Publications

Abstract

Gamma-band neuronal synchronization during sentence-level language comprehension has previously been linked with semantic unification. Here, we attempt to further narrow down the functional significance of gamma during language comprehension, by distinguishing between two aspects of semantic unification: successful integration of word meaning into the sentence context, and prediction of upcoming words. We computed event-related potentials (ERPs) and frequency band-specific electroencephalographic (EEG) power changes while participants read sentences that contained a critical word (CW) that was (1) both semantically congruent and predictable (high cloze, HC), (2) semantically congruent but unpredictable (low cloze, LC), or (3) semantically incongruent (and therefore also unpredictable; semantic violation, SV). The ERP analysis showed the expected parametric N400 modulation (HC < LC < SV). The time-frequency analysis showed qualitatively different results. In the gamma-frequency range, we observed a power increase in response to the CW in the HC condition, but not in the LC and the SV conditions. Additionally, in the theta frequency range we observed a power increase in the SV condition only. Our data provide evidence that gamma power increases are related to the predictability of an upcoming word based on the preceding sentence context, rather than to the integration of the incoming word’s semantics into the preceding context. Further, our theta band data are compatible with the notion that theta band synchronization in sentence comprehension might be related to the detection of an error in the language input.

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.

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.

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

Previous studies have shown that spoken-language processing is inhibited by violation of obligatory regressive assimilation. Weber (2001) replicated this inhibitory effect in a phoneme-monitoring study examining regressive place assimilation of nasals, but found facilitation for violation of progressive assimilation. German listeners detected the velar fricative [x] more quickly when fricative assimilation was violated (e.g., *[bIxt] or *[blInx@n]) than when no violation occurred (e.g., [baxt] or [blu:x@n]). It was argued that a combination of two factors caused facilitation:(1) progressive assimilation creates different restrictions for the monitoring target than regressive assimilation does, and (2) the sequences violating assimilation (e.g., *[Ix]) are novel for German listeners and therefore facilitate fricative detection (novel popout). The present study tested progressive assimilation violation in non-novel sequences using the palatal fricative [C]. Stimuli either violated fricative assimilation (e.g., *[ba:C@l ]) or did not (e.g., [bi: C@l ]). This manipulation does not create novel sequences: sequences like *[a:C] can occur across word boundaries, while *[Ix] cannot. No facilitation was found. However, violation also did not significantly inhibit processing. The results confirm that facilitation depends on the combination of progressive assimilation with novelty of the sequence.

Abstract

All words of the languages we know are stored in the mental lexicon. Psycholinguistic models describe in which format lexical knowledge is stored and how it is accessed when needed for language use. The present article summarizes key findings in spoken-word recognition by humans and describes how models of spoken-word recognition account for them. Although current models of spoken-word recognition differ considerably in the details of implementation, there is general consensus among them on at least three aspects: multiple word candidates are activated in parallel as a word is being heard, activation of word candidates varies with the degree of match between the speech signal and stored lexical representations, and activated candidate words compete for recognition. No consensus has been reached on other aspects such as the flow of information between different processing levels, and the format of stored prelexical and lexical representations. WIREs Cogn Sci 2012

Abstract

We present two eye-tracking experiments that investigate lexical frequency and semantic context constraints in spoken-word recognition in German. In both experiments, the pivotal words were pairs of nouns overlapping at onset but varying in lexical frequency. In Experiment 1, German listeners showed an expected frequency bias towards high-frequency competitors (e.g., Blume, ‘flower’) when instructed to click on low-frequency targets (e.g., Bluse, ‘blouse’). In Experiment 2, semantically constraining context increased the availability of appropriate low-frequency target words prior to word onset, but did not influence the availability of semantically inappropriate high-frequency competitors at the same time. Immediately after target word onset, however, the activation of high-frequency competitors was reduced in semantically constraining sentences, but still exceeded that of unrelated distractor words significantly. The results suggest that (1) semantic context acts to downgrade activation of inappropriate competitors rather than to exclude them from competition, and (2) semantic context influences spoken-word recognition, over and above anticipation of upcoming referents.

