Publications

Abstract

This article presents electrophysiological data on on-line syntactic processing during auditory sentence comprehension in patients with Broca's aphasia. Event-related brain potentials (ERPs) were recorded from the scalp while subjects listened to sentences that were either syntactically correct or contained violations of subject-verb agreement. Three groups of subjects were tested: Broca patients (n = 10), nonaphasic patients with a right-hemisphere (RH) lesion (n = 5), and healthy agedmatched controls (n = 12). The healthy, control subjects showed a P600/SPS effect as response to the agreement violations. The nonaphasic patients with an RH lesion showed essentially the same pattern. The overall group of Broca patients did not show this sensitivity. However, the sensitivity was modulated by the severity of the syntactic comprehension impairment. The largest deviation from the standard P600/SPS effect was found in the patients with the relatively more severe syntactic comprehension impairment. In addition, ERPs to tones in a classical tone oddball paradigm were also recorded. Similar to the normal control subjects and RH patients, the group of Broca patients showed a P300 effect in the tone oddball condition. This indicates that aphasia in itself does not lead to a general reduction in all cognitive ERP effects. It was concluded that deviations from the standard P600/SPS effect in the Broca patients reflected difficulties with on-line maintaining of number information across clausal boundaries for establishing subject-verb agreement.

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.

Abstract

Four eye-tracking experiments examined lexical competition in non-native spoken-word recognition. Dutch listeners hearing English fixated longer on distractor pictures with names containing vowels that Dutch listeners are likely to confuse with vowels in a target picture name (pencil, given target panda) than on less confusable distractors (beetle, given target bottle). English listeners showed no such viewing time difference. The confusability was asymmetric: given pencil as target, panda did not distract more than distinct competitors. Distractors with Dutch names phonologically related to English target names (deksel, ‘lid,’ given target desk) also received longer fixations than distractors with phonologically unrelated names. Again, English listeners showed no differential effect. With the materials translated into Dutch, Dutch listeners showed no activation of the English words (desk, given target deksel). The results motivate two conclusions: native phonemic categories capture second-language input even when stored representations maintain a second-language distinction; and lexical competition is greater for non-native than for native listeners.

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.

Abstract

Three experiments examined the time course of phonological encoding in speech production. A new methodology is introduced in which subjects are required to monitor their internal speech production for prespecified target segments and syllables. Experiment 1 demonstrated that word initial target segments are monitored significantly faster than second syllable initial target segments. The addition of a concurrent articulation task (Experiment 1b) had a limited effect on performance, excluding the possibility that subjects are monitoring a subvocal articulation of the carrier word. Moreover, no relationship was observed between the pattern of monitoring latencies and the timing of the targets in subjects′ overt speech. Subjects are not, therefore, monitoring an internal phonetic representation of the carrier word. Experiment 2 used the production monitoring task to replicate the syllable monitoring effect observed in speech perception experiments: responses to targets were faster when they corresponded to the initial syllable of the carrier word than when they did not. We conclude that subjects are monitoring their internal generation of a syllabified phonological representation. Experiment 3 provides more detailed evidence concerning the time course of the generation of this representation by comparing monitoring latencies to targets within, as well as between, syllables. Some amendments to current models of phonological encoding are suggested in light of these results.

Abstract

The purpose of this paper is to question some of the basic assumpiions concerning motion verbs. In particular, it examines the assumption that "come" and "go" are lexical universals which manifest a universal deictic Opposition. Against the background offive working hypotheses about the nature of'come" and ''go", this study presents a comparative investigation of t wo unrelated languages—Mparntwe Arrernte (Pama-Nyungan, Australian) and Longgu (Oceanic, Austronesian). Although the pragmatic and deictic "suppositional" complexity of"come" and "go" expressions has long been recognized, we argue that in any given language the analysis of these expressions is much more semantically and systemically complex than has been assumed in the literature. Languages vary at the lexical semantic level äs t o what is entailed by these expressions, äs well äs differing äs t o what constitutes the prototype and categorial structure for such expressions. The data also strongly suggest that, ifthere is a lexical universal "go", then this cannof be an inherently deictic expression. However, due to systemic Opposition with "come", non-deictic "go" expressions often take on a deictic Interpretation through pragmatic attribution. Thus, this crosslinguistic investigation of "come" and "go" highlights the need to consider semantics and pragmatics äs modularly separate.

