Publications

Abstract

Although visual imagery is argued to be an essential component of autobiographical memory, there have been surprisingly few studies on autobiographical memory processes in blind individuals, who have had no or limited visual input. The purpose of the present study was to investigate how blindness affects retrieval and phenomenology of autobiographical memories. We asked 48 congenital/early blind and 48 sighted participants to recall autobiographical memories in response to six cue words, and to fill out the Autobiographical Memory Questionnaire measuring a number of variables including imagery, belief and recollective experience associated with each memory. Blind participants retrieved fewer memories and reported higher auditory imagery at retrieval than sighted participants. Moreover, within the blind group, participants with total blindness reported higher auditory imagery than those with some light perception. Blind participants also assigned higher importance, belief and recollection ratings to their memories than sighted participants. Importantly, these group differences remained the same for recent as well as childhood memories.

Abstract

Temporal cues can be used to selectively attend to relevant information during abundant sensory stimulation. However, such cues differ vastly in the accuracy of their temporal estimates, ranging from very predictable to very unpredictable. When cues are strongly predictable, attention may facilitate selective processing by aligning relevant incoming information to high neuronal excitability phases of ongoing low-frequency oscillations. However, top-down effects on ongoing oscillations when temporal cues have some predictability, but also contain temporal uncertainties, are unknown. Here, we experimentally created such a situation of mixed predictability and uncertainty: A target could occur within a limited time window after cue but was always unpredictable in exact timing. Crucially to assess top-down effects in such a mixed situation, we manipulated target probability. High target likelihood, compared with low likelihood, enhanced delta oscillations more strongly as measured by evoked power and intertrial coherence. Moreover, delta phase modulated detection rates for probable targets. The delta frequency range corresponds with half-a-period to the target occurrence window and therefore suggests that low-frequency phase reset is engaged to produce a long window of high excitability when event timing is uncertain within a restricted temporal window.

Abstract

The role of oscillatory phase for perceptual and cognitive processes is being increasingly acknowledged. To date, little is known about the direct role of phase in categorical perception. Here we show in two separate experiments that the identification of ambiguous syllables that can either be perceived as / da/ or / ga/ is biased by the underlying oscillatory phase as measured with EEG and sensory entrainment to rhythmic stimuli. The measured phase difference in which perception is biased toward / da/ or / ga/ exactly matched the different temporal onset delays in natural audiovisual speech between mouth movements and speech sounds, which last 80 ms longer for / ga/ than for / da/. These results indicate the functional relationship between prestimulus phase and syllable identification, and signify that the origin of this phase relationship could lie in exposure and subsequent learning of unique audiovisual temporal onset differences.

Abstract

To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a parahippocampal area, which decreased with time. In turn, mPFC-parahippocampal connectivity increased progressively. These findings support a model in which thalamic midline nuclei serve as a hub linking hippocampus, mPFC, and posterior representational areas during memory retrieval at an early (2 h) stage of consolidation, extending classical systems consolidation models by attributing a transient role to midline thalamic nuclei.

Abstract

Infants expect people to direct actions toward objects, and they respond to actions directed to themselves, but do they have expectations about actions directed to third parties? In two experiments, we used eye tracking to investigate 1- and 2-year-olds’ expectations about communicative actions addressed to a third party. Experiment 1 presented infants with videos where an adult (the Emitter) either uttered a sentence or produced non-speech sounds. The Emitter was either face-to-face with another adult (the Recipient) or the two were back-to-back. The Recipient did not respond to any of the sounds. We found that 2-, but not 1-year-olds looked quicker and longer at the Recipient following speech than non-speech, suggesting that they expected her to respond to speech. These effects were specific to the face-to-face context. Experiment 2 presented 1-year-olds with similar face-to-face exchanges but modified to engage infants and minimize task demands. The infants looked quicker to the Recipient following speech than non-speech, suggesting that they expected a response to speech. The study suggests that by 1 year of age infants expect communicative actions to be directed at a third-party listener.

Abstract

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

Abstract

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

Abstract

Germline mutations in PTEN, which encodes a widely expressed phosphatase, was mapped to 10q23 and identified as the susceptibility gene for Cowden syndrome, characterized by macrocephaly and high risks of breast, thyroid, and other cancers. The phenotypic spectrum of PTEN mutations expanded to include autism with macrocephaly only 10 years ago. Neurological studies of patients with PTEN-associated autism spectrum disorder (ASD) show increases in cortical white matter and a distinctive cognitive profile, including delayed language development with poor working memory and processing speed. Once a germline PTEN mutation is found, and a diagnosis of phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome made, the clinical outlook broadens to include higher lifetime risks for multiple cancers, beginning in childhood with thyroid cancer. First described as a tumor suppressor, PTEN is a major negative regulator of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) signaling pathway—controlling growth, protein synthesis, and proliferation. This canonical function combines with less well-understood mechanisms to influence synaptic plasticity and neuronal cytoarchitecture. Several excellent mouse models of Pten loss or dysfunction link these neural functions to autism-like behavioral abnormalities, such as altered sociability, repetitive behaviors, and phenotypes like anxiety that are often associated with ASD in humans. These models also show the promise of mTOR inhibitors as therapeutic agents capable of reversing phenotypes ranging from overgrowth to low social behavior. Based on these findings, therapeutic options for patients with PTEN hamartoma tumor syndrome and ASD are coming into view, even as new discoveries in PTEN biology add complexity to our understanding of this master regulator.

Abstract

Synesthesia is a rare nonpathological phenomenon where stimulation of one sense automatically provokes a secondary perception in another. Hypothesized to result from differences in cortical wiring during development, synesthetes show atypical structural and functional neural connectivity, but the underlying molecular mechanisms are unknown. The trait also appears to be more common among people with autism spectrum disorder and savant abilities. Previous linkage studies searching for shared loci of large effect size across multiple families have had limited success. To address the critical lack of candidate genes, we applied whole-exome sequencing to three families with sound–color (auditory–visual) synesthesia affecting multiple relatives across three or more generations. We identified rare genetic variants that fully cosegregate with synesthesia in each family, uncovering 37 genes of interest. Consistent with reports indicating genetic heterogeneity, no variants were shared across families. Gene ontology analyses highlighted six genes—COL4A1, ITGA2, MYO10, ROBO3, SLC9A6, and SLIT2—associated with axonogenesis and expressed during early childhood when synesthetic associations are formed. These results are consistent with neuroimaging-based hypotheses about the role of hyperconnectivity in the etiology of synesthesia and offer a potential entry point into the neurobiology that organizes our sensory experiences.