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

Corrigendum to CNTNAP2 variants affect early language development in the general population A. J. O. Whitehouse, D. V. M. Bishop, Q. W. Ang, C. E. Pennell and S. E. Fisher Genes Brain Behav (2011) doi: 10.1111/j.1601-183X.2011.00684.x. The authors have detected a typographical error in the Abstract of this paper. The error is in the fifth sentence, which reads: ‘‘On the basis of these findings, we performed analyses of four-marker haplotypes of rs2710102–rs759178–rs17236239–rs2538976 and identified significant association (haplotype TTAA, P = 0.049; haplotype GCAG,P = .0014).’’ Rather than ‘‘GCAG’’, the final haplotype should read ‘‘CGAG’’. This typographical error was made in the Abstract only and this has no bearing on the results or conclusions of the study, which remain unchanged. Reference Whitehouse, A. J. O., Bishop, D. V. M., Ang, Q. W., Pennell, C. E. & Fisher, S. E. (2011) CNTNAP2 variants affect early language development in the general population. Genes Brain Behav 10, 451–456. doi: 10.1111/j.1601-183X.2011.00684.x.

Abstract

Beller, Bender, and Medin question the necessity of including social anthropology within the cognitive sciences. We argue that there is great scope for fruitful rapprochement while agreeing that there are obstacles (even if we might wish to debate some of those specifically identified by Beller and colleagues). We frame the general problem differently, however: not in terms of the problem of reconciling disciplines and research cultures, but rather in terms of the prospects for collaborative deployment of expertise (methodological and theoretical) in problem-driven research. For the purposes of illustration, our focus in this article is on the evolution of cooperation

Abstract

Recent years have seen a large amount of empirical studies related to ‘embodied cognition’. While interesting and valuable, there is something dissatisfying with the current state of affairs in this research domain. Hypotheses tend to be underspecified, testing in general terms for embodied versus disembodied processing. The lack of specificity of current hypotheses can easily lead to an erosion of the embodiment concept, and result in a situation in which essentially any effect is taken as positive evidence. Such erosion is not helpful to the field and does not do justice to the importance of embodiment. Here we want to take stock, and formulate directions for how it can be studied in a more fruitful fashion. As an example we will describe few example studies that have investigated the role of sensori-motor systems in the coding of meaning (‘embodied semantics’). Instead of focusing on the dichotomy between embodied and disembodied theories, we suggest that the field move forward and ask how and when sensori-motor systems and behavior are involved in cognition.

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

We carried out the first study on the relationship between individual language aptitude and structural connectivity of language pathways in the adult brain. We measured four components of language aptitude (vocabulary learning, VocL; sound recognition, SndRec; sound-symbol correspondence, SndSym; and grammatical inferencing, GrInf) using the LLAMA language aptitude test (Meara, 2005). Spatial working memory (SWM), verbal working memory (VWM) and IQ were also measured as control factors. Diffusion Tensor Imaging (DTI) was employed to investigate the structural connectivity of language pathways in the perisylvian language network. Principal Component Analysis (PCA) on behavioural measures suggests that a general ability might be important to the first stages of L2 acquisition. It also suggested that VocL, SndSy and SWM are more closely related to general IQ than SndRec and VocL, and distinguished the tasks specifically designed to tap into L2 acquisition (VocL, SndRec,SndSym and GrInf) from more generic measures (IQ, SWM and VWM). Regression analysis suggested significant correlations between most of these behavioural measures and the structural connectivity of certain language pathways, i.e., VocL and BA47-Parietal pathway, SndSym and inter-hemispheric BA45 pathway, GrInf and BA45-Temporal pathway and BA6-Temporal pathway, IQ and BA44-Parietal pathway, BA47-Parietal pathway, BA47-Temporal pathway and inter-hemispheric BA45 pathway, SWM and inter-hemispheric BA6 pathway and BA47-Parietal pathway, and VWM and BA47-Temporal pathway. These results are discussed in relation to relevant findings in the literature.

