Publications

Abstract

Over 15% of probands in a large cohort of more than 1500 inherited retinal degeneration patients present with a clinical diagnosis of Stargardt disease (STGD1), a recessive form of macular dystrophy caused by biallelic variants in the ABCA4 gene. Participants were clinically examined and underwent either target capture sequencing of the exons and some pathogenic intronic regions of ABCA4, sequencing of the entire ABCA4 gene or whole genome sequencing. ABCA4 c.4539 + 2028C > T, p.[= ,Arg1514Leufs*36] is a pathogenic deep intronic variant that results in a retina-specific 345-nucleotide pseudoexon inclusion. Through analysis of the Irish STGD1 cohort, 25 individuals across 18 pedigrees harbour ABCA4 c.4539 + 2028C > T and another pathogenic variant. This includes, to the best of our knowledge, the only two homozygous patients identified to date. This provides important evidence of variant pathogenicity for this deep intronic variant, highlighting the value of homozygotes for variant interpretation. 15 other heterozygous incidents of this variant in patients have been reported globally, indicating significant enrichment in the Irish population. We provide detailed genetic and clinical characterization of these patients, illustrating that ABCA4 c.4539 + 2028C > T is a variant of mild to intermediate severity. These results have important implications for unresolved STGD1 patients globally with approximately 10% of the population in some western countries claiming Irish heritage. This study exemplifies that detection and characterization of founder variants is a diagnostic imperative.

Abstract

In this paper, we report an experiment on the naming of household containers in Dutch and Icelandic carried out as part of the Evolution of Semantic Systems project (EoSS; Majid et al., 2011). This naming experiment allows us to support and elaborate on a hypothesis by Malt et al. (2003) that productive morphology in the naming domain can have an influence on boundary placement within the extensional space. Specifically, we demonstrate that the Dutch diminutive -(t)je favours a cut between small items versus others, whereas Icelandic, which does not use the diminutive in this domain, favours a cut between large items and others. This is not a typological effect, as Dutch and Icelandic are both Germanic languages and both have diminutive morphology available in principle. We find no evidence that the diminutive produces a proliferation of terms and/or fine-grained nesting within the extensional domain. Rather, the Dutch diminutive favours a more even distribution of terms across the space whereas Icelandic favours broad inclusive terms with a number of narrower specialist terms. Further, the extensional space defined by the diminutive is not associated with its own clear prototypical exemplar. Using evidence from compounding and modification, we also consider which semantic features are prominent in differentiating categories within the domain. By far the most prominent in both languages is the inferred contents of the container. Other than contents, however, the languages differ in the range and prominence of features such as intended usage or material of composition. Our results demonstrate that in order to understand the processes that produce semantic divisions of basic object classes, we should consider fine-grained analyses of closely related languages alongside analyses of typologically different languages.

Abstract

Even before it became a common place to assume that “the Eskimo have a hundred words for snow” the languages of hunting and gathering people have played an important role in debates about linguistic relativity concerning geographical ontologies. Evidence from languages of hunter-gatherers has been used in radical relativist challenges to the overall notion of a comparative typology of generic natural forms and landscapes as terms of reference. It has been invoked to emphasize a personalized relationship between humans and the non-human world. It is against this background that this contribution discusses the landscape terminology of ≠Akhoe Hai//om, a Khoisan language spoken by “Bushmen” in Namibia. Landscape vocabulary is ubiquitous in ≠Akhoe Hai//om due to the fact that the landscape plays a critical role in directionals and other forms of “topographical gossip” and due to merges between landscape and group terminology. This system of landscape-cum-group terminology is outlined and related to the use of place names in the area.

