Publications

Abstract

Large-scale genome-wide association studies (GWAS) have implicated many low-penetrance loci in schizophrenia. However, its pathological mechanisms are poorly understood, which in turn hampers the development of novel pharmacological treatments. Pathway and gene set analyses carry the potential to generate hypotheses about disease mechanisms and have provided biological context to genome-wide data of schizophrenia. We aimed to examine which biological processes are likely candidates to underlie schizophrenia by integrating novel and powerful pathway analysis tools using data from the largest Psychiatric Genomics Consortium schizophrenia GWAS (N=79,845) and the most recent 2018 schizophrenia GWAS (N=105,318). By applying a primary unbiased analysis (Multi-marker Analysis of GenoMic Annotation; MAGMA) to weigh the role of biological processes from the Molecular Signatures Database (MSigDB), we identified enrichment of common variants in synaptic plasticity and neuron differentiation gene sets. We supported these findings using MAGMA, Meta-Analysis Gene-set Enrichment of variaNT Associations (MAGENTA) and Interval Enrichment Analysis (INRICH) on detailed synaptic signaling pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and found enrichment in mainly the dopaminergic and cholinergic synapses. Moreover, shared genes involved in these neurotransmitter systems had a large contribution to the observed enrichment, protein products of top genes in these pathways showed more direct and indirect interactions than expected by chance, and expression profiles of these genes were largely similar among brain tissues. In conclusion, we provide strong and consistent genetics and protein-interaction informed evidence for the role of postsynaptic signaling processes in schizophrenia, opening avenues for future translational and psychopharmacological studies.

Abstract

Exposure to traumatic stress increases the odds of developing a broad range of psychiatric conditions. Genetic studies targeting multiple stress-related quantitative phenotypes may shed light on mechanisms underlying vulnerability to psychopathology in the aftermath of stressful events. We applied a multivariate genome-wide association study (GWAS) to a unique military cohort (N = 583) in which we measured biochemical and behavioral phenotypes. The availability of pre- and post-deployment measurements allowed to capture changes in these phenotypes in response to stress. For genome-wide significant loci, we performed functional annotation, phenome-wide analysis and quasi-replication in PTSD case-control GWASs. We discovered one genetic variant reaching genome-wide significant association, surviving permutation and sensitivity analyses (rs10100651, p = 9.9 × 10−9). Functional annotation prioritized the genes INTS8 and TP53INP1. A phenome-wide scan revealed a significant association of these same genes with sleeping problems, hypertension and subjective well-being. Finally, a targeted lookup revealed nominally significant association of rs10100651 in a PTSD case-control GWAS in the UK Biobank (p = 0.02). We provide comprehensive evidence from multiple resources hinting at a role of the highlighted genetic variant in the human stress response, marking the power of multivariate genome-wide analysis of quantitative measures in stress research. Future genetic and functional studies can target this locus to further assess its effects on stress mediation and its possible role in psychopathology or resilience.

Abstract

The assessment of corticospinal excitability by means of transcranial magnetic stimulation-induced motor evoked potentials is an established diagnostic tool in neurophysiology and a widely used procedure in fundamental brain research. However, concern about low reliability of these measures has grown recently. One possible cause of high variability of MEPs under identical acquisition conditions could be the influence of oscillatory neuronal activity on corticospinal excitability. Based on research showing that transcranial alternating current stimulation can entrain neuronal oscillations we here test whether alpha or beta frequency tACS can influence corticospinal excitability in a phase-dependent manner. We applied tACS at individually calibrated alpha- and beta-band oscillation frequencies, or we applied sham tACS. Simultaneous single TMS pulses time locked to eight equidistant phases of the ongoing tACS signal evoked MEPs. To evaluate offline effects of stimulation frequency, MEP amplitudes were measured before and after tACS. To evaluate whether tACS influences MEP amplitude, we fitted one-cycle sinusoids to the average MEPs elicited at the different phase conditions of each tACS frequency. We found no frequency-specific offline effects of tACS. However, beta-frequency tACS modulation of MEPs was phase-dependent. Post hoc analyses suggested that this effect was specific to participants with low (<19 Hz) intrinsic beta frequency. In conclusion, by showing that beta tACS influences MEP amplitude in a phase-dependent manner, our results support a potential role attributed to neuronal oscillations in regulating corticospinal excitability. Moreover, our findings may be useful for the development of TMS protocols that improve the reliability of MEPs as a meaningful tool for research applications or for clinical monitoring and diagnosis. (C) 2018 Elsevier Ltd. All rights reserved.

Abstract

In language production research, the latency with which speakers produce a spoken response to a stimulus and the onset and offset times of words in longer utterances are key dependent variables. Measuring these variables automatically often yields partially incorrect results. However, exact measurements through the visual inspection of the recordings are extremely time-consuming. We present AlignTool, an open-source alignment tool that establishes preliminarily the onset and offset times of words and phonemes in spoken utterances using Praat, and subsequently performs a forced alignment of the spoken utterances and their orthographic transcriptions in the automatic speech recognition system MAUS. AlignTool creates a Praat TextGrid file for inspection and manual correction by the user, if necessary. We evaluated AlignTool’s performance with recordings of single-word and four-word utterances as well as semi-spontaneous speech. AlignTool performs well with audio signals with an excellent signal-to-noise ratio, requiring virtually no corrections. For audio signals of lesser quality, AlignTool still is highly functional but its results may require more frequent manual corrections. We also found that audio recordings including long silent intervals tended to pose greater difficulties for AlignTool than recordings filled with speech, which AlignTool analyzed well overall. We expect that by semi-automatizing the temporal analysis of complex utterances, AlignTool will open new avenues in language production research.

Abstract

Speakers can use pronouns when their conceptual referents are accessible from the preceding discourse, as in 'The flower is red. It turns blue'. Theories of language production agree that in order to produce a noun semantic, syntactic, and phonological information must be accessed. However, little is known about lexical access to pronouns. In this paper, we propose a model of pronoun access in German. Since the forms of German pronouns depend on the grammatical gender of the nouns they replace, the model claims that speakers must access the syntactic representation of the replaced noun (its lemma) to select a pronoun. In two experiments using the lexical decision during naming paradigm [Levelt, W.J.M., Schriefers, H., Vorberg, D., Meyer, A.S., Pechmann, T., Havinga, J., 1991a. The time course of lexical access in speech production: a study of picture naming. Psychological Review 98, 122-142], we investigated whether lemma access automatically entails the activation of the corresponding word form or whether a word form is only activated when the noun itself is produced, but not when it is replaced by a pronoun. Experiment 1 showed that during pronoun production the phonological form of the replaced noun is activated. Experiment 2 demonstrated that this phonological activation was not a residual of the use of the noun in the preceding sentence. Thus, when a pronoun is produced, the lemma and the phonological form of the replaced noun become reactivated.

Abstract

This dataset, colloquially known as the Mother Of Unification Studies (MOUS) dataset, contains multimodal neuroimaging data that has been acquired from 204 healthy human subjects. The neuroimaging protocol consisted of magnetic resonance imaging (MRI) to derive information at high spatial resolution about brain anatomy and structural connections, and functional data during task, and at rest. In addition, magnetoencephalography (MEG) was used to obtain high temporal resolution electrophysiological measurements during task, and at rest. All subjects performed a language task, during which they processed linguistic utterances that either consisted of normal or scrambled sentences. Half of the subjects were reading the stimuli, the other half listened to the stimuli. The resting state measurements consisted of 5 minutes eyes-open for the MEG and 7 minutes eyes-closed for fMRI. The neuroimaging data, as well as the information about the experimental events are shared according to the Brain Imaging Data Structure (BIDS) format. This unprecedented neuroimaging language data collection allows for the investigation of various aspects of the neurobiological correlates of language.

Abstract

Speakers are influenced by the linguistic context: hearing one syntactic alternative leads to an increased chance that the speaker will repeat this structure in the subsequent utterance (i.e., syntactic priming, or structural persistence). Top-down influences, such as whether a conversation partner (or, interlocutor) is present, may modulate the degree to which syntactic priming occurs. In the current study, we indeed show that the magnitude of syntactic alignment increases when speakers are interacting with an interlocutor as opposed to doing the experiment alone. The structural persistence effect for passive sentences is stronger in the presence of an interlocutor than when no interlocutor is present (i.e., when the participant is primed by a recording). We did not find evidence, however, that a speaker’s syntactic priming magnitude is influenced by the degree of their conversation partner’s priming magnitude. Together, these results support a mediated account of syntactic priming, in which syntactic choices are not only affected by preceding linguistic input, but also by top-down influences, such as the speakers’ communicative intent.

Abstract

Hoewel de spelling van Nederlandse verledentijdsvormen van zwakke werkwoorden algemeen als eenvoudig wordt beschouwd (ze zijn immers klankzuiver) maken zelfs universiteitsstudenten opvallend veel fouten bij de keuze tussen de uitgangen -te en -de. Voor een deel zijn die fouten ‘natuurlijk’ in die zin dat ze het gevolg zijn van de werking van frequentie en analogie. Anderzijds stellen we vast dat Nederlanders veel meer fouten maken dan Vlamingen, althans als de stam op een coronale fricatief eindigt (s, z, f, v). Aangezien de Nederlandse proefpersonen de ‘regel’ (het ezelsbruggetje ’t kofschip) beter lijken te beheersen dan de Vlamingen, moet de verklaring voor het verschil gezocht worden in een klankverandering die zich wel in Nederland maar niet of nauwelijks in Vlaanderen voordoet, de verstemlozing van de fricatieven. Het spellingprobleem vraagt om didactische maatregelen en/of politieke: het kan wellicht grotendeels worden opgelost door de spellingregels een weinig aan te passen.

