Publications

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.

Abstract

Im ISOcat-Datenkategorie-Register (Data Category Registry, www.isocat.org) des Technischen Komitees ISO/TC 37 (Terminology and other language and content resources) werden Feldnamen und Werte für Sprachressourcen beschrieben. Empfohlene Feldnamen und zuverlässige Definitionen sollen dazu beitragen, dass Sprachdaten unabhängig von Anwendungen, Plattformen und Communities of Practice (CoP) wiederverwendet werden können. Datenkategorie-Gruppen (Data Category Selections) können eingesehen, ausgedruckt, exportiert und nach kostenloser Registrierung auch neu erstellt werden.

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.

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.

Abstract

This article presents data on cardinal numerals in three sign languages from small-scale communities with hereditary deafness. The unusual features found in these data considerably extend the known range of typological variety across sign languages. Some features, such as non-decimal numeral bases, are unattested in sign languages, but familiar from spoken languages, while others, such as subtractive sub-systems, are rare in sign and speech. We conclude that for a complete typological appraisal of a domain, an approach to cross-modal typology, which includes a typologically diverse range of sign languages in addition to spoken languages, is both instructive and feasible.

Abstract

This article provides a first overview of some striking grammatical structures in Türk Idotscedilaret Dili (Turkish Sign Language, TID), the sign language used by the Deaf community in Turkey. The data are described with a typological perspective in mind, focusing on aspects of TID grammar that are typologically unusual across sign languages. After giving an overview of the historical, sociolinguistic and educational background of TID and the language community using this sign language, five domains of TID grammar are investigated in detail. These include a movement derivation signalling completive aspect, three types of nonmanual negation — headshake, backward head tilt, and puffed cheeks — and their distribution, cliticization of the negator NOT to a preceding predicate host sign, an honorific whole-entity classifier used to refer to humans, and a question particle, its history and current status in the language. A final evaluation points out the significance of these data for sign language research and looks at perspectives for a deeper understanding of the language and its history.

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.

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.

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.

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.

Abstract

Psycholinguistic research has typically portrayed speech production as a relatively automatic process. This is because when errors are made, they occur as seldom as one in every thousand words we utter. However, it has long been recognised that we need some form of control over what we are currently saying and what we plan to say. This capacity to both monitor our inner speech and self-correct our speech output has often been assumed to be a property of the language comprehension system. More recently, it has been demonstrated that speech production benefits from interfacing with more general cognitive processes such as selective attention, short-term memory (STM) and online response monitoring to resolve potential conflict and successfully produce the output of a verbal plan. The conditions and levels of representation according to which these more general planning, monitoring and control processes are engaged during speech production remain poorly understood. Moreover, there remains a paucity of information about their neural substrates, despite some of the first evidence of more general monitoring having come from electrophysiological studies of error related negativities (ERNs). While aphasic speech errors continue to be a rich source of information, there has been comparatively little research focus on instances of speech repair. The purpose of this Frontiers Research Topic is to provide a forum for researchers to contribute investigations employing behavioural, neuropsychological, electrophysiological, neuroimaging and virtual lesioning techniques. In addition, while the focus of the research topic is on novel findings, we welcome submission of computational simulations, review articles and methods papers.

Abstract

This study investigates the morphological and morphosyntactic characteristics of hand configurations in signs, particularly in Nederlandse Gebarentaal (NGT). The literature on sign languages in general acknowledges that hand configurations can function as morphemes, more specifically as classifiers , in a subset of signs: verbs expressing the motion, location, and existence of referents (VELMs). These verbs are considered the output of productive sign formation processes. In contrast, other signs in which similar hand configurations appear ( iconic or motivated signs) have been considered to be lexicalized signs, not involving productive processes. This research report shows that meaningful hand configurations have (at least) two very different functions in the grammar of NGT (and presumably in other sign languages, too). First, they are agreement markers on VELMs, and hence are functional elements. Second, they are roots in motivated signs, and thus lexical elements. The latter signs are analysed as root compounds and are formed from various roots by productive processes. The similarities in surface form and differences in morphosyntactic characteristics observed in comparison of VELMs and root compounds are attributed to their different structures and to the sign language interface between grammar and phonetic form

Abstract

The Corpus NGT

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.