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

Four experiments investigated the role of the syllable in Chinese spoken word production. Chen, Chen and Ferrand (2003) reported a syllable priming effect when primes and targets shared the first syllable using a masked priming paradigm in Chinese. Our Experiment 1 was a direct replication of Chen et al.'s (2003) Experiment 3 employing CV (e. g., /ba2.ying2/, strike camp) and CVG (e. g., /bai2.shou3/, white haired) syllable types. Experiment 2 tested the syllable priming effect using different syllable types: e. g., CV (/qi4.qiu2/, balloon) and CVN (/qing1.ting2/, dragonfly). Experiment 3 investigated this issue further using line drawings of common objects as targets that were preceded either by a CV (e. g., /qi3/, attempt), or a CVN (e. g., /qing2/, affection) prime. Experiment 4 further examined the priming effect by a comparison between CV or CVN priming and an unrelated priming condition using CV-NX (e. g., /mi2.ni3/, mini) and CVN-CX (e. g., /min2.ju1/, dwellings) as target words. These four experiments consistently found that CV targets were named faster when preceded by CV primes than when they were preceded by CVG, CVN or unrelated primes, whereas CVG or CVN targets showed the reverse pattern. These results indicate that the priming effect critically depends on the match between the structure of the prime and that of the first syllable of the target. The effect obtained in this study was consistent across different stimuli and different tasks (word and picture naming), and provides more conclusive and consistent data regarding the role of the syllable in Chinese speech production.

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

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

Semantic unification, the process by which small blocks of semantic information are combined into a coherent utterance, has been studied with various types of tasks. However, whether the brain activations reported in these studies are attributed to semantic unification per se or to other task-induced concomitant processes still remains unclear. The neural basis for semantic unification in sentence comprehension was examined using event-related potentials (ERP) and functional Magnetic Resonance Imaging (fMRI). The semantic unification load was manipulated by varying the goodness of fit between a critical word and its preceding context (in high cloze, low cloze and violation sentences). The sentences were presented in a serial visual presentation mode. The participants were asked to perform one of three tasks: semantic congruency judgment (SEM), silent reading for comprehension (READ), or font size judgment (FONT), in separate sessions. The ERP results showed a similar N400 amplitude modulation by the semantic unification load across all of the three tasks. The brain activations associated with the semantic unification load were found in the anterior left inferior frontal gyrus (aLIFG) in the FONT task and in a widespread set of regions in the other two tasks. These results suggest that the aLIFG activation reflects a semantic unification, which is different from other brain activations that may reflect task-specific strategic processing.

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

How does language comprehension interact with motor activity? We investigated the conditions under which comprehending an action sentence affects people's balance. We performed two experiments to assess whether sentences describing forward or backward movement modulate the lateral movements made by subjects who made sensibility judgments about the sentences. In one experiment subjects were standing on a balance board and in the other they were seated on a balance board that was mounted on a chair. This allowed us to investigate whether the action compatibility effect (ACE) is robust and persists in the face of salient incompatibilities between sentence content and subject movement. Growth-curve analysis of the movement trajectories produced by the subjects in response to the sentences suggests that the ACE is indeed robust. Sentence content influenced movement trajectory despite salient inconsistencies between implied and actual movement. These results are interpreted in the context of the current discussion of embodied, or grounded, language comprehension and meaning representation.

Abstract

This paper explores the expression of multiple entities in Turkish Sign Language (Türk İşaret Dili; TİD), a less well-studied sign language. It aims to provide a comprehensive description of the ways and frequencies in which entity plurality in this language is expressed, both within and outside the noun phrase. We used a corpus that includes both elicited and spontaneous data from native signers. The results reveal that most of the expressions of multiple entities in TİD are iconic, spatial strategies (i.e. localization and spatial plural predicate inflection) none of which, we argue, should be considered as genuine plural marking devices with the main aim of expressing plurality. Instead, the observed devices for localization and predicate inflection allow for a plural interpretation when multiple locations in space are used. Our data do not provide evidence that TİD employs (productive) morphological plural marking (i.e. reduplication) on nouns, in contrast to some other sign languages and many spoken languages. We relate our findings to expression of multiple entities in other signed languages and in spoken languages and discuss these findings in terms of modality effects on expression of multiple entities in human language.