Abstract

Speakers can adapt their speech and co-speech gestures based on knowledge shared with an addressee (common ground-based recipient design). Here, we investigate whether these adaptations are modulated by the speaker’s age and cognitive abilities. Younger and older participants narrated six short comic stories to a same-aged addressee. Half of each story was known to both participants, the other half only to the speaker. The two age groups did not differ in terms of the number of words and narrative events mentioned per narration, or in terms of gesture frequency, gesture rate, or percentage of events expressed multimodally. However, only the younger participants reduced the amount of verbal and gestural information when narrating mutually known as opposed to novel story content. Age-related differences in cognitive abilities did not predict these differences in common ground-based recipient design. The older participants’ communicative behaviour may therefore also reflect differences in social or pragmatic goals.

Abstract

Background

Voluntary shifts of visuospatial attention are associated with a lateralization of parieto-occipital alpha power (7-13Hz), i.e. higher power in the hemisphere ipsilateral and lower power contralateral to the locus of attention. Recent noninvasive neuromodulation studies demonstrated that alpha power can be experimentally increased using transcranial alternating current stimulation (tACS).
Objective/Hypothesis

We hypothesized that tACS at alpha frequency over the left parietal cortex induces shifts of attention to the left hemifield. However, spatial attention shifts not only occur voluntarily (endogenous/ top-down), but also stimulus-driven (exogenous/ bottom-up). To study the task-specificity of the potential effects of tACS on attentional processes, we administered three conceptually different spatial attention tasks.
Methods

36 healthy volunteers were recruited from an academic environment. In two separate sessions, we applied either high-density tACS at 10Hz, or sham tACS, for 35–40 minutes to their left parietal cortex. We systematically compared performance on endogenous attention, exogenous attention, and stimulus detection tasks.
Results

In the endogenous attention task, a greater leftward bias in reaction times was induced during left parietal 10Hz tACS as compared to sham. There were no stimulation effects in either the exogenous attention or the stimulus detection task.
Conclusion

The study demonstrates that high-density tACS at 10Hz can be used to modulate visuospatial attention performance. The tACS effect is task-specific, indicating that not all forms of attention are equally susceptible to the stimulation.

Abstract

Exposure to trauma strongly increases the risk to develop stress-related psychopathology, such as post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). In addition, liability to develop these moderately heritable disorders is partly determined by common genetic variance, which is starting to be uncovered by genome-wide association studies (GWASs). However, it is currently unknown to what extent genetic vulnerability and trauma interact. We investigated whether genetic risk based on summary statistics of large GWASs for PTSD and MDD predisposed individuals to report an increase in MDD and PTSD symptoms in a prospective military cohort (N = 516) at five time points after deployment to Afghanistan: one month, six months and one, two and five years. Linear regression was used to analyze the contribution of polygenic risk scores (PRSs, at multiple p-value thresholds) and their interaction with deployment-related trauma to the development of PTSD- and depression-related symptoms. We found no main effects of PRSs nor evidence for interactions with trauma on the development of PTSD or depressive symptoms at any of the time points in the five years after military deployment. Our results based on a unique long-term follow-up of a deployed military cohort suggest limited validity of current PTSD and MDD polygenic risk scores, albeit in the presence of minimal severe psychopathology in the target cohort. Even though the predictive value of PRSs will likely benefit from larger sample sizes in discovery and target datasets, progress will probably also depend on (endo)phenotype refinement that in turn will reduce etiological heterogeneity.

Abstract

Although there is good evidence that social animals show elaborate cognitive skills to deal with others, there are few reports of animals physically using social agents and their respective responses as means to an end—social tool use. In this case study, we investigated spontaneous and repeated social tool use behavior in chimpanzees (Pan troglodytes). We presented a group of chimpanzees with an apparatus, in which pushing two buttons would release juice from a distantly located fountain. Consequently, any one individual could only either push the buttons or drink from the fountain but never push and drink simultaneously. In this scenario, an adult male attempted to retrieve three other individuals and push them toward the buttons that, if pressed, released juice from the fountain. With this strategy, the social tool user increased his juice intake 10-fold. Interestingly, the strategy was stable over time, which was possibly enabled by playing with the social tools. With over 100 instances, we provide the biggest data set on social tool use recorded among nonhuman animals so far. The repeated use of other individuals as social tools may represent a complex social skill linked to Machiavellian intelligence.

Abstract

Recent research in speech production has shown that syntactic structure is reflected in segmental phonology--the application of certain phonological rules of English (e.g., palatalization and alveolar flapping) is inhibited across phrase boundaries. We examined whether such segmental effects can be used in speech perception as cues to syntactic structure, and the relation between the use of these segmental features as syntactic markers in production and perception. Speakers of American English (a dialect in which the above segmental effects occur) could indeed use the segmental cues in syntax perception; speakers of British English (in which the effects do not occur) were unable to make use of them, while speakers of British English who were long-term residents of the United States showed intermediate performance.

Abstract

Encoding the temporal properties of external signals that comprise multimodal events is a major factor guiding everyday experience. However, during the natural aging process, impairments to sensory processing can profoundly affect multimodal temporal perception. Various mechanisms can contribute to temporal perception, and thus it is imperative to understand how each can be affected by age. In the current study, using three different temporal order judgement tasks (unisensory, multisensory, and sensorimotor), we investigated the effects of age on two separate temporal processes: synchronization and integration of multiple signals. These two processes rely on different aspects of temporal information, either the temporal alignment of processed signals or the integration/segregation of signals arising from different modalities, respectively. Results showed that the ability to integrate/segregate multiple signals decreased with age regardless of the task, and that the magnitude of such impairment correlated across tasks, suggesting a widespread mechanism affected by age. In contrast, perceptual synchrony remained stable with age, revealing a distinct intact mechanism. Overall, results from this study suggest that aging has differential effects on temporal processing, and general impairments with aging may impact global temporal sensitivity while context-dependent processes remain unaffected.

Abstract

Representations learned by deep convolutional neural networks (CNNs) for object recognition are a widely
investigated model of the processing hierarchy in the human visual system. Using functional magnetic resonance
imaging, CNN representations of visual stimuli have previously been shown to correspond to processing stages in
the ventral and dorsal streams of the visual system. Whether this correspondence between models and brain
signals also holds for activity acquired at high temporal resolution has been explored less exhaustively. Here, we
addressed this question by combining CNN-based encoding models with magnetoencephalography (MEG).
Human participants passively viewed 1,000 images of objects while MEG signals were acquired. We modelled
their high temporal resolution source-reconstructed cortical activity with CNNs, and observed a feed-forward
sweep across the visual hierarchy between 75 and 200 ms after stimulus onset. This spatiotemporal cascade
was captured by the network layer representations, where the increasingly abstract stimulus representation in the
hierarchical network model was reflected in different parts of the visual cortex, following the visual ventral
stream. We further validated the accuracy of our encoding model by decoding stimulus identity in a left-out
validation set of viewed objects, achieving state-of-the-art decoding accuracy.

Abstract

Syntactic binding refers to combining words into larger structures. Using EEG, we investigated the neural processes involved in syntactic binding. Participants were auditorily presented two-word sentences (i.e. pronoun and pseudoverb such as ‘I grush’, ‘she grushes’, for which syntactic binding can take place) and wordlists (i.e. two pseudoverbs such as ‘pob grush’, ‘pob grushes’, for which no binding occurs). Comparing these two conditions, we targeted syntactic binding while minimizing contributions of semantic binding and of other cognitive processes such as working memory. We found a converging pattern of results using two distinct analysis approaches: one approach using frequency bands as defined in previous literature, and one data-driven approach in which we looked at the entire range of frequencies between 3-30 Hz without the constraints of pre-defined frequency bands. In the syntactic binding (relative to the wordlist) condition, a power increase was observed in the alpha and beta frequency range shortly preceding the presentation of the target word that requires binding, which was maximal over frontal-central electrodes. Our interpretation is that these signatures reflect that language comprehenders expect the need for binding to occur. Following the presentation of the target word in a syntactic binding context (relative to the wordlist condition), an increase in alpha power maximal over a left lateralized cluster of frontal-temporal electrodes was observed. We suggest that this alpha increase relates to syntactic binding taking place. Taken together, our findings suggest that increases in alpha and beta power are reflections of distinct the neural processes underlying syntactic binding.

Abstract

Behavioral syntactic priming effects during sentence comprehension are typically observed only if both the syntactic structure and lexical head are repeated. In contrast, during production syntactic priming occurs with structure repetition alone, but the effect is boosted by repetition of the lexical head. We used fMRI to investigate the neuronal correlates of syntactic priming and lexical boost effects during sentence production and comprehension. The critical measure was the magnitude of fMRI adaptation to repetition of sentences in active or passive voice, with or without verb repetition. In conditions with repeated verbs, we observed adaptation to structure repetition in the left IFG and MTG, for active and passive voice. However, in the absence of repeated verbs, adaptation occurred only for passive sentences. None of the fMRI adaptation effects yielded differential effects for production versus comprehension, suggesting that sentence comprehension and production are subserved by the same neuronal infrastructure for syntactic processing.

Abstract

Repetition suppression in fMRI studies is generally thought to underlie behavioural facilitation effects (i.e., priming) and it is often used to identify the neuronal representations associated with a stimulus. However, this pays little heed to the large number of repetition enhancement effects observed under similar conditions. In this review, we identify several cognitive variables biasing repetition effects in the BOLD response towards enhancement instead of suppression. These variables are stimulus recognition, learning, attention, expectation and explicit memory. We also evaluate which models can account for these repetition effects and come to the conclusion that there is no one single model that is able to embrace all repetition enhancement effects. Accumulation, novel network formation as well as predictive coding models can all explain subsets of repetition enhancement effects.