Abstract

The neural response to a stimulus is influenced by endogenous factors such as expectation and attention. Current research suggests that expectation and attention exert their effects in opposite directions, where expectation decreases neural activity in sensory areas, while attention increases it. However, expectation and attention are usually studied either in isolation or confounded with each other. A recent study suggests that expectation and attention may act jointly on sensory processing, by increasing the neural response to expected events when they are attended, but decreasing it when they are unattended. Here we test this hypothesis in an auditory temporal cueing paradigm using magnetoencephalography in humans. In our study participants attended to, or away from, tones that could arrive at expected or unexpected moments. We found a decrease in auditory beta band synchrony to expected (versus unexpected) tones if they were unattended, but no difference if they were attended. Modulations in beta power were already evident prior to the expected onset times of the tones. These findings suggest that expectation and attention jointly modulate sensory processing.

Abstract

In this study, we investigate the timing of pre-answer inbreaths in order to shed light on the time course of response planning and execution in conversational turn-taking. Using acoustic and inductive plethysmography recordings of seven dyadic conversations in Dutch, we show that pre-answer inbreaths in conversation typically begin briefly after the end of questions. We also show that the presence of a pre-answer inbreath usually co-occurs with substantially delayed answers, with a modal latency of 576 ms vs. 100 ms for answers not preceded by an inbreath. Based on previously reported minimal latencies for internal intercostal activation and the production of speech sounds, we propose that vocal responses, either in the form of a pre-utterance inbreath or of speech proper when an inbreath is not produced, are typically launched in reaction to information present in the last portion of the interlocutor’s turn. We also show that short responses are usually made on residual breath, while longer responses are more often preceded by an inbreath. This relation of inbreaths to answer length suggests that by the time an inbreath is launched, typically during the last few hundred milliseconds of the question, the length of the answer is often prepared to some extent. Together, our findings are consistent with a two-stage model of response planning in conversational turn-taking: early planning of content often carried out in overlap with the incoming turn, and late launching of articulation based on the identification of turn-final cues

Abstract

This paper explores phrase-length-related alternations in the association of tones to positions in metrical structure in two melodic constructions of Spanish. An imitation-and-completion task eliciting (a) the low–falling–rising contour and (b) the circumflex contour on intonation phrases (IPs) of one, two, and three prosodic words revealed that, although the focus structure and pragmatic context is constant across conditions, phrases containing one prosodic word differ in their nuclear (i.e. final) pitch accents and edge tones from phrases containing more than one prosodic word. For contour (a), short intonation phrases (e.g. [ Ma no lo ] IP ) were produced with a low accent followed by a high edge tone (L ∗ H% in ToBI notation), whereas longer phrases (e.g. [ El her ma no de la a m igadeMa no lo ] IP ‘Manolo’s friend’s brother’) had a low accent on the first stressed syllable, a rising accent on the last stressed syllable, and a low edge tone (L ∗ L+H ∗ L%). For contour (b), short phrases were produced with a high–rise (L+H ∗ ¡H%), whereas longer phrases were produced with an initial accentual rise followed by an upstepped rise–fall (L+H ∗ ¡H ∗ L%). These findings imply that the common practice of describing the structure of intonation contours as consisting of a constant nuclear pitch accent and following edge tone is not adequate for modeling Spanish intonation. To capture the observed melodic alternations, we argue for clearer separation between tones and metrical structure, whereby intonational tones do not necessarily have an intrinsic culminative or delimitative function (i.e. as pitch accents or as edge tones). Instead, this function results from melody-specific principles of tonal–metrical association.

Abstract

We investigate the extent to which French polar questions and continuation statements, two types of utterances with similar morphosyntactic and intonational forms but different pragmatic functions, can be distinguished in conversational data based on phonetic and visual bodily information. We show that the two utterance types can be distinguished well over chance level by automatic classification models including several phonetic and visual cues. We also show that a considerable amount of relevant phonetic and visual information is present before the last portion of the utterances, potentially assisting early speech act recognition by addressees. These findings indicate that bottom-up phonetic and visual cues may play an important role during the production and recognition of speech acts alongside top-down contextual information.

Abstract

Purpose: To determine clinical phenotypes, evolution and genetic background of a large family with a combination of two unusual forms of reflex epilepsies. Method: Phenotyping was performed in eighteen family members (10 F, 8 M) including standardized EEG recordings with intermittent photic stimulation (IPS). Genetic analyses (linkage scans, Whole Exome Sequencing (WES) and Functional studies) were performed using photoparoxysmal EEG responses (PPRs) as affection status. Results: The proband suffered from speaking induced jaw-jerks and increasing limb jerks evoked by flickering sunlight since about 50 years of age. Three of her family members had the same phenotype. Generalized PPRs were found in seven members (six above 50 years of age) with myoclonus during the PPR. Evolution was typical: Sensitivity to lights with migraine-like complaints around adolescence, followed by jerks evoked by lights and spontaneously with dropping of objects, and strong increase of light sensitivity and onset of talking induced jaw jerks around 50 years. Linkage analysis showed suggestive evidence for linkage to four genomic regions. All photosensitive family members shared a heterozygous R129C mutation in the SCNM1 gene that regulates splicing of voltage gated ion channels. Mutation screening of 134 unrelated PPR patients and 95 healthy controls, did not replicate these findings. Conclusion: This family presents a combination of two rare reflex epilepsies. Genetic analysis favors four genomic regions and points to a shared SCNM1 mutation that was not replicated in a general cohort of photosensitive subjects. Further genetic studies in families with similar combination of features are warranted. (C) 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Abstract

Bilingual children with reduced exposure to one or both languages may have language profiles that are
apparently similar to those of children with developmental language disorder (DLD). Children with
DLD receive enough input, but have difficulty using this input for acquisition due to processing deficits.
The present investigation aims to determine aspects of adjective production that are differentially
affected by reduced input (in bilingualism) and reduced intake (in DLD). Adjectives were elicited
from Dutch–Russian simultaneous bilinguals with limited exposure to Russian and Russian-speaking
monolinguals with andwithout DLD.Anantonymelicitation taskwas used to assess the size of adjective
vocabularies, and a degree task was employed to compare the preferences of the three groups in the
use of morphological, lexical, and syntactic degree markers. The results revealed that adjective–noun
agreement is affected to the same extent by both reduced input and reduced intake. The size of adjective
lexicons is also negatively affected by both, but more so by reduced exposure. However, production
of morphological degree markers and learning of semantic paradigms are areas of relative strength in
which bilinguals outperform monolingual children with DLD.We suggest that reduced input might be
counterbalanced by linguistic and cognitive advantages of bilingualism

