Publications

Abstract

Osteoblast induction and differentiation in developing long bones is dynamically controlled by the opposing action of transcriptional activators and repressors. In contrast to the long list of activators that have been discovered over past decades, the network of repressors is not well-defined. Here we identify the expression of Foxp1/2/4 proteins, comprised of Forkhead-box (Fox) transcription factors of the Foxp subfamily, in both perichondrial skeletal progenitors and proliferating chondrocytes during endochondral ossification. Mice carrying loss-of-function and gain-of-function Foxp mutations had gross defects in appendicular skeleton formation. At the cellular level, over-expression of Foxp1/2/4 in chondroctyes abrogated osteoblast formation and chondrocyte hypertrophy. Conversely, single or compound deficiency of Foxp1/2/4 in skeletal progenitors or chondrocytes resulted in premature osteoblast differentiation in the perichondrium, coupled with impaired proliferation, survival, and hypertrophy of chondrocytes in the growth plate. Foxp1/2/4 and Runx2 proteins interacted in vitro and in vivo, and Foxp1/2/4 repressed Runx2 transactivation function in heterologous cells. This study establishes Foxp1/2/4 proteins as coordinators of osteogenesis and chondrocyte hypertrophy in developing long bones and suggests that a novel transcriptional repressor network involving Foxp1/2/4 may regulate Runx2 during endochondral ossification.

Abstract

Introduction It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related. Aim Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO. Methods Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO. Results We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10–4). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue. Conclusions Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.

Abstract

Face-selective regions (FSRs) are among the most widely studied functional regions in the human brain. However, individual variability of the FSRs has not been well quantified. Here we use functional magnetic resonance imaging (fMRI) to localize the FSRs and quantify their spatial and functional variabilities in 202 healthy adults. The occipital face area (OFA), posterior and anterior fusiform face areas (pFFA and aFFA), posterior continuation of the superior temporal sulcus (pcSTS), and posterior and anterior STS (pSTS and aSTS) were delineated for each individual with a semi-automated procedure. A probabilistic atlas was constructed to characterize their interindividual variability, revealing that the FSRs were highly variable in location and extent across subjects. The variability of FSRs was further quantified on both functional (i.e., face selectivity) and spatial (i.e., volume, location of peak activation, and anatomical location) features. Considerable interindividual variability and rightward asymmetry were found in all FSRs on these features. Taken together, our work presents the first effort to characterize comprehensively the variability of FSRs in a large sample of healthy subjects, and invites future work on the origin of the variability and its relation to individual differences in behavioral performance. Moreover, the probabilistic functional atlas will provide an adequate spatial reference for mapping the face network.

Abstract

In sentences like “the mouse that chased the cat was hungry”, the syntactically correct interpretation (the mouse chases the cat) is contradicted by semantic and pragmatic knowledge. Previous research has shown that L1 speakers sometimes base sentence interpretation on this type of knowledge (so-called “shallow” or “good-enough” processing). We made use of both behavioural and ERP measurements to investigate whether L2 learners differ from native speakers in the extent to which they engage in “shallow” syntactic processing. German learners of Dutch as well as Dutch native speakers read sentences containing relative clauses (as in the example above) for which the plausible thematic roles were or were not reversed, and made plausibility judgments. The results show that behaviourally, L2 learners had more difficulties than native speakers to discriminate plausible from implausible sentences. In the ERPs, we replicated the previously reported finding of a “semantic P600” for semantic reversal anomalies in native speakers, probably reflecting the effort to resolve the syntax-semantics conflict. In L2 learners, though, this P600 was largely attenuated and surfaced only in those trials that were judged correctly for plausibility. These results generally point at a more prevalent, but not exclusive occurrence of shallow syntactic processing in L2 learners.

Abstract

Statistical learning (SL) is postulated to play an important role in the process of language acquisition as well as in other cognitive functions. It was found to enable learning of various types of statistical patterns across different sensory modalities. However, few studies have distinguished distributional SL (DSL) from sequential and spatial SL, or examined DSL across modalities using comparable tasks. Considering the relevance of such findings to the nature of SL, the current study investigated the modality- and stimulus-specificity of DSL. Using a within-subject design we compared DSL performance in auditory and visual modalities. For each sensory modality, two stimulus types were used: linguistic versus non-linguistic auditory stimuli and temporal versus spatial visual stimuli. In each condition, participants were exposed to stimuli that varied in their length as they were drawn from two categories (short versus long). DSL was assessed using a categorization task and a production task. Results showed that learners’ performance was only correlated for tasks in the same sensory modality. Moreover, participants were better at categorizing the temporal signals in the auditory conditions than in the visual condition, where in turn an advantage of the spatial condition was observed. In the production task participants exaggerated signal length more for linguistic signals than non-linguistic signals. Together, these findings suggest that DSL is modality- and stimulus-sensitive.

