tested the modality effect with 80 children in the highest grade of elementary school, in a naturalistic setting. In a between-subjects design children either saw representational pictures with speech or representational pictures with text. Retention and transfer knowledge was tested at three moments: immediately after the intervention, one day after, and after one week. The present study did not find any evidence for a modality effect in children when the lesson is learner-paced. Instead, we found a reversed modality effect directly after the intervention for retention. A reversed modality effect was also found for the transfer questions one day later. This effect was robust, even when controlling for individual differences.
  • Wittenburg, P. (2008). Die CLARIN Forschungsinfrastruktur. ÖGAI-journal (Österreichische Gesellschaft für Artificial Intelligence), 27, 10-17.
  • Wittenburg, P., & Trilsbeek, P. (2010). Digital archiving - a necessity in documentary linguistics. In G. Senft (Ed.), Endangered Austronesian and Australian Aboriginal languages: Essays on language documentation, archiving and revitalization (pp. 111-136). Canberra: Pacific Linguistics.
  • Wittenburg, P. (2010). Archiving and accessing language resources. Concurrency and Computation: Practice and Experience, 22(17), 2354-2368. doi:10.1002/cpe.1605.

    Abstract

    Languages are among the most complex systems that evolution has created. With an unforeseen speed many of these unique results of evolution are currently disappearing: every two weeks one of the 6500 still spoken languages is dying and many are subject to extreme changes due to globalization. Experts understood the need to document the languages and preserve the cultural and linguistic treasures embedded in them for future generations. Also linguistic theory will need to consider the variation of the linguistic systems encoded in languages to improve our understanding of how human minds process language material, thus accessibility to all types of resources is increasingly crucial. Deeper insights into human language processing and a higher degree of integration and interoperability between resources will also improve our language processing technology. The DOBES programme is focussing on the documentation and preservation of language material. The Max Planck Institute developed the Language Archiving Technology to help researchers when creating, archiving and accessing language resources. The recently started CLARIN research infrastructure has as main goals to achieve a broad visibility and an easy
    accessibility of language resources.
  • Wolters, G., & Poletiek, F. H. (2008). Beslissen over aangiftes van seksueel misbruik bij kinderen. De Psycholoog, 43, 29-29.
  • Wong, M. M. K., Hoekstra, S. D., Vowles, J., Watson, L. M., Fuller, G., Németh, A. H., Cowley, S. A., Ansorge, O., Talbot, K., & Becker, E. B. E. (2018). Neurodegeneration in SCA14 is associated with increased PKCγ kinase activity, mislocalization and aggregation. Acta Neuropathologica Communications, 6: 99. doi:10.1186/s40478-018-0600-7.

    Abstract

    Spinocerebellar ataxia type 14 (SCA14) is a subtype of the autosomal dominant cerebellar ataxias that is characterized by slowly progressive cerebellar dysfunction and neurodegeneration. SCA14 is caused by mutations in the PRKCG gene, encoding protein kinase C gamma (PKCγ). Despite the identification of 40 distinct disease-causing mutations in PRKCG, the pathological mechanisms underlying SCA14 remain poorly understood. Here we report the molecular neuropathology of SCA14 in post-mortem cerebellum and in human patient-derived induced pluripotent stem cells (iPSCs) carrying two distinct SCA14 mutations in the C1 domain of PKCγ, H36R and H101Q. We show that endogenous expression of these mutations results in the cytoplasmic mislocalization and aggregation of PKCγ in both patient iPSCs and cerebellum. PKCγ aggregates were not efficiently targeted for degradation. Moreover, mutant PKCγ was found to be hyper-activated, resulting in increased substrate phosphorylation. Together, our findings demonstrate that a combination of both, loss-of-function and gain-of-function mechanisms are likely to underlie the pathogenesis of SCA14, caused by mutations in the C1 domain of PKCγ. Importantly, SCA14 patient iPSCs were found to accurately recapitulate pathological features observed in post-mortem SCA14 cerebellum, underscoring their potential as relevant disease models and their promise as future drug discovery tools.