Abstract

When we comprehend language, we often do this in rich settings in which we can use many cues to understand what someone is saying. However, it has traditionally been difficult to design experiments with rich three-dimensional contexts that resemble our everyday environments, while maintaining control over the linguistic and non-linguistic information that is available. Here we test the validity of combining electroencephalography (EEG) and Virtual Reality (VR) to overcome this problem. We recorded electrophysiological brain activity during language processing in a well-controlled three-dimensional virtual audiovisual environment. Participants were immersed in a virtual restaurant, while wearing EEG equipment. In the restaurant participants encountered virtual restaurant guests. Each guest was seated at a separate table with an object on it (e.g. a plate with salmon). The restaurant guest would then produce a sentence (e.g. “I just ordered this salmon.”). The noun in the spoken sentence could either match (“salmon”) or mismatch (“pasta”) with the object on the table, creating a situation in which the auditory information was either appropriate or inappropriate in the visual context. We observed a reliable N400 effect as a consequence of the mismatch. This finding validates the combined use of VR and EEG as a tool to study the neurophysiological mechanisms of everyday language comprehension in rich, ecologically valid settings.

Abstract

Narrative fiction may invite us to share the perspective of characters which are very much unlike ourselves. Inanimate objects featuring as protagonists or narrators are an extreme example of this. The way readers experience these characters was examined by means of a narrative immersion study. Participants (N = 200) judged narratives containing animate or inanimate characters in predominantly Agent or Experiencer roles. Narratives with inanimate characters were judged to be less emotionally engaging. This effect was influenced by the dominant thematic role associated with the character: inanimate Agents led to more defamiliarization compared to their animate counterparts than inanimate Experiencers. I argue for an integrated account of thematic roles and animacy in literary experience and linguistics in general.

Abstract

We show by means of a corpus study that the language used by the inanimate first person narrator in the novel Specht en zoon deviates from what we would expect on the basis of the fact that the narrator is inanimate, but at the same time also differsfrom the language of a human narrator in the novel De wijde blik on several linguistic dimensions. Whereas the human narrator is associated strongly with action verbs, preferring the Agent role, the inanimate narrator is much more limited to the Experiencer role, predominantly associated with cognition and sensory verbs. Our results show that animacy as a linguistic concept may be refined by taking into account the myriad ways in which an entity’s conceptual animacy may be expressed: we accept the conceptual animacy of the inanimate narrator despite its inability to act on its environment, showing this need not be a requirement for animacy

Abstract

Actions may be used to directly act on the world around us, or as a means of communication. Effective communication requires the addressee to recognize the act as being communicative. Humans are sensitive to ostensive communicative cues, such as direct eye gaze (Csibra & Gergely, 2009). However, there may be additional cues present in the action or gesture itself. Here we investigate features that characterize the initiation of a communicative interaction in both production and comprehension.

We asked 40 participants to perform 31 pairs of object-directed actions and representational gestures in more- or less- communicative contexts. Data were collected using motion capture technology for kinematics and video recording for eye-gaze. With these data, we focused on two issues. First, if and how actions and gestures are systematically modulated when performed in a communicative context. Second, if observers exploit such kinematic information to classify an act as communicative.

Our study showed that during production the communicative context modulates space–time dimensions of kinematics and elicits an increase in addressee-directed eye-gaze. Naïve participants detected communicative intent in actions and gestures preferentially using eye-gaze information, only utilizing kinematic information when eye-gaze was unavailable.

Our study highlights the general communicative modulation of action and gesture kinematics during production but also shows that addressees only exploit this modulation to recognize communicative intention in the absence of eye-gaze. We discuss these findings in terms of distinctive but potentially overlapping functions of addressee directed eye-gaze and kinematic modulations within the wider context of human communication and learning.

Abstract

Objective: Patients with Parkinson's disease (PD) often suffer from impairments in executive functions, such as working memory deficits. It is widely held that dopamine depletion in the striatum contributes to these impairments through decreased activity and connectivity between task-related brain networks. We investigated this hypothesis by studying task-related network activity and connectivity within a sample of de novo patients with PD, versus healthy controls, during a visuospatial working memory task. Methods: Sixteen de novo PD patients and 35 matched healthy controls performed a visuospatial n-back task while we measured their behavioral performance and neural activity using functional magnetic resonance imaging. We constructed regions-of-interest in the bilateral inferior parietal cortex (IPC), bilateral dorsolateral prefrontal cortex (DLPFC), and bilateral caudate nucleus to investigate group differences in task-related activity. We studied network connectivity by assessing the functional connectivity of the bilateral DLPFC and by assessing effective connectivity within the frontoparietal and the frontostriatal networks. Results: PD patients, compared with controls, showed trend-significantly decreased task accuracy, significantly increased task-related activity in the left DLPFC and a trend-significant increase in activity of the right DLPFC, left caudate nucleus, and left IPC. Furthermore, we found reduced functional connectivity of the DLPFC with other task-related regions, such as the inferior and superior frontal gyri, in the PD group, and group differences in effective connectivity within the frontoparietal network. Interpretation: These findings suggest that the increase in working memory-related brain activity in PD patients is compensatory to maintain behavioral performance in the presence of network deficits. Hum Brain Mapp 36:1554-1566, 2015. (c) 2015 Wiley Periodicals, Inc.

Abstract

Numerous studies have revealed an asymmetry tied to the perception of coronal place of articulation: participants accept a labial mispronunciation of a coronal target, but not vice versa. Whether or not this asymmetry is based on language-general properties or arises from language-specific experience has been a matter of debate. The current study suggests a bias of the first type by documenting an early, cross-linguistic asymmetry related to coronal place of articulation. Japanese and Dutch 4- and 6-month-old infants showed evidence of discrimination if they were habituated to a labial and then tested on a coronal sequence, but not vice versa. This finding has important implications for both phonological theories and infant speech perception research

Abstract

The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.

Abstract

Synapse development and neuronal activity represent fundamental processes for the establishment of cognitive function. Structural organization as well as signalling pathways from receptor stimulation to gene expression regulation are mediated by synaptic activity and misregulated in neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID). Deleterious mutations in the PTCHD1 (Patched domain containing 1) gene have been described in male patients with X-linked ID and/or ASD. The structure of PTCHD1 protein is similar to the Patched (PTCH1) receptor; however, the cellular mechanisms and pathways associated with PTCHD1 in the developing brain are poorly determined. Here we show that PTCHD1 displays a C-terminal PDZ-binding motif that binds to the postsynaptic proteins PSD95 and SAP102. We also report that PTCHD1 is unable to rescue the canonical sonic hedgehog (SHH) pathway in cells depleted of PTCH1, suggesting that both proteins are involved in distinct cellular signalling pathways. We find that Ptchd1 deficiency in male mice (Ptchd1−/y) induces global changes in synaptic gene expression, affects the expression of the immediate-early expression genes Egr1 and Npas4 and finally impairs excitatory synaptic structure and neuronal excitatory activity in the hippocampus, leading to cognitive dysfunction, motor disabilities and hyperactivity. Thus our results support that PTCHD1 deficiency induces a neurodevelopmental disorder causing excitatory synaptic dysfunction.

