Publications

Abstract

Many psycholinguistic models of speech sequence planning make claims about the onset and offset times of planning units, such as words, syllables, and phonemes. These predictions typically go untested, however, since psycholinguists have assumed that the temporal dynamics of the speech signal is a poor index of the temporal dynamics of the underlying speech planning process. This article argues that this problem is tractable, and presents and validates two simple metrics that derive planning unit onset and offset times from the acoustic signal and articulatographic data.

Abstract

In a recent series of papers, Caramazza and Miozzo [Caramazza, A., 1997. How many levels of processing are there in lexical access? Cognitive Neuropsychology 14, 177-208; Caramazza, A., Miozzo, M., 1997. The relation between syntactic and phonological knowledge in lexical access: evidence from the 'tip-of-the-tongue' phenomenon. Cognition 64, 309-343; Miozzo, M., Caramazza, A., 1997. On knowing the auxiliary of a verb that cannot be named: evidence for the independence of grammatical and phonological aspects of lexical knowledge. Journal of Cognitive Neuropsychology 9, 160-166] argued against the lemma/lexeme distinction made in many models of lexical access in speaking, including our network model [Roelofs, A., 1992. A spreading-activation theory of lemma retrieval in speaking. Cognition 42, 107-142; Levelt, W.J.M., Roelofs, A., Meyer, A.S., 1998. A theory of lexical access in speech production. Behavioral and Brain Sciences, (in press)]. Their case was based on the observations that grammatical class deficits of brain-damaged patients and semantic errors may be restricted to either spoken or written forms and that the grammatical gender of a word and information about its form can be independently available in tip-of-the-tongue stales (TOTs). In this paper, we argue that though our model is about speaking, not taking position on writing, extensions to writing are possible that are compatible with the evidence from aphasia and speech errors. Furthermore, our model does not predict a dependency between gender and form retrieval in TOTs. Finally, we argue that Caramazza and Miozzo have not accounted for important parts of the evidence motivating the lemma/lexeme distinction, such as word frequency effects in homophone production, the strict ordering of gender and pho neme access in LRP data, and the chronometric and speech error evidence for the production of complex morphology.

Abstract

According to most models of speech production, the planning of spoken words involves the independent retrieval of segments and metrical frames followed by segment-to-frame association. In some models, the metrical frame includes a specification of the number and ordering of consonants and vowels, but in the word-form encoding by activation and verification (WEAVER) model (A. Roelofs, 1997), the frame specifies only the stress pattern across syllables. In 6 implicit priming experiments, on each trial, participants produced 1 word out of a small set as quickly as possible. In homogeneous sets, the response words shared word-initial segments, whereas in heterogeneous sets, they did not. Priming effects from shared segments depended on all response words having the same number of syllables and stress pattern, but not on their having the same number of consonants and vowels. No priming occurred when the response words had only the same metrical frame but shared no segments. Computer simulations demonstrated that WEAVER accounts for the findings.

Abstract

P. A. Starreveld and W. La Heij (1995) tested the seriality view of lexical access in speech production, according to which lexical selection and the encoding of a word's form proceed in serial order without feedback. In 2 experiments, they looked at the combined effect of semantic and orthographic relatedness of written distracter words in tasks that required conceptually driven naming. They found an interaction between semantic relatedness and orthographic relatedness and argued that the observed interaction refutes the seriality view of lexical access. In this comment, the authors argue that Starreveld and La Heij's rejection of serial access was based on an oversimplified conception of the seriality view and that interaction, rather than additivity, is predicted by existing conceptions of serial access.

Abstract

This article reports 7 experiments investigating whether utterances are planned in a parallel or rightward incremental fashion during language production. The experiments examined the role of linear order, length, frequency, and repetition in producing Dutch verb–particle combinations. On each trial, participants produced 1 utterance out of a set of 3 as quickly as possible. The responses shared part of their form or not. For particle-initial infinitives, facilitation was obtained when the responses shared the particle but not when they shared the verb. For verb-initial imperatives, however, facilitation was obtained for the verbs but not for the particles. The facilitation increased with length, decreased with frequency, and was independent of repetition. A simple rightward incremental model accounts quantitatively for the results.

Abstract

This article is concerned with how social categories (e.g., wife, mother, sister, tenant, guest) become visible through the actions that individuals perform in social interaction. Using audio and video recordings of social interaction as data and conversation analysis as a method, we examine how individuals display their rights or constraints to perform certain actions by virtue of occupying a certain social category. We refer to actions whose performance is sensitive to membership in a certain social category as category-sensitive actions. Most of the time, the social boundaries surrounding these actions remain invisible because participants in interaction typically act in ways that are consistent with their social status and roles. In this study, however, we specifically examine instances where category boundaries become visible as participants approach, expose, or transgress them. Our focus is on actions with relatively stringent category sensitivity such as requests, offers, invitations, or handling one’s possessions. Ultimately, we believe these are the tip of an iceberg that potentially includes most, if not all, actions.

Abstract

Clinical neuroscience research relying on animal models brought valuable translational insights into the function and pathologies of the human brain. The anatomical, physiological, and behavioural similarities between humans and mammals have prompted researchers to study cerebral mechanisms at different levels to develop and test new treatments. The vast majority of biomedical research uses rodent models, which are easily manipulable and have a broadly resembling organisation to the human nervous system but cannot satisfactorily mimic some disorders. For these disorders, macaque monkeys have been used as they have a more comparable central nervous system. Still, this research has been hampered by limitations, including high costs and reduced samples. This review argues that a squirrel monkey model might bridge the gap by complementing translational research from rodents, macaque, and humans. With the advent of promising new methods such as ultrasound imaging, tool miniaturisation, and a shift towards open science, the squirrel monkey model represents a window of opportunity that will potentially fuel new translational discoveries in the diagnosis and treatment of brain pathologies.

Abstract

A psychophysical analysis of referential communication establishes a causal link between a visual stimulus and a speaker’s perception of this stimulus, and between the speaker’s internal representation and their reference production. Here, I argue that, in addition to visual perception and language, social cognition plays an integral part in this complex process, as it enables successful speaker-listener coordination. This pragmatic analysis of referential communication tries to explain the redundant use of color adjectives. It is well documented that people use color words when it is not necessary to identify the referent; for instance, they may refer to “the blue star” in a display of shapes with a single star. This type of redundancy challenges influential work from cognitive science and philosophy of language, suggesting that human communication is fundamentally efficient. Here, I explain these seemingly contradictory findings by confirming the visual efficiency hypothesis: redundant color words can facilitate the listener’s visual search for a referent, despite making the description unnecessarily long. Participants’ eye movements revealed that they were faster to find “the blue star” than “the star” in a display of shapes with only one star. A language production experiment further revealed that speakers are highly sensitive to a target’s discriminability, systematically reducing their use of redundant color adjectives as the color of the target became more pervasive in a display. It is concluded that a referential expression’s efficiency should be based not only on its informational value, but also on its discriminatory value, which means that redundant color words can be more efficient than shorter descriptions.