    Additional information

    additional file
  • Xiang, H.-D., Fonteijn, H. M., Norris, D. G., & Hagoort, P. (2010). Topographical functional connectivity pattern in the perisylvian language networks. Cerebral Cortex, 20, 549-560. doi:10.1093/cercor/bhp119.

    Abstract

    We performed a resting-state functional connectivity study to investigate directly the functional correlations within the perisylvian language networks by seeding from 3 subregions of Broca's complex (pars opercularis, pars triangularis, and pars orbitalis) and their right hemisphere homologues. A clear topographical functional connectivity pattern in the left middle frontal, parietal, and temporal areas was revealed for the 3 left seeds. This is the first demonstration that a functional connectivity topology can be observed in the perisylvian language networks. The results support the assumption of the functional division for phonology, syntax, and semantics of Broca's complex as proposed by the memory, unification, and control (MUC) model and indicated a topographical functional organization in the perisylvian language networks, which suggests a possible division of labor for phonological, syntactic, and semantic function in the left frontal, parietal, and temporal areas.
  • Li, X., Yang, Y., & Hagoort, P. (2008). Pitch accent and lexical tone processing in Chinese discourse comprehension: An ERP study. Brain Research, 1222, 192-200. doi:10.1016/j.brainres.2008.05.031.

    Abstract

    In the present study, event-related brain potentials (ERP) were recorded to investigate the role of pitch accent and lexical tone in spoken discourse comprehension. Chinese was used as material to explore the potential difference in the nature and time course of brain responses to sentence meaning as indicated by pitch accent and to lexical meaning as indicated by tone. In both cases, the pitch contour of critical words was varied. The results showed that both inconsistent pitch accent and inconsistent lexical tone yielded N400 effects, and there was no interaction between them. The negativity evoked by inconsistent pitch accent had the some topography as that evoked by inconsistent lexical tone violation, with a maximum over central–parietal electrodes. Furthermore, the effect for the combined violations was the sum of effects for pure pitch accent and pure lexical tone violation. However, the effect for the lexical tone violation appeared approximately 90 ms earlier than the effect of the pitch accent violation. It is suggested that there might be a correspondence between the neural mechanism underlying pitch accent and lexical meaning processing in context. They both reflect the integration of the current information into a discourse context, independent of whether the current information was sentence meaning indicated by accentuation, or lexical meaning indicated by tone. In addition, lexical meaning was processed earlier than sentence meaning conveyed by pitch accent during spoken language processing.
  • Yang, J., Zhu, H., & Tian, X. (2018). Group-level multivariate analysis in EasyEEG toolbox: Examining the temporal dynamics using topographic responses. Frontiers in Neuroscience, 12: 468. doi:10.3389/fnins.2018.00468.

    Abstract

    Electroencephalography (EEG) provides high temporal resolution cognitive information from non-invasive recordings. However, one of the common practices-using a subset of sensors in ERP analysis is hard to provide a holistic and precise dynamic results. Selecting or grouping subsets of sensors may also be subject to selection bias, multiple comparison, and further complicated by individual differences in the group-level analysis. More importantly, changes in neural generators and variations in response magnitude from the same neural sources are difficult to separate, which limit the capacity of testing different aspects of cognitive hypotheses. We introduce EasyEEG, a toolbox that includes several multivariate analysis methods to directly test cognitive hypotheses based on topographic responses that include data from all sensors. These multivariate methods can investigate effects in the dimensions of response magnitude and topographic patterns separately using data in the sensor space, therefore enable assessing neural response dynamics. The concise workflow and the modular design provide user-friendly and programmer-friendly features. Users of all levels can benefit from the open-sourced, free EasyEEG to obtain a straightforward solution for efficient processing of EEG data and a complete pipeline from raw data to final results for publication.
  • Zeshan, U., & Perniss, P. M. (2008). Possessive and existential constructions in sign languages. Nijmegen: Ishara Press.
  • Zheng, X., Roelofs, A., Farquhar, J., & Lemhöfer, K. (2018). Monitoring of language selection errors in switching: Not all about conflict. PLoS One, 13(11): e0200397. doi:10.1371/journal.pone.0200397.