Abstract

Understanding language always occurs within a situational context and, therefore, often implies combining streams of information from different domains and modalities. One such combination is that of spoken language and visual information, which are perceived together in a variety of ways during everyday communication. Here we investigate whether and how words and pictures differ in terms of their neural correlates when they are integrated into a previously built-up sentence context. This is assessed in two experiments looking at the time course (measuring event-related potentials, ERPs) and the locus (using functional magnetic resonance imaging, fMRI) of this integration process. We manipulated the ease of semantic integration of word and/or picture to a previous sentence context to increase the semantic load of processing. In the ERP study, an increased semantic load led to an N400 effect which was similar for pictures and words in terms of latency and amplitude. In the fMRI study, we found overlapping activations to both picture and word integration in the left inferior frontal cortex. Specific activations for the integration of a word were observed in the left superior temporal cortex. We conclude that despite obvious differences in representational format, semantic information coming from pictures and words is integrated into a sentence context in similar ways in the brain. This study adds to the growing insight that the language system incorporates (semantic) information coming from linguistic and extralinguistic domains with the same neural time course and by recruitment of overlapping brain areas.

Abstract

If motor imagery uses neural structures involved in action execution, then the neural correlates of imagining an action should differ between individuals who tend to execute the action differently. Here we report fMRI data showing that motor imagery is influenced by the way people habitually perform motor actions with their particular bodies; that is, motor imagery is ‘body-specific’ (Casasanto, 2009). During mental imagery for complex hand actions, activation of cortical areas involved in motor planning and execution was left-lateralized in right-handers but right-lateralized in left-handers. We conclude that motor imagery involves the generation of an action plan that is grounded in the participant’s motor habits, not just an abstract representation at the level of the action’s goal. People with different patterns of motor experience form correspondingly different neurocognitive representations of imagined actions.

Abstract

Should cognitive scientists and neuroscientists care about Dostoyevsky? Engaging with fiction is a natural and rich behavior, providing a unique window onto the mind and brain, particularly for mental simulation, emotion, empathy, and immersion. With advances in analysis techniques, it is time that cognitive scientists and neuroscientists embrace literature and fiction.

Abstract

Several studies indicate that both posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG) and left inferior frontal gyrus (LIFG) are involved in integrating information from different modalities. Here we investigated the respective roles of these two areas in integration of action and language information. We exploited the fact that the semantic relationship between language and different forms of action (i.e. co-speech gestures and pantomimes) is radically different. Speech and co-speech gestures are always produced together, and gestures are not unambiguously understood without speech. On the contrary, pantomimes are not necessarily produced together with speech and can be easily understood without speech. We presented speech together with these two types of communicative hand actions in matching or mismatching combinations to manipulate semantic integration load. Left and right pSTS/MTG were only involved in semantic integration of speech and pantomimes. Left IFG on the other hand was involved in integration of speech and co-speech gestures as well as of speech and pantomimes. Effective connectivity analyses showed that depending upon the semantic relationship between language and action, LIFG modulates activation levels in left pSTS.

This suggests that integration in pSTS/MTG involves the matching of two input streams for which there is a relatively stable common object representation, whereas integration in LIFG is better characterized as the on-line construction of a new and unified representation of the input streams. In conclusion, pSTS/MTG and LIFG are differentially involved in multimodal integration, crucially depending upon the semantic relationship between the input streams.

Abstract

Language is often perceived together with visual information. This raises the question on how the brain integrates information conveyed in visual and/or linguistic format during spoken language comprehension. In this study we investigated the dynamics of semantic integration of visual and linguistic information by means of time-frequency analysis of the EEG signal. A modified version of the N400 paradigm with either a word or a picture of an object being semantically incongruous with respect to the preceding sentence context was employed. Event-Related Potential (ERP) analysis showed qualitatively similar N400 effects for integration of either word or picture. Time-frequency analysis revealed early specific decreases in alpha and gamma band power for linguistic and visual information respectively. We argue that these reflect a rapid context-based analysis of acoustic (word) or visual (picture) form information. We conclude that although full semantic integration of linguistic and visual information occurs through a common mechanism, early differences in oscillations in specific frequency bands reflect the format of the incoming information and, importantly, an early context-based detection of its congruity with respect to the preceding language context

Abstract

It has been argued that we map observed actions onto our own motor system. Here we added to this issue by investigating whether hand preference influences the neural correlates of action observation of simple, essentially meaningless hand actions. Such an influence would argue for an intricate neural coupling between action production and action observation, which goes beyond effects of motor repertoire or explicit motor training, as has been suggested before. Indeed, parts of the human motor system exhibited a close coupling between action production and action observation. Ventral premotor and inferior and superior parietal cortices showed differential activation for left- and right-handers that was similar during action production as well as during action observation. This suggests that mapping observed actions onto the observer's own motor system is a core feature of action observation - at least for actions that do not have a clear goal or meaning. Basic differences in the way we act upon the world are not only reflected in neural correlates of action production, but can also influence the brain basis of action observation.