Abstract

Pragmatic theories and computational models of reference must account for people’s frequent use of redundant color adjectives (e.g., referring to a single triangle as “the blue triangle”). The standard pragmatic view holds that the informativity of a referential expression depends on pragmatic contrast: Color adjectives should be used to contrast competitors of the same kind to preempt an ambiguity (e.g., between several triangles of different colors), otherwise they are redundant. Here we propose an alternative to the standard view, the incremental efficiency hypothesis, according to which the efficiency of a referential expression must be calculated incrementally over the entire visual context. This is the first theoretical account of referential efficiency that is sensitive to the incrementality of language processing, making different cross-linguistic predictions depending on word order. Experiment 1 confirmed that English speakers produced more redundant color adjectives (e.g., “the blue triangle”) than Spanish speakers (e.g., “el triángulo azul”), but both language groups used more redundant color adjectives in denser displays where it would be more efficient. In Experiments 2A and 2B, we used eye tracking to show that pragmatic contrast is not a processing constraint. Instead, incrementality and efficiency determine that English listeners establish color contrast across categories (BLUE SHAPES > TRIANGULAR ONE), whereas Spanish listeners establish color contrast within a category (TRIANGLES > BLUE ONE). Spanish listeners, however, reversed their visual search strategy when tested in English immediately after. Our results show that speakers and listeners of different languages exploit word order to increase communicative efficiency.

Abstract

This study investigated the extent to which 3- and 4-year-old children may rely on associative memory representations to pass an unexpected-contents false-belief task. In Experiment 1, 4-year-olds performed at chance in both a standard Smarties task and a modified version highlighting the secrecy of the contents of the tube. These results were interpreted as evidence that having to infer the answer to a false-belief question (without relying on memory representations) is generally difficult for preschool children. In Experiments 2a, 2b, and 2c, 3-year-olds were tested at 3-month intervals during their first year of preschool and showed better performance in a narrative version of the Smarties task (chance level) than in the standard version (below-chance level). These children performed even better in an associative version of the narrative task (above-chance level) where they could form a memory representation associating the protagonist with the expected contents of a box. The results of a true-belief control suggest that some of these children may have relied on their memory of the protagonist’s preference for the original contents of the box (rather than their understanding of what the protagonist was expecting to find inside). This suggests that when 3-year-olds passed the associative unexpected-contents task, some may have been keeping track of the protagonist’s initial preference and not only (or not necessarily) of the protagonist’s false belief. These results are interpreted in the light of current accounts of Theory of Mind development and failed replications of verbal false-belief tasks.

Abstract

Language and Theory of Mind come together in communication, but their relationship has been intensely contested. I hypothesize that pragmatic markers connect language and Theory of Mind and enable their co-development and co-evolution through a positive feedback loop, whereby the development of one skill boosts the development of the other. I propose to test this hypothesis by investigating two types of pragmatic markers: demonstratives (e.g., ‘this’ vs. ‘that’ in English) and articles (e.g., ‘a’ vs. ‘the’). Pragmatic markers are closed-class words that encode non-representational information that is unavailable to consciousness, but accessed automatically in processing. These markers have been associated with implicit Theory of Mind because they are used to establish joint attention (e.g., ‘I prefer that one’) and mark shared knowledge (e.g., ‘We bought the house’ vs. ‘We bought a house’). Here I develop a theoretical account of how joint attention (as driven by the use of demonstratives) is the basis for children’s later tracking of common ground (as marked by definite articles). The developmental path from joint attention to common ground parallels language change, with demonstrative forms giving rise to definite articles. This parallel opens the possibility of modelling the emergence of Theory of Mind in human development in tandem with its routinization across language communities and generations of speakers. I therefore propose that, in order to understand the relationship between language and Theory of Mind, we should study pragmatics at three parallel timescales: during language acquisition, language use, and language change.

Abstract

The Violation-of-Expectation paradigm is a widespread paradigm in infancy research that relies on looking time as an index of surprise. This methodological review aims to increase the reliability of future VoE studies by proposing to standardize reporting practices in this literature. I review 15 VoE studies on false-belief reasoning, which used a variety of experimental parameters. An analysis of the distribution of p-values across experiments suggests an absence of p-hacking. However, there are potential concerns with the accuracy of their measures of infants’ attention, as well as with the lack of a consensus on the parameters that should be used to set up VoE studies. I propose that (i) future VoE studies ought to report not only looking times (as a measure of attention) but also looking-away times (as an equally important measure of distraction); (ii) VoE studies must offer theoretical justification for the parameters they use, and (iii) when parameters are selected through piloting, pilot data must be reported in order to understand how parameters were selected. Future VoE studies ought to maximize the accuracy of their measures of infants’ attention since the reliability of their results and the validity of their conclusions both depend on the accuracy of their measures.

Abstract

There is an ongoing debate, both in philosophy and psychology, as to whether people are able to automatically infer what others may know, or whether they can only derive belief inferences by deploying cognitive resources. Evidence from laboratory tasks, often involving false beliefs or visual-perspective taking, has suggested that belief inferences are cognitively costly, controlled processes. Here we suggest that in everyday conversation, belief reasoning is pervasive and therefore potentially automatic in some cases. To test this hypothesis, we conducted two pre-registered self-paced reading experiments (N1 = 91, N2 = 89). The results of these experiments showed that participants slowed down when a stranger commented ‘That greasy food is bad for your ulcer’ relative to conditions where a stranger commented on their own ulcer or a friend made either comment – none of which violated participants’ common-ground expectations. We conclude that Theory of Mind models need to account for belief reasoning in conversation as it is at the center of everyday social interaction

Abstract

A pragmatic account of referential communication is developed which presents an alternative to traditional Gricean accounts by focusing on cooperativeness and efficiency, rather than informativity. The results of four language-production experiments support the view that speakers can be cooperative when producing redundant adjectives, doing so more often when color modification could facilitate the listener's search for the referent in the visual display (Experiment 1a). By contrast, when the listener knew which shape was the target, speakers did not produce redundant color adjectives (Experiment 1b). English speakers used redundant color adjectives more often than Spanish speakers, suggesting that speakers are sensitive to the differential efficiency of prenominal and postnominal modification (Experiment 2). Speakers were also cooperative when using redundant size adjectives (Experiment 3). Overall, these results show how discriminability affects a speaker's choice of referential expression above and beyond considerations of informativity, supporting the view that redundant speakers can be cooperative.