    Abstract

    Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. To investigate how bilinguals monitor their speech errors and control their languages in use, we recorded event-related potentials (ERPs) in unbalanced Dutch-English bilingual speakers in a cued language-switching task. We tested the conflict-based monitoring model of Nozari and colleagues by investigating the error-related negativity (ERN) and comparing the effects of the two switching directions (i.e., to the first language, L1 vs. to the second language, L2). Results show that the speakers made more language selection errors when switching from their L2 to the L1 than vice versa. In the EEG, we observed a robust ERN effect following language selection errors compared to correct responses, reflecting monitoring of speech errors. Most interestingly, the ERN effect was enlarged when the speakers were switching to their L2 (less conflict) compared to switching to the L1 (more conflict). Our findings do not support the conflict-based monitoring model. We discuss an alternative account in terms of error prediction and reinforcement learning.
  • Zheng, X., Roelofs, A., & Lemhöfer, K. (2018). Language selection errors in switching: language priming or cognitive control? Language, Cognition and Neuroscience, 33(2), 139-147. doi:10.1080/23273798.2017.1363401.

    Abstract

    Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. We examined the relative contribution of top-down cognitive control and bottom-up language priming to these errors. Unbalanced Dutch-English bilinguals named pictures and were cued to switch between languages under time pressure. We also manipulated the number of same-language trials before a switch (long vs. short runs). Results show that speakers made more language selection errors when switching from their second language (L2) to the first language (L1) than vice versa. Furthermore, they made more errors when switching to the L1 after a short compared to a long run of L2 trials. In the reverse switching direction (L1 to L2), run length had no effect. These findings are most compatible with an account of language selection errors that assigns a strong role to top-down processes of cognitive control.

    Additional information

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  • Zhernakova, A., Elbers, C. C., Ferwerda, B., Romanos, J., Trynka, G., Dubois, P. C., De Kovel, C. G. F., Franke, L., Oosting, M., Barisani, D., Bardella, M. T., Joosten, L. A. B., Saavalainen, P., van Heel, D. A., Catassi, C., Netea, M. G., Wijmenga, C., & Finnish Celiac Dis Study, G. (2010). Evolutionary and Functional Analysis of Celiac Risk Loci Reveals SH2B3 as a Protective Factor against Bacterial Infection. American Journal of Human Genetics, 86(6), 970-977. doi:10.1016/j.ajhg.2010.05.004.

    Abstract

    Celiac disease (CD) is an intolerance to dietary proteins of wheat, barley, and rye. CD may have substantial morbidity, yet it is quite common with a prevalence of 1%-2% in Western populations. It is not clear why the CD phenotype is so prevalent despite its negative effects on human health, especially because appropriate treatment in the form of a gluten-free diet has only been available since the 1950s, when dietary gluten was discovered to be the triggering factor. The high prevalence of CD might suggest that genes underlying this disease may have been favored by the process of natural selection. We assessed signatures of selection for ten confirmed CD-associated loci in several genome-wide data sets, comprising 8154 controls from four European populations and 195 individuals from a North African population, by studying haplotype lengths via the integrated haplotype score (iHS) method. Consistent signs of positive selection for CD-associated derived alleles were observed in three loci: IL12A, IL18RAP, and SH2B3. For the SH2B3 risk allele, we also show a difference in allele frequency distribution (F(st)) between HapMap phase II populations. Functional investigation of the effect of the SH2B3 genotype in response to lipopolysaccharide and muramyl dipeptide revealed that carriers of the SH2B3 rs3184504*A risk allele showed stronger activation of the NOD2 recognition pathway. This suggests that SH2B3 plays a role in protection against bacteria infection, and it provides a possible explanation for the selective sweep on SH2B3, which occurred sometime between 1200 and 1700 years ago.
  • Zoefel, B., Ten Oever, S., & Sack, A. T. (2018). The involvement of endogenous neural oscillations in the processing of rhythmic input: More than a regular repetition of evoked neural responses. Frontiers in Neuroscience, 12: 95. doi:10.3389/fnins.2018.00095.