Abstract

Perceptual and sensorimotor timing skills can be thoroughly assessed with the Battery for the Assessment of Auditory Sensorimotor and Timing Abilities (BAASTA). The battery has been used for testing rhythmic skills in healthy adults and patient populations (e.g., with Parkinson disease), showing sensitivity to timing and rhythm deficits. Here we assessed the test-retest reliability of the BAASTA in 20 healthy adults. Participants were tested twice with the BAASTA, implemented on a tablet interface, with a 2-week interval. They completed 4 perceptual tasks, namely, duration discrimination, anisochrony detection with tones and music, and the Beat Alignment Test (BAT). Moreover, they completed motor tasks via finger tapping, including unpaced and paced tapping with tones and music, synchronization-continuation, and adaptive tapping to a sequence with a tempo change. Despite high variability among individuals, the results showed good test-retest reliability in most tasks. A slight but significant improvement from test to retest was found in tapping with music, which may reflect a learning effect. In general, the BAASTA was found a reliable tool for evaluating timing and rhythm skills.

Abstract

In normal conversation, speakers translate thoughts into words at high speed. To enable this speed, the retrieval of distinct types of linguistic knowledge has to be orchestrated with millisecond precision. The nature of this orchestration is still largely unknown. This report presents dynamic measures of the real-time activation of two basic types of linguistic knowledge, syntax and phonology. Electrophysiological data demonstrate that during noun-phrase production speakers retrieve the syntactic gender of a noun before its abstract phonological properties. This two-step process operates at high speed: the data show that phonological information is already available 40 milliseconds after syntactic properties have been retrieved.

Abstract

Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.

Abstract

Learning new vocabulary from context typically requires multiple encounters during which word meaning can be retrieved from memory or inferred from context. We compared the effect of memory retrieval and context inferences on short‐ and long‐term retention in three experiments. Participants studied novel words and then practiced the words either in an uninformative context that required the retrieval of word meaning from memory (“I need the funguo”) or in an informative context from which word meaning could be inferred (“I want to unlock the door: I need the funguo”). The informative context facilitated word comprehension during practice. However, later recall of word form and meaning and word recognition in a new context were better after successful retrieval practice and retrieval practice with feedback than after context‐inference practice. These findings suggest benefits of retrieval during contextualized vocabulary learning whereby the uninformative context enhanced word retention by triggering memory retrieval.

Abstract

The syntactic structure of main and subordinate clauses is determined to a considerable extent by verb biases. For example, some English and Dutch ditransitive verbs have a preference for the prepositional object dative, whereas others are typically used with the double object dative. In this study, we compare the effect of these biases on structure selection in (S)VO and (S)OV dative clauses in the Corpus of Spoken Dutch (CGN). This comparison allowed us to make inferences about the size of the advance planning scope during spontaneous speaking: If the verb is an obligatory component of clause-level advance planning scope, as is claimed by the hypothesis of hierarchical incrementality, then biases should exert their influence on structure choices, regardless of early (VO) or late (OV) position of the verb in the clause. Conversely, if planning proceeds in a piecemeal fashion, strictly guided by lexical availability, as claimed by linear incrementality, then the verb and its associated biases can only influence structure choices in VO sentences. We tested these predictions by analyzing structure choices in the CGN, using mixed logit models. Our results support a combination of linear and hierarchical incrementality, showing a significant influence of verb bias on structure choices in VO, and a weaker (but still significant) effect in OV clauses

Abstract

An essential phenomenon in the development towards syntactic maturity after early childhood is the increasing use of so-called sentence-combining transformations. Especially by using subordination, complex sentences are produced. The research reported here is an attempt to arrive at a more adequate characterization and explanation. Our starting point was an analysis of 280 texts written by Dutch-speaking pupils of the two highest grades of the primary school and the four lowest grades of three different types of secondary education. It was examined whether systematic shifts in the use of certain groups of so-called function words could be traced. We concluded that the development of the syntactic formulating ability can be characterized as an increase in connectivity: the use of all kinds of function words which explicitly mark logico-semantic relations between propositions. This development starts by inserting special adverbs and coordinating conjunctions resulting in various types of coordination. In a later stage, the syntactic patterning of the sentence is affected as well (various types of subordination). The increase in sentence complexity is only one aspect of the entire development. An explanation for the increase in connectivity is offered based upon a distinction between narrative and expository language use. The latter, but not the former, is characterized by frequent occurrence of connectives. The development in syntactic formulating ability includes a high level of skill in expository language use. Speed of development is determined by intensity of training, e.g. in scholastic and occupational settings.

Abstract

The temporal properties of semantic and phonological processes in speech production were investigated in a new experimental paradigm using movement-related brain potentials. The main experimental task was picture naming. In addition, a 2-choice reaction go/no-go procedure was included, involving a semantic and a phonological categorization of the picture name. Lateralized readiness potentials (LRPs) were derived to test whether semantic and phonological information activated motor processes at separate moments in time. An LRP was only observed on no-go trials when the semantic (not the phonological) decision determined the response hand. Varying the position of the critical phoneme in the picture name did not affect the onset of the LRP but rather influenced when the LRP began to differ on go and no-go trials and allowed the duration of phonological encoding of a word to be estimated. These results provide electrophysiological evidence for early semantic activation and later phonological encoding.

Abstract

Heterozygous mutations of the Forkhead-box protein 2 (FOXP2) gene in humans cause childhood apraxia of speech. Loss of Foxp2 in mice is known to affect striatal development and impair motor skills. However, it is unknown if striatal excitatory/inhibitory balance is affected during development and if the imbalance persists into adulthood. We investigated the effect of reduced Foxp2 expression, via a loss-of-function mutation, on striatal medium spiny neurons (MSNs). Our data show that heterozygous loss of Foxp2 decreases excitatory (AMPA receptor-mediated) and increases inhibitory (GABA receptor-mediated) currents in D1 dopamine receptor positive MSNs of juvenile and adult mice. Furthermore, reduced Foxp2 expression increases GAD67 expression, leading to both increased presynaptic content and release of GABA. Finally, pharmacological blockade of inhibitory activity in vivo partially rescues motor skill learning deficits in heterozygous Foxp2 mice. Our results suggest a novel role for Foxp2 in the regulation of striatal direct pathway activity through managing inhibitory drive.

