Publications

Abstract

Neurodevelopmental disorders have a strong genetic component, but despite widespread efforts, the specific genetic factors underlying these disorders remain undefined for a large proportion of affected individuals. Given the accessibility of exome-sequencing, this problem has thus far been addressed from a protein-centric standpoint; however, protein-coding regions only make up ∼1-2% of the human genome. With the advent of whole-genome sequencing we are in the midst of a paradigm shift as it is now possible to interrogate the entire sequence of the human genome (coding and non-coding) to fill in the missing heritability of complex disorders. These new technologies bring new challenges, as the number of non-coding variants identified per individual can be overwhelming, making it prudent to focus on non-coding regions of known function, for which the effects of variation can be predicted and directly tested to assess pathogenicity. The 3’UTRome is a region of the non-coding genome that perfectly fulfils these criteria and is of high interest when searching for pathogenic variation related to complex neurodevelopmental disorders. Herein, we review the regulatory roles of the 3’UTRome as binding sites for microRNAs, RNA binding proteins or during alternative polyadenylation. We detail existing evidence that these regions contribute to neurodevelopmental disorders and outline strategies for identification and validation of novel putatively pathogenic variation in these regions. This evidence suggests that studying the 3’UTRome will lead to the identification of new risk factors, new candidate disease genes and a better understanding of the molecular mechanisms contributing to NDDs.

Abstract

Natural, spontaneous speech (and even quite careful speech) often shows extreme reduction in many speech segments, even resulting in apparent deletion of consonants. Where the flap ([(sic)]) allophone of /t/ and /d/ is expected in American English, one frequently sees an approximant-like or even vocalic pattern, rather than a clear flap. Still, the /t/ or /d/ is usually perceived, suggesting the acoustic characteristics of a reduced flap are sufficient for perception of a consonant. This paper identifies several acoustic characteristics of reduced flaps based on previous acoustic research (size of intensity dip, consonant duration, and F4 valley) and presents phonetic identification data for continua that manipulate these acoustic characteristics of reduction. The results indicate that the most obvious types of acoustic variability seen in natural flaps do affect listeners' percept of a consonant, but not sufficiently to completely account for the percept. Listeners are affected by the acoustic characteristics of consonant reduction, but they are also very skilled at evaluating variability along the acoustic dimensions that realize reduction.

Abstract

Words which are expected to contain the same surface string of segments may, under identical prosodic circumstances, sometimes be realized with slight differences in duration. Some researchers have attributed such effects to differences in the words’ underlying forms (incomplete neutralization), while others have suggested orthographic influence and extremely careful speech as the cause. In this paper, we demonstrate such sub-phonemic durational differences in Dutch, a language which some past research has found not to have such effects. Past literature has also shown that listeners can often make use of incomplete neutralization to distinguish apparent homophones. We extend perceptual investigations of this topic, and show that listeners can perceive even durational differences which are not consistently observed in production. We further show that a difference which is primarily orthographic rather than underlying can also create such durational differences. We conclude that a wide variety of factors, in addition to underlying form, can induce speakers to produce slight durational differences which listeners can also use in perception.

Abstract

This article addresses revitalization of a dormant language whose prospective speakers live in scattered geographical areas. In comparison to increasing the usage of an endangered language, revitalizing a dormant language (one with no living speakers) requires different methods to gain knowledge of the language. Language teaching for a dormant language with a scattered community presents different problems from other teaching situations. In this article, we discuss the types of tasks that must be accomplished for dormant-language revitalization, with particular focus on development of teaching materials. We also address the role of computer technologies, arguing that each use of technology should be evaluated for how effectively it increases fluency. We discuss methods for achieving semi-fluency for the first new speakers of a dormant language, and for spreading the language through the community.