Abstract

The nature of phonological representations has been extensively studied in phonology and psycholinguistics. While full specification is still the norm in psycholinguistic research, underspecified representations may better account for perceptual asymmetries. In this paper, we report on a mismatch negativity (MMN) study with Dutch listeners who took part in a passive oddball paradigm to investigate when the brain notices the difference between expected and observed vowels. In particular, we tested neural discrimination (indicating perceptual discrimination) of the tense mid vowel pairs /o/-/ø/ (place contrast), /e/-/ø/ (labiality or rounding contrast), and /e/-/o/ (place and labiality contrast). Our results show (a) a perceptual asymmetry for place in the /o/-/ø/ contrast, supporting underspecification of [CORONAL] and replicating earlier results for German, and (b) a perceptual asymmetry for labiality for the /e/-/ø/ contrast, which was not reported in the German study. A labial deviant [ø] (standard /e/) yielded a larger MMN than a deviant [e] (standard /ø/). No asymmetry was found for the two-feature contrast. This study partly replicates a similar MMN study on German vowels, and partly presents new findings indicating cross-linguistic differences. Although the vowel inventory of Dutch and German is to a large extent comparable, their (morpho)phonological systems are different, which is reflected in processing.

Abstract

Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide.

Abstract

We analysed both structural and functional aspects of sentences containing the four
adverbials “after”, “before”, “because”, and “if” in two dense corpora of parent-child
interactions from two British English-acquiring children (2;00–4;07). In comparing
mothers’ and children’s usage we separate out the effects of frequency, cognitive
complexity and pragmatics in explaining the course of acquisition of adverbial
sentences. We also compare these usage patterns to stimuli used in a range of
experimental studies and show how differences may account for some of the difficulties
that children have shown in experiments. In addition, we report descriptive data on
various aspects of adverbial sentences that have not yet been studied as a resource for
future investigations.

Abstract

We study how people attend to and memorize endings of events that differ in the degree to which objects in them are affected by an action: Resultative events show objects that undergo a visually salient change in state during the course of the event (peeling a potato), and non‐resultative events involve objects that undergo no, or only partial state change (stirring in a pan). We investigate general cognitive principles, and potential language‐specific influences, in verbal and nonverbal event encoding and memory, across two experiments with Dutch and Estonian participants. Estonian marks a viewer's perspective on an event's result obligatorily via grammatical case on direct object nouns: Objects undergoing a partial/full change in state in an event are marked with partitive/accusative case, respectively. Therefore, we hypothesized increased saliency of object states and event results in Estonian speakers, as compared to speakers of Dutch. Findings show (a) a general cognitive principle of attending carefully to endings of resultative events, implying cognitive saliency of object states in event processing; (b) a language‐specific boost on attention and memory of event results under verbal task demands in Estonian speakers. Results are discussed in relation to theories of event cognition, linguistic relativity, and thinking for speaking.

Abstract

In recent years, it has become clear that attention plays an important role in spoken word production. Some of this evidence comes from distributional analyses of reaction time (RT) in regular picture naming and picture-word interference. Yet we lack a mechanistic account of how the properties of RT distributions come to reflect attentional processes and how these processes may in turn modulate the amount of conflict between lexical representations. Here, we present a computational account according to which attentional lapses allow for existing conflict to build up unsupervised on a subset of trials, thus modulating the shape of the resulting RT distribution. Our process model resolves discrepancies between outcomes of previous studies on semantic interference. Moreover, the model's predictions were confirmed in a new experiment where participants' motivation to remain attentive determined the size and distributional locus of semantic interference in picture naming. We conclude that process modeling of RT distributions importantly improves our understanding of the interplay between attention and conflict in word production. Our model thus provides a framework for interpreting distributional analyses of RT data in picture naming tasks.

Abstract

Memory is fundamental for comprehending and segmenting the flow of activity around us into units called “events”. Here, we investigate the effect of the movement dynamics of actions (ceased, ongoing) and the inner structure of events (with or without object-state change) on people's event memory. Furthermore, we investigate how describing events, and the meaning and form of verb predicates used (denoting a culmination moment, or not, in single verbs or verb-satellite constructions), affects event memory. Before taking a surprise recognition task, Spanish and Mandarin speakers (who lexicalise culmination in different verb predicate forms) watched short videos of events, either in a non-verbal (probe-recognition) or a verbal experiment (event description). Results show that culminated events (i.e. ceased change-of-state events) were remembered best across experiments. Language use showed to enhance memory overall. Further, the form of the verb predicates used for denoting culmination had a moderate effect on memory.

Abstract

Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.

Abstract

Human experience and communication are centred on events, and event apprehension is a rapid process that draws on the visual perception and immediate categorization of event roles (“who does what to whom”). We demonstrate a role for syntactic structure in visual information uptake for event apprehension. An event structure foregrounding either the agent or patient was activated during speaking, transiently modulating the apprehension of subsequently viewed unrelated events. Speakers of Dutch described pictures with actives and passives (agent and patient foregrounding, respectively). First fixations on pictures of unrelated events that were briefly presented (for 300 ms) next were influenced by the active or passive structure of the previously produced sentence. Going beyond the study of how single words cue object perception, we show that sentence structure guides the viewpoint taken during rapid event apprehension.