Abstract

Although generally studied in isolation, language and action often co-occur in everyday life. Here we investigated one particular form of simultaneous language and action, namely speech and gestures that speakers use in everyday communication. In a functional magnetic resonance imaging study, we identified the neural networks involved in the integration of semantic information from speech and gestures. Verbal and/or gestural content could be integrated easily or less easily with the content of the preceding part of speech. Premotor areas involved in action observation (Brodmann area [BA] 6) were found to be specifically modulated by action information "mismatching" to a language context. Importantly, an increase in integration load of both verbal and gestural information into prior speech context activated Broca's area and adjacent cortex (BA 45/47). A classical language area, Broca's area, is not only recruited for language-internal processing but also when action observation is integrated with speech. These findings provide direct evidence that action and language processing share a high-level neural integration system.

Abstract

Co-speech gestures embody a form of manual action that is tightly coupled to the language system. As such, the co-occurrence of speech and co-speech gestures is an excellent example of the interplay between language and action. There are, however, other ways in which language and action can be thought of as closely related. In this paper we will give an overview of studies in cognitive neuroscience that examine the neural underpinnings of links between language and action. Topics include neurocognitive studies of motor representations of speech sounds, action-related language, sign language and co-speech gestures. It will be concluded that there is strong evidence on the interaction between speech and gestures in the brain. This interaction however shares general properties with other domains in which there is interplay between language and action.

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

Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions.

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

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

Abstract

This article reports on results from a broad crosslinguistic study based on data from thirty-five signed languages around the world. The study is the first of its kind, and the typological generalizations presented here cover the domain of interrogative structures as they appear across a wide range of geographically and genetically distinct signed languages. Manual and nonmanual ways of marking basic types of questions in signed languages are investigated. As a result, it becomes clear that the range of crosslinguistic variation is extensive for some subparameters, such as the structure of question-word paradigms, while other parameters, such as the use of nonmanual expressions in questions, show more similarities across signed languages. Finally, it is instructive to compare the findings from signed language typology to relevant data from spoken languages at a more abstract, crossmodality level.

Abstract

This article presents a typology of negative constructions across a substantial number of sign languages from around the globe. After situating the topic within the wider context of linguistic typology, the main negation strategies found across sign languages are described. Nonmanual negation includes the use of head movements and facial expressions for negation and is of great importance in sign languages as well as particularly interesting from a typological point of view. As far as manual signs are concerned, independent negative particles represent the dominant strategy, but there are also instances of irregular negation in most sign languages. Irregular negatives may take the form of suppletion, cliticisation, affixing, or internal modification of a sign. The results of the study lead to interesting generalisations about similarities and differences between negatives in signed and spoken languages.

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

Genome-wide association studies using thousands to hundreds of thousands of single nucleotide polymorphism (SNP) markers and region-wide association studies using a dense panel of SNPs are already in use to identify disease susceptibility genes and to predict disease risk in individuals. Because these tasks become increasingly important, three different data sets were provided for the Genetic Analysis Workshop 15, thus allowing examination of various novel and existing data mining methods for both classification and identification of disease susceptibility genes, gene by gene or gene by environment interaction. The approach most often applied in this presentation group was random forests because of its simplicity, elegance, and robustness. It was used for prediction and for screening for interesting SNPs in a first step. The logistic tree with unbiased selection approach appeared to be an interesting alternative to efficiently select interesting SNPs. Machine learning, specifically ensemble methods, might be useful as pre-screening tools for large-scale association studies because they can be less prone to overfitting, can be less computer processor time intensive, can easily include pair-wise and higher-order interactions compared with standard statistical approaches and can also have a high capability for classification. However, improved implementations that are able to deal with hundreds of thousands of SNPs at a time are required.

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.