Abstract

This discussion note reviews responses of the linguistics profession to the grave issues of language
endangerment identified a quarter of a century ago in the journal Language by Krauss,
Hale, England, Craig, and others (Hale et al. 1992). Two and a half decades of worldwide research
not only have given us a much more accurate picture of the number, phylogeny, and typological
variety of the world’s languages, but they have also seen the development of a wide range of new
approaches, conceptual and technological, to the problem of documenting them. We review these
approaches and the manifold discoveries they have unearthed about the enormous variety of linguistic
structures. The reach of our knowledge has increased by about 15% of the world’s languages,
especially in terms of digitally archived material, with about 500 languages now
reasonably documented thanks to such major programs as DoBeS, ELDP, and DEL. But linguists
are still falling behind in the race to document the planet’s rapidly dwindling linguistic diversity,
with around 35–42% of the world’s languages still substantially undocumented, and in certain
countries (such as the US) the call by Krauss (1992) for a significant professional realignment toward
language documentation has only been heeded in a few institutions. Apart from the need for
an intensified documentarist push in the face of accelerating language loss, we argue that existing
language documentation efforts need to do much more to focus on crosslinguistically comparable
data sets, sociolinguistic context, semantics, and interpretation of text material, and on methods
for bridging the ‘transcription bottleneck’, which is creating a huge gap between the amount we
can record and the amount in our transcribed corpora.*

Abstract

We examined gesture representation of motion events in narratives produced by three- and nine-year-olds, and adults. Two aspects of gestural depiction were analysed: how protagonists were depicted, and how gesture space was used. We found that older groups were more likely to express protagonists as an object that a gesturing hand held and manipulated, and less likely to express protagonists with whole-body enactment gestures. Furthermore, for older groups, gesture space increasingly became less similar to narrated space. The older groups were less likely to use large gestures or gestures in the periphery of the gesture space to represent movements that were large relative to a protagonist’s body or that took place next to a protagonist. They were also less likely to produce gestures on a physical surface (e.g. table) to represent movement on a surface in narrated events. The development of gestural depiction indicates that older speakers become less immersed in the story world and start to control and manipulate story representation from an outside perspective in a bounded and stage-like gesture space. We discuss this developmental shift in terms of increasing symbolic distancing (Werner & Kaplan, 1963).

Abstract

Background: Gesture frequently accompanies speech in healthy speakers. For many individuals with aphasia, gestures are a target of speech-language pathology intervention, either as an alternative form of communication or as a facilitative device for language restoration. The patterns of gesture production for people with aphasia and the participant variables that predict these patterns remain unclear. Aims: We aimed to examine gesture production during conversational discourse in a large sample of individuals with aphasia. We used a detailed gesture coding system to determine patterns of gesture production associated with specific aphasia types and severities. Methods & Procedures: We analysed conversation samples from AphasiaBank, gathered from 46 people with post-stroke aphasia and 10 healthy matched controls all of whom had gestured at least once during a story re-tell task. Twelve gesture types were coded. Descriptive statistics were used to describe the patterns of gesture production. Possible significant differences in production patterns according to aphasia type and severity were examined with a series of analyses of variance (ANOVA) statistics, and multiple regression analysis was used to examine these potential predictors of gesture production patterns. Outcomes & Results: Individuals with aphasia gestured significantly more frequently than healthy controls. Aphasia type and severity impacted significantly on gesture type in specific identified patterns detailed here, especially on the production of meaning-laden gestures. Conclusions: These patterns suggest the opportunity for gestures as targets of aphasia therapy. Aphasia fluency accounted for a greater degree of data variability than aphasia severity or naming skills. More work is required to delineate predictive factors.

Abstract

Purpose For many individuals with aphasia, gestures form a vital component of message transfer and are the target of speech-language pathology intervention. What remains unclear are the participant variables that predict successful outcomes from gesture treatments. The authors examined the gesture production of a large number of individuals with aphasia—in a consistent discourse sampling condition and with a detailed gesture coding system—to determine patterns of gesture production associated with specific types of aphasia. Method The authors analyzed story retell samples from AphasiaBank (TalkBank, n.d.), gathered from 98 individuals with aphasia resulting from stroke and 64 typical controls. Twelve gesture types were coded. Descriptive statistics were used to describe the patterns of gesture production. Possible significant differences in production patterns according to aphasia type were examined using a series of chi-square, Fisher exact, and logistic regression statistics. Results A significantly higher proportion of individuals with aphasia gestured as compared to typical controls, and for many individuals with aphasia, this gesture was iconic and was capable of communicative load. Aphasia type impacted significantly on gesture type in specific identified patterns, detailed here. Conclusion These type-specific patterns suggest the opportunity for gestures as targets of aphasia therapy.

Abstract

Visiting the Trobriand Islands is advertised as being the highlight of a trip for tourists to Papua New Guinea who want, and can afford, to experience this 'ultimate adventure' with 'expeditionary cruises aboard the luxurious Melanesian Discoverer. The advertisements also promise that the tourists can 'meet the friendly people' and 'observe their unique culture, dances, and art'. During my research in Kaibola and Nuwebila, two neighbouring villages on the northern tip of Kiriwina Island, I studied and analysed the encounters of tourists with Trobriand Islanders, who sing and dance for the Europeans. The analyses of the islanders' tourist performances are based on Erving Goffman's now classic study The Presentation of Self in Everyday Life, which was first published in 1959. In this study Goffmann analyses the structures of social encounters from the perspective of the dramatic performance. The situational context within which the encounter between tourists and Trobriand Islanders takes place frames the tourists as the audience and the Trobriand Islanders as a team of performers. The inherent structure of the parts of the overall performance presented in the two villages can be summarized - within the framework of Goffman's approach - in analogy with the structure of drama. We find parts that constitute the 'exposition', the 'complication', and the 'resolution' of a drama; we even observe an equivalent to the importance of the 'Second Act Curtain' in modern drama theory. Deeper analyses of this encounter show that the motives of the performers and their 'art of impression management' are to control the impression their audience receives in this encounter situation. This analysis reveals that the Trobriand Islanders sell their customers the expected images of what Malinowski (1929) once termed the '...Life of Savages in North-Western Melanesia' in a staged 'illusion'. With the conscious realization of the part they as performers play in this encounter, the Trobriand Islanders are in a position that is superior to that of their audience. Their merchandise or commodity is 'not real', as it is sold 'out of its true cultural context'. It is staged - and thus cannot be taken by any customer whatsoever because it (re)presents just an 'illusion'. The Trobriand Islanders know that neither they nor the core aspects of their culture will suffer any damage within a tourist encounter that is defined by the structure and the kind of their performance. Their pride and self-confidence enable them to bring their superior position into play in their dealings with tourists. With their indigenous humour, they even use this encounter for ridiculing their visitors. It turns out that the encounter is another manifestation of the Trobriand Islanders' self-consciousness, self-confidence, and pride with which they manage to protect core aspects of their cultural identity, while at the same time using and 'selling' parts of their culture as a kind of commodity to tourists.

Abstract

The Open Access Movement promotes free and unfettered access to research publications and, increasingly, to the primary data which underly those publications. As the field of documentary linguistics seeks to record and preserve culturally and linguistically relevant materials, the question of how openly accessible these materials should be becomes increasingly important. This paper aims to guide researchers and other stakeholders in finding an appropriate balance between accessibility and confidentiality of data, addressing community questions and legal, institutional, and intellectual issues that pose challenges to accessible data.

Abstract

Autism spectrum disorder is increasingly associated with atypical perceptual and sensory symptoms. Here we explore the hypothesis
that aberrant sensory processing in autism spectrum disorder could be linked to atypical intra- (local) and interregional (global)
brain connectivity. To elucidate oscillatory dynamics and connectivity in the visual domain we used magnetoencephalography and
a simple visual grating paradigm with a group of 18 adolescent autistic participants and 18 typically developing control subjects.
Both groups showed similar increases in gamma (40–80 Hz) and decreases in alpha (8–13 Hz) frequency power in occipital cortex.
However, systematic group differences emerged when analysing intra- and interregional connectivity in detail. First, directed
connectivity was estimated using non-parametric Granger causality between visual areas V1 and V4. Feedforward V1-to-V4
connectivity, mediated by gamma oscillations, was equivalent between autism spectrum disorder and control groups, but importantly,
feedback V4-to-V1 connectivity, mediated by alpha (8–13 Hz) oscillations, was significantly reduced in the autism spectrum
disorder group. This reduction was positively correlated with autistic quotient scores, consistent with an atypical visual hierarchy
in autism, characterized by reduced top-down modulation of visual input via alpha-band oscillations. Second, at the local level in
V1, coupling of alpha-phase to gamma amplitude (alpha-gamma phase amplitude coupling) was reduced in the autism spectrum
disorder group. This implies dysregulated local visual processing, with gamma oscillations decoupled from patterns of wider alphaband
phase synchrony (i.e. reduced phase amplitude coupling), possibly due to an excitation-inhibition imbalance. More generally,
these results are in agreement with predictive coding accounts of neurotypical perception and indicate that visual processes in
autism are less modulated by contextual feedback information.

Abstract

Background Cognitive dysfunction is one of the most prominent characteristics of psychiatric disorders. At present, the neural correlates of cognitive dysfunction across psychiatric disorders are poorly understood. The aim of this study was to investigate functional connectivity and structural perturbations across psychiatric diagnoses in three neurocognitive networks of interest, including the default-mode (DMN), the frontoparietal (FPN) and the salience network (SN). Methods We performed meta-analyses of resting-state functional MRI (R-fMRI) whole-brain seed-based functional connectivity in 8,298 patients (involving 8 disorders) and 8,165 healthy controls and a voxel-based morphometry analysis of structural MRI data in 14,027 patients (involving 8 disorders) and healthy 14,504 controls. To aid the interpretation of the results, we examined neurocognitive function in 776 healthy participants from the Human Connectome Project. Results We found that the three neurocognitive networks of interest were characterized by shared alterations of functional connectivity architecture across psychiatric disorders. More specifically, hypoconnectivity was expressed between the DMN and ventral SN and between the SN and FPN, whereas hyperconnectivity was evident between the DMN and FPN and between the DMN and dorsal SN. This pattern of network alterations was associated with gray matter reductions in patients, and was localized in regions that subserve general cognitive performance. Conclusions This study is the first to provide meta-analytic evidence of common alterations of functional connectivity within and between neurocognitive networks. The findings suggest a shared mechanism of network interactions that may associate with the generalized cognitive deficits observed in psychiatric disorders.