Abstract

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

Abstract

The establishment of a reliable model for the study of Purkinje cells in vitro is of particular importance, given their central role in cerebellar function and pathology. Recent advances in induced pluripotent stem cell (iPSC) technology offer the opportunity to generate multiple neuronal subtypes for study in vitro. However, to date, only a handful of studies have generated Purkinje cells from human pluripotent stem cells, with most of these protocols proving challenging to reproduce. Here, we describe a simplified method for the reproducible generation of Purkinje cells from human iPSCs. After 21 days of treatment with factors selected to mimic the self-inductive properties of the isthmic organiser—insulin, fibroblast growth factor 2 (FGF2), and the transforming growth factor β (TGFβ)-receptor blocker SB431542—hiPSCs could be induced to form En1-positive cerebellar progenitors at efficiencies of up to 90%. By day 35 of differentiation, subpopulations of cells representative of the two cerebellar germinal zones, the rhombic lip (Atoh1-positive) and ventricular zone (Ptf1a-positive), could be identified, with the latter giving rise to cells positive for Purkinje cell progenitor-specific markers, including Lhx5, Kirrel2, Olig2 and Skor2. Further maturation was observed following dissociation and co-culture of these cerebellar progenitors with mouse cerebellar cells, with 10% of human cells staining positive for the Purkinje cell marker calbindin by day 70 of differentiation. This protocol, which incorporates modifications designed to enhance cell survival and maturation and improve the ease of handling, should serve to make existing models more accessible, in order to enable future advances in the field.

Abstract

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

Abstract

Recent studies using phoneme detection tasks have shown that spoken-language processing is neither facilitated nor interfered with by optional assimilation, but is inhibited by violation of obligatory assimilation. Interpretation of these results depends on an assessment of their generality, specifically, whether they also obtain when listeners are processing nonnative language. Two separate experiments are presented in which native listeners of German and native listeners of Dutch had to detect a target fricative in legal monosyllabic Dutch nonwords. All of the nonwords were correct realisations in standard Dutch. For German listeners, however, half of the nonwords contained phoneme strings which violate the German fricative assimilation rule. Whereas the Dutch listeners showed no significant effects, German listeners detected the target fricative faster when the German fricative assimilation was violated than when no violation occurred. The results might suggest that violation of assimilation rules does not have to make processing more difficult per se.

Abstract

A longstanding question in bilingualism is whether syntactic information is shared between the two language processing systems. We used an fMRI repetition suppression paradigm to investigate syntactic priming in reading comprehension in German–English late-acquisition bilinguals. In comparison to conventional subtraction analyses in bilingual experiments, repetition suppression has the advantage of being able to detect neuronal populations that are sensitive to properties that are shared by consecutive stimuli. In this study, we manipulated the syntactic structure between prime and target sentences. A sentence with a passive sentence structure in English was preceded either by a passive or by an active sentence in English or German. We looked for repetition suppression effects in left inferior frontal, left precentral and left middle temporal regions of interest. These regions were defined by a contrast of all non-target sentences in German and English versus the baseline of sentence-format consonant strings. We found decreases in activity (repetition suppression effects) in these regions of interest following the repetition of syntactic structure from the first to the second language and within the second language.
Moreover, a separate behavioural experiment using a word-by-word reading paradigm similar to the fMRI experiment showed faster reading times for primed compared to unprimed English target sentences regardless of whether they were preceded by an English or a German sentence of the same structure.
We conclude that there is interaction between the language processing systems and that at least some syntactic information is shared between a bilingual's languages with similar syntactic structures.

Abstract

Two eye-tracking experiments examined linguistic gender effects in non-native spoken-word recognition. French participants, who knew German well, followed spoken instructions in German to click on pictures on a computer screen (e.g., Wo befindet sich die Perle, “where is the pearl”) while their eye movements were monitored. The name of the target picture was preceded by a gender-marked article in the instructions. When a target and a competitor picture (with phonologically similar names) were of the same gender in both German and French, French participants fixated competitor pictures more than unrelated pictures. However, when target and competitor were of the same gender in German but of different gender in French, early fixations to the competitor picture were reduced. Competitor activation in the non-native language was seemingly constrained by native gender information. German listeners showed no such viewing time difference. The results speak against a form-based account of the linguistic gender effect. They rather support the notion that the effect originates from the grammatical level of language processing.