Abstract

The epigenetic enzyme p300/CBP-associated factor (PCAF) belongs to the GCN5-related N-acetyltransferase (GNAT) family together with GCN5. Although its transcriptional and post-translational function is well characterized, little is known about its properties as regulator of cell metabolism. Here, we report the mitochondrial localization of PCAF conferred by an 85 aa mitochondrial targeting sequence (MTS) at the N-terminal region of the protein. In mitochondria, one of the PCAF targets is the isocitrate dehydrogenase 2 (IDH2) acetylated at lysine 180. This PCAF-regulated post-translational modification might reduce IDH2 affinity for isocitrate as a result of a conformational shift involving predictively the tyrosine at position 179. Site-directed mutagenesis and functional studies indicate that PCAF regulates IDH2, acting at dual level during myoblast differentiation: at a transcriptional level together with MyoD, and at a post-translational level by direct modification of lysine acetylation in mitochondria. The latter event determines a decrease in IDH2 function with negative consequences on muscle fiber formation in C2C12 cells. Indeed, a MTS-deprived PCAF does not localize into mitochondria, remains enriched into the nucleus, and contributes to a significant increase of muscle-specific gene expression enhancing muscle differentiation. The role of PCAF in mitochondria is a novel finding shedding light on metabolic processes relevant to early muscle precursor differentiation.—Savoia, M., Cencioni, C., Mori, M., Atlante, S., Zaccagnini, G., Devanna, P., Di Marcotullio, L., Botta, B., Martelli, F., Zeiher, A. M., Pontecorvi, A., Farsetti, A., Spallotta, F., Gaetano, C. P300/CBP-associated factor regulates transcription and function of isocitrate dehydrogenase 2 during muscle differentiation.

Abstract

Background

Heterozygous variants in CNTNAP2 have been implicated in a wide range of neurological phenotypes, including intellectual disability (ID), epilepsy, autistic spectrum disorder (ASD), and impaired language. However, heterozygous variants can also be found in unaffected individuals. Biallelic CNTNAP2 variants are rarer and cause a well-defined genetic syndrome known as CASPR2 deficiency disorder, a condition characterised by ID, early-onset refractory epilepsy, language impairment, and autistic features.
Case-report

A 7-year-old boy presented with hyperkinetic stereotyped movements that started during early infancy and persisted over childhood. Abnormal movements consisted of rhythmic and repetitive shaking of the four limbs, with evident stereotypic features. Additional clinical features included ID, attention deficit-hyperactivity disorder (ADHD), ASD, and speech impairment, consistent with CASPR2 deficiency disorder. Whole-genome array comparative genomic hybridization detected a maternally inherited 0.402 Mb duplication, which involved intron 1, exon 2, and intron 2 of CNTNAP2 (c.97 +?_209-?dup). The affected region in intron 1 contains a binding site for the transcription factor FOXP2, potentially leading to abnormal CNTNAP2 expression regulation. Sanger sequencing of the coding region of CNTNAP2 also identified a paternally-inherited missense variant c.2752C > T, p.(Leu918Phe).
Conclusion

This case expands the molecular and phenotypic spectrum of CASPR2 deficiency disorder, suggesting that Hyperkinetic stereotyped movements may be a rare, yet significant, clinical feature of this complex neurological disorder. Furthermore, the identification of an in-frame, largely non-coding duplication in CNTNAP2 points to a sophisticated underlying molecular mechanism, likely involving impaired FOXP2 binding.

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 evaluation of transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) promises valuable information about fundamental brain related mechanisms and may serve as a diagnostic tool for clinical monitoring of therapeutic progress or surgery procedures. However, reports about spontaneous fluctuations of MEP amplitudes causing high intra-individual variability have led to increased concerns about the reliability of this measure. One possible cause for high variability of MEPs could be neuronal oscillatory activity, which reflects fluctuations of membrane potentials that systematically increase and decrease the excitability of neuronal networks. Here, we investigate the dependence of MEP amplitude on oscillation power and phase by combining the application of single pulse TMS over the primary motor cortex with concurrent recordings of electromyography and electroencephalography. Our results show that MEP amplitude is correlated to alpha phase, alpha power as well as beta phase. These findings may help explain corticospinal excitability fluctuations by highlighting the modulatory effect of alpha and beta phase on MEPs. In the future, controlling for such a causal relationship may allow for the development of new protocols, improve this method as a (diagnostic) tool and increase the specificity and efficacy of general TMS applications.

Abstract

The CELEX lexical database includes a list of Dutch syllables and their frequencies, based on syllabification of isolated word forms. In connected speech, however, sentence-level phonological rules can modify the syllables and their token frequencies. In order to estimate the changes syllables may undergo in connected speech, an empirical investigation was carried out. A large Dutch text corpus (TROUW) was transcribed, processed by word level rules, and syllabified. The resulting lexeme syllables were evaluated by comparing them to the CELEX lexical database for Dutch. Then additional phonological sentence-level rules were applied to the TROUW corpus, and the frequencies of the resulting connected speech syllables were compared with those of the lexeme syllables from TROUW. The overall correlation between lexeme and speech syllables was very high. However, speech syllables generally had more complex CV structures than lexeme syllables. Implications of the results for research involving syllables are discussed. With respect to the notion of a mental syllabary (a store for precompiled articulatory programs for syllables, see Levelt & Wheeldon, 1994) this study revealed an interesting statistical result. The calculation of the cumulative syllable frequencies showed that 85% of the syllable tokens in Dutch can be covered by the 500 most frequent syllable types, which makes the idea of a syllabary very attractive.

Abstract

To investigate the role of the syllable in Dutch speech production, five experiments were carried out to examine the effect of visually masked syllable primes on the naming latencies for written words and pictures. Targets had clear syllable boundaries and began with a CV syllable (e.g., ka.no) or a CVC syllable (e.g., kak.tus), or had ambiguous syllable boundaries and began with a CV[C] syllable (e.g., ka[pp]er). In the syllable match condition, bisyllabic Dutch nouns or verbs were preceded by primes that were identical to the target’s first syllable. In the syllable mismatch condition, the prime was either shorter or longer than the target’s first syllable. A neutral condition was also included. None of the experiments showed a syllable priming effect. Instead, all related primes facilitated the naming of the targets. It is concluded that the syllable does not play a role in the process of phonological encoding in Dutch. Because the amount of facilitation increased with increasing overlap between prime and target, the priming effect is accounted for by a segmental overlap hypothesis.

Abstract

In certain varieties of Dutch spoken among young people, the preposition and determiner in locative and directional PPs can sometimes be omitted. We argue on the basis of language data taken from Twitter and intuitions of young speakers of Dutch that nominal arguments in these constructions do not have a DP layer, the absence of which leads to a special interpretation. The option to omit the preposition is related to the structural and semantic complexity of the verb. The bare construction is possible only with simple verbs, and not with manner-of-motion verbs. We present an analysis that accounts for the non-pronunciation of prepositions in directional predicates by claiming that they can be licensed through incorporation into the verb. This type of incorporation is blocked if the verb is structurally complex.