Abstract

This study investigated whether the negative effect of complexity on artificial grammar learning could be compensated by adding semantics. Participants were exposed to exemplars from a simple or a complex finite state grammar presented with or without a semantic reference field. As expected, performance on a grammaticality judgment test was higher for the simple grammar than for the complex grammar. For the simple grammar, the results also showed that participants presented with a reference field and instructed to decode the meaning of each exemplar (decoding condition) did better than participants who memorized the exemplars without semantic referents (memorize condition). Contrary to expectations, however, there was no significant difference between the decoding condition and the memorize condition for the complex grammar. These findings indicated that the negative effect of complexity remained, despite the addition of semantics. To clarify how the presence of a reference field influenced the learning process, its effects on the acquisition of two types of knowledge (first- and second-order dependencies) and on participants’ awareness of their knowledge were examined. The results tentatively suggested that the reference field enhanced the learning of second-order dependencies. In addition, participants in the decoding condition realized when they had knowledge relevant to making a grammaticality judgment, whereas participants in the memorize condition demonstrated some knowledge of which they were unaware. These results are in line with the view that the reference field enhanced structure learning by making certain dependencies more salient. Moreover, our findings stress the influence of complexity on artificial grammar learning

Abstract

According to the complementary learning systems (CLS) account of word learning, novel words are rapidly acquired (learning system 1), but slowly integrated into the mental lexicon (learning system 2). This two-step learning process has been shown to apply to novel word forms. In this study, we investigated whether novel word meanings are also gradually integrated after acquisition by measuring the extent to which newly learned words were able to prime semantically related words at two different time points. In addition, we investigated whether modality at study modulates this integration process. Sixty-four adult participants studied novel words together with written or spoken definitions. These words did not prime semantically related words directly following study, but did so after a 24-hour delay. This significant increase in the magnitude of the priming effect suggests that semantic integration occurs over time. Overall, words that were studied with a written definition showed larger priming effects, suggesting greater integration for the written study modality. Although the process of integration, reflected as an increase in the priming effect over time, did not significantly differ between study modalities, words studied with a written definition showed the most prominent positive effect after a 24-hour delay. Our data suggest that semantic integration requires time, and that studying in written format benefits semantic integration more than studying in spoken format. These findings are discussed in light of the CLS theory of word learning.

Abstract

Interpersonal discourse particles (DPs), such as Dutch inderdaad (≈‘indeed’) and eigenlijk (≈‘actually’) are highly frequent in everyday conversational interaction. Despite extensive theoretical descriptions of their polyfunctionality, little is known about how they are used by language comprehenders. In two visual world eye-tracking experiments involving an online dialogue completion task, we asked to what extent inderdaad, confirming an inferred expectation, and eigenlijk, contrasting with an inferred expectation, influence real-time understanding of dialogues. Answers in the dialogues contained a DP or a control adverb, and a critical discourse referent was replaced by a beep; participants chose the most likely dialogue completion by clicking on one of four referents in a display. Results show that listeners make rapid and fine-grained situation-specific inferences about the use of DPs, modulating their expectations about how the dialogue will unfold. Findings further specify and constrain theories about the conversation-managing function and polyfunctionality of DPs.

Abstract

In the recent literature, the effects of noninvasive neurostimulation on cognitive functioning appear to lack consistency and replicability. We propose that such effects may be concealed unless dedicated, sensitive, and process-specific dependent measures are used. The expression and subsequent suppression of response capture are often studied using conflict tasks. Response-time distribution analyses have been argued to provide specific measures of the susceptibility to make fast impulsive response errors, as well as the proficiency of the selective suppression of these impulses. These measures of response capture and response inhibition are particularly sensitive to experimental manipulations and clinical deficiencies that are typically obfuscated in commonly used overall performance analyses. Recent work using structural and functional imaging techniques links these behavioral outcome measures to the integrity of frontostriatal networks. These studies suggest that the presupplementary motor area (pre-SMA) is linked to the susceptibility to response capture whereas the right inferior frontal cortex (rIFC) is associated with the selective suppression of action impulses. Here, we used repetitive transcranial magnetic stimulation (rTMS) to test the causal involvement of these two cortical areas in response capture and inhibition in the Simon task. Disruption of rIFC function specifically impaired selective suppression of conflicting action tendencies, whereas the anticipated increase of fast impulsive errors after perturbing pre-SMA function was not confirmed. These results provide a proof of principle of the notion that the selection of appropriate dependent measures is perhaps crucial to establish the effects of neurostimulation on specific cognitive functions.

Abstract

Social information use is a pivotal characteristic of the human species. Avoiding the cost of individual exploration, social learning confers substantial fitness benefits under a wide variety of environmental conditions, especially when the process is governed by biases toward relative superiority (e.g., experts, the majority). Here, we examine the development of social information use in children aged 4–14 years (n = 605) across seven societies in a standardised social learning task. We measured two key aspects of social information use: general reliance on social information and majority preference. We show that the extent to which children rely on social information depends on children’s cultural background. The extent of children’s majority preference also varies cross-culturally, but in contrast to social information use, the ontogeny of majority preference follows a U-shaped trajectory across all societies. Our results demonstrate both cultural continuity and diversity in the realm of human social learning.

Abstract

Jescheniak and Levelt (Jescheniak, J.-D., Levelt, W.J.M. 1994. Journal of Experimental Psychology: Learning, Memory and Cognition 20 (4), 824–843) have suggested that the speed with which native speakers of a gender-marking language retrieve the grammatical gender of a noun from their mental lexicon may depend on the recency of earlier access to that same noun's gender, as the result of a mechanism that is dedicated to facilitate gender-marked anaphoric reference to recently introduced discourse entities. This hypothesis was tested in two picture naming experiments. Recent gender access did not facilitate the production of gender-marked adjective noun phrases (Experiment 1), nor that of gender-marked definite article noun phrases (Experiment 2), even though naming times for the latter utterances were sensitive to the gender of a written distractor word superimposed on the picture to be named. This last result replicates and extends earlier gender-specific picture-word interference results (Schriefers, H. 1993. Journal of Experimental Psychology: Learning, Memory, and Cognition 19 (4), 841–850), showing that one can selectively tap into the production of grammatical gender agreement during speaking. The findings are relevant to theories of speech production and the representation of grammatical gender for that process.