Abstract

Semantic unification during sentence comprehension has been associated with amplitude change of the N400 in event-related potential (ERP) studies, and activation in the left inferior frontal gyrus (IFG) in functional magnetic resonance imaging (fMRI) studies. However, the specificity of this activation to semantic unification remains unknown. To more closely examine the brain processes involved in semantic unification, we employed simultaneous EEG-fMRI to time-lock the semantic unification related N400 change, and integrated trial-by-trial variation in both N400 and BOLD change beyond the condition-level BOLD change difference measured in traditional fMRI analyses. Participants read sentences in which semantic unification load was parametrically manipulated by varying cloze probability. Separately, ERP and fMRI results replicated previous findings, in that semantic unification load parametrically modulated the amplitude of N400 and cortical activation. Integrated EEG-fMRI analyses revealed a different pattern in which functional activity in the left IFG and bilateral supramarginal gyrus (SMG) was associated with N400 amplitude, with the left IFG activation and bilateral SMG activation being selective to the condition-level and trial-level of semantic unification load, respectively. By employing the EEG-fMRI integrated analyses, this study among the first sheds light on how to integrate trial-level variation in language comprehension.

Abstract

How do object perception and action interact at a neural level? Here we test the hypothesis that perceptual
features, processed by the ventral visuoperceptual stream, are used as priors by the dorsal visuomotor stream to
specify goal-directed grasping actions. We present three main findings, which were obtained by combining
time-resolved transcranial magnetic stimulation and kinematic tracking of grasp-and-rotate object manipulations,
in a group of healthy human participants (N 22). First, the extrastriate body area (EBA), in the ventral stream,
provides an initial structure to motor plans, based on current and desired states of a grasped object and of the
grasping hand. Second, the contributions of EBA are earlier in time than those of a caudal intraparietal region
known to specify the action plan. Third, the contributions of EBA are particularly important when desired and
current object configurations differ, and multiple courses of actions are possible. These findings specify the
temporal and functional characteristics for a mechanism that integrates perceptual processing with motor
planning.

Abstract

In their analysis of methods that participants use to manage the realization of practical courses of action, Kendrick and Drew (2016/this issue) focus on cases of assistance, where the need to be addressed is Self’s, and Other lends a helping hand. In our commentary, we point to other forms of cooperative engagement that are ubiquitously recruited in interaction. Imperative requests characteristically expect compliance on the grounds of Other’s already established commitment to a wider and shared course of actions. Established commitments can also provide the engine behind recruitment sequences that proceed nonverbally. And forms of cooperative engagement that are well glossed as assistance can nevertheless be demonstrably oriented to established commitments. In sum, we find commitment to shared courses of action to be an important element in the design and progression of certain recruitment sequences, where the involvement of Other is best defined as contribution. The commentary highlights the importance of interdependent orientations in the organization of cooperation. Data are in German, Italian, and Polish.

Abstract

We describe ViCoS, a tool for constructing and visualising conceptual spaces in the area of language documentation. ViCoS allows users to enrich existing lexical information about the words of a language with conceptual knowledge. Their work towards language-based, informal ontology building must be supported by easy-to-use workflows and supporting software, which we will demonstrate.

Abstract

Research into the role of brain oscillations in basic perceptual and cognitive functions has suggested that the alpha rhythm reflects functional inhibition while the beta rhythm reflects neural ensemble (re)activation. However, little is known regarding the generalization of these proposed fundamental operations to linguistic processes, such as speech comprehension and production. Here, we recorded magnetoencephalography in participants performing a novel rule-switching paradigm. Specifically, Dutch native speakers had to produce an alternative exemplar from the same category or a feature of a given target word embedded in spoken sentences (e.g., for the word “tuna”, an exemplar from the same category—“seafood”—would be “shrimp”, and a feature would be “pink”). A cue indicated the task rule—exemplar or feature—either before (pre-cue) or after (retro-cue) listening to the sentence. Alpha power during the working memory delay was lower for retro-cue compared with that for pre-cue in the left hemispheric language-related regions. Critically, alpha power negatively correlated with reaction times, suggestive of alpha facilitating task performance by regulating inhibition in regions linked to lexical retrieval. Furthermore, we observed a different spatiotemporal pattern of beta activity for exemplars versus features in the right temporoparietal regions, in line with the proposed role of beta in recruiting neural networks for the encoding of distinct categories. Overall, our study provides evidence for the generalizability of the role of alpha and beta oscillations from perceptual to more “complex, linguistic processes” and offers a novel task to investigate links between rule-switching, working memory, and word production.

