Publications

Displaying 1001 - 1042 of 1042
  • Wang, L., Hagoort, P., & Jensen, O. (2018). Language prediction is reflected by coupling between frontal gamma and posterior alpha oscillations. Journal of Cognitive Neuroscience, 30(3), 432-447. doi:10.1162/jocn_a_01190.

    Abstract

    Readers and listeners actively predict upcoming words during language processing. These predictions might serve to support the unification of incoming words into sentence context and thus rely on interactions between areas in the language network. In the current magnetoencephalography study, participants read sentences that varied in contextual constraints so that the predictability of the sentence-final words was either high or low. Before the sentence-final words, we observed stronger alpha power suppression for the highly compared with low constraining sentences in the left inferior frontal cortex, left posterior temporal region, and visual word form area. Importantly, the temporal and visual word form area alpha power correlated negatively with left frontal gamma power for the highly constraining sentences. We suggest that the correlation between alpha power decrease in temporal language areas and left prefrontal gamma power reflects the initiation of an anticipatory unification process in the language network.
  • Wang, L., Hagoort, P., & Jensen, O. (2018). Gamma oscillatory activity related to language prediction. Journal of Cognitive Neuroscience, 30(8), 1075-1085. doi:10.1162/jocn_a_01275.

    Abstract

    Using magnetoencephalography, the current study examined gamma activity associated with language prediction. Participants read high- and low-constraining sentences in which the final word of the sentence was either expected or unexpected. Although no consistent gamma power difference induced by the sentence-final words was found between the expected and unexpected conditions, the correlation of gamma power during the prediction and activation intervals of the sentence-final words was larger when the presented words matched with the prediction compared with when the prediction was violated or when no prediction was available. This suggests that gamma magnitude relates to the match between predicted and perceived words. Moreover, the expected words induced activity with a slower gamma frequency compared with that induced by unexpected words. Overall, the current study establishes that prediction is related to gamma power correlations and a slowing of the gamma frequency.
  • Wang, M., Shao, Z., Chen, Y., & Schiller, N. O. (2018). Neural correlates of spoken word production in semantic and phonological blocked cyclic naming. Language, Cognition and Neuroscience, 33(5), 575-586. doi:10.1080/23273798.2017.1395467.

    Abstract

    The blocked cyclic naming paradigm has been increasingly employed to investigate the mechanisms underlying spoken word production. Semantic homogeneity typically elicits longer naming latencies than heterogeneity; however, it is debated whether competitive lexical selection or incremental learning underlies this effect. The current study manipulated both semantic and phonological homogeneity and used behavioural and electrophysiological measurements to provide evidence that can distinguish between the two accounts. Results show that naming latencies are longer in semantically homogeneous blocks, but shorter in phonologically homogeneous blocks, relative to heterogeneity. The semantic factor significantly modulates electrophysiological waveforms from 200 ms and the phonological factor from 350 ms after picture presentation. A positive component was demonstrated in both manipulations, possibly reflecting a task-related top-down bias in performing blocked cyclic naming. These results provide novel insights into the neural correlates of blocked cyclic naming and further contribute to the understanding of spoken word production.
  • Wanke, K., Devanna, P., & Vernes, S. C. (2018). Understanding neurodevelopmental disorders: The promise of regulatory variation in the 3’UTRome. Biological Psychiatry, 83(7), 548-557. doi:10.1016/j.biopsych.2017.11.006.

    Abstract

    Neurodevelopmental disorders have a strong genetic component, but despite widespread efforts, the specific genetic factors underlying these disorders remain undefined for a large proportion of affected individuals. Given the accessibility of exome-sequencing, this problem has thus far been addressed from a protein-centric standpoint; however, protein-coding regions only make up ∼1-2% of the human genome. With the advent of whole-genome sequencing we are in the midst of a paradigm shift as it is now possible to interrogate the entire sequence of the human genome (coding and non-coding) to fill in the missing heritability of complex disorders. These new technologies bring new challenges, as the number of non-coding variants identified per individual can be overwhelming, making it prudent to focus on non-coding regions of known function, for which the effects of variation can be predicted and directly tested to assess pathogenicity. The 3’UTRome is a region of the non-coding genome that perfectly fulfils these criteria and is of high interest when searching for pathogenic variation related to complex neurodevelopmental disorders. Herein, we review the regulatory roles of the 3’UTRome as binding sites for microRNAs, RNA binding proteins or during alternative polyadenylation. We detail existing evidence that these regions contribute to neurodevelopmental disorders and outline strategies for identification and validation of novel putatively pathogenic variation in these regions. This evidence suggests that studying the 3’UTRome will lead to the identification of new risk factors, new candidate disease genes and a better understanding of the molecular mechanisms contributing to NDDs.