Abstract

The notion of prediction is studied in cognitive neuroscience with increasing intensity. We investigated the neural basis of 2 distinct aspects of word prediction, derived from information theory, during story comprehension. We assessed the effect of entropy of next-word probability distributions as well as surprisal. A computational model determined entropy and surprisal for each word in 3 literary stories. Twenty-four healthy participants listened to the same 3 stories while their brain activation was measured using fMRI. Reversed speech fragments were presented as a control condition. Brain areas sensitive to entropy were left ventral premotor cortex, left middle frontal gyrus, right inferior frontal gyrus, left inferior parietal lobule, and left supplementary motor area. Areas sensitive to surprisal were left inferior temporal sulcus (“visual word form area”), bilateral superior temporal gyrus, right amygdala, bilateral anterior temporal poles, and right inferior frontal sulcus. We conclude that prediction during language comprehension can occur at several levels of processing, including at the level of word form. Our study exemplifies the power of combining computational linguistics with cognitive neuroscience, and additionally underlines the feasibility of studying continuous spoken language materials with fMRI.

Abstract

Over recent years small submicroscopic DNA copy-number variants (CNVs) have been highlighted as an important source of variation in the human genome, human phenotypic diversity and disease susceptibility. Consequently, there is a pressing need for the development of methods that allow the efficient, accurate and cheap measurement of genomic copy number polymorphisms in clinical cohorts. We have developed a simple competitive PCR based method to determine DNA copy number which uses the entire genome of a single chimpanzee as a competitor thus eliminating the requirement for competitive sequences to be synthesized for each assay. This results in the requirement for only a single reference sample for all assays and dramatically increases the potential for large numbers of loci to be analysed in multiplex. In this study we establish proof of concept by accurately detecting previously characterized mutations at the PARK2 locus and then demonstrating the potential of quantitative interspecies competitive PCR (qicPCR) to accurately genotype CNVs in association studies by analysing chromosome 22q11 deletions in a sample of previously characterized patients and normal controls.

Abstract

Impaired emotion regulation may underlie exaggerated emotional reactivity in patients with obsessive compulsive disorder (OCD), yet instructed emotion regulation has never been studied in the disorder. METHOD: This study aimed to assess the neural correlates of emotion processing and regulation in 43 medication-free OCD patients and 38 matched healthy controls, and additionally test if these can be modulated by stimulatory (patients) and inhibitory (controls) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (dlPFC). Participants performed an emotion regulation task during functional magnetic resonance imaging before and after a single session of randomly assigned real or sham rTMS. Effect of group and rTMS were assessed on self-reported distress ratings and brain activity in frontal-limbic regions of interest. RESULTS: Patients had higher distress ratings than controls during emotion provocation, but similar rates of distress reduction after voluntary emotion regulation. OCD patients compared with controls showed altered amygdala responsiveness during symptom provocation and diminished left dlPFC activity and frontal-amygdala connectivity during emotion regulation. Real v. sham dlPFC stimulation differentially modulated frontal-amygdala connectivity during emotion regulation in OCD patients. CONCLUSIONS: We propose that the increased emotional reactivity in OCD may be due to a deficit in emotion regulation caused by a failure of cognitive control exerted by the dorsal frontal cortex. Modulatory rTMS over the left dlPFC may influence automatic emotion regulation capabilities by influencing frontal-limbic connectivity.