Abstract

Lexical recognition is typically slower in L2 than in L1. Part of the difficulty comes from a not precise enough processing of L2 phonemes. Consequently, L2 listeners fail to eliminate candidate words that L1 listeners can exclude from competing for recognition. For instance, the inability to distinguish /r/ from /l/ in rocket and locker makes for Japanese listeners both words possible candidates when hearing their onset (e.g., Cutler, Weber, and Otake, 2006). The L2 disadvantage can, however, be dispelled: For L2 listeners, but not L1 listeners, L2 speech from a non-native talker with the same language background is known to be as intelligible as L2 speech from a native talker (e.g., Bent and Bradlow, 2003). A reason for this may be that L2 listeners have ample experience with segmental deviations that are characteristic for their own accent. On this account, only phonemic deviations that are typical for the listeners’ own accent will cause spurious lexical activation in L2 listening (e.g., English magic pronounced as megic for Dutch listeners). In this talk, I will present evidence from cross-modal priming studies with a variety of L2 listener groups, showing how the processing of phonemic deviations is accent-specific but withstands fine phonetic differences.

Abstract

In this paper, we present empirical data from a corpus study on the linear order of subjects and objects in German main clauses. The aim was to establish the validity of three well-known ordering constraints: given complements tend to occur before new complements, definite before indefinite, and pronoun before full noun phrase complements. Frequencies of occurrences were derived for subject-first and object-first sentences from the German Negra corpus. While all three constraints held on subject-first sentences, results for object-first sentences varied. Our findings suggest an influence of grammatical functions on the ordering of verb complements.

Abstract

Reports of an advantage of bilingualism on brain structure in young adult participants
are inconsistent. Abutalebi et al. (2012) reported more efficient monitoring of conflict during the
Flanker task in young bilinguals compared to young monolingual speakers. The present study
compared young adult (mean age = 24) Cantonese-English bilinguals in Hong Kong and young
adult monolingual speakers. We expected (a) differences in metabolites in neural tissue to result
from bilingual experience, as measured by 1H-MRS at 3T, (b) correlations between metabolic
levels and Flanker conflict and interference effects (c) different associations in bilingual and
monolingual speakers. We found evidence of metabolic differences in the ACC due to bilingualism,
specifically in metabolites Cho, Cr, Glx and NAA. However, we found no significant correlations
between metabolic levels and conflict and interference effects and no significant evidence of
differential relationships between bilingual and monolingual speakers. Furthermore, we found no
evidence of significant differences in the mean size of conflict and interference effects between
groups i.e. no bilingual advantage. Lower levels of Cho, Cr, Glx and NAA in bilingual adults
compared to monolingual adults suggest that the brains of bilinguals develop greater adaptive
control during conflict monitoring because of their extensive bilingual experience.

Abstract

Many explanations of the difficulties associated with interpreting object relative clauses appeal to the demands that object relatives make on working memory. MacDonald and Christiansen [MacDonald, M. C., & Christiansen, M. H. (2002). Reassessing working memory: Comment on Just and Carpenter (1992) and Waters and Caplan (1996). Psychological Review, 109, 35-54] pointed to variations in reading experience as a source of differences, arguing that the unique word order of object relatives makes their processing more difficult and more sensitive to the effects of previous experience than the processing of subject relatives. This hypothesis was tested in a large-scale study manipulating reading experiences of adults over several weeks. The group receiving relative clause experience increased reading speeds for object relatives more than for subject relatives, whereas a control experience group did not. The reading time data were compared to performance of a computational model given different amounts of experience. The results support claims for experience-based individual differences and an important role for statistical learning in sentence comprehension processes.