Abstract

Meermalen is getracht om syntactische formuleenuuirdigheid direct en objectief te meten aan de hand van gesproken of geschreven teksten. Uitgangspunt hierbij vormde in de regel de syntactische complexiteit van de geproduceerde taaluitingen. Dit heeft echter niet geleid tot een plausibele, duidelijk omschreven en praktisch bruikbare index. N.a.v. een kritische bespreking van de notie complexiteit wordt in dit artikel als nieuw criterium voorgesteld de connectiviteit van de taaluitingen; de expliciete aanduiding van logiscli-scmantische relaties tussen proposities. Connectiviteit is gemakkelijk scoorbaar aan de hand van functiewoorden die verschillende vormen van nevenschikkend en onderschikkend zinsverband markeren. Deze nieuwe index ondetrangt de kritiek die op complexiteit gegeven kon worden, blijkt duidelijk te discrimineren tussen groepen leerlingen die van elkaar verschillen naar leeftijd en opleidingsniveau, en sluit aan bij recente taalpsychologische en sociolinguïstische theorie. Tot besluit worden enige onderwijskundige implicaties aangegeven.

Abstract

Speech requires precise motor control and rapid sequencing of highly complex vocal musculature. Despite its complexity, most people produce spoken language effortlessly. This is due to activity in distributed neuronal circuitry including cortico-striato-thalamic loops that control speech-motor output. Understanding the neuro-genetic mechanisms that encode these pathways will shed light on how humans can effortlessly and innately use spoken language and could elucidate what goes wrong in speech-language disorders.
FOXP2 was the first single gene identified to cause speech and language disorder. Individuals with FOXP2 mutations display a severe speech deficit that also includes receptive and expressive language impairments. The underlying neuro-molecular mechanisms controlled by FOXP2, which will give insight into our capacity for speech-motor control, are only beginning to be unraveled. Recently FOXP2 was found to regulate genes involved in retinoic acid signaling and to modify the cellular response to retinoic acid, a key regulator of brain development. Herein we explore the evidence that FOXP2 and retinoic acid signaling function in the same pathways. We present evidence at molecular, cellular and behavioral levels that suggest an interplay between FOXP2 and retinoic acid that may be important for fine motor control and speech-motor output.
We propose that retinoic acid signaling is an exciting new angle from which to investigate how neurogenetic mechanisms can contribute to the (spoken) language ready brain.

Abstract

Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG). Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms) duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process

Abstract

Reactive and proactive subtypes of aggression have been recognized to help parse etiological heterogeneity of this complex phenotype. With a heritability of about 50%, genetic factors play a role in the development of aggressive behavior. Imaging studies implicate brain structures related to social behavior in aggression etiology, most notably the amygdala and striatum. This study aimed to gain more insight into the pathways from genetic risk factors for aggression to aggression phenotypes. To this end, we conducted genome-wide gene-based cross-trait meta-analyses of aggression with the volumes of amygdala, nucleus accumbens and caudate nucleus to identify genes influencing both aggression and aggression-related brain volumes. We used data of large-scale genome-wide association studies (GWAS) of: (a) aggressive behavior in children and adolescents (EAGLE, N = 18,988); and (b) Magnetic Resonance Imaging (MRI)-based volume measures of aggression-relevant subcortical brain regions (ENIGMA2, N = 13,171). Second, the identified genes were further investigated in a sample of healthy adults (mean age (SD) = 25.28 (4.62) years; 43% male) who had genome-wide genotyping data and questionnaire data on aggression subtypes available (Brain Imaging Genetics, BIG, N = 501) to study their effect on reactive and proactive subtypes of aggression. Our meta-analysis identified two genes, MECOM and AVPR1A, significantly associated with both aggression risk and nucleus accumbens (MECOM) and amygdala (AVPR1A) brain volume. Subsequent in-depth analysis of these genes in healthy adults (BIG), including sex as an interaction term in the model, revealed no significant subtype-specific gene-wide associations. Using cross-trait meta-analysis of brain measures and psychiatric phenotypes, this study generated new hypotheses about specific links between genes, the brain and behavior. Results indicate that MECOM and AVPR1A may exert an effect on aggression through mechanisms involving nucleus accumbens and amygdala volumes, respectively.

Abstract

Understanding intraspecific variation in sociality is essential for characterizing the flexibility and evolution of social systems, yet its study in nonhuman animals is rare. Here, we investigated whether chimpanzees exhibit population-level differences in sociality that cannot be easily explained by differences in genetics or ecology. We compared social proximity and grooming tendencies across four semiwild populations of chimpanzees living in the same ecological environment over three consecutive years, using both linear mixed models and social network analysis. Results indicated temporally stable, population-level differences in dyadic-level sociality. Moreover, group cohesion measures capturing network characteristics beyond dyadic interactions (clustering, modularity, and social differentiation) showed population-level differences consistent with the dyadic indices. Subsequently, we explored whether the observed intraspecific variation in sociality could be attributed to cultural processes by ruling out alternative sources of variation including the influences of ecology, genetics, and differences in population demographics. We conclude that substantial variation in social behavior exists across neighboring populations of chimpanzees and that this variation is in part shaped by cultural processes.

Abstract

In natural conversations, words are generally shorter and they often lack segments. It is unclear to what extent such durational and segmental reductions affect word recognition. The present study investigates to what extent reduction in the initial syllable hinders word comprehension, which types of segments listeners mostly rely on, and whether listeners use word duration as a cue in word recognition. We conducted three experiments in Dutch, in which we adapted the gating paradigm to study the comprehension of spontaneously uttered conversational speech by aligning the gates with the edges of consonant clusters or vowels. Participants heard the context and some segmental and/or durational information from reduced target words with unstressed initial syllables. The initial syllable varied in its degree of reduction, and in half of the stimuli the vowel was not clearly present. Participants gave too short answers if they were only provided with durational information from the target words, which shows that listeners are unaware of the reductions that can occur in spontaneous speech. More importantly, listeners required fewer segments to recognize target words if the vowel in the initial syllable was absent. This result strongly suggests that this vowel hardly plays a role in word comprehension, and that its presence may even delay this process. More important are the consonants and the stressed vowel.

Abstract

The present research investigates how consumer choice is affected by Terror Management Theory’s proposition of Mortality Salience increasing one’s cultural worldview defense and self-esteem striving. The study builds empirically upon prior theorizing by Arndt, Solomon, Kasser and Sheldon (2004). During an experiment, we manipulated Mortality Salience and measured product preferences for conspicuousness and familiarity. Participants primed with death were more likely to choose conspicuous products, corroborating previous research of mortality salience raising materialistic tendencies. In addition, participants showed a tendency to prefer familiar brands. These results are in line with the Terror Management Theory framework.