Abstract

In three cross-modal priming experiments we asked whether adaptation to a foreign-accented speaker is automatic, and whether adaptation can be seen after a long delay between initial exposure and test. Dutch listeners were exposed to a Hebrew-accented Dutch speaker with two types of Dutch words: those that contained [ɪ] (globally accented words), and those in which the Dutch [i] was shortened to [ɪ] (specific accent marker words). Experiment 1, which served as a baseline, showed that native Dutch participants showed facilitatory priming for globally accented, but not specific accent, words. In experiment 2, participants performed a 3.5-minute phoneme monitoring task, and were tested on their comprehension of the accented speaker 24 hours later using the same cross-modal priming task as in experiment 1. During the phoneme monitoring task, listeners were asked to detect a consonant that was not strongly accented. In experiment 3, the delay between exposure and test was extended to 1 week. Listeners in experiments 2 and 3 showed facilitatory priming for both globally accented and specific accent marker words. Together, these results show that adaptation to a foreign-accented speaker can be rapid and automatic, and can be observed after a prolonged delay in testing.

Abstract

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E−8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E−07), TOX (rs7823467, P = 3.47E−07) and LINC00340 (rs12212674, P = 1.49E−06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = −0.59, P = 2.10E−04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

Abstract

In het onderwijs wordt aangenomen dat hardop en stillezen dezelfde processen zijn. In dit onderzoek wordt gekeken naar het verschil tussen hardop en stillezen wat betreft leessnelheid en tekstbegrip bij 90 kinderen uit groep 4. Ook wordt de invloed van de cognitieve vaardigheden fonologisch bewustzijn, benoemsnelheid en visuele aandachtsspanne op de verschillende leesmodi onderzocht. De participanten lazen stil sneller, maar begrepen de tekst beter hardop. De cognitieve vaardigheden correleerden met hardop en stillezen wat betreft leessnelheid, maar hingen in beide leesmodi niet samen met tekstbegrip. Hoewel hardop en stillezen samenhangen, onderstrepen deze bevindingen dat het verschillende leesmodi zijn.

Abstract

s Metrics Comments Related Content Abstract Introduction Materials and Methods Results Discussion Supporting Information Acknowledgments Author Contributions References Reader Comments (0) Media Coverage Figures Abstract Copy number variants (CNVs) at the Breakpoint 1 to Breakpoint 2 region at 15q11.2 (BP1-2) are associated with language-related difficulties and increased risk for developmental disorders in which language is compromised. Towards underlying mechanisms, we investigated relationships between single nucleotide polymorphisms (SNPs) across the region and quantitative measures of human brain structure obtained by magnetic resonance imaging of healthy subjects. We report an association between rs4778298, a common variant at CYFIP1, and inter-individual variation in surface area across the left supramarginal gyrus (lh.SMG), a cortical structure implicated in speech and language in independent discovery (n = 100) and validation cohorts (n = 2621). In silico analyses determined that this same variant, and others nearby, is also associated with differences in levels of CYFIP1 mRNA in human brain. One of these nearby polymorphisms is predicted to disrupt a consensus binding site for FOXP2, a transcription factor implicated in speech and language. Consistent with a model where FOXP2 regulates CYFIP1 levels and in turn influences lh.SMG surface area, analysis of publically available expression data identified a relationship between expression of FOXP2 and CYFIP1 mRNA in human brain. We propose that altered CYFIP1 dosage, through aberrant patterning of the lh.SMG, may contribute to language-related difficulties associated with BP1-2 CNVs. More generally, this approach may be useful in clarifying the contribution of individual genes at CNV risk loci.

Abstract

Diffusion tensor imaging (DTI) and a longitudinal language learning approach were applied to investigate the relationship between the achieved second language (L2) proficiency during L2 learning and the reorganization of structural connectivity between core language areas. Language proficiency tests and DTI scans were obtained from German students before and after they completed an intensive 6-week course of the Dutch language. In the initial learning stage, with increasing L2 proficiency, the hemispheric dominance of the BA6-temporal pathway (mainly along the arcuate fasciculus) shifted from the left to the right hemisphere. With further increased proficiency, however, lateralization dominance was again found in the left BA6-temporal pathway. This result is consistent with reports in the literature that imply a stronger involvement of the right hemisphere in L2-processing especially for less proficient L2-speakers. This is the first time that a L2-proficiency-dependent laterality shift in structural connectivity of language pathways during L2 acquisition has been observed to shift from left to right, and back to left hemisphere dominance with increasing L2-proficiency. We additionally find that changes in fractional anisotropy values after the course are related to the time elapsed between the two scans. The results suggest that structural connectivity in (at least part of) the perisylvian language network may be subject to fast dynamic changes following language learning