Abstract

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

Abstract

Field data are drawn from a particular speech community at a certain place and time. The intent of this survey is to enrich understanding of the various socio-cultural contexts in which linguistic and “cognitive” data may have been collected, so that we can explore the role which societal, cultural and contextual factors may play in this material. The questionnaire gives guidelines concerning types of ethnographic information that are important to cross-cultural and cross-linguistic enquiry, and will be especially useful to researchers who do not have specialised training in anthropology.

Abstract

How do languages encode different kinds of movement, and what features do people pay attention to when describing motion events? This document outlines topics concerning the investigation of “enter” and “exit” events. It helps contextualise research tasks that examine this domain (see 'Motion Elicitation' and 'Enter/Exit animation') and gives some pointers about what other questions can be explored.

Abstract

How do languages encode different kinds of movement, and what features do people pay attention to when describing motion events? This task investigates the expression of “enter” and “exit” activities, that is, events involving motion in(to) and motion out (of) container-like items. The researcher first uses particular stimuli (a ball, a cup, rice, etc.) to elicit descriptions of enter/exit events from one consultant, and then asks another consultant to demonstrate the event based on these descriptions. See also the related entries Enter/Exit Animation and Background Questions for Enter/Exit Research.

Abstract

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

Abstract

Exceptionally long-lived species, including many bats, rarely show overt signs of aging, making it difficult to determine why species differ in lifespan. Here, we use DNA methylation (DNAm) profiles from 712 known-age bats, representing 26 species, to identify epigenetic changes associated with age and longevity. We demonstrate that DNAm accurately predicts chronological age. Across species, longevity is negatively associated with the rate of DNAm change at age-associated sites. Furthermore, analysis of several bat genomes reveals that hypermethylated age- and longevity-associated sites are disproportionately located in promoter regions of key transcription factors (TF) and enriched for histone and chromatin features associated with transcriptional regulation. Predicted TF binding site motifs and enrichment analyses indicate that age-related methylation change is influenced by developmental processes, while longevity-related DNAm change is associated with innate immunity or tumorigenesis genes, suggesting that bat longevity results from augmented immune response and cancer suppression.

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

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

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

Cognitive processes—from basic sensory analysis to language understanding—are typically contextualized. While the importance of considering context for understanding cognition has long been recognized in psychology and philosophy, it has not yet had much impact on cognitive neuroscience research, where cognition is often studied in decontextualized paradigms. Here, we present examples of recent studies showing that context changes the neural basis of diverse cognitive processes, including perception, attention, memory, and language. Within the domains of perception and language, we review neuroimaging results showing that context interacts with stimulus processing, changes activity in classical perception and language regions, and recruits additional brain regions that contribute crucially to naturalistic perception and language. We discuss how contextualized cognitive neuroscience will allow for discovering new principles of the mind and brain.

Abstract

Background

The biological mechanisms of headache chronification are poorly understood. We aimed to identify changes in DNA methylation associated with the transformation from episodic to chronic headache.
Methods

Participants were recruited from the population-based Norwegian HUNT Study. Thirty-six female headache patients who transformed from episodic to chronic headache between baseline and follow-up 11 years later were matched against 35 controls with episodic headache. DNA methylation was quantified at 485,000 CpG sites, and changes in methylation level at these sites were compared between cases and controls by linear regression analysis. Data were analyzed in two stages (Stages 1 and 2) and in a combined meta-analysis.
Results

None of the top 20 CpG sites identified in Stage 1 replicated in Stage 2 after multiple testing correction. In the combined meta-analysis the strongest associated CpG sites were related to SH2D5 and NPTX2, two brain-expressed genes involved in the regulation of synaptic plasticity. Functional enrichment analysis pointed to processes including calcium ion binding and estrogen receptor pathways.
Conclusion