    Abstract

    It is undisputed that presenting a rhythmic stimulus leads to a measurable brain response that follows the rhythmic structure of this stimulus. What is still debated, however, is the question whether this brain response exclusively reflects a regular repetition of evoked responses, or whether it also includes entrained oscillatory activity. Here we systematically present evidence in favor of an involvement of entrained neural oscillations in the processing of rhythmic input while critically pointing out which questions still need to be addressed before this evidence could be considered conclusive. In this context, we also explicitly discuss the potential functional role of such entrained oscillations, suggesting that these stimulus-aligned oscillations reflect, and serve as, predictive processes, an idea often only implicitly assumed in the literature.
  • Zwitserlood, I., van den Bogaerde, B., & Terpstra, A. (2010). De Nederlandse Gebarentaal en het ERK. Levende Talen Magazine, 2010(5), 50-51.
  • Zwitserlood, I. (2010). De Nederlandse Gebarentaal, het Corpus NGT en het ERK. Levende Talen Magazine, 2010(8), 44-45.
  • Zwitserlood, I. (2008). Grammatica-vertaalmethode en nederlandse gebarentaal. Levende Talen Magazine, 95(5), 28-29.
  • Zwitserlood, I. (2008). Morphology below the level of the sign - frozen forms and classifier predicates. In J. Quer (Ed.), Proceedings of the 8th Conference on Theoretical Issues in Sign Language Research (TISLR) (pp. 251-272). Hamburg: Signum Verlag.

    Abstract

    The lexicons of many sign languages hold large proportions of “frozen” forms, viz. signs that are generally considered to have been formed productively (as classifier predicates), but that have diachronically undergone processes of lexicalisation. Nederlandse Gebarentaal (Sign Language of the Netherlands; henceforth: NGT) also has many of these signs (Van der Kooij 2002, Zwitserlood 2003). In contrast to the general view on “frozen” forms, a few researchers claim that these signs may be formed according to productive sign formation rules, notably Brennan (1990) for BSL, and Meir (2001, 2002) for ISL. Following these claims, I suggest an analysis of “frozen” NGT signs as morphologically complex, using the framework of Distributed Morphology. The signs in question are derived in a similar way as classifier predicates; hence their similar form (but diverging characteristics). I will indicate how and why the structure and use of classifier predicates and “frozen” forms differ. Although my analysis focuses on NGT, it may also be applicable to other sign languages.
  • Zwitserlood, I. (2010). Laat je vingers spreken: NGT en vingerspelling. Levende Talen Magazine, 2010(2), 46-47.
  • Zwitserlood, I. (2010). Het Corpus NGT en de dagelijkse lespraktijk (2). Levende Talen Magazine, 2010(3), 47-48.
  • Zwitserlood, I. (2010). Sign language lexicography in the early 21st century and a recently published dictionary of Sign Language of the Netherlands. International Journal of Lexicography, 23, 443-476. doi:10.1093/ijl/ecq031.

    Abstract

    Sign language lexicography has thus far been a relatively obscure area in the world of lexicography. Therefore, this article will contain background information on signed languages and the communities in which they are used, on the lexicography of sign languages, the situation in the Netherlands as well as a review of a sign language dictionary that has recently been published in the Netherlands.
  • Zwitserlood, I., & Crasborn, O. (2010). Wat kunnen we leren uit een Corpus Nederlandse Gebarentaal? WAP Nieuwsbrief, 28(2), 16-18.
  • Zwitserlood, I. (2010). Verlos ons van de glos. Levende Talen Magazine, 2010(7), 40-41.

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