Abstract

There is mounting evidence that the ease of producing and understanding language depends not only on the frequencies of individual words but also on the frequencies of word combinations. However, in two picture description experiments, Janssen and Barber (2012) found that French and Spanish speakers' speech onset latencies for short phrases depended exclusively on the frequencies of the phrases but not on the frequencies of the individual words. They suggested that speakers retrieved phrase-sized units from the mental lexicon. In the present study, we examined whether the time required to plan complex noun phrases in Dutch would likewise depend only on phrase frequencies. Participants described line drawings in phrases such as rode schoen [red shoe] (Experiments 1 and 2) or de rode schoen [the red shoe] (Experiment 3). Replicating Janssen and Barber's findings, utterance onset latencies depended on the frequencies of the phrases but, deviating from their findings, also depended on the frequencies of the adjectives in adjective-noun phrases and the frequencies of the nouns in determiner-adjective-noun phrases. We conclude that individual word frequencies and phrase frequencies both affect the time needed to produce noun phrases and discuss how these findings may be captured in models of the mental lexicon and of phrase production

Abstract

The present study examined the relation between nonselective inhibition and selective inhibition in picture naming performance. Nonselective inhibition refers to the ability to suppress any unwanted response, whereas selective inhibition refers to the ability to suppress specific competing responses. The degree of competition in picture naming was manipulated by presenting targets along with distractor words that could be semantically related (e.g., a picture of a dog combined with the word cat) or unrelated (tree) to the picture name. The mean naming response time (RT) was longer in the related than in the unrelated condition, reflecting semantic interference. Delta plot analyses showed that participants with small mean semantic interference effects employed selective inhibition more effectively than did participants with larger semantic interference effects. The participants were also tested on the stop-signal task, which taps nonselective inhibition. Their performance on this task was correlated with their mean naming RT but, importantly, not with the selective inhibition indexed by the delta plot analyses and the magnitude of the semantic interference effect. These results indicate that nonselective inhibition ability and selective inhibition of competitors in picture naming are separable to some extent.

Abstract

Interactions between top-down and bottom-up information streams are integral to brain function but challenging to measure noninvasively. Laminar resolution, functional MRI (lfMRI) is sensitive to depth-dependent properties of the blood oxygen level-dependent (BOLD) response, which can be potentially related to top-down and bottom-up signal contributions. In this work, we used lfMRI to dissociate the top-down and bottom-up signal contributions to the left occipitotemporal sulcus (LOTS) during word reading. We further demonstrate that laminar resolution measurements could be used to identify condition-specific distributed networks on the basis of whole-brain connectivity patterns specific to the depth-dependent BOLD signal. The networks corresponded to top-down and bottom-up signal pathways targeting the LOTS during word reading. We show that reading increased the top-down BOLD signal observed in the deep layers of the LOTS and that this signal uniquely related to the BOLD response in other language-critical regions. These results demonstrate that lfMRI can reveal important patterns of activation that are obscured at standard resolution. In addition to differences in activation strength as a function of depth, we also show meaningful differences in the interaction between signals originating from different depths both within a region and with the rest of the brain. We thus show that lfMRI allows the noninvasive measurement of directed interaction between brain regions and is capable of resolving different connectivity patterns at submillimeter resolution, something previously considered to be exclusively in the domain of invasive recordings.

Abstract

A t(X;1)(p11.2;q21.2) has been reported in cases of papillary renal cell tumors arising in males. In this study two cell lines derived from this tumor type have been used to indicate the breakpoint region on the X chromosome. Both cell lines have the translocation in addition to other rearrangements and one is derived from the first female case to be reported with the t(X;1)(p11.2;q21.2). Fluorescence in situ hybridization (FISH) has been used to position YACs belonging to contigs in the Xp11.2 region relative to the breakpoint. When considered together with detailed mapping information from the Xp11.2 region the position of the breakpoint in both cell lines was suggested as follows: Xpter-->Xp11.23-OATL1-GATA1-WAS-TFE3-SY P-t(X;1)-DXS255-CLCN5-DXS146-OATL2- Xp11.22-->Xcen. The breakpoint was determined to lie in an uncloned region between SYP and a YAC called FTDM/1 which extends 1 Mb distal to DXS255. These results are contrary to the conclusion from previous FISH studies that the breakpoint was near the OATL2 locus, but are consistent with, and considerably refine, the position that had been established by molecular analysis.

Abstract

Since Pillsbury [1908. Attention. London: Swan Sonnenschein & Co], the issue of whether attention operates through inhibition or enhancement has been on the scientific agenda. We examined whether overcoming previous attentional inhibition or enhancement is the source of asymmetrical switch costs in spoken noun-phrase production and colour-word Stroop tasks. In Experiment 1, using bivalent stimuli, we found asymmetrical costs in response times for switching between long and short phrases and between Stroop colour naming and reading. However, in Experiment 2, using bivalent stimuli for the weaker tasks (long phrases, colour naming) and univalent stimuli for the stronger tasks (short phrases, word reading), we obtained an asymmetrical switch cost for phrase production, but a symmetrical cost for Stroop. The switch cost evidence was quantified using Bayesian statistical analyses. Our findings suggest that switching between phrase types involves inhibition, whereas switching between colour naming and reading involves enhancement. Thus, the attentional mechanism depends on the language-production task involved. The results challenge theories of task switching that assume only one attentional mechanism, inhibition or enhancement, rather than both mechanisms.

Abstract

Recently, it has been proposed that sequence learning engages a combination of modality-specific operating networks and modality-independent computational principles. In the present study, we compared the behavioural and EEG outcomes of implicit artificial grammar learning in the visual vs. auditory modality. We controlled for the influence of surface characteristics of sequences (Associative Chunk Strength), thus focusing on the strictly structural aspects of sequence learning, and we adapted the paradigms to compensate for known frailties of the visual modality compared to audition (temporal presentation, fast presentation rate). The behavioural outcomes were similar across modalities. Favouring the idea of modality-specificity, ERPs in response to grammar violations differed in topography and latency (earlier and more anterior component in the visual modality), and ERPs in response to surface features emerged only in the auditory modality. In favour of modality-independence, we observed three common functional properties in the late ERPs of the two grammars: both were free of interactions between structural and surface influences, both were more extended in a grammaticality classification test than in a preference classification test, and both correlated positively and strongly with theta event-related-synchronization during baseline testing. Our findings support the idea of modality-specificity combined with modality-independence, and suggest that memory for visual vs. auditory sequences may largely contribute to cross-modal differences.

Abstract

Perceptual compensation for speaker vocal tract properties was investigated in four groups of listeners: native speakers of English and native speakers of Dutch, native speakers of Spanish with low proficiency in English, and Spanish-English bilinguals. Listeners categorized targets on a [sofo] to [sufu] continuum. Targets were preceded by sentences that were manipulated to have either a high or a low F1 contour. All listeners performed the categorization task for targets that were preceded by Spanish, English and Dutch precursors. Results show that listeners from each of the four language backgrounds compensate for speaker vocal tract properties regardless of language-specific vowel inventory properties. Listeners also compensate when they listen to stimuli in another language. The results suggest that patterns of compensation are mainly determined by auditory properties of precursor sentences.

Abstract

One of the important challenges for the development of science communication concerns the current problems with the under-exposure of null results. I suggest that each article published in a top scientific journal can get tagged (online) with attempts to replicate. As such, a future reader of an article will also be able to see whether replications have been attempted and how these turned out. Editors and/or reviewers decide whether a replication is of sound quality. The authors of the main article have the option to review the replication and can provide a supplementary comment with each attempt that is added. After 5 or 10 years, and provided enough attempts to replicate, the authors of the main article get the opportunity to discuss/review their original study in light of the outcomes of the replications. This approach has two important strengths: 1) The approach would provide researchers with the opportunity to show that they deliver scientifically thorough work, but sometimes just fail to replicate the result that others have reported. This can be especially valuable for the career opportunities of promising young researchers; 2) perhaps even more important, the visibility of replications provides an important incentive for researchers to publish findings only if they are sure that their effects are reliable (and thereby reduce the influence of "experimenter degrees of freedom" or even outright fraud). The proposed approach will stimulate researchers to look beyond the point of publication of their studies.

Abstract

Important speech cues such as lexical tone and vowel quality are perceptually contrasted to the distribution of those same cues in surrounding contexts. However, it is unclear whether preceding and following contexts have similar influences, and to what extent those influences are modulated by the auditory history of previous trials. To investigate this, Cantonese participants labeled sounds from (a) a tone continuum (mid- to high-level), presented with a context that had raised or lowered F0 values and (b) a vowel quality continuum (/u/ to /o/), where the context had raised or lowered F1 values. Contexts with high or low F0/F1 were presented in separate blocks or intermixed in 1 block. Contexts were presented following (Experiment 1) or preceding the target continuum (Experiment 2). Contrastive effects were found for both tone and vowel quality (e.g., decreased F0 values in contexts lead to more high tone target judgments and vice versa). Importantly, however, lexical tone was only influenced by F0 in immediately preceding and following contexts. Vowel quality was only influenced by the F1 in preceding contexts, but this extended to contexts from preceding trials. Contextual influences on tone and vowel quality are qualitatively different, which has important implications for understanding the mechanism of context effects in speech perception.