In this first genome-wide study of DNA methylation in headache chronification several potentially implicated loci and processes were identified. The study exemplifies the use of prospectively collected population cohorts to search for epigenetic mechanisms of disease

Abstract

Researchers have suggested that the vocabularies of languages are oriented towards the communicative needs of language users. Here, we provide evidence demonstrating that the higher frequency of visual words in a large variety of English corpora is reflected in greater lexical differentiation—a greater number of unique words—for the visual domain in the English lexicon. In comparison, sensory modalities that are less frequently talked about, particularly taste and smell, show less lexical differentiation. In addition, we show that even though sensory language can be expected to change across historical time and between contexts of use (e.g., spoken language versus fiction), the pattern of visual dominance is a stable property of the English language. Thus, we show that across the board, precisely those semantic domains that are more frequently talked about are also more lexically differentiated, for perceptual experiences. This correlation between type and token frequencies suggests that the sensory lexicon of English is geared towards communicative efficiency.

Abstract

Several evolutionary accounts of human social cognition posit that language has co-evolved with the sophisticated mindreading abilities of modern humans. It has also been argued that these mindreading abilities are the product of cultural, rather than biological, evolution. Taken together, these claims suggest that the evolution of language has played an important role in the cultural evolution of human social cognition. Here we present a new computational model which formalises the assumptions that underlie this hypothesis, in order to explore how language and mindreading interact through cultural evolution. This model treats communicative behaviour as an interplay between the context in which communication occurs, an agent’s individual perspective on the world, and the agent’s lexicon. However, each agent’s perspective and lexicon are private mental representations, not directly observable to other agents. Learners are therefore confronted with the task of jointly inferring the lexicon and perspective of their cultural parent, based on their utterances in context. Simulation results show that given these assumptions, an informative lexicon evolves not just under a pressure to be successful at communicating, but also under a pressure for accurate perspective-inference. When such a lexicon evolves, agents become better at inferring others’ perspectives; not because their innate ability to learn about perspectives changes, but because sharing a language (of the right type) with others helps them to do so.

Abstract

Language users encounter words in at least two different modalities. Arguably, the most frequent encounters are in spoken or written form. Previous research has shown that – compared to the spoken modality – written language features more difficult words. Thus, frequent reading might have effects on word recognition. In the present study, we investigated 1) whether input modality (spoken, written, or bimodal) has an effect on word recognition accuracy, 2) whether this modality effect interacts with word difficulty, 3) whether the interaction of word difficulty and reading experience impacts word recognition accuracy, and 4) whether this interaction is influenced by input modality. To do so, we re-analysed a dataset that was collected in the context of a vocabulary test development to assess in which modality test words should be presented. Participants had carried out a word recognition task, where non-words and words of varying difficulty were presented in auditory, visual and audio-visual modalities. In addition to this main experiment, participants had completed a receptive vocabulary and an author recognition test to measure their reading experience. Our re-analyses did not reveal evidence for an effect of input modality on word recognition accuracy, nor for interactions with word difficulty or language experience. Word difficulty interacted with reading experience in that frequent readers were more accurate in recognizing difficult words than individuals who read less frequently. Practical implications are discussed.

Abstract

Spinocerebellar ataxia type 14 (SCA14) is a subtype of the autosomal dominant cerebellar ataxias that is characterized by slowly progressive cerebellar dysfunction and neurodegeneration. SCA14 is caused by mutations in the PRKCG gene, encoding protein kinase C gamma (PKCγ). Despite the identification of 40 distinct disease-causing mutations in PRKCG, the pathological mechanisms underlying SCA14 remain poorly understood. Here we report the molecular neuropathology of SCA14 in post-mortem cerebellum and in human patient-derived induced pluripotent stem cells (iPSCs) carrying two distinct SCA14 mutations in the C1 domain of PKCγ, H36R and H101Q. We show that endogenous expression of these mutations results in the cytoplasmic mislocalization and aggregation of PKCγ in both patient iPSCs and cerebellum. PKCγ aggregates were not efficiently targeted for degradation. Moreover, mutant PKCγ was found to be hyper-activated, resulting in increased substrate phosphorylation. Together, our findings demonstrate that a combination of both, loss-of-function and gain-of-function mechanisms are likely to underlie the pathogenesis of SCA14, caused by mutations in the C1 domain of PKCγ. Importantly, SCA14 patient iPSCs were found to accurately recapitulate pathological features observed in post-mortem SCA14 cerebellum, underscoring their potential as relevant disease models and their promise as future drug discovery tools.