Abstract

In the present study, event-related brain potentials (ERP) were recorded to investigate the role of pitch accent and lexical tone in spoken discourse comprehension. Chinese was used as material to explore the potential difference in the nature and time course of brain responses to sentence meaning as indicated by pitch accent and to lexical meaning as indicated by tone. In both cases, the pitch contour of critical words was varied. The results showed that both inconsistent pitch accent and inconsistent lexical tone yielded N400 effects, and there was no interaction between them. The negativity evoked by inconsistent pitch accent had the some topography as that evoked by inconsistent lexical tone violation, with a maximum over central–parietal electrodes. Furthermore, the effect for the combined violations was the sum of effects for pure pitch accent and pure lexical tone violation. However, the effect for the lexical tone violation appeared approximately 90 ms earlier than the effect of the pitch accent violation. It is suggested that there might be a correspondence between the neural mechanism underlying pitch accent and lexical meaning processing in context. They both reflect the integration of the current information into a discourse context, independent of whether the current information was sentence meaning indicated by accentuation, or lexical meaning indicated by tone. In addition, lexical meaning was processed earlier than sentence meaning conveyed by pitch accent during spoken language processing.

Abstract

Faces contain a variety of information such as one’s identity and expression. One prevailing model suggests a functional division of labor in processing faces that different aspects of facial information are processed in anatomically separated and functionally encapsulated brain regions. Here, we demonstrate that facial identity and expression can be processed in the same region, yet with different neural coding strategies. To this end, we employed functional magnetic resonance imaging to examine two types of coding schemes, namely univariate activity and multivariate pattern, in the posterior superior temporal cortex (pSTS) - a face-selective region that is traditionally viewed as being specialized for processing facial expression. With the individual difference approach, we found that participants with higher overall face selectivity in the right pSTS were better at differentiating facial expressions measured outside of the scanner. In contrast, individuals whose spatial pattern for faces in the right pSTS was less similar to that for objects were more accurate in identifying previously presented faces. The double dissociation of behavioral relevance between overall neural activity and spatial neural pattern suggests that the functional-division-of-labor model on face processing is over-simplified, and that coding strategies shall be incorporated in a revised model.

Abstract

Dual-process models of the mind, as well as the relation between analytic thinking and religious belief, have aroused interest in recent years. However, few studies have examined this relation experimentally. We predicted that religious belief might be one of the causes of prejudice, while analytic thinking reduces both. The first experiment replicated, in a mostly Muslim sample, past research showing that analytic thinking promotes religious disbelief. The second experiment investigated the effect of Muslim religious priming and analytic priming on prejudice and showed that, although the former significantly increased the total prejudice score, the latter had an effect only on antigay prejudice. Thus, the findings partially support our proposed pattern of relationships in that analytic thinking might be one of the cognitive factors that prevents prejudice, whereas religious belief might be the one that increases it.

Abstract

Some problems of resource distribution can be solved on equal terms only by taking turns. We presented such a problem to 168 pairs of 5- to 10-year-old children from one Western and two non-Western societies (German, Samburu, Kikuyu). Almost all German pairs solved the problem by taking turns immediately, resulting in an equal distribution of resources throughout the game. In the other groups, one child usually monopolized the resource in Trial 1 and sometimes let the partner monopolize it in Trial 2, resulting in an equal distribution in only half the dyads. These results suggest that turn-taking is not a natural strategy uniformly across human cultures, but rather that different cultures use it to different degrees and in different contexts.