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

When comprehending speech-in-noise (SiN), younger and older adults benefit from seeing the speaker’s mouth, i.e. visible speech. Younger adults additionally benefit from manual iconic co-speech gestures. Here, we investigate to what extent younger and older adults benefit from perceiving both visual articulators while comprehending SiN, and whether this is modulated by working memory and inhibitory control. Twenty-eight younger and 28 older adults performed a word recognition task in three visual contexts: mouth blurred (speech-only), visible speech, or visible speech + iconic gesture. The speech signal was either clear or embedded in multitalker babble. Additionally, there were two visual-only conditions (visible speech, visible speech + gesture). Accuracy levels for both age groups were higher when both visual articulators were present compared to either one or none. However, older adults received a significantly smaller benefit than younger adults, although they performed equally well in speech-only and visual-only word recognition. Individual differences in verbal working memory and inhibitory control partly accounted for age-related performance differences. To conclude, perceiving iconic gestures in addition to visible speech improves younger and older adults’ comprehension of SiN. Yet, the ability to benefit from this additional visual information is modulated by age and verbal working memory. Future research will have to show whether these findings extend beyond the single word level.

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

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

Although feedforward activity may suffice for recognizing objects in isolation, additional visual operations that aid object recognition might be needed for real-world scenes. One such additional operation is figure-ground segmentation, extracting the relevant features and locations of the target object while ignoring irrelevant features. In this study of 60 human participants (female and male), we show objects on backgrounds of increasing complexity to investigate whether recurrent computations are increasingly important for segmenting objects from more complex backgrounds. Three lines of evidence show that recurrent processing is critical for recognition of objects embedded in complex scenes. First, behavioral results indicated a greater reduction in performance after masking objects presented on more complex backgrounds, with the degree of impairment increasing with increasing background complexity. Second, electroencephalography (EEG) measurements showed clear differences in the evoked response potentials between conditions around time points beyond feedforward activity, and exploratory object decoding analyses based on the EEG signal indicated later decoding onsets for objects embedded in more complex backgrounds. Third, deep convolutional neural network performance confirmed this interpretation. Feedforward and less deep networks showed a higher degree of impairment in recognition for objects in complex backgrounds compared with recurrent and deeper networks. Together, these results support the notion that recurrent computations drive figure-ground segmentation of objects in complex scenes.SIGNIFICANCE STATEMENT The incredible speed of object recognition suggests that it relies purely on a fast feedforward buildup of perceptual activity. However, this view is contradicted by studies showing that disruption of recurrent processing leads to decreased object recognition performance. Here, we resolve this issue by showing that how object recognition is resolved and whether recurrent processing is crucial depends on the context in which it is presented. For objects presented in isolation or in simple environments, feedforward activity could be sufficient for successful object recognition. However, when the environment is more complex, additional processing seems necessary to select the elements that belong to the object and by that segregate them from the background.

Abstract

Object and scene recognition both require mapping of incoming sensory information to existing conceptual knowledge about the world. A notable finding in brain-damaged patients is that they may show differentially impaired performance for specific categories, such as for “living exemplars”. While numerous patients with category-specific impairments have been reported, the explanations for these deficits remain controversial. In the current study, we investigate the ability of a brain injured patient with a well-established category-specific impairment of semantic memory to perform two categorization experiments: ‘natural’ vs. ‘manmade’ scenes (experiment 1) and objects (experiment 2). Our findings show that the pattern of categorical impairment does not respect the natural versus manmade distinction. This suggests that the impairments may be better explained by differences in visual features, rather than by category membership. Using Deep Convolutional Neural Networks (DCNNs) as ‘artificial animal models’ we further explored this idea. Results indicated that DCNNs with ‘lesions’ in higher order layers showed similar response patterns, with decreased relative performance for manmade scenes (experiment 1) and natural objects (experiment 2), even though they have no semantic category knowledge, apart from a mapping between pictures and labels. Collectively, these results suggest that the direction of category-effects to a large extent depends, at least in MS′ case, on the degree of perceptual differentiation called for, and not semantic knowledge.

Abstract

This article discusses how the Trobriand Islanders speak about body and mind. It addresses the following questions: do the linguistic datafit into theories about lexical universals of body-part terminology? Can we make inferences about the Trobrianders' conceptualization of psychological and physical states on the basis of these data? If a Trobriand Islander sees these idioms as external manifestations of inner states, then can we interpret them as a kind of ethnopsychological theory about the body and its role for emotions, knowledge, thought, memory, and so on? Can these idioms be understood as representation of Trobriand ethnopsychological theory?

Abstract

Contrary to received opinion, the Aristotelian Square of Opposition (square) is logically sound, differing from standard modern predicate logic (SMPL) only in that it restricts the universe U of cognitively constructible situations by banning null predicates, making it less unnatural than SMPL. U-restriction strengthens the logic without making it unsound. It also invites a cognitive approach to logic. Humans are endowed with a cognitive predicate logic (CPL), which checks the process of cognitive modelling (world construal) for consistency. The square is considered a first approximation to CPL, with a cognitive set-theoretic semantics. Not being cognitively real, the null set Ø is eliminated from the semantics of CPL. Still rudimentary in Aristotle’s On Interpretation (Int), the square was implicitly completed in his Prior Analytics (PrAn), thereby introducing U-restriction. Abelard’s reconstruction of the logic of Int is logically and historically correct; the loca (Leaking O-Corner Analysis) interpretation of the square, defended by some modern logicians, is logically faulty and historically untenable. Generally, U-restriction, not redefining the universal quantifier, as in Abelard and loca, is the correct path to a reconstruction of CPL. Valuation Space modelling is used to compute the effects of U-restriction.