Abstract

OBJECTIVES: Deficits in response inhibition have been associated with attention-deficit/hyperactivity disorder (ADHD). Given the role of serotonin in ADHD and impulsivity, we postulated that genetic variants within the serotonin pathway might influence response inhibition. METHODS: We measured neural activation during stop-signal task performance in adolescents with ADHD (N = 185), their unaffected siblings (N = 111), and healthy controls (N = 124), and investigated the relationship of two serotonin gene polymorphisms (the rs6296 SNP of the HTR1B gene and HTTLPR variants of the 5-HTT gene) with the neural correlates of response inhibition. RESULTS: The whole-brain analyses demonstrated large scale neural activation differences in the inferior and medial frontal and temporal/parietal regions of the response inhibition network between the different variants of both the HTR1B and 5HTT genes. Activation in these regions was significantly associated with stop-task performance, but not with ADHD diagnosis or severity. No associations were found between HTR1B and 5HTT variants and ADHD or ADHD-related neural activation. CONCLUSIONS: These results provide novel evidence that serotonin may play an important role in the neurobiology of response inhibition. Although response inhibition is strongly linked to ADHD, serotonin linked genetic variants associated with response inhibition and its neural correlates do not explain variance of the ADHD phenotype.

Abstract

Insight in the developmental trajectory of the neuroanatomical reading correlates is important to understand related cognitive processes and disorders. In adults, a dual pathway model has been suggested encompassing a dorsal phonological and a ventral orthographic white matter system. This dichotomy seems not present in pre-readers, and the specific role of ventral white matter in reading remains unclear. Therefore, the present longitudinal study investigated the relation between ventral white matter and cognitive processes underlying reading in children with a broad range of reading skills (n = 61). Ventral pathways of the reading network were manually traced using diffusion tractography: the inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF). Pathways were examined pre-reading (5–6 years) and after two years of reading acquisition (7–8 years). Dimension reduction for the cognitive measures resulted in one component for pre-reading cognitive measures and a separate phonological and orthographic component for the early reading measures. Regression analyses revealed a relation between the pre-reading cognitive component and bilateral IFOF and left ILF. Interestingly, exclusively the left IFOF was related to the orthographic component, whereas none of the pathways was related to the phonological component. Hence, the left IFOF seems to serve as the lexical reading route, already in the earliest reading stages.

Abstract

Learning often occurs in communicative and collaborative settings, yet almost all research into the neural basis of memory relies on participants encoding and retrieving information on their own. We investigated whether learning linguistic labels in a collaborative context at least partly relies on cognitively and neurally distinct representations, as compared to learning in an individual context. Healthy human participants learned labels for sets of abstract shapes in three different tasks. They came up with labels with another person in a collaborative communication task (collaborative condition), by themselves (individual condition), or were given pre-determined unrelated labels to learn by themselves (arbitrary condition). Immediately after learning, participants retrieved and produced the labels aloud during a communicative task in the MRI scanner. The fMRI results show that the retrieval of collaboratively generated labels as compared to individually learned labels engages brain regions involved in understanding others (mentalizing or theory of mind) and autobiographical memory, including the medial prefrontal cortex, the right temporoparietal junction and the precuneus. This study is the first to show that collaboration during encoding affects the neural networks involved in retrieval.

Abstract

During a post-encoding delay period, the ongoing consolidation of recently acquired memories can suffer interference if the delay period involves encoding of new memories, or sensory stimulation tasks. Interestingly, two recent independent studies suggest that (i) autobiographical thinking also interferes markedly with ongoing consolidation of recently learned wordlist material, while (ii) a 2-Back task might not interfere with ongoing consolidation, possibly due to the suppression of autobiographical thinking. In this study, we directly compare these conditions against a quiet wakeful rest baseline to test whether the promotion (via familiar sound-cues) or suppression (via a 2-Back task) of autobiographical thinking during the post-encoding delay period can affect consolidation of studied wordlists in a negative or a positive way, respectively. Our results successfully replicate previous studies and show a significant interference effect (as compared to the rest condition) when learning is followed by familiar sound-cues that promote autobiographical thinking, whereas no interference effect is observed when learning is followed by the 2-Back task. Results from a post-experimental experience-sampling questionnaire further show significant differences in the degree of autobiographical thinking reported during the three post-encoding periods: highest in the presence of sound-cues and lowest during the 2-Back task. In conclusion, our results suggest that varying levels of autobiographical thought during the post-encoding period may modulate episodic memory consolidation.

Abstract

An important issue in current psycholinguistics is how the time course of utterance planning affects the generation of grammatical structures. The current study investigated the influence of parallel activation of the components of complex noun phrases on the generation of subject-verb agreement. Specifically, the lexical interference account (Gillespie, M. and Pearlmutter, N. J., 2011b and Solomon, E. S. and Pearlmutter, N. J., 2004) predicts more agreement errors (i.e., attraction) for subject phrases in which the head and local noun mismatch in number (e.g., the apple next to the pears) when nouns are planned in parallel than when they are planned in sequence. We used a speeded picture description task that yielded sentences such as the apple next to the pears is red. The objects mentioned in the noun phrase were either semantically related or unrelated. To induce agreement errors, pictures sometimes mismatched in number. In order to manipulate the likelihood of parallel processing of the objects and to test the hypothesized relationship between parallel processing and the rate of agreement errors, the pictures were either placed close together or far apart. Analyses of the participants' eye movements and speech onset latencies indicated slower processing of the first object and stronger interference from the related (compared to the unrelated) second object in the close than in the far condition. Analyses of the agreement errors yielded an attraction effect, with more errors in mismatching than in matching conditions. However, the magnitude of the attraction effect did not differ across the close and far conditions. Thus, spatial proximity encouraged parallel processing of the pictures, which led to interference of the associated conceptual and/or lexical representation, but, contrary to the prediction, it did not lead to more attraction errors.

Abstract

Objective: To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). Methods: We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared. Results: Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p < 0.001) but not in age at first nonvaccination-associated seizure, age at first report of developmental delay, or cognitive outcome. The risk of subsequent vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination. Conclusions: Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific.