Abstract

Three experiments investigated whether extrinsic vowel normalization takes place largely at a categorical or a precategorical level of processing. Traditional vowel normalization effects in categorization were replicated in Experiment 1: Vowels taken from an [ɪ]-[ε] continuum were more often interpreted as /ɪ/ (which has a low first formant, F (1)) when the vowels were heard in contexts that had a raised F (1) than when the contexts had a lowered F (1). This was established with contexts that consisted of only two syllables. These short contexts were necessary for Experiment 2, a discrimination task that encouraged listeners to focus on the perceptual properties of vowels at a precategorical level. Vowel normalization was again found: Ambiguous vowels were more easily discriminated from an endpoint [ε] than from an endpoint [ɪ] in a high-F (1) context, whereas the opposite was true in a low-F (1) context. Experiment 3 measured discriminability between pairs of steps along the [ɪ]-[ε] continuum. Contextual influences were again found, but without discrimination peaks, contrary to what was predicted from the same participants' categorization behavior. Extrinsic vowel normalization therefore appears to be a process that takes place at least in part at a precategorical processing level.

Abstract

The acoustic dimensions that distinguish speech sounds (like the vowel differences in “boot” and “boat”) also differentiate speakers’ voices. Therefore, listeners must normalize across speakers without losing linguistic information. Past behavioral work suggests an important role for auditory contrast enhancement in normalization: preceding context affects listeners’ perception of subsequent speech sounds. Here, using intracranial electrocorticography in humans, we investigate whether and how such context effects arise in auditory cortex. Participants identified speech sounds that were preceded by phrases from two different speakers whose voices differed along the same acoustic dimension as target words (the lowest resonance of the vocal tract). In every participant, target vowels evoke a speaker-dependent neural response that is consistent with the listener’s perception, and which follows from a contrast enhancement model. Auditory cortex processing thus displays a critical feature of normalization, allowing listeners to extract meaningful content from the voices of diverse speakers.

Abstract

Young children's visual environments are dynamic, changing moment-by-moment as children physically and visually explore spaces and objects and interact with people around them. Head-mounted eye tracking offers a unique opportunity to capture children's dynamic egocentric views and how they allocate visual attention within those views. This protocol provides guiding principles and practical recommendations for researchers using head-mounted eye trackers in both laboratory and more naturalistic settings. Head-mounted eye tracking complements other experimental methods by enhancing opportunities for data collection in more ecologically valid contexts through increased portability and freedom of head and body movements compared to screen-based eye tracking. This protocol can also be integrated with other technologies, such as motion tracking and heart-rate monitoring, to provide a high-density multimodal dataset for examining natural behavior, learning, and development than previously possible. This paper illustrates the types of data generated from head-mounted eye tracking in a study designed to investigate visual attention in one natural context for toddlers: free-flowing toy play with a parent. Successful use of this protocol will allow researchers to collect data that can be used to answer questions not only about visual attention, but also about a broad range of other perceptual, cognitive, and social skills and their development.

Abstract

It is widely accepted that specific memory processes, such as serial-order memory, are involved in written language development and predictive of reading and spelling abilities. The reverse question, namely whether orthographic abilities also affect serial-order memory, has hardly been investigated. In the current study, we compared 20 illiterate people with a group of 20 literate matched controls on a verbal and a visuospatial version of the Hebb paradigm, measuring both short- and long-term serial-order memory abilities. We observed better short-term serial-recall performance for the literate compared with the illiterate people. This effect was stronger in the verbal than in the visuospatial modality, suggesting that the improved capacity of the literate group is a consequence of learning orthographic skills. The long-term consolidation of ordered information was comparable across groups, for both stimulus modalities. The implications of these findings for current views regarding the bi-directional interactions between memory and written language development are discussed.

Abstract

Abstract In the past, several assessment reports on writing repeatedly showed that elementary school students do not develop the essential writing skills to be successful in school. In this respect, prior research has pointed to the fact that cognitive and motivational challenges are at the root of the rather basic level of elementary students' writing performance. Additionally, previous research has revealed gender and achievement-level differences in elementary students' writing. In view of providing effective writing instruction for all students to overcome writing difficulties, the present study provides more in-depth insight into (a) how cognitive and motivational challenges mediate and correlate with students' writing performance and (b) whether and how these relations vary for boys and girls and for writers of different achievement levels. In the present study, 1,577 fifth- and sixth-grade students completed questionnaires regarding their writing self-efficacy, writing motivation, and writing strategies. In addition, half of the students completed two writing tests, respectively focusing on the informational or narrative text genre. Based on multiple group structural equation modeling (MG-SEM), we put forward two models: a MG-SEM model for boys and girls and a MG-SEM model for low, average, and high achievers. The results underline the importance of studying writing models for different groups of students in order to gain more refined insight into the complex interplay between motivational and cognitive challenges related to students' writing performance.

Abstract

Language-mediated visual attention describes the interaction of two fundamental components of the human cognitive system, language and vision. Within this paper we present an amodal shared resource model of language-mediated visual attention that offers a description of the information and processes involved in this complex multimodal behavior and a potential explanation for how this ability is acquired. We demonstrate that the model is not only sufficient to account for the experimental effects of Visual World Paradigm studies but also that these effects are emergent properties of the architecture of the model itself, rather than requiring separate information processing channels or modular processing systems. The model provides an explicit description of the connection between the modality-specific input from language and vision and the distribution of eye gaze in language-mediated visual attention. The paper concludes by discussing future applications for the model, specifically its potential for investigating the factors driving observed individual differences in language-mediated eye gaze.

Abstract

Blindsight refers to the observation of residual visual abilities in the hemianopic field of patients without a functional V1. Given the within- and between-subject variability in the preserved abilities and the phenomenal experience of blindsight patients, the fine-grained description of the phenomenon is still debated. Here we tested a patient with established “perceptual” and “attentional” blindsight (c.f. Danckert and Rossetti, 2005). Using a pointing paradigm patient MS, who suffers from a complete left homonymous hemianopia, showed clear above chance manual localisation of ‘unseen’ targets. In addition, target presentations in his blind field led MS, on occasion, to spontaneous responses towards his sighted field. Structural and functional magnetic resonance imaging was conducted to evaluate the magnitude of V1 damage. Results revealed the presence of a calcarine sulcus in both hemispheres, yet his right V1 is reduced, structurally disconnected and shows no fMRI response to visual stimuli. Thus, visual stimulation of his blind field can lead to “action blindsight” and spontaneous antipointing, in absence of a functional right V1. With respect to the antipointing, we suggest that MS may have registered the stimulation and subsequently presumes it must have been in his intact half field.

Abstract

The appropriate definition and scaling of the magnitude of electroencephalogram (EEG) oscillations is an underdeveloped area. The aim of this study was to optimize the analysis of resting EEG alpha magnitude, focusing on alpha peak frequency and nonlinear transformation of alpha power. A family of nonlinear transforms, Box-Cox transforms, were applied to find the transform that (a) maximized a non-disputed effect: the increase in alpha magnitude when the eyes are closed (Berger effect), and (b) made the distribution of alpha magnitude closest to normal across epochs within each participant, or across participants. The transformations were performed either at the single epoch level or at the epoch-average level. Alpha peak frequency showed large individual differences, yet good correspondence between various ways to estimate it in 2min of eyes-closed and 2min of eyes-open resting EEG data. Both alpha magnitude and the Berger effect were larger for individual alpha than for a generic (8-12Hz) alpha band. The log-transform on single epochs (a) maximized the t-value of the contrast between the eyes-open and eyes-closed conditions when tested within each participant, and (b) rendered near-normally distributed alpha power across epochs and participants, thereby making further transformation of epoch averages superfluous. The results suggest that the log-normal distribution is a fundamental property of variations in alpha power across time in the order of seconds. Moreover, effects on alpha power appear to be multiplicative rather than additive. These findings support the use of the log-transform on single epochs to achieve appropriate scaling of alpha magnitude.

Abstract

Atypical visual perception in people with autism spectrum disorders (ASD) is hypothesized to stem from an imbalance in excitatory and inhibitory processes in the brain. We used neuronal oscillations in the gamma frequency range (30 – 90 Hz), which emerge from a balanced interaction of excitation and inhibition in the brain, to assess contextual modulation processes in early visual perception. Electroencephalography was recorded in 12 high-functioning adults with ASD and 12 age- and IQ-matched control participants. Oscilla- tions in the gamma frequency range were analyzed in response to stimuli consisting of small line-like elements. Orientation-speci fi c contextual modulation was manipulated by parametrically increasing the amount of homogeneously oriented elements in the stimuli. The stimuli elicited a strong steady-state gamma response around the refresh-rate of 60 Hz, which was larger for controls than for participants with ASD. The amount of orientation homogeneity (contextual modulation) in fl uenced the gamma response in control subjects, while for subjects with ASD this was not the case. The atypical steady-state gamma response to contextual modulation in subjects with ASD may capture the link between an imbalance in excitatory and inhibitory neuronal processing and atypical visual processing in ASD

Abstract

Chromatin remodeling is of crucial importance during brain development. Pathogenic
alterations of several chromatin remodeling ATPases have been implicated in neurodevelopmental
disorders. We describe an index case with a de novo missense mutation in CHD3,
identified during whole genome sequencing of a cohort of children with rare speech disorders.
To gain a comprehensive view of features associated with disruption of this gene, we use a
genotype-driven approach, collecting and characterizing 35 individuals with de novo CHD3
mutations and overlapping phenotypes. Most mutations cluster within the ATPase/helicase
domain of the encoded protein. Modeling their impact on the three-dimensional structure
demonstrates disturbance of critical binding and interaction motifs. Experimental assays with
six of the identified mutations show that a subset directly affects ATPase activity, and all but
one yield alterations in chromatin remodeling. We implicate de novo CHD3 mutations in a
syndrome characterized by intellectual disability, macrocephaly, and impaired speech and
language.