Abstract

Semantic Syntax (SeSyn), originally called Generative Semantics, is an offshoot of Chomskyan generative grammar (ChoGG), rejected by Chomsky and his school in the late 1960s. SeSyn is the theory of algorithmical grammars producing the well-formed sentences of a language L from the corresponding semantic input, the Semantic Analysis (SA), represented as a traditional tree structure diagram in a specific formal language of incremental predicate logic with quantifying and qualifying operators (including the truth functions), and with all lexical items filled in. A SeSyn-type grammar is thus by definition transformational, but not generative. The SA originates in cognition in a manner that is still largely mysterious, but its actual form can be distilled from the Surface Structure (SS) of the sentences of L following the principles set out in SeSyn. In this presentation we provide a more or less technical résumé of the SeSyn theory. A comparison is made with ChoGG-type grammars, which are rejected on account of their intrinsic unsuitability as a cognitive-realist grammar model. The ChoGG model follows the pattern of a 1930s neopositivist Carnap-type grammar for formal logical languages. Such grammars are random sentence generators, whereas, obviously, (nonpathological) humans are not. A ChoGG-type grammar is fundamentally irreconcilable with a mentalist-realist theory of grammar. The body of the paper consists in a demonstration of the production of an English and a French sentence, the latter containing a classic instance of the cyclic rule of Predicate Raising (PR), essential in the general theory of clausal complementation yet steadfastly repudiated in ChoGG for reasons that have never been clarified. The processes and categories defined in SeSyn are effortlessly recognised in languages all over the world, whether indigenous or languages of a dominant culture—taking into account language-specific values for the general theoretical parameters involved. This property makes SeSyn particularly relevant for linguistic typology, which now ranks as the most promising branch of linguistics but has so far conspicuously lacked an adequate theoretical basis.

Abstract

One of the challenges in speech perception is that listeners must deal with considerable
segmental and suprasegmental variability in the acoustic signal due to differences between talkers. Most previous studies have focused on how listeners deal with segmental variability.
In this EEG experiment, we investigated whether listeners track talker-specific usage of suprasegmental cues to lexical stress to recognize spoken words correctly. In a three-day training phase, Dutch participants learned to map non-word minimal stress pairs onto different object referents (e.g., USklot meant “lamp”; usKLOT meant “train”). These non-words were
produced by two male talkers. Critically, each talker used only one suprasegmental cue to signal stress (e.g., Talker A used only F0 and Talker B only intensity). We expected participants to learn which talker used which cue to signal stress. In the test phase, participants indicated whether spoken sentences including these non-words were correct (“The word for lamp is…”).
We found that participants were slower to indicate that a stimulus was correct if the non-word was produced with the unexpected cue (e.g., Talker A using intensity). That is, if in training Talker A used F0 to signal stress, participants experienced a mismatch between predicted and perceived phonological word-forms if, at test, Talker A unexpectedly used intensity to cue
stress. In contrast, the N200 amplitude, an event-related potential related to phonological
prediction, was not modulated by the cue mismatch. Theoretical implications of these
contrasting results are discussed. The behavioral findings illustrate talker-specific prediction of prosodic cues, picked up through perceptual learning during training.

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

Autism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing versus empathizing cognitive styles, with resemblances to male versus female average sex differences. Left-right asymmetry of the brain is an important aspect of its organization that shows average differences between the sexes, and can be altered in both ASD and schizophrenia. Here we mapped multivariate associations of polygenic risk scores for ASD and schizophrenia with asymmetries of regional cerebral cortical surface area, thickness and subcortical volume measures in 32,256 participants from the UK Biobank. Polygenic risks for the two disorders were positively correlated (r=0.08, p=7.13×10-50), and both were higher in females compared to males, consistent with biased participation against higher-risk males. Each polygenic risk score was associated with multivariate brain asymmetry after adjusting for sex, ASD r=0.03, p=2.17×10-9, schizophrenia r=0.04, p=2.61×10-11, but the multivariate patterns were mostly distinct for the two polygenic risks, and neither resembled average sex differences. Annotation based on meta-analyzed functional imaging data showed that both polygenic risks were associated with asymmetries of regions important for language and executive functions, consistent with behavioural associations that arose in phenome-wide association analysis. Overall, the results indicate that distinct patterns of subtly altered brain asymmetry may be functionally relevant manifestations of polygenic risks for ASD and schizophrenia, but do not support brain masculinization or feminization in their etiologies.

Abstract

Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We resampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers compared to right-handers showed average differences of surface area asymmetry within the fusiform cortex, the anterior insula, the anterior middle cingulate cortex, and the precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB, TUBA1B, TUBB3, TUBB4A, MAP2, and NME7—mutations in the latter can cause left to right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness: on the postcentral gyrus and the inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas nonheritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.

Abstract

Left–right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and it can be altered in cognitive and psychiatric disorders. No mechanism has yet been identified for establishing the human brain’s left–right axis. We performed multivariate genome-wide association scanning of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci associated with different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left–right axis determination in other organs of invertebrates and frogs. Genetic variants associated with brain asymmetry overlapped with those associated with autism, educational attainment and schizophrenia. Comparably large datasets will likely be required in future studies, to replicate and further clarify the associations of microtubule-related genes with variation in brain asymmetry, behavioural and psychiatric traits.

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

Several abilities outside literacy proper are associated with reading and spelling, both phenotypically and genetically, though our knowledge of multivariate genomic covariance structures is incomplete. Here, we introduce structural models describing genetic and residual influences between traits to study multivariate links across measures of literacy, phonological awareness, oral language, and phonological working memory (PWM) in unrelated UK youth (8-13 years, N=6,453). We find that all phenotypes share a large proportion of underlying genetic variation, although especially oral language and PWM reveal substantial differences in their genetic variance composition with substantial trait-specific genetic influences. Multivariate genetic and residual trait covariance showed concordant patterns, except for marked differences between oral language and literacy/phonological awareness, where strong genetic links contrasted near-zero residual overlap. These findings suggest differences in etiological mechanisms, acting beyond a pleiotropic set of genetic variants, and implicate variation in trait modifiability even among phenotypes that have high genetic correlations.

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

This article addresses the problem of computing an upper bound of
the degree d of a polynomial solution P(x) of an algebraic differ-
ence equation of the form Gx)(P(x −τ1), . . . , P(x −τs) + G0(x) =

0 when such P(x) with the coefficients in a field K of character-
istic zero exists and where G is a non-linear s-variable polynomial
with coefficients in K[x] and G0 is a polynomial with coefficients
in K.
It will be shown that if G is a quadratic polynomial with constant
coefficients then one can construct a countable family of polynomi-
als fl(u0) such that if there exists a (minimal) index l0 with fl0(u0)
being a non-zero polynomial, then the degree d is one of its roots
or d ≤ l0, or d < deg(G0). Moreover, the existence of such l0 will
be proven for K being the field of real numbers. These results are
based on the properties of the modules generated by special fami-
lies of homogeneous symmetric polynomials.
A sufficient condition for the existence of a similar bound of the
degree of a polynomial solution for an algebraic difference equation
with G of arbitrary total degree and with variable coefficients will
be proven as well.