Abstract

Objective: Patients with medication-related osteonecrosis of the jaw (MRONJ) often visit their dentists at advanced stages and subsequently require treatments that greatly affect quality of life. Currently, no clear diagnostic criteria exist to assess MRONJ, and the definitive diagnosis solely relies on clinical bone exposure. This ambiguity leads to a diagnostic delay, complications, and unnecessary burden. This article aims to identify imaging modalities' usage and findings of MRONJ to provide possible approaches for early detection.

Methods: Literature searches were conducted using PubMed, Web of Science, Scopus, and Cochrane Library to review all diagnostic imaging modalities for MRONJ.

Results: Panoramic radiography offers a fundamental understanding of the lesions. Imaging findings were comparable between non-exposed and exposed MRONJ, showing osteolysis, osteosclerosis, and thickened lamina dura. Mandibular cortex index Class II could be a potential early MRONJ indicator. While three-dimensional modalities, CT and CBCT, were able to show more features unique to MRONJ such as a solid type periosteal reaction, buccal predominance of cortical perforation, and bone-within-bone appearance. MRI signal intensities of vital bones are hypointense on T1WI and hyperintense on T2WI and STIR when necrotic bone shows hypointensity on all T1WI, T2WI, and STIR. Functional imaging is the most sensitive method but is usually performed in metastasis detection rather than being a diagnostic tool for early MRONJ.

Conclusion: Currently, MRONJ-specific imaging features cannot be firmly established. However, the current data are valuable as it may lead to a more efficient diagnostic procedure along with a more suitable selection of imaging modalities.

Abstract

Set is widely used as a kind of basic data structure. However, when it is used for large scale data set the cost of storage, search and transport is overhead. The bloom filter uses a fixed size bit string to represent elements in a static set, which can reduce storage space and search cost that is a fixed constant. The time-space efficiency is achieved at the cost of a small probability of false positive in membership query. However, for many applications the space savings and locating time constantly outweigh this drawback. Dynamic bloom filter (DBF) can support concisely representation and approximate membership queries of dynamic set instead of static set. It has been proved that DBF not only possess the advantage of standard bloom filter, but also has better features when dealing with dynamic set. This paper proposes a time-dependent multiple bit-strings bloom filter (TMBF) which roots in the DBF and targets on dynamic incremental set. TMBF uses multiple bit-strings in time order to present a dynamic increasing set and uses backward searching to test whether an element is in a set. Based on the system logs from a real P2P file sharing system, the evaluation shows a 20% reduction in searching cost compared to DBF.

Abstract

Electroencephalography (EEG) provides high temporal resolution cognitive information from non-invasive recordings. However, one of the common practices-using a subset of sensors in ERP analysis is hard to provide a holistic and precise dynamic results. Selecting or grouping subsets of sensors may also be subject to selection bias, multiple comparison, and further complicated by individual differences in the group-level analysis. More importantly, changes in neural generators and variations in response magnitude from the same neural sources are difficult to separate, which limit the capacity of testing different aspects of cognitive hypotheses. We introduce EasyEEG, a toolbox that includes several multivariate analysis methods to directly test cognitive hypotheses based on topographic responses that include data from all sensors. These multivariate methods can investigate effects in the dimensions of response magnitude and topographic patterns separately using data in the sensor space, therefore enable assessing neural response dynamics. The concise workflow and the modular design provide user-friendly and programmer-friendly features. Users of all levels can benefit from the open-sourced, free EasyEEG to obtain a straightforward solution for efficient processing of EEG data and a complete pipeline from raw data to final results for publication.