    Additional information

    1-s2.0-S0006322317321911-mmc1.pdf
  • 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.
  • Warner, N., & Cutler, A. (2017). Stress effects in vowel perception as a function of language-specific vocabulary patterns. Phonetica, 74, 81-106. doi:10.1159/000447428.

    Abstract

    Background/Aims: Evidence from spoken word recognition suggests that for English listeners, distinguishing full versus reduced vowels is important, but discerning stress differences involving the same full vowel (as in mu- from music or museum) is not. In Dutch, in contrast, the latter distinction is important. This difference arises from the relative frequency of unstressed full vowels in the two vocabularies. The goal of this paper is to determine how this difference in the lexicon influences the perception of stressed versus unstressed vowels. Methods: All possible sequences of two segments (diphones) in Dutch and in English were presented to native listeners in gated fragments. We recorded identification performance over time throughout the speech signal. The data were here analysed specifically for patterns in perception of stressed versus unstressed vowels. Results: The data reveal significantly larger stress effects (whereby unstressed vowels are harder to identify than stressed vowels) in English than in Dutch. Both language-specific and shared patterns appear regarding which vowels show stress effects. Conclusion: We explain the larger stress effect in English as reflecting the processing demands caused by the difference in use of unstressed vowels in the lexicon. The larger stress effect in English is due to relative inexperience with processing unstressed full vowels
  • Wassenaar, M., Hagoort, P., & Brown, C. M. (1997). Syntactic ERP effects in Broca's aphasics with agrammatic comprehension. Brain and Language, 60, 61-64. doi:10.1006/brln.1997.1911.
  • 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
  • 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.
  • Wegman, J., Tyborowska, A., Hoogman, M., Vasquez, A. A., & Janzen, G. (2017). The brain-derived neurotrophic factor Val66Met polymorphism affects encoding of object locations during active navigation. European Journal of Neuroscience, 45(12), 1501-1511. doi:10.1111/ejn.13416.

    Abstract

    The brain-derived neurotrophic factor (BDNF) was shown to be involved in spatial memory and spatial strategy preference. A naturally occurring single nucleotide polymorphism of the BDNF gene (Val66Met) affects activity-dependent secretion of BDNF. The current event-related fMRI study on preselected groups of ‘Met’ carriers and homozygotes of the ‘Val’ allele investigated the role of this polymorphism on encoding and retrieval in a virtual navigation task in 37 healthy volunteers. In each trial, participants navigated toward a target object. During encoding, three positional cues (columns) with directional cues (shadows) were available. During retrieval, the invisible target had to be replaced while either two objects without shadows (objects trial) or one object with a shadow (shadow trial) were available. The experiment consisted of blocks, informing participants of which trial type would be most likely to occur during retrieval. We observed no differences between genetic groups in task performance or time to complete the navigation tasks. The imaging results show that Met carriers compared to Val homozygotes activate the left hippocampus more during successful object location memory encoding. The observed effects were independent of non-significant performance differences or volumetric differences in the hippocampus. These results indicate that variations of the BDNF gene affect memory encoding during spatial navigation, suggesting that lower levels of BDNF in the hippocampus results in less efficient spatial memory processing
  • Wiese, R., Orzechowska, P., Alday, P. M., & Ulbrich, C. (2017). Structural Principles or Frequency of Use? An ERP Experiment on the Learnability of Consonant Clusters. Frontiers in Psychology, 7: 2005. doi:10.3389/fpsyg.2016.02005.