Abstract

Perceptual correlates of Turkish word stress and their contribution to lexical access were studied using the mismatch negativity (MMN) component in event-related potentials (ERPs). The MMN was expected to indicate if segmentally identical Turkish words were distinguished on the sole basis of prosodic features such as fundamental frequency (f0), spectral emphasis (SE), and duration. The salience of these features in lexical access was expected to be reflected in the amplitude of MMN responses. In a multi-deviant oddball paradigm, neural responses to changes in f0, SE, and duration individually, as well as to all three features combined, were recorded for words and pseudowords presented to 14 native speakers of Turkish. The word and pseudoword contrast was used to differentiate language-related effects from acoustic-change effects on the neural responses. First and in line with previous findings, the overall MMN was maximal over frontal and central scalp locations. Second, changes in prosodic features elicited neural responses both in words and pseudowords, confirming the brain's automatic response to any change in auditory input. However, there were processing differences between the prosodic features, most significantly in f0: While f0 manipulation elicited a slightly right-lateralized frontally-maximal MMN in words, it elicited a frontal P3a in pseudowords. Considering that P3a is associated with involuntary allocation of attention to salient changes, the manipulations of f0 in the absence of lexical processing lead to an intentional evaluation of pitch change. f0 is therefore claimed to be lexically specified in Turkish. Rather than combined features, individual prosodic features differentiate language-related effects from acoustic-change effects. The present study confirms that segmentally identical words can be distinguished on the basis of prosodic information alone, and establishes the salience of f0 in lexical access.

Abstract

Like that of many other Germanic languages, the stress system of Swedish has mainly undergone phonological analysis. Recently, however, researchers have begun to recognize the central role of morphology in these systems. Similar to the lexical specification of tonal accent, the Swedish stress system is claimed to be morphologically determined and morphemes are thus categorized as prosodically specified and prosodically unspecified. Prosodically specified morphemes bear stress information as part of their lexical representations and are classified as tonic (i.e., lexically stressed), pretonic and posttonic, whereas prosodically unspecified morphemes receive stress through a phonological rule that is right-edge oriented, but is sensitive to prosodic specification at that edge. The presence of prosodic specification is inferred from vowel quality and vowel quantity; if stress moves elsewhere, vowel quality and quantity change radically in phonologically stressed morphemes, whereas traces of stress remain in lexically stressed morphemes. The present study is the first to investigate whether stress is a lexical property of Swedish morphemes by comparing mismatch negativity (MMN) responses to vowel quality and quantity changes in phonologically stressed and lexically stressed words. In a passive oddball paradigm, 15 native speakers of Swedish were presented with standards and deviants, which differed from the standards in formant frequency and duration. Given that vowel quality and quantity changes are associated with morphological derivations only in phonologically stressed words, MMN responses are expected to be greater in phonologically stressed words than in lexically stressed words that lack such an association. The results indicated that the processing differences between phonologically and lexically stressed words were reflected in the amplitude and topography of MMN responses. Confirming the expectation, MMN amplitude was greater for the phonologically stressed word than for the lexically stressed word and showed a more widespread topographic distribution. The brain did not only detect vowel quality and quantity changes but also used them to activate memory traces associated with derivations. The present study therefore implies that morphology is directly involved in the Swedish stress system and that changes in phonological shape due to stress shift cue upcoming stress and potential addition of a morpheme.

Abstract

Neural correlates of lexical stress were studied using the mismatch negativity (MMN) component in event-related potentials. The MMN responses were expected to reveal the encoding of stress information into long-term memory and the contributions of prosodic features such as fundamental frequency (F0) and intensity toward lexical access. In a passive oddball paradigm, neural responses to changes in F0, intensity, and in both features together were recorded for words and pseudowords. The findings showed significant differences not only between words and pseudowords but also between prosodic features. Early processing of prosodic information in words was indexed by an intensity-related MMN and an F0-related P200. These effects were stable at right-anterior and mid-anterior regions. At a later latency, MMN responses were recorded for both words and pseudowords at the mid-anterior and posterior regions. The P200 effect observed for F0 at the early latency for words developed into an MMN response. Intensity elicited smaller MMN for pseudowords than for words. Moreover, a larger brain area was recruited for the processing of words than for the processing of pseudowords. These findings suggest earlier and higher sensitivity to prosodic changes in words than in pseudowords, reflecting a language-related process. The present study, therefore, not only establishes neural correlates of lexical stress but also confirms the presence of long-term memory traces for prosodic information in the brain.