Abstract

In attempting to understand mental processes, it is important to use a task that appropriately reflects the underlying processes being investigated. Recently, Verdonschot and Kinoshita (Memory & Cognition, 46,410-425, 2018) proposed that a variant of the Stroop task-the "phonological Stroop task"-might be a suitable tool for investigating speech production. The major advantage of this task is that the task is apparently not affected by the orthographic properties of the stimuli, unlike other, commonly used, tasks (e.g., associative-cuing and word-reading tasks). The viability of this proposal was examined in the present experiments by manipulating the script types of Japanese distractors. For Romaji distractors (e.g., "kushi"), color-naming responses were faster when the initial phoneme was shared between the color name and the distractor than when the initial phonemes were different, thereby showing a phoneme-based phonological Stroop effect (Experiment1). In contrast, no such effect was observed when the same distractors were presented in Katakana (e.g., "< ") pound, replicating Verdonschot and Kinoshita's original results (Experiment2). A phoneme-based effect was again found when the Katakana distractors used in Verdonschot and Kinoshita's original study were transcribed and presented in Romaji (Experiment3). Because the observation of a phonemic effectdirectly depended on the orthographic properties of the distractor stimuli, we conclude that the phonological Stroop task is also susceptible to orthographic influences.

Abstract

Online testing holds great promise for infant scientists. It could increase participant diversity, improve reproducibility and collaborative possibilities, and reduce costs for researchers and participants. However, despite the rise of platforms and participant databases, little work has been done to overcome the challenges of making this approach available to researchers across the world. In this paper, we elaborate on the benefits of online infant testing from a global perspective and identify challenges for the international community that have been outside of the scope of previous literature. Furthermore, we introduce ManyBabies-AtHome, an international, multi-lab collaboration that is actively working to facilitate practical and technical aspects of online testing as well as address ethical concerns regarding data storage and protection, and cross-cultural variation. The ultimate goal of this collaboration is to improve the method of testing infants online and make it globally available.

Abstract

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

Abstract

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

Abstract

Language is multimodal: non-linguistic cues, such as prosody,
gestures and mouth movements, are always present in face-to-
face communication and interact to support processing. In this
paper, we ask whether and how multimodal cues affect L2
processing by recording EEG for highly proficient bilinguals
when watching naturalistic materials. For each word, we
quantified surprisal and the informativeness of prosody,
gestures, and mouth movements. We found that each cue
modulates the N400: prosodic accentuation, meaningful
gestures, and informative mouth movements all reduce N400.
Further, effects of meaningful gestures but not mouth
informativeness are enhanced by prosodic accentuation,
whereas effects of mouth are enhanced by meaningful gestures
but reduced by beat gestures. Compared with L1, L2
participants benefit less from cues and their interactions, except
for meaningful gestures and mouth movements. Thus, in real-
world language comprehension, L2 comprehenders use
multimodal cues just as L1 speakers albeit to a lesser extent.

Abstract

The learning of first object names is deemed a hard problem due to the uncertainty inherent in mapping a heard name to the intended referent in a cluttered and variable world. However, human infants readily solve this problem. Despite considerable theoretical discussion, relatively little is known about the uncertainty infants face in the real world. We used head-mounted eye tracking during parent–infant toy play and quantified the uncertainty by measuring the distribution of infant attention to the potential referents when a parent named both familiar and unfamiliar toy objects. The results show that infant gaze upon hearing an object name is often directed to a single referent which is equally likely to be a wrong competitor or the intended target. This bimodal gaze distribution clarifies and redefines the uncertainty problem and constrains possible solutions.