Abstract

Many genetic causes of developmental delay and/or intellectual disability (DD/ID) are extremely rare, and robust discovery of these requires both large-scale DNA sequencing and data sharing. Here we describe a GeneMatcher collaboration which led to a cohort of 13 affected individuals harboring protein-altering variants, 11 of which are de novo, in MED13; the only inherited variant was transmitted to an affected child from an affected mother. All patients had intellectual disability and/or developmental delays, including speech delays or disorders. Other features that were reported in two or more patients include autism spectrum disorder, attention deficit hyperactivity disorder, optic nerve abnormalities, Duane anomaly, hypotonia, mild congenital heart abnormalities, and dysmorphisms. Six affected individuals had mutations that are predicted to truncate the MED13 protein, six had missense mutations, and one had an in-frame-deletion of one amino acid. Out of the seven non-truncating mutations, six clustered in two specific locations of the MED13 protein: an N-terminal and C-terminal region. The four N-terminal clustering mutations affect two adjacent amino acids that are known to be involved in MED13 ubiquitination and degradation, p.Thr326 and p.Pro327. MED13 is a component of the CDK8-kinase module that can reversibly bind Mediator, a multi-protein complex that is required for Polymerase II transcription initiation. Mutations in several other genes encoding subunits of Mediator have been previously shown to associate with DD/ID, including MED13L, a paralog of MED13. Thus, our findings add MED13 to the group of CDK8-kinase module-associated disease genes

Abstract

POU3F3, also referred to as Brain-1, is a well-known transcription factor involved in the development of the central nervous system, but it has not previously been associated with a neurodevelopmental disorder. Here, we report the identification of 19 individuals with heterozygous POU3F3 disruptions, most of which are de novo variants. All individuals had developmental delays and/or intellectual disability and impairments in speech and language skills. Thirteen individuals had characteristic low-set, prominent, and/or cupped ears. Brain abnormalities were observed in seven of eleven MRI reports. POU3F3 is an intronless gene, insensitive to nonsense-mediated decay, and 13 individuals carried protein-truncating variants. All truncating variants that we tested in cellular models led to aberrant subcellular localization of the encoded protein. Luciferase assays demonstrated negative effects of these alleles on transcriptional activation of a reporter with a FOXP2-derived binding motif. In addition to the loss-of-function variants, five individuals had missense variants that clustered at specific positions within the functional domains, and one small in-frame deletion was identified. Two missense variants showed reduced transactivation capacity in our assays, whereas one variant displayed gain-of-function effects, suggesting a distinct pathophysiological mechanism. In bioluminescence resonance energy transfer (BRET) interaction assays, all the truncated POU3F3 versions that we tested had significantly impaired dimerization capacities, whereas all missense variants showed unaffected dimerization with wild-type POU3F3. Taken together, our identification and functional cell-based analyses of pathogenic variants in POU3F3, coupled with a clinical characterization, implicate disruptions of this gene in a characteristic neurodevelopmental disorder.

Abstract

The anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC) are involved in conflict detection and
conflict resolution, respectively. Here, we investigate how lifelong bilingualism induces neuroplasticity to these structures by
employing a novel analysis of behavioural performance. We correlated grey matter volume (GMV) in seniors reported by
Abutalebi et al. (2015) with behavioral Flanker task performance fitted using the diffusion model (Ratcliff, 1978). As
predicted, we observed significant correlations between GMV in the DLPFC and Flanker performance. However, for
monolinguals the non-decision time parameter was significantly correlated with GMV in the left DLPFC, whereas for
bilinguals the correlation was significant in the right DLPFC. We also found a significant correlation between age and GMV
in left DLPFC and the non-decision time parameter for the conflict effect for monolinguals only.
We submit that this is due to cumulative demands on cognitive control over a lifetime of bilingual language processing

Abstract

In language comprehension, a variety of contextual cues act in unison to render upcoming words more or less predictable. As a sentence unfolds, we use prior context (sentential constraints) to predict what the next words might be. Additionally, in a conversation, we can predict upcoming sounds through observing the mouth movements of a speaker (visual constraints). In electrophysiological studies, effects of visual constraints have typically been observed early in language processing, while effects of sentential constraints have typically been observed later. We hypothesized that the visual and the sentential constraints might feed into the same predictive process such that effects of sentential constraints might also be detectable early in language processing through modulations of the early effects of visual salience. We presented participants with audiovisual speech while recording their brain activity with magnetoencephalography. Participants saw videos of a person saying sentences where the last word was either sententially constrained or not, and began with a salient or non-salient mouth movement. We found that sentential constraints indeed exerted an early (N1) influence on language processing. Sentential modulations of the N1 visual predictability effect were visible in brain areas associated with semantic processing, and were differently expressed in the two hemispheres. In the left hemisphere, visual and sentential constraints jointly suppressed the auditory evoked field, while the right hemisphere was sensitive to visual constraints only in the absence of strong sentential constraints. These results suggest that sentential and visual constraints can jointly influence even very early stages of audiovisual speech comprehension.

Abstract

We present results from cross-modal priming experiments on German participles and noun plurals. The experiments produced parallel results for both inflectional systems. Regular inflection exhibits full priming whereas irregularly inflected word forms show only partial priming: after hearing regularly inflected words (-t participles and -s plurals), lexical decision times on morphologically related word forms (presented visually) were similar to reaction times for a base-line condition in which prime and target were identical, but significantly shorter than in a control condition where prime and target were unrelated. In contrast, prior presentation of irregular words (-n participles and -er plurals) led to significantly longer response times on morphologically related word forms than the prior presentation of the target itself. Hence, there are clear priming differences between regularly and irregularly inflected German words. We compare the findings on German with experimental results on regular and irregular inflection in English and Italian, and discuss theoretical implications for single versus dual-mechanism models of inflection.

Abstract

Do we mentally simulate olfactory information? We investigated mental simulation of odors and sounds in two experiments. Participants retained a word while they smelled an odor or heard a sound, then rated odor/sound intensity and recalled the word. Later odor/sound recognition was also tested, and pleasantness and familiarity judgments were collected. Word recall was slower when the sound and sound-word mismatched (e.g., bee sound with the word typhoon). Sound recognition was higher when sounds were paired with a match or near-match word (e.g., bee sound with bee or buzzer). This indicates sound-words are mentally simulated. However, using the same paradigm no memory effects were observed for odor. Instead it appears odor-words only affect lexical-semantic representations, demonstrated by higher ratings of odor intensity and pleasantness when an odor was paired with a match or near-match word (e.g., peach odor with peach or mango). These results suggest fundamental differences in how odor and sound-words are represented.

Abstract

Odors are often difficult to identify and name, which leaves them vulnerable to the influence of language. The present study tests the boundaries of the effect of language on odor cognition by examining the effect of grammatical gender. We presented participants with male and female fragrances paired with descriptions of masculine or feminine grammatical gender. In Experiment 1 we found that memory for fragrances was enhanced when the grammatical gender of a fragrance description matched the gender of the fragrance. In Experiment 2 we found memory for fragrances was affected by both grammatical gender and gender associations in fragrance descriptions – recognition memory for odors was higher when the gender was incongruent. In sum, we demonstrated that even subtle aspects of language can affect odor cognition.

Abstract

Olfaction is often considered a vestigial sense in humans, demoted throughout evolution to make way for the dominant sense of vision. This perspective on olfaction is reflected in how we think and talk about smells in the West, with odor imagery and odor language reported to be difficult. In the present study we demonstrate odor cognition is superior in odor-color synaesthesia, where there are additional sensory connections to odor concepts. Synaesthesia is a neurological phenomenon in which input in 1 modality leads to involuntary perceptual associations. Semantic accounts of synaesthesia posit synaesthetic associations are mediated by activation of inducing concepts. Therefore, synaesthetic associations may strengthen conceptual representations. To test this idea, we ran 6 odor-color synaesthetes and 17 matched controls on a battery of tasks exploring odor and color cognition. We found synaesthetes outperformed controls on tests of both odor and color discrimination, demonstrating for the first time enhanced perception in both the inducer (odor) and concurrent (color) modality. So, not only do synaesthetes have additional perceptual experiences in comparison to controls, their primary perceptual experience is also different. Finally, synaesthetes were more consistent and accurate at naming odors. We propose synaesthetic associations to odors strengthen odor concepts, making them more differentiated (facilitating odor discrimination) and easier to link with lexical representations (facilitating odor naming). In summary, we show for the first time that both odor language and perception is enhanced in people with synaesthetic associations to odors

Abstract

The response exclusion account (REA), advanced by Mahon and colleagues, localises the distractor frequency effect and the semantic interference effect in picture naming at the level of the response output buffer. We derive four predictions from the REA: (1) the size of the distractor frequency effect should be identical to the frequency effect obtained when distractor words are read aloud, (2) the distractor frequency effect should not change in size when stimulus-onset asynchrony (SOA) is manipulated, (3) the interference effect induced by a distractor word (as measured from a nonword control distractor) should increase in size with increasing SOA, and (4) the word frequency effect and the semantic interference effect should be additive. The results of the picture-naming task in Experiment 1 and the word-reading task in Experiment 2 refute all four predictions. We discuss a tentative account of the findings obtained within a traditional selection-by-competition model in which both context effects are localised at the level of lexical selection.

Abstract

Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype

Abstract

The principle of common coding suggests that a joint representation is formed when actions are repeatedly paired with a specific perceptual event. Musicians are occupationally specialized with regard to the coupling between actions and their auditory effects. In the present study, we employed a novel paradigm to demonstrate automatic action–effect associations in pianists. Pianists and nonmusicians pressed keys according to aurally presented number sequences. Numbers were presented at pitches that were neutral, congruent, or incongruent with respect to pitches that would normally be produced by such actions. Response time differences were seen between congruent and incongruent sequences in pianists alone. A second experiment was conducted to determine whether these effects could be attributed to the existence of previously documented spatial/pitch compatibility effects. In a “stretched” version of the task, the pitch distance over which the numbers were presented was enlarged to a range that could not be produced by the hand span used in Experiment 1. The finding of a larger response time difference between congruent and incongruent trials in the original, standard, version compared with the stretched version, in pianists, but not in nonmusicians, indicates that the effects obtained are, at least partially, attributable to learned action effects.

