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

To understand the origins of interhemispheric differences and commonalities/coupling in human brain wiring, it is crucial to determine how homologous interregional connectivities of the left and right hemispheres are genetically determined and related. To address this, in the present study, we analyzed human twin and pedigree samples with high-quality diffusion magnetic resonance imaging tractography and estimated the heritability and genetic correlation of homologous left and right white matter (WM) connections. The results showed that the heritability of WM connectivity was similar and coupled between the 2 hemispheres and that the degree of overlap in genetic factors underlying homologous WM connectivity (i.e., interhemispheric genetic correlation) varied substantially across the human brain: from complete overlap to complete nonoverlap. Particularly, the heritability was significantly stronger and the chance of interhemispheric complete overlap in genetic factors was higher in subcortical WM connections than in cortical WM connections. In addition, the heritability and interhemispheric genetic correlations were stronger for long-range connections than for short-range connections. These findings highlight the determinants of the genetics underlying WM connectivity and its interhemispheric relationships, and provide insight into genetic basis of WM connectivity asymmetries in both healthy and disease states.

Abstract

Adults who as children were adopted into a different linguistic community retain knowledge of their birth language. The possession (without awareness) of such knowledge is known to facilitate the (re)learning of birth-language speech patterns; this perceptual learning predicts such adults' production success as well, indicating that the retained linguistic knowledge is abstract in nature. Adoptees' acquisition of their adopted language is fast and complete; birth-language mastery disappears rapidly, although this latter process has been little studied. Here, 46 international adoptees from China aged four to 10 years, with Dutch as their new language, plus 47 matched non-adopted Dutch-native controls and 40 matched non-adopted Chinese controls, undertook across a two-week period 10 blocks of training in perceptually identifying Chinese speech contrasts (one segmental, one tonal) which were unlike any Dutch contrasts. Chinese controls easily accomplished all these tasks. The same participants also provided speech production data in an imitation task. In perception, adoptees and Dutch controls scored equivalently poorly at the outset of training; with training, the adoptees significantly improved while the Dutch controls did not. In production, adoptees' imitations both before and after training could be better identified, and received higher goodness ratings, than those of Dutch controls. The perception results confirm that birth-language knowledge is stored and can facilitate re-learning in post-adoption childhood; the production results suggest that although processing of phonological category detail appears to depend on access to the stored knowledge, general articulatory dimensions can at this age also still be remembered, and may facilitate spoken imitation.

Abstract

This paper examines adjectival placement in Griko, an Italian-Greek lan-
guage variety. Guardiano and Stavrou (2019, 2014) have argued that
there is a gap of evidence in the diachrony of adjectives in prenominal
position and in particular, of measuring adjectives. Evidence is presented
in this paper contradicting the aforementioned claims. After considering
the placement of adjectives in Greek and Italian, and their similarities
and differences, the adjectival pattern of Griko is analysed. The analysis
is based mostly on written data from the early 20th century proving the
prenominal position of adjectives and adding to the diachronic schema of
adjectival placement in Griko.

Abstract

This study investigates the difficulty of people with Mild Cognitive Impairment (MCI), mild and moderate Alzheimer’s disease (AD) in the production and comprehension of psychological verbs, as thematic realization may involve both the canonical and non-canonical realization of arguments. More specifically, we aim to examine whether there is a deficit in the mapping of syntactic and semantic representations in psych-predicates regarding Greek-speaking individuals with MCI and AD, and whether the linguistic abilities associated with θ-role assignment decrease as the disease progresses. Moreover, given the decline of cognitive abilities in people with MCI and AD, we explore the effects of components of memory (Semantic, Episodic, and Working Memory) on the assignment of thematic roles in constructions with psychological verbs.

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

The present paper explores how rules are enforced and talked about in everyday life. Drawing on a corpus of board game recordings across European languages, we identify a sequential and praxeological context for rule talk. After a game rule is breached, a participant enforces proper play and then formulates a rule with an impersonal deontic statement (e.g. ‘It’s not allowed to do this’). Impersonal deontic statements express what may or may not be done without tying the obligation to a particular individual. Our analysis shows that such statements are used as part of multi-unit and multi-modal turns where rule talk is accomplished through both grammatical and embodied means. Impersonal deontic statements serve multiple interactional goals: they account for having changed another’s behavior in the moment and at the same time impart knowledge for the future. We refer to this complex action as an “instruction”. The results of this study advance our understanding of rules and rule-following in everyday life, and of how resources of language and the body are combined to enforce and formulate rules.

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

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

Dealing with phonological variations is important for speech processing. This article addresses whether phonological variations introduced by assimilatory processes are compensated for at the pre-lexical or lexical level, and whether the nature of variation and the phonological context influence this process. To this end, Swedish nasal regressive place assimilation was investigated using the mismatch negativity (MMN) component. In nasal regressive assimilation, the coronal nasal assimilates to the place of articulation of a following segment, most clearly with a velar or labial place of articulation, as in utan mej “without me” > [ʉːtam mɛjː]. In a passive auditory oddball paradigm, 15 Swedish speakers were presented with Swedish phrases with attested and unattested phonological variations and contexts for nasal assimilation. Attested variations – a coronal-to-labial change as in utan “without” > [ʉːtam] – were contrasted with unattested variations – a labial-to-coronal change as in utom “except” > ∗[ʉːtɔn] – in appropriate and inappropriate contexts created by mej “me” [mɛjː] and dej “you” [dɛjː]. Given that the MMN amplitude depends on the degree of variation between two stimuli, the MMN responses were expected to indicate to what extent the distance between variants was tolerated by the perceptual system. Since the MMN response reflects not only low-level acoustic processing but also higher-level linguistic processes, the results were predicted to indicate whether listeners process assimilation at the pre-lexical and lexical levels. The results indicated no significant interactions across variations, suggesting that variations in phonological forms do not incur any cost in lexical retrieval; hence such variation is compensated for at the lexical level. However, since the MMN response reached significance only for a labial-to-coronal change in a labial context and for a coronal-to-labial change in a coronal context, the compensation might have been influenced by the nature of variation and the phonological context. It is therefore concluded that while assimilation is compensated for at the lexical level, there is also some influence from pre-lexical processing. The present results reveal not only signal-based perception of phonological units, but also higher-level lexical processing, and are thus able to reconcile the bottom-up and top-down models of speech processing.

Abstract

How listeners handle prosodic cues of linguistic and paralinguistic origin is a central question for spoken communication. In the present EEG study, we addressed this question by examining neural responses to variations in pitch accent (linguistic) and affective (paralinguistic) prosody in Swedish words, using a passive auditory oddball paradigm. The results indicated that changes in pitch accent and affective prosody elicited mismatch negativity (MMN) responses at around 200 ms, confirming the brain’s pre-attentive response to any prosodic modulation. The MMN amplitude was, however, statistically larger to the deviation in affective prosody in comparison to the deviation in pitch accent and affective prosody combined, which is in line with previous research indicating not only a larger MMN response to affective prosody in comparison to neutral prosody but also a smaller MMN response to multidimensional deviants than unidimensional ones. The results, further, showed a significant P3a response to the affective prosody change in comparison to the pitch accent change at around 300 ms, in accordance with previous findings showing an enhanced positive response to emotional stimuli. The present findings provide evidence for distinct neural processing of different prosodic cues, and statistically confirm the intrinsic perceptual and motivational salience of paralinguistic information in spoken communication.