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

A doubly quantified sentence, such as All hikers climbed a hill, allows two interpretations: Did all hikers climb different hills, or did they climb the same hill? Previous work has shown that comprehenders construct disambiguated logical representations of these interpretations (Raffray & Pickering, 2010). We extended this line of research by investigating whether bilingual logical representations are shared between languages or separate per language. We conducted four sentence-picture matching experiments in which we primed interpretations of doubly quantified sentences in Dutch and French monolingual and bilingual language comprehension. These experiments showed that bilinguals have fully shared logical representations and that logical representations constructed in the L1 and the L2 are comparable. Moreover, a control experiment ruled out that the priming effects were driven by visual overlap between prime and target pictures. We discuss these findings in terms of a language-dependent account of logical representations, although these findings can also be reconciled with the idea that logical representations involve conceptual mental models of sentence meaning.

Abstract

Linguistic labels exert a particularly strong top-down influence on perception. The potency of this influence has been ascribed to their ability to evoke category-diagnostic features of concepts. In doing this, they facilitate the formation of a perceptual template concordant with those features, effectively biasing perceptual activation towards the labelled category. In this study, we employ a cueing paradigm with moving, point-light stimuli across three experiments, in order to examine how the number of biological motion features (form and kinematics) encoded in lexical cues modulates the efficacy of lexical top-down influence on perception. We find that the magnitude of lexical influence on biological motion perception rises as a function of the number of biological motion-relevant features carried by both cue and target. When lexical cues encode multiple biological motion features, this influence is robust enough to mislead participants into reporting erroneous percepts, even when a masking level yielding high performance is used.

Abstract

Meanings communicated with depictions constitute an integral part of how speakers and signers actually use language (Clark, 2016). Recent studies have argued that, in sign languages, depicting strategy like constructed action (CA), in which a signer enacts the referent, is used for referential purposes in narratives. Here, we tested the referential function of CA in a more controlled experimental setting and outside narrative context. Given the iconic properties of CA we hypothesized that this strategy could be used for efficient information transmission. Thus, we asked if use of CA increased with the increase in the information required to be communicated. Twenty-three deaf signers of LIS described unconnected images, which varied in the amount of information represented, to another player in a director–matcher game. Results revealed that participants used CA to communicate core information about the images and also increased the use of CA as images became informatively denser. The findings show that iconic features of CA can be used for referential function in addition to its depictive function outside narrative context and to achieve communicative efficiency.

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

Spinocerebellar ataxia type 23 (SCA23) is a late‐onset neurodegenerative disorder characterized by slowly progressive gait and limb ataxia, for which there is no therapy available. It is caused by pathogenic variants in PDYN, which encodes prodynorphin (PDYN). PDYN is processed into the opioid peptides α‐neoendorphin and dynorphins (Dyn) A and B; inhibitory neurotransmitters that function in pain signaling, stress‐induced responses and addiction. Variants causing SCA23 mostly affect Dyn A, leading to loss of secondary structure and increased peptide stability. PDYNR212W mice express human PDYN containing the SCA23 variant p.R212W. These mice show progressive motor deficits from 3 months of age, climbing fiber (CF) deficits from 3 months of age, and Purkinje cell (PC) loss from 12 months of age. A mouse model for SCA1 showed similar CF deficits, and a recent study found additional developmental abnormalities, namely increased GABAergic interneuron connectivity and non‐cell autonomous disruption of PC function. As SCA23 mice show a similar pathology to SCA1 mice in adulthood, we hypothesized that SCA23 may also follow SCA1 pathology during development. Examining PDYNR212W cerebella during development, we uncovered developmental deficits from 2 weeks of age, namely a reduced number of GABAergic synapses on PC soma, possibly leading to the observed delay in early phase CF elimination between 2 and 3 weeks of age. Furthermore, CFs did not reach terminal height, leaving proximal PC dendrites open to be occupied by parallel fibers (PFs). The observed increase in vGlut1 protein—a marker for PF‐PC synapses—indicates that PFs indeed take over CF territory and have increased connectivity with PCs. Additionally, we detected altered expression of several critical Ca2+ channel subunits, potentially contributing to altered Ca2+ transients in PDYNR212W cerebella. These findings indicate that developmental abnormalities contribute to the SCA23 pathology and uncover a developmental role for PDYN in the cerebellum.

Abstract

Orthographic systems vary dramatically in the extent to which they encode a language’s phonological and lexico-semantic structure. Studies of the effects of orthographic transparency suggest that such variation is likely to have major implications for how the reading system operates. However, such studies have been unable to examine in isolation the contributory effect of transparency on reading due to co-varying linguistic or socio-cultural factors. We first investigated the phonological properties of languages using the range of the world’s orthographic systems (alphabetic; alphasyllabic; consonantal; syllabic; logographic), and found that, once geographical proximity is taken into account, phonological properties do not relate to orthographic system. We then explored the processing implications of orthographic variation by training a connectionist implementation of the triangle model of reading on the range of orthographic systems whilst controlling for phonological and semantic structure. We show that the triangle model is effective as a universal model of reading, able to replicate key behavioural and neuroscientific results. Importantly, the model also generates new predictions deriving from an explicit description of the effects of orthographic transparency on how reading is realised and defines the consequences of orthographic systems on reading processes.

Abstract

A quantitative model of human categorization behavior is proposed, which can be applied to 4-alternative forced-choice categorization data involving two binary classifications. A number of processing dependencies between the two classifications are explicitly formulated, such as the dependence of the location, orientation, and steepness of the class boundary for one classification on the outcome of the other classification. The significance of various types of dependencies can be tested statistically. Analyses of a data set from the literature shows that interesting dependencies in human speech recognition can be uncovered using the model.

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

SATB2-associated syndrome (SAS) is a neurodevelopmental disorder caused by heterozygous pathogenic variants in the SATB2 gene, and is typically characterized by intellectual disability and severely impaired communication skills. The goal of this study was to contribute to the understanding of speech and language impairments in SAS, in the context of general developmental skills and cognitive and adaptive functioning. We performed detailed oral motor, speech and language profiling in combination with neuropsychological assessments in 23 individuals with a molecularly confirmed SAS diagnosis: 11 primarily verbal individuals and 12 primarily nonverbal individuals, independent of their ages. All individuals had severe receptive language delays. For all verbal individuals, we were able to define underlying speech conditions. While childhood apraxia of speech was most prevalent, oral motor problems appeared frequent as well and were more present in the nonverbal group than in the verbal group. For seven individuals, age-appropriate Wechsler indices could be derived, showing that the level of intellectual functioning of these individuals varied from moderate–mild ID to mild ID-borderline intellectual functioning. Assessments of adaptive functioning with the Vineland Screener showed relatively high scores on the domain “daily functioning” and relatively low scores on the domain “communication” in most individuals. Altogether, this study provides a detailed delineation of oral motor, speech and language skills and neuropsychological functioning in individuals with SAS, and can provide families and caregivers with information to guide diagnosis, management and treatment approaches.