Abstract

Bilingual children are often exposed to non-native speech through their parents. Yet, little is known about the relation between bilingual preschoolers’ speech production and their speech input. The present study investigated the production of voice onset time (VOT) by Dutch-German bilingual preschoolers and their sequential bilingual mothers. The findings reveal an association between maternal VOT and bilingual children’s VOT in the heritage language German as well as in the majority language Dutch. By contrast, no input-production association was observed in the VOT production of monolingual German-speaking children and monolingual Dutch-speaking children. The results of this study provide the first empirical evidence that non-native and attrited maternal speech contributes to the often-observed linguistic differences between bilingual children and their monolingual peers.

Abstract

This study assesses the effects of age and language exposure on VOT production in 29 simultaneous bilingual children aged 3;7 to 5;11 who speak German as a heritage language in the Netherlands. Dutch and German have a binary voicing contrast, but the contrast is implemented with different VOT values in the two languages. The results suggest that bilingual children produce ‘voiced’ plosives similarly in their two languages, and these productions are not monolingual-like in either language. Bidirectional cross-linguistic influence between Dutch and German can explain these results. Yet, the bilinguals seemingly have two autonomous categories for Dutch and German ‘voiceless’ plosives. In German, the bilinguals’ aspiration is not monolingual-like, but bilinguals with more heritage language exposure produce more target-like aspiration. Importantly, the amount of exposure to German has no effect on the majority language's ‘voiceless’ category. This implies that more heritage language exposure is associated with more language-specific voicing systems.

Abstract

Human intracranial electroencephalography (iEEG) recordings provide data with much greater spatiotemporal precision
than is possible from data obtained using scalp EEG, magnetoencephalography (MEG), or functional MRI. Until recently,
the fusion of anatomical data (MRI and computed tomography (CT) images) with electrophysiological data and their
subsequent analysis have required the use of technologically and conceptually challenging combinations of software.
Here, we describe a comprehensive protocol that enables complex raw human iEEG data to be converted into more readily
comprehensible illustrative representations. The protocol uses an open-source toolbox for electrophysiological data
analysis (FieldTrip). This allows iEEG researchers to build on a continuously growing body of scriptable and reproducible
analysis methods that, over the past decade, have been developed and used by a large research community. In this
protocol, we describe how to analyze complex iEEG datasets by providing an intuitive and rapid approach that can handle
both neuroanatomical information and large electrophysiological datasets. We provide a worked example using
an example dataset. We also explain how to automate the protocol and adjust the settings to enable analysis of
iEEG datasets with other characteristics. The protocol can be implemented by a graduate student or postdoctoral
fellow with minimal MATLAB experience and takes approximately an hour to execute, excluding the automated cortical
surface extraction.

Abstract

Human referential communication is often thought as coding-decoding a set of symbols, neglecting that establishing shared meanings requires a computational mechanism powerful enough to mutually negotiate them. Sharing the meaning of a novel symbol might rely on similar conceptual inferences across communicators or on statistical similarities in their sensorimotor behaviors. Using magnetoencephalography, we assess spectral, temporal, and spatial characteristics of neural activity evoked when people generate and understand novel shared symbols during live communicative interactions. Solving those communicative problems induced comparable changes in the spectral profile of neural activity of both communicators and addressees. This shared neuronal up-regulation was spatially localized to the right temporal lobe and the ventromedial prefrontal cortex and emerged already before the occurrence of a specific communicative problem. Communicative innovation relies on neuronal computations that are shared across generating and understanding novel shared symbols, operating over temporal scales independent from transient sensorimotor behavior.

Abstract

Magnetoencephalography (MEG) is measured above the head, which makes it sensitive to variations of the head position with respect to the sensors. Head movements blur the topography of the neuronal sources of the MEG signal, increase localization errors, and reduce statistical sensitivity. Here we describe two novel and readily applicable methods that compensate for the detrimental effects of head motion on the statistical sensitivity of MEG experiments. First, we introduce an online procedure that continuously monitors head position. Second, we describe an offline analysis method that takes into account the head position time-series. We quantify the performance of these methods in the context of three different experimental settings, involving somatosensory, visual and auditory stimuli, assessing both individual and group-level statistics. The online head localization procedure allowed for optimal repositioning of the subjects over multiple sessions, resulting in a 28% reduction of the variance in dipole position and an improvement of up to 15% in statistical sensitivity. Offline incorporation of the head position time-series into the general linear model resulted in improvements of group-level statistical sensitivity between 15% and 29%. These tools can substantially reduce the influence of head movement within and between sessions, increasing the sensitivity of many cognitive neuroscience experiments.

Abstract

As participants repeatedly interact using graphical signals (as in a game of Pictionary), the signals gradually shift from being iconic (or motivated) to being symbolic (or arbitrary). The aim here is to test experimentally whether this change in the form of the signal implies a concomitant shift in the inferential mechanisms needed to understand it. The results show that, during early, iconic stages, there is more reliance on creative inferential processes associated with insight problem solving, and that the recruitment of these cognitive mechanisms decreases over time. The variation in inferential mechanism is not predicted by the sign’s visual complexity or iconicity, but by its familiarity, and by the complexity of the relevant mental representations. The discussion explores implications for pragmatics, language evolution, and iconicity research.

Abstract

There exists a clear association between animacy and the grammatical function of transitive subject. The grammar of some languages require the transitive subject to be high in animacy, or at least higher than the object. A similar animacy preference has been observed in processing studies in languages without such a categorical animacy effect. This animacy preference has been mainly established in structures in which either one or both arguments are provided before the verb. Our goal was to establish (i) whether this preference can already be observed before any argument is provided, and (ii) whether this preference is mediated by verbal information. To this end we exploited the V2 property of Dutch which allows the verb to precede its arguments. Using a visual-world eye-tracking paradigm we presented participants with V2 structures with either an auxiliary (e.g. Gisteren heeft X … ‘Yesterday, X has …’) or a lexical main verb (e.g. Gisteren motiveerde X … ‘Yesterday, X motivated …’) and we measured looks to the animate referent. The results indicate that the animacy preference can already be observed before arguments are presented and that the selectional restrictions of the verb mediate this bias, but do not override it completely.

Abstract

Memory representations of words are thought to undergo changes with consolidation: Episodic memories of novel words are transformed into lexical representations that interact with other words in the mental dictionary. Behavioral studies have shown that this lexical integration process is enhanced when there is more time for consolidation. Neuroimaging studies have further revealed that novel word representations are initially represented in a hippocampally-centered system, whereas left posterior middle temporal cortex activation increases with lexicalization. In this study, we measured behavioral and brain responses to newly-learned words in children. Two groups of Dutch children, aged between 8-10 and 14-16 years, were trained on 30 novel Japanese words depicting novel concepts. Children were tested on word-forms, word-meanings, and the novel words’ influence on existing word processing immediately after training, and again after a week. In line with the adult findings, hippocampal involvement decreased with time. Lexical integration, however, was not observed immediately or after a week, neither behaviorally nor neurally. It appears that time alone is not always sufficient for lexical integration to occur. We suggest that other factors (e.g., the novelty of the concepts and familiarity with the language the words are derived from) might also influence the integration process.

Abstract

The aim of the present study was to examine whether repetition of radicals during training of Chinese characters leads to better word acquisition performance in beginning learners of Chinese as a foreign language. Thirty Dutch university students were trained on 36 Chinese one-character words for their pronunciations and meanings. They were also exposed to the specifics of the radicals, that is, for phonetic radicals, the associated pronunciation was explained, and for semantic radicals the associated categorical meanings were explained. Results showed that repeated exposure to phonetic and semantic radicals through character pronunciation and meaning trainings indeed induced better understanding of those radicals that were shared among different characters. Furthermore, characters in the training set that shared phonetic radicals were pronounced better than those that did not. Repetition of semantic radicals across different characters, however, hindered the learning of exact meanings. Students generally confused the meanings of other characters that shared the semantic radical. The study shows that in the initial stage of learning, overlapping information of the shared radicals are effectively learned. Acquisition of the specifics of individual characters, however, requires more training.

Abstract

We investigate the emergence of iconicity, specifically a bouba-kiki effect in miniature artificial languages under different functional constraints: when the languages are reproduced and when they are used communicatively. We ran transmission chains of (a) participant dyads who played an interactive communicative game and (b) individual participants who played a matched learning game. An analysis of the languages over six generations in an iterated learning experiment revealed that in the Communication condition, but not in the Reproduction condition, words for spiky shapes tend to be rated by naive judges as more spiky than the words for round shapes. This suggests that iconicity may not only be the outcome of innovations introduced by individuals, but, crucially, the result of interlocutor negotiation of new communicative conventions. We interpret our results as an illustration of cultural evolution by random mutation and selection (as opposed to by guided variation).

Abstract

This study examined the role of verbal short-term memory (STM) and executive function (EF) underlying semantic and syntactic interference resolution during sentence comprehension for persons with aphasia (PWA) with varying degrees of STM and EF deficits. Semantic interference was manipulated by varying the semantic plausibility of the intervening NP as subject of the verb and syntactic interference was manipulated by varying whether the NP was another subject or an object. Nine PWA were assessed on sentence reading times and on comprehension question performance. PWA showed exaggerated semantic and syntactic interference effects relative to healthy age-matched control subjects. Importantly, correlational analyses showed that while answering comprehension questions, PWA’ semantic STM capacity related to their ability to resolve semantic but not syntactic interference. In contrast, PWA’ EF abilities related to their ability to resolve syntactic but not semantic interference. Phonological STM deficits were not related to the ability to resolve either type of interference. The results for semantic STM are consistent with prior findings indicating a role for semantic but not phonological STM in sentence comprehension, specifically with regard to maintaining semantic information prior to integration. The results for syntactic interference are consistent with the recent findings suggesting that EF is critical for syntactic processing.