    Abstract

    Phonological knowledge of a language involves knowledge about which segments can be combined under what conditions. Languages vary in the quantity and quality of licensed combinations, in particular sequences of consonants, with Polish being a language with a large inventory of such combinations. The present paper reports on a two-session experiment in which Polish-speaking adult participants learned nonce words with final consonant clusters. The aim was to study the role of two factors which potentially play a role in the learning of phonotactic structures: the phonological principle of sonority (ordering sound segments within the syllable according to their inherent loudness) and the (non-) existence as a usage-based phenomenon. EEG responses in two different time windows (adversely to behavioral responses) show linguistic processing by native speakers of Polish to be sensitive to both distinctions, in spite of the fact that Polish is rich in sonority-violating clusters. In particular, a general learning effect in terms of an N400 effect was found which was demonstrated to be different for sonority-obeying clusters than for sonority-violating clusters. Furthermore, significant interactions of formedness and session, and of existence and session, demonstrate that both factors, the sonority principle and the frequency pattern, play a role in the learning process.
  • 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., 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
  • 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. (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.
  • Wnuk, E., De Valk, J. M., Huisman, J. L. A., & Majid, A. (2017). Hot and cold smells: Odor-temperature associations across cultures. Frontiers in Psychology, 8: 1373. doi:10.3389/fpsyg.2017.01373.

    Abstract

    It is often assumed odors are associated with hot and cold temperature, since odor processing may trigger thermal sensations, such as coolness in the case of mint. It is unknown, however, whether people make consistent temperature associations for a variety of everyday odors, and, if so, what determines them. Previous work investigating the bases of cross-modal associations suggests a number of possibilities, including universal forces (e.g., perception), as well as culture-specific forces (e.g., language and cultural beliefs). In this study, we examined odor-temperature associations in three cultures—Maniq (N = 11), Thai (N = 24), and Dutch (N = 24)—who differ with respect to their cultural preoccupation with odors, their odor lexicons, and their beliefs about the relationship of odors (and odor objects) to temperature. Participants matched 15 odors to temperature by touching cups filled with hot or cold water, and described the odors in their native language. The results showed no consistent associations among the Maniq, and only a handful of consistent associations between odor and temperature among the Thai and Dutch. The consistent associations differed across the two groups, arguing against their universality. Further analysis revealed cross-modal associations could not be explained by language, but could be the result of cultural beliefs
  • 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
  • Wong, M. M. K., Watson, L. M., & Becker, E. B. E. (2017). Recent advances in modelling of cerebellar ataxia using induced pluripotent stem cells. Journal of Neurology & Neuromedicine, 2(7), 11-15. doi:10.29245/2572.942X/2017/7.1134.

    Abstract

    The cerebellar ataxias are a group of incurable brain disorders that are caused primarily by the progressive dysfunction and degeneration of cerebellar Purkinje cells. The lack of reliable disease models for the heterogeneous ataxias has hindered the understanding of the underlying pathogenic mechanisms as well as the development of effective therapies for these devastating diseases. Recent advances in the field of induced pluripotent stem cell (iPSC) technology offer new possibilities to better understand and potentially reverse disease pathology. Given the neurodevelopmental phenotypes observed in several types of ataxias, iPSC-based models have the potential to provide significant insights into disease progression, as well as opportunities for the development of early intervention therapies. To date, however, very few studies have successfully used iPSC-derived cells to cerebellar ataxias. In this review, we focus on recent breakthroughs in generating human iPSC-derived Purkinje cells. We also highlight the future challenges that will need to be addressed in order to fully exploit these models for the modelling of the molecular mechanisms underlying cerebellar ataxias and the development of effective therapeutics.
  • 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.
  • Yager, J., & Burenhult, N. (2017). Jedek: a newly discovered Aslian variety of Malaysia. Linguistic Typology, 21(3), 493-545. doi:10.1515/lingty-2017-0012.