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

Heterozygous pathogenic variants in various FOXP genes cause specific developmental disorders. The phenotype associated with heterozygous variants in FOXP4 has not been previously described.
We assembled a cohort of eight individuals with heterozygous and mostly de novo variants in FOXP4: seven individuals with six different missense variants and one individual with a frameshift variant. We collected clinical data to delineate the phenotypic spectrum, and used in silico analyses and functional cell-based assays to assess pathogenicity of the variants.
We collected clinical data for six individuals: five individuals with a missense variant in the forkhead box DNA-binding domain of FOXP4, and one individual with a truncating variant. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia, cervical spine abnormalities, and ptosis. Luciferase assays showed loss-of-function effects for all these variants, and aberrant subcellular localization patterns were seen in a subset. The remaining two missense variants were located outside the functional domains of FOXP4, and showed transcriptional repressor capacities and localization patterns similar to the wild-type protein.
Collectively, our findings show that heterozygous loss-of-function variants in FOXP4 are associated with an autosomal dominant neurodevelopmental disorder with speech/language delays, growth defects, and variable congenital abnormalities.

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

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Abstract

Do we structure object-related conceptual information according to real-world sensorimotor experience, or can it also be shaped by linguistic information? This study investigates whether a feature of language coded in grammar—numeral classifiers—affects the conceptual representation of objects. We compared speakers of Mandarin (a classifier language) with speakers of Dutch (a language without classifiers) on how they judged object similarity in four studies. In the first three studies, participants had to rate how similar a target object was to four comparison objects, one of which shared a classifier with the target. Objects were presented as either words or pictures. Overall, the target object was always rated as most similar to the object with the shared classifier, but this was the case regardless of the language of the participant. In a final study employing a successive pile-sorting task, we also found that the underlying object concepts were similar for speakers of Mandarin and Dutch. Speakers of a non-classifier language are therefore sensitive to the same conceptual similarities that underlie classifier systems in a classifier language. Classifier systems may therefore reflect conceptual structure, rather than shape it.

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

We present the first ERP experiments that test the online processing of the scalar implicature some ⇝ not all in contexts where the speaker competence assumption is violated. Participants observe game scenarios with four open cards on the table and two closed cards outside of the table, while listening to statements made by a virtual player. In the full access context, the player makes a fully informed statement by referring only to the open cards, as cards on the table; in the partial access context, she makes a partially informed statement by referring to the whole set of cards, as cards in the game. If all of the open cards contain a given object X (Fullset condition), then some cards on the table contain Xs is inconsistent with the not all reading, whereas it is unknown whether some cards in the game contain X is consistent with this reading. If only a subset of the open cards contains X (Subset condition), then both utterances are known to be consistent with the not all implicature. Differential effects are observed depending on the quantifier reading adopted by the participant: For those participants who adopt the not all reading in the full access context, but not in the partial access context (weak pragmatic reading), a late posterior negativity effect is observed in the partial access context for the Fullset relative to the Subset condition. This effect is argued to reflect inference-driven context retrieval and monitoring processes related to epistemic reasoning involved in evaluating the competence assumption. By contrast, for participants who adopt the logical interpretation of some (some and possibly all), an N400 effect is observed in the partial access context, when comparing the Subset against the Fullset condition, which is argued to result from the competition between the two quantifying expressions some cards on the table and some cards in the game functioning in the experiment as scalar alternatives.

Abstract

Purpose: When we speak, we gesture, and indeed, persons with aphasia gesture more frequently. The reason(s) for this is still being investigated, spurring an increase in the number of studies of gesture in persons with aphasia. As the number of studies increases, so too does the need for a shared set of best practices for gesture research in aphasia. After briefly reviewing the importance and use of gesture in persons with aphasia, this viewpoint puts forth methodological and design considerations when evaluating gesture in persons with aphasia.
Method & Results: We explore several different design and methodological considerations for gesture research specific to persons with aphasia, such as video angle specifications, data collection techniques, and analysis considerations. The goal of these suggestions is to develop transparent and reproducible methods for evaluating gesture in aphasia to build a solid foundation for continued work in this area.
Conclusions: We have proposed that it is critical to evaluate multimodal communication in a methodologically robust way to facilitate increased knowledge about the relationship of gesture to spoken language, cognition, and to other aspects of living with aphasia and recovery from aphasia. We conclude by postulating future directions for gesture research in aphasia.

Abstract

Abstract Objective Paroxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations. Methods Confounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses. Results Our analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations. Significance Our results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

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

Lesch-Nyhan disease (LND) is an inherited disorder caused by pathogenic variants in the HPRT1 gene, which encodes the purine recycling enzyme hypoxanthine–guanine phosphoribosyltransferase (HGprt). We generated 6 induced pluripotent stem cell (iPSC) lines from 3 individuals with LND, along with 6 control lines from 3 normal individuals. All 12 lines had the characteristics of pluripotent stem cells, as assessed by immunostaining for pluripotency markers, expression of pluripotency genes, and differentiation into the 3 primary germ cell layers. Gene expression profiling with RNAseq demonstrated significant heterogeneity among the lines. Despite this heterogeneity, several anticipated abnormalities were readily detectable across all LND lines, including reduced HPRT1 mRNA. Several unexpected abnormalities were also consistently detectable across the LND lines, including decreases in FAR2P1 and increases in RNF39. Shotgun proteomics also demonstrated several expected abnormalities in the LND lines, such as absence of HGprt protein. The proteomics study also revealed several unexpected abnormalities across the LND lines, including increases in GNAO1 decreases in NSE4A. There was a good but partial correlation between abnormalities revealed by the RNAseq and proteomics methods. Finally, functional studies demonstrated LND lines had no HGprt enzyme activity and resistance to the toxic pro-drug 6-thioguanine. Intracellular purines in the LND lines were normal, but they did not recycle hypoxanthine. These cells provide a novel resource to reveal insights into the relevance of heterogeneity among iPSC lines and applications for modeling LND.