Publications

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

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.

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

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 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

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

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

Although in many respects sign languages have a similar structure to that of spoken languages, the different modalities in which both types of languages are expressed cause differences in structure as well. One of the most striking differences between spoken and sign languages is the influence of the interface between grammar and PF on the surface form of utterances. Spoken language words and phrases are in general characterized by sequential strings of sounds, morphemes and words, while in sign languages we find that many phonemes, morphemes, and even words are expressed simultaneously. A linguistic model should be able to account for the structures that occur in both spoken and sign languages. In this paper, I will discuss the morphological/ morphosyntactic structure of signs in Nederlandse Gebarentaal (Sign Language of the Netherlands, henceforth NGT), with special focus on the components ‘place of articulation’ and ‘handshape’. I will focus on their multiple functions in the grammar of NGT and argue that the framework of Distributed Morphology (DM), which accounts for word formation in spoken languages, is also suited to account for the formation of structures in sign languages. First I will introduce the phonological and morphological structure of NGT signs. Then, I will briefly outline the major characteristics of the DM framework. Finally, I will account for signs that have the same surface form but have a different morphological structure by means of that framework.