Abstract

Recent laboratory experiments have shown that both infant and adult learners can acquire word-referent mappings using cross-situational statistics. The vast majority of the work on this topic has used unfamiliar objects presented on neutral backgrounds as the visual contexts for word learning. However, these laboratory contexts are much different than the real-world contexts in which learning occurs. Thus, the feasibility of generalizing cross-situational learning beyond the laboratory is in question. Adapting the Human Simulation Paradigm, we conducted a series of experiments examining cross-situational learning from children's egocentric videos captured during naturalistic play. Focusing on individually ambiguous naming moments that naturally occur during toy play, we asked how statistical learning unfolds in real time through accumulating cross-situational statistics in naturalistic contexts. We found that even when learning situations were individually ambiguous, learners' performance gradually improved over time. This improvement was driven in part by learners' use of partial knowledge acquired from previous learning situations, even when they had not yet discovered correct word-object mappings. These results suggest that word learning is a continuous process by means of real-time information integration.

Abstract

Learning verbs is challenging because it is difficult to infer the precise meaning of a verb when there are a multitude of relations that one can derive from a single event. To study this verb learning challenge, we used children's egocentric view collected from naturalistic toy-play interaction as learning materials and investigated how visual and linguistic information provided in individual naming moments as well as cross-situational information provided from multiple learning moments can help learners resolve this mapping problem using the Human Simulation Paradigm. Our results show that learners benefit from seeing children's egocentric views compared to third-person observations. In addition, linguistic information can help learners identify the correct verb meaning by eliminating possible meanings that do not belong to the linguistic category. Learners are also able to integrate visual and linguistic information both within and across learning situations to reduce the ambiguity in the space of possible verb meanings.

Abstract

Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. To investigate how bilinguals monitor their speech errors and control their languages in use, we recorded event-related potentials (ERPs) in unbalanced Dutch-English bilingual speakers in a cued language-switching task. We tested the conflict-based monitoring model of Nozari and colleagues by investigating the error-related negativity (ERN) and comparing the effects of the two switching directions (i.e., to the first language, L1 vs. to the second language, L2). Results show that the speakers made more language selection errors when switching from their L2 to the L1 than vice versa. In the EEG, we observed a robust ERN effect following language selection errors compared to correct responses, reflecting monitoring of speech errors. Most interestingly, the ERN effect was enlarged when the speakers were switching to their L2 (less conflict) compared to switching to the L1 (more conflict). Our findings do not support the conflict-based monitoring model. We discuss an alternative account in terms of error prediction and reinforcement learning.

Abstract

Although bilingual speakers are very good at selectively using one language rather than another, sometimes language selection errors occur. We examined the relative contribution of top-down cognitive control and bottom-up language priming to these errors. Unbalanced Dutch-English bilinguals named pictures and were cued to switch between languages under time pressure. We also manipulated the number of same-language trials before a switch (long vs. short runs). Results show that speakers made more language selection errors when switching from their second language (L2) to the first language (L1) than vice versa. Furthermore, they made more errors when switching to the L1 after a short compared to a long run of L2 trials. In the reverse switching direction (L1 to L2), run length had no effect. These findings are most compatible with an account of language selection errors that assigns a strong role to top-down processes of cognitive control.

Abstract

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

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

It is undisputed that presenting a rhythmic stimulus leads to a measurable brain response that follows the rhythmic structure of this stimulus. What is still debated, however, is the question whether this brain response exclusively reflects a regular repetition of evoked responses, or whether it also includes entrained oscillatory activity. Here we systematically present evidence in favor of an involvement of entrained neural oscillations in the processing of rhythmic input while critically pointing out which questions still need to be addressed before this evidence could be considered conclusive. In this context, we also explicitly discuss the potential functional role of such entrained oscillations, suggesting that these stimulus-aligned oscillations reflect, and serve as, predictive processes, an idea often only implicitly assumed in the literature.

Abstract

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.

Abstract

The Corpus NGT