    Abstract

    Jedek is a previously unrecognized variety of the Northern Aslian subgroup of the Aslian branch of the Austroasiatic language family. It is spoken by c. 280 individuals in the resettlement area of Sungai Rual, near Jeli in Kelantan state, Peninsular Malaysia. The community originally consisted of several bands of foragers along the middle reaches of the Pergau river. Jedek’s distinct status first became known during a linguistic survey carried out in the DOBES project Tongues of the Semang (2005-2011). This paper describes the process leading up to its discovery and provides an overview of its typological characteristics.
  • 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.
  • Yoshihara, M., Nakayama, M., Verdonschot, R. G., & Hino, Y. (2017). The phonological unit of Japanese Kanji compounds: A masked priming investigation. Journal of Experimental Psychology: Human Perception and Performance, 43(7), 1303-1328. doi:10.1037/xhp0000374.

    Abstract

    Using the masked priming paradigm, we examined which phonological unit is used when naming Kanji compounds. Although the phonological unit in the Japanese language has been suggested to be the mora, Experiment 1 found no priming for mora-related Kanji prime-target pairs. In Experiment 2, significant priming was only found when Kanji pairs shared the whole sound of their initial Kanji characters. Nevertheless, when the same Kanji pairs used in Experiment 2 were transcribed into Kana, significant mora priming was observed in Experiment 3. In Experiment 4, matching the syllable structure and pitch-accent of the initial Kanji characters did not lead to mora priming, ruling out potential alternative explanations for the earlier absence of the effect. A significant mora priming effect was observed, however, when the shared initial mora constituted the whole sound of their initial Kanji characters in Experiments 5. Lastly, these results were replicated in Experiment 6. Overall, these results indicate that the phonological unit involved when naming Kanji compounds is not the mora but the whole sound of each Kanji character. We discuss how different phonological units may be involved when processing Kanji and Kana words as well as the implications for theories dealing with language production processes.
  • Zavala, R. (1997). Functional analysis of Akatek voice constructions. International Journal of American Linguistics, 63(4), 439-474.

    Abstract

    L'A. étudie les corrélations entre structure syntaxique et fonction pragmatique dans les alternances de voix en akatek, une langue maya appartenant au sous-groupe Q'anjob'ala. Les alternances pragmatiques de voix sont les mécanismes par lesquels les langues encodent les différents degrés de topicalité des deux principaux participants d'un événement sémantiquement transitif, l'agent et le patient. A l'aide d'une analyse quantitative, l'A. évalue la topicalité de ces participants et identifie les structures syntaxiques permettant d'exprimer les quatre principales fonctions de voix en akatek : active-directe, inverse, passive et antipassive
  • Zhen, Z., Kong, X., Huang, L., Yang, Z., Wang, X., Hao, X., Huang, T., Song, Y., & Liu, J. (2017). Quantifying the variability of scene-selective regions: Interindividual, interhemispheric, and sex differences. Human Brain Mapping, 38(4), 2260-2275. doi:10.1002/hbm.23519.

    Abstract

    Scene-selective regions (SSRs), including the parahippocampal place area (PPA), retrosplenial cortex (RSC), and transverse occipital sulcus (TOS), are among the most widely characterized functional regions in the human brain. However, previous studies have mostly focused on the commonality within each SSR, providing little information on different aspects of their variability. In a large group of healthy adults (N = 202), we used functional magnetic resonance imaging to investigate different aspects of topographical and functional variability within SSRs, including interindividual, interhemispheric, and sex differences. First, the PPA, RSC, and TOS were delineated manually for each individual. We then demonstrated that SSRs showed substantial interindividual variability in both spatial topography and functional selectivity. We further identified consistent interhemispheric differences in the spatial topography of all three SSRs, but distinct interhemispheric differences in scene selectivity. Moreover, we found that all three SSRs showed stronger scene selectivity in men than in women. In summary, our work thoroughly characterized the interindividual, interhemispheric, and sex variability of the SSRs and invites future work on the origin and functional significance of these variabilities. Additionally, we constructed the first probabilistic atlases for the SSRs, which provide the detailed anatomical reference for further investigations of the scene network.
  • 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.
  • De Zubicaray, G., & Fisher, S. E. (Eds.). (2017). Genes, brain and language [Special Issue]. Brain and Language, 172.
  • De Zubicaray, G., & Fisher, S. E. (2017). Genes, Brain, and Language: A brief introduction to the Special Issue. Brain and Language, 172, 1-2. doi:10.1016/j.bandl.2017.08.003.
  • 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. (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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