Abstract

Swedish morphemes are classified as prosodically specified or prosodically unspecified, depending on lexical or phonological stress, respectively. Here, we investigate the allomorphy of the suffix -(i)sk, which indicates the distinction between lexical and phonological stress; if attached to a lexically stressed morpheme, it takes a non-syllabic form (-sk), whereas if attached to a phonologically stressed morpheme, an epenthetic vowel is inserted (-isk). Using mismatch negativity (MMN), we explored the neural processing of this allomorphy across lexically stressed and phonologically stressed morphemes. In an oddball paradigm, participants were occasionally presented with congruent and incongruent derivations, created by the suffix -(i)sk, within the repetitive presentation of their monomorphemic stems. The results indicated that the congruent derivation of the lexically stressed stem elicited a larger MMN than the incongruent sequences of the same stem and the derivational suffix, whereas after the phonologically stressed stem a non-significant tendency towards an opposite pattern was observed. We argue that the significant MMN response to the congruent derivation in the lexical stress condition is in line with lexical MMN, indicating a holistic processing of the sequence of lexically stressed stem and derivational suffix. The enhanced MMN response to the incongruent derivation in the phonological stress condition, on the other hand, is suggested to reflect combinatorial processing of the sequence of phonologically stressed stem and derivational suffix. These findings bring a new aspect to the dual-system approach to neural processing of morphologically complex words, namely the specification of word stress.

Abstract

Speakers remember their own utterances better than those of their interlocutors, suggesting that language production is beneficial to memory. This may be partly explained by a generation effect: The act of generating a word is known to lead to a memory advantage (Slamecka & Graf, 1978). In earlier work, we showed a generation effect for recognition of images (Zormpa, Brehm, Hoedemaker, & Meyer, 2019). Here, we tested whether the recognition of their names would also benefit from name generation. Testing whether picture naming improves memory for words was our primary aim, as it serves to clarify whether the representations affected by generation are visual or conceptual/lexical. A secondary aim was to assess the influence of processing time on memory. Fifty-one participants named pictures in three conditions: after hearing the picture name (identity condition), backward speech, or an unrelated word. A day later, recognition memory was tested in a yes/no task. Memory in the backward speech and unrelated conditions, which required generation, was superior to memory in the identity condition, which did not require generation. The time taken by participants for naming was a good predictor of memory, such that words that took longer to be retrieved were remembered better. Importantly, that was the case only when generation was required: In the no-generation (identity) condition, processing time was not related to recognition memory performance. This work has shown that generation affects conceptual/lexical representations, making an important contribution to the understanding of the relationship between memory and language.

Abstract

The production effect (better memory for words read aloud than words read silently) and the picture superiority effect (better memory for pictures than words) both improve item memory in a picture naming task (Fawcett, J. M., Quinlan, C. K., & Taylor, T. L. (2012). Interplay of the production and picture superiority effects: A signal detection analysis. Memory (Hove, England), 20(7), 655–666. doi:10.1080/09658211.2012.693510). Because picture naming requires coming up with an appropriate label, the generation effect (better memory for generated than read words) may contribute to the latter effect. In two forced-choice memory experiments, we tested the role of generation in a picture naming task on later recognition memory. In Experiment 1, participants named pictures silently or aloud with the correct name or an unreadable label superimposed. We observed a generation effect, a production effect, and an interaction between the two. In Experiment 2, unreliable labels were included to ensure full picture processing in all conditions. In this experiment, we observed a production and a generation effect but no interaction, implying the effects are dissociable. This research demonstrates the separable roles of generation and production in picture naming and their impact on memory. As such, it informs the link between memory and language production and has implications for memory asymmetries between language production and comprehension.

Abstract

This paper discusses the construction of a cross-linguistic, bimodal corpus containing three modes of expression: expressions from two sign languages, speech and gestural expressions in two spoken languages and pantomimic expressions by users of two spoken languages who are requested to convey information without speaking. We discuss some problems and tentative solutions for the annotation of utterances expressing spatial information about referents in these three modes, suggesting a set of comparable codes for the description of both sign and gesture. Furthermore, we discuss the processing of entered annotations in ELAN, e.g. relating descriptive annotations to analytic annotations in all three modes and performing relational searches across annotations on different tiers.

Abstract

The lexicons of many sign languages hold large proportions of “frozen” forms, viz. signs that are generally considered to have been formed productively (as classifier predicates), but that have diachronically undergone processes of lexicalisation. Nederlandse Gebarentaal (Sign Language of the Netherlands; henceforth: NGT) also has many of these signs (Van der Kooij 2002, Zwitserlood 2003). In contrast to the general view on “frozen” forms, a few researchers claim that these signs may be formed according to productive sign formation rules, notably Brennan (1990) for BSL, and Meir (2001, 2002) for ISL. Following these claims, I suggest an analysis of “frozen” NGT signs as morphologically complex, using the framework of Distributed Morphology. The signs in question are derived in a similar way as classifier predicates; hence their similar form (but diverging characteristics). I will indicate how and why the structure and use of classifier predicates and “frozen” forms differ. Although my analysis focuses on NGT, it may also be applicable to other sign languages.