Abstract

Right hand responds faster than left hand when shown larger numbers and vice-versa when shown smaller numbers (the SNARC effect). Accumulating evidence suggests that the SNARC effect may not be exclusive for numbers and can be extended to other ordinal sequences (e.g., months or letters in the alphabet) as well. In this study, we tested the SNARC effect with a non-numerically ordered sequence: the Chinese notations for the color spectrum (Red, Orange, Yellow, Green, Blue, Indigo, and Violet). Chinese color word sequence reserves relatively weak ordinal information, because each element color in the sequence normally appears in non-sequential contexts, making it ideal to test the spatial organization of sequential information that was stored in the long-term memory. This study found a reliable SNARC-like effect for Chinese color words (deciding whether the presented color word was before or after the reference color word “green”), suggesting that, without access to any quantitative information or exposure to any previous training, ordinal representation can still activate a sense of space. The results support that weak ordinal information without quantitative magnitude encoded in the long-term memory can activate spatial representation in a comparison task

Abstract

In face-to-face communication, multimodal cues such as prosody, gestures, and mouth movements can play a crucial role in language processing. While several studies have addressed how these cues contribute to native (L1) language processing, their impact on non-native (L2) comprehension is largely unknown. Comprehension of naturalistic language by L2 comprehenders may be supported by the presence of (at least some) multimodal cues, as these provide correlated and convergent information that may aid linguistic processing. However, it is also the case that multimodal cues may be less used by L2 comprehenders because linguistic processing is more demanding than for L1 comprehenders, leaving more limited resources for the processing of multimodal cues. In this study, we investigated how L2 comprehenders use multimodal cues in naturalistic stimuli (while participants watched videos of a speaker), as measured by electrophysiological responses (N400) to words, and whether there are differences between L1 and L2 comprehenders. We found that prosody, gestures, and informative mouth movements each reduced the N400 in L2, indexing easier comprehension. Nevertheless, L2 participants showed weaker effects for each cue compared to L1 comprehenders, with the exception of meaningful gestures and informative mouth movements. These results show that L2 comprehenders focus on specific multimodal cues – meaningful gestures that support meaningful interpretation and mouth movements that enhance the acoustic signal – while using multimodal cues to a lesser extent than L1 comprehenders overall.

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

Background: Developmental language disorder (DLD) is a condition that significantly affects children's achievement but has been understudied. We aim to estimate the prevalence of DLD in Shanghai, compare the co-occurrence of difficulties between children with DLD and those with typical development (TD), and investigate the early risk factors for DLD.

Methods: We estimated DLD prevalence using data from a population-based survey with a cluster random sampling design in Shanghai, China. A subsample of children (aged 5-6 years) received an onsite evaluation, and each child was categorized as TD or DLD. The proportions of children with socio-emotional behavior (SEB) difficulties, low non-verbal IQ (NVIQ), and poor school readiness were calculated among children with TD and DLD. We used multiple imputation to address the missing values of risk factors. Univariate and multivariate regression models adjusted with sampling weights were used to estimate the correlation of each risk factor with DLD.

Findings: Of 1082 children who were approached for the onsite evaluation, 974 (90.0%) completed the language ability assessments, of whom 74 met the criteria for DLD, resulting in a prevalence of 8.5% (95% CI 6.3-11.5) when adjusted with sampling weights. Compared with TD children, children with DLD had higher rates of concurrent difficulties, including SEB (total difficulties score at-risk: 156 [17.3%] of 900 TD vs. 28 [37.8%] of 74 DLD, p < 0.0001), low NVIQ (3 [0.3%] of 900 TD vs. 8 [10.8%] of 74 DLD, p < 0.0001), and poor school readiness (71 [7.9%] of 900 TD vs. 13 [17.6%] of 74 DLD, p = 0.0040). After accounting for all other risk factors, a higher risk of DLD was associated with a lack of parent-child interaction diversity (adjusted odds ratio [aOR] = 3.08, 95% CI = 1.29-7.37; p = 0.012) and lower kindergarten levels (compared to demonstration and first level: third level (aOR = 6.15, 95% CI = 1.92-19.63; p = 0.0020)).

Interpretation: The prevalence of DLD and its co-occurrence with other difficulties suggest the need for further attention. Family and kindergarten factors were found to contribute to DLD, suggesting that multi-sector coordinated efforts are needed to better identify and serve DLD populations at home, in schools, and in clinical settings.