Abstract

The murine homologue of the human chloride channel gene, CLCN5, defects in which are responsible for Dent disease, has been cloned and characterized. We isolated the entire coding region of mouse Clcn5 cDNA and approximately 45 kb of genomic sequence embracing the gene. To study its transcriptional control, the 5' upstream sequences of the mouse Clcn5 gene were cloned into a luciferase reporter vector. Deletion analysis of 1.5 kb of the 5' flanking sequence defined an active promoter region within 128 bp of the putative transcription start site, which is associated with a TATA motif but lacks a CAAT consensus. Within this sequence, there is a motif with homology to a purine-rich sequence responsible for the kidney-specific promoter activity of the rat CLC-K1 gene, another member of the chloride-channel gene family expressed in kidney. An enhancer element that confers a 10- to 20-fold increase in the promoter activity of the mouse Clcn5 gene was found within the first intron. The organization of the human CLCN5 and mouse Clcn5 gene structures is highly conserved, and the sequence of the murine protein is 98% similar to that of human, with its highest expression seen in the kidney. This study thus provides the first identification of the transcriptional control region of, and the basis for an understanding of the regulatory mechanism that controls, this kidney-specific, chloride-channel gene.

Abstract

Bats are unique among mammals, possessing some of the rarest mammalian adaptations, including true self-powered flight, laryngeal echolocation, exceptional longevity, unique immunity, contracted genomes, and vocal learning. They provide key ecosystem services, pollinating tropical plants, dispersing seeds, and controlling insect pest populations, thus driving healthy ecosystems. They account for more than 20% of all living mammalian diversity, and their crown-group evolutionary history dates back to the Eocene. Despite their great numbers and diversity, many species are threatened and endangered. Here we announce Bat1K, an initiative to sequence the genomes of all living bat species (n∼1,300) to chromosome-level assembly. The Bat1K genome consortium unites bat biologists (>132 members as of writing), computational scientists, conservation organizations, genome technologists, and any interested individuals committed to a better understanding of the genetic and evolutionary mechanisms that underlie the unique adaptations of bats. Our aim is to catalog the unique genetic diversity present in all living bats to better understand the molecular basis of their unique adaptations; uncover their evolutionary history; link genotype with phenotype; and ultimately better understand, promote, and conserve bats. Here we review the unique adaptations of bats and highlight how chromosome-level genome assemblies can uncover the molecular basis of these traits. We present a novel sequencing and assembly strategy and review the striking societal and scientific benefits that will result from the Bat1K initiative.

Abstract

Content and temporal cues have been shown to interact during audio-visual (AV) speech identification. Typically, the most reliable unimodal cue is used more strongly to identify specific speech features; however, visual cues are only used if the AV stimuli are presented within a certain temporal window of integration (TWI). This suggests that temporal cues denote whether unimodal stimuli belong together, that is, whether they should be integrated. It is not known whether temporal cues also provide information about the identity of a syllable. Since spoken syllables have naturally varying AV onset asynchronies, we hypothesize that for suboptimal AV cues presented within the TWI, information about the natural AV onset differences can aid in speech identification. To test this, we presented low-intensity auditory syllables concurrently with visual speech signals, and varied the stimulus onset asynchronies (SOA) of the AV pair, while participants were instructed to identify the auditory syllables. We revealed that specific speech features (e.g., voicing) were identified by relying primarily on one modality (e.g., auditory). Additionally, we showed a wide window in which visual information influenced auditory perception, that seemed even wider for congruent stimulus pairs. Finally, we found a specific response pattern across the SOA range for syllables that were not reliably identified by the unimodal cues, which we explained as the result of the use of natural onset differences between AV speech signals. This indicates that temporal cues not only provide information about the temporal integration of AV stimuli, but additionally convey information about the identity of AV pairs. These results provide a detailed behavioral basis for further neuro-imaging and stimulation studies to unravel the neurofunctional mechanisms of the audio-visual-temporal interplay within speech perception.

Abstract

The brain is inherently proactive, constantly predicting the when (moment) and what (content) of future input in order to optimize information processing. Previous research on such predictions has mainly studied the “when” or “what” domain separately, missing to investigate the potential integration of both types of predictive information. In the absence of such integration, temporal cues are assumed to enhance any upcoming content at the predicted moment in time (general temporal predictor). However, if the when and what prediction domain were integrated, a much more flexible neural mechanism may be proposed in which temporal-feature interactions would allow for the creation of multiple concurrent time-content predictions (parallel time-content predictor). Here, we used a temporal association paradigm in two experiments in which sound identity was systematically paired with a specific time delay after the offset of a rhythmic visual input stream. In Experiment 1, we revealed that participants associated the time delay of presentation with the identity of the sound. In Experiment 2, we unexpectedly found that the strength of this temporal association was negatively related to the EEG steady-state evoked responses (SSVEP) in preceding trials, showing that after high neuronal responses participants responded inconsistent with the time-content associations, similar to adaptation mechanisms. In this experiment, time-content associations were only present for low SSVEP responses in previous trials. These results tentatively show that it is possible to represent multiple time-content paired predictions in parallel, however, future research is needed to investigate this interaction further.

Abstract

This paper presents electrophysiological data on the on-line processing of open- and closed-class words in patients with Broca’s aphasia with agrammatic comprehension. Event-related brain potentials were recorded from the scalp when Broca patients and nonaphasic control subjects were visually presented with a story in which the words appeared one at a time on the screen. Separate waveforms were computed for open- and closed-class words. The non-aphasic control subjects showed clear differences between the processing of open- and closed-class words in an early (210-375 ms) and a late (400-700 ms) time-window.The early electrophysiological differences reflect the first manifestation of the availability of word-category information from the mental lexicon. The late differences presumably relate to post-lexical semantic and syntactic processing. In contrast to the control subjects, the Broca patients showed no early vocabulary class effect and only a limited late effect. The results suggest that an important factor in the agrammatic comprehension deficit of Broca’s aphasics is a delayed and/or incomplete availability of word-class information.

Abstract

Our understanding of the functioning of the brain is primarily based on an average model of the brain's functional organisation, and any deviation from the standard is considered as random noise or a pathological appearance. Studying pathologies has, however, greatly contributed to our understanding of brain functions. For instance, the study of naturally-occurring or surgically-induced brain lesions revealed that language is predominantly lateralised to the left hemisphere while perception/action and emotion are commonly lateralised to the right hemisphere. The lateralisation of function was subsequently replicated by task-related functional neuroimaging in the healthy population. Despite its high significance and reproducibility, this pattern of lateralisation of function is true for most, but not all participants. Bilateral and flipped representations of classically lateralised functions have been reported during development and in the healthy adult population for language, perception/action and emotion. Understanding these different functional representations at an individual level is crucial to improve the sophistication of our models and account for the variance in developmental trajectories, cognitive performance differences and clinical recovery. With the availability of in vivo neuroimaging, it has become feasible to study large numbers of participants and reliably characterise individual differences, also referred to as phenotypes. Yet, we are at the beginning of inter-individual variability modelling, and new theories of brain function will have to account for these differences across participants.

Abstract

Establishing non-native phoneme categories can be a notoriously difficult endeavour—in both speech perception and speech production. This study asks how these two domains interact in the course of this learning process. It investigates the effect of perceptual learning and related production practice of a challenging non-native category on the perception and/or production of that category. A four-day perceptual training protocol on the British English /æ/-/ɛ/ vowel contrast was combined with either related or unrelated production practice. After feedback on perceptual categorisation of the contrast, native Dutch participants in the related production group (N = 19) pronounced the trial's correct answer, while participants in the unrelated production group (N = 19) pronounced similar but phonologically unrelated words. Comparison of pre- and post-tests showed significant improvement over the course of training in both perception and production, but no differences between the groups were found. The lack of an effect of production practice is discussed in the light of previous, competing results and models of second-language speech perception and production. This study confirms that, even in the context of related production practice, perceptual training boosts production learning.

Abstract

The way top-down and bottom-up processes interact to shape our perception and behaviour is a fundamental question and remains highly controversial. How early in a processing stream do such interactions occur, and what factors govern such interactions? The degree of abstractness of a perceptual attribute (for example, orientation versus shape in vision, or loudness versus sound identity in hearing) may determine the locus of neural processing and interaction between bottom-up and internal information. Using an imagery-perception repetition paradigm, we find that imagined speech affects subsequent auditory perception, even for a low-level attribute such as loudness. This effect is observed in early auditory responses in magnetoencephalography and electroencephalography that correlate with behavioural loudness ratings. The results suggest that the internal reconstruction of neural representations without external stimulation is flexibly regulated by task demands, and that such top-down processes can interact with bottom-up information at an early perceptual stage to modulate perception.

Abstract

Synaesthesia is a neurological phenomenon affecting perception, where triggering stimuli (e.g. letters and numbers) elicit unusual secondary sensory experiences (e.g. colours). Family-based studies point to a role for genetic factors in the development of this trait. However, the contributions of common genomic variation to synaesthesia have not yet been investigated. Here, we present the SynGenes cohort, the largest genotyped collection of unrelated people with grapheme–colour synaesthesia (n = 723). Synaesthesia has been associated with a range of other neuropsychological traits, including enhanced memory and mental imagery, as well as greater sensory sensitivity. Motivated by the prior literature on putative trait overlaps, we investigated polygenic scores derived from published genome-wide scans of schizophrenia and autism spectrum disorder (ASD), comparing our SynGenes cohort to 2181 non-synaesthetic controls. We found a very slight association between schizophrenia polygenic scores and synaesthesia (Nagelkerke's R2 = 0.0047, empirical p = 0.0027) and no significant association for scores related to ASD (Nagelkerke's R2 = 0.00092, empirical p = 0.54) or body mass index (R2 = 0.00058, empirical p = 0.60), included as a negative control. As sample sizes for studying common genomic variation continue to increase, genetic investigations of the kind reported here may yield novel insights into the shared biology between synaesthesia and other traits, to complement findings from neuropsychology and brain imaging.