Funding: The study was supported by Shanghai Municipal Education Commission (No. 2022you1-2, D1502), the Innovative Research Team of High-level Local Universities in Shanghai (No. SHSMU-ZDCX20211900), Shanghai Municipal Health Commission (No.GWV-10.1-XK07), and the National Key Research and Development Program of China (No. 2022YFC2705201).

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

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

Brain oscillations are prevalent in all species and are involved in numerous perceptual operations. α oscillations are thought to facilitate processing through the inhibition of task-irrelevant networks, while β oscillations are linked to the putative reactivation of content representations. Can the proposed functional role of α and β oscillations be generalized from low-level operations to higher-level cognitive processes? Here we address this question focusing on naturalistic spoken language comprehension. Twenty-two (18 female) Dutch native speakers listened to stories in Dutch and French while MEG was recorded. We used dependency parsing to identify three dependency states at each word: the number of (1) newly opened dependencies, (2) dependencies that remained open, and (3) resolved dependencies. We then constructed forward models to predict α and β power from the dependency features. Results showed that dependency features predict α and β power in language-related regions beyond low-level linguistic features. Left temporal, fundamental language regions are involved in language comprehension in α, while frontal and parietal, higher-order language regions, and motor regions are involved in β. Critically, α- and β-band dynamics seem to subserve language comprehension tapping into syntactic structure building and semantic composition by providing low-level mechanistic operations for inhibition and reactivation processes. Because of the temporal similarity of the α-β responses, their potential functional dissociation remains to be elucidated. Overall, this study sheds light on the role of α and β oscillations during naturalistic spoken language comprehension, providing evidence for the generalizability of these dynamics from perceptual to complex linguistic processes.

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

Research into the neural foundation of perception asserts a model where top-down predictions modulate the bottom-up processing of sensory input. Despite becoming increasingly influential in cognitive neuroscience, the precise account of this predictive coding framework remains debated. In this study, we aim to contribute to this debate by investigating how predictions about prosody facilitate speech perception, and to shed light especially on lexical access influenced by simultaneous predictions in different domains, inter alia, prosodic and semantic. Using a passive auditory oddball paradigm, we examined neural responses to prosodic changes, leading to a semantic change as in Dutch nouns canon [ˈkaːnɔn] ‘cannon’ vs kanon [kaːˈnɔn] ‘canon’, and used acoustically identical pseudowords as controls. Results from twenty-eight native speakers of Dutch (age range 18–32 years) indicated an enhanced P50/N100 complex to prosodic change in pseudowords as well as an MMN response to both words and pseudowords. The enhanced P50/N100 response to pseudowords is claimed to indicate that all relevant auditory information is still processed by the brain, whereas the reduced response to words might reflect the suppression of information that has already been encoded. The MMN response to pseudowords and words, on the other hand, is best justified by the unification of previously established prosodic representations with sensory and semantic input respectively. This pattern of results is in line with the predictive coding framework acting on multiple levels and is of crucial importance to indicate that predictions about linguistic prosodic information are utilized by the brain as early as 50 ms.

Abstract

Language is used in communicative contexts to identify and successfully transmit new information that should be later remembered. In three studies, we used question–answer pairs, a naturalistic device for focusing information, to examine how properties of conversations inform later item memory. In Experiment 1, participants viewed three pictures while listening to a recorded question–answer exchange between two people about the locations of two of the displayed pictures. In a memory recognition test conducted online a day later, participants recognized the names of pictures that served as answers more accurately than the names of pictures that appeared as questions. This suggests that this type of focus indeed boosts memory. In Experiment 2, participants listened to the same items embedded in declarative sentences. There was a reduced memory benefit for the second item, confirming the role of linguistic focus on later memory beyond a simple serial-position effect. In Experiment 3, two participants asked and answered the same questions about objects in a dialogue. Here, answers continued to receive a memory benefit, and this focus effect was accentuated by language production such that information-seekers remembered the answers to their questions better than information-givers remembered the questions they had been asked. Combined, these studies show how people’s memory for conversation is modulated by the referential status of the items mentioned and by the speaker’s roles of the conversation participants.

Abstract

The Corpus NGT