Abstract

In English, Dutch, and other European languages, it is well established that the fundamental phonological unit in word production is the phoneme; in contrast, recent studies have shown that in Chinese it is the (atonal) syllable and in Japanese the mora. The present study investigated whether this cross-language variation in the size of the unit of word production is due to the type of script used in the language (i.e., alphabetic, morphosyllabic, or moraic). Capitalizing on the multiscriptal nature of Japanese, and using the Stroop color naming task, we show that the overlap in the initial mora between the color name and the written distractor facilitates color naming independent of script type. These results confirm the mora as the phonological unit of word production in Japanese, and establish the Stroop color naming task as a useful task for investigating the fundamental (or "proximate") phonological unit used in speech production.

Abstract

Recent research has put forward the idea that Chinese speech production is governed by the syllable as the fundamental phonological unit. However, it may be that onset priming might be more difficult to obtain in Mandarin Chinese. Therefore, in this study, the degree of overlap between prime and target was increased from C to CV (i.e., extending beyond the phoneme) as well as whether primes and targets had an overlapping structure (CV vs. CVN). Subsyllabic priming effects were found (i.e., onset + vowel overlap but not purely onset overlap), contrasting with the claim that the syllable is the compulsory building block in the initial construction of Mandarin Chinese phonology.

Abstract

The Microsoft KINECT is a 3D sensing device originally developed for the XBOX. The Microsoft KINECT opens up many exciting new opportunities for conducting experimental research on human behavior. We investigated some of these possibilities within the field of psycholinguistics (specifically: language production) by creating software, using C#, allowing for the KINECT to be used in a typical psycholinguistic experimental setting. The results of a naming experiment using this software confirmed that the KINECT was able to measure the effects of a robust psycholinguistic variable (word frequency) on naming latencies. However, although the current version of the software is able to measure psycholinguistic variables of interest, we also discuss several points where the software can still stand to be improved. The main aim of this paper is to make the software freely available for assessment and use by the psycholinguistic community and to illustrate the KINECT as a potentially valuable tool for investigating human behavior, especially in the field of psycholinguistics.

Abstract

Learning new words is an increasingly common necessity in everyday life. External factors, among which music and social interaction are particularly debated, are claimed to facilitate this task. Due to their influence on the learner’s temporal behavior, these stimuli are able to drive the learner’s attention to the correct referent of new words at the correct point in time. However, do music and social interaction impact learning behavior in the same way? The current study aims to answer this question. Native German speakers (N = 80) were requested to learn new words (pseudo-words) during a contextual learning game. This learning task was performed alone with a computer or with a partner, with or without music. Results showed that music and social interaction had a different impact on the learner’s behavior: Participants tended to temporally coordinate their behavior more with a partner than with music, and in both cases more than with a computer. However, when both music and social interaction were present, this temporal coordination was hindered. These results suggest that while music and social interaction do influence participants’ learning behavior, they have a different impact. Moreover, impaired behavior when both music and a partner are present suggests that different mechanisms are employed to coordinate with the two types of stimuli. Whether one or the other approach is more efficient for word learning, however, is a question still requiring further investigation, as no differences were observed between conditions in a retrieval phase, which took place immediately after the learning session. This study contributes to the literature on word learning in adults by investigating two possible facilitating factors, and has important implications for situations such as music therapy, in which music and social interaction are present at the same time.

Abstract

The classic account of language is that language processing occurs in isolation from other cognitive systems, like perception, motor action, and emotion. The central theme of this paper is the relationship between a participant’s emotional state and language comprehension. Does emotional context affect how we process neutral words? Recent studies showed that processing of word meaning – traditionally conceived as an automatic process – is affected by emotional state. The influence of emotional state on syntactic processing is less clear. One study reported a mood-related P600 modulation, while another study did not observe an effect of mood on syntactic processing. The goals of this study were: First, to clarify whether and if so how mood affects syntactic processing. Second, to shed light on the underlying mechanisms by separating possible effects of mood from those of attention on syntactic processing. Event-related potentials (ERPs) were recorded while participants read syntactically correct or incorrect sentences. Mood (happy vs. sad) was manipulated by presenting film clips. Attention was manipulated by directing attention to syntactic features vs. physical features. The mood induction was effective. Interactions between mood, attention and syntactic correctness were obtained, showing that mood and attention modulated P600. The mood manipulation led to a reduction in P600 for sad as compared to happy mood when attention was directed at syntactic features. The attention manipulation led to a reduction in P600 when attention was directed at physical features compared to syntactic features for happy mood. From this we draw two conclusions: First, emotional state does affect syntactic processing. We propose mood-related differences in the reliance on heuristics as the underlying mechanism. Second, attention can contribute to emotion-related ERP effects in syntactic language processing. Therefore, future studies on the relation between language and emotion will have to control for effects of attention

Abstract

TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically diagnosed with Alzheimer's disease and a positive family history of ALS. We did not observe enrichment of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFκB induction. Of 3 common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13–1.9]; p-value 0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS cohorts. © 2017 The Author(s)

Abstract

Over 25 genes are known to affect the risk of developing Alzheimer disease (AD), the most common neurodegenerative dementia. However, mechanistic insights and improved disease management remains limited, due to difficulties in determining the functional consequences of genetic associations. Transcriptomics is increasingly being used to corroborate or enhance interpretation of genetic discoveries. These approaches, which include second and third generation sequencing, single-cell sequencing, and bioinformatics, reveal allele-specific events connecting AD risk genes to expression profiles, and provide converging evidence of pathophysiological pathways underlying AD. Simultaneously, they highlight brain region- and cell-type-specific expression patterns, and alternative splicing events that affect the straightforward relation between a genetic variant and AD, re-emphasizing the need for an integrated approach of genetics and transcriptomics in understanding AD. © 2018 The Authors

Abstract

The last four decades have seen huge progress in the description and analysis of cross-linguistic diversity in the encoding of motion (Talmy 1985, 1991, Slobin 1996, 2004). Comparisons between satellite-framed and verb-framed languages suggest that satellite-framed languages typically have a larger manner of motion verb lexicon (swim, dash), while verb-framed languages typically have a larger path of motion verb lexicon (enter, cross) (Slobin 2004, Verkerk 2013, 2014b). This paper investigates how differences between the motion verb lexicons of satellite-framed and verb-framed languages emerge. Phylogenetic comparative methods adopted from biology and an etymological study are used to investigate manner verb lexicons and path verb lexicons in an Indo-European dataset. I show that manner verbs and path verbs typically have different types of etymological origins and that manner verbs emerge faster in satellite-framed subgroups, while path verbs emerge faster in verb-framed subgroups.

Abstract

This study examines the influence of orthography on the processing of reduced word forms. For this purpose, we compared the impact of phonological variation with the impact of spelling-sound consistency on the processing of words that may be produced with or without the vowel schwa. Participants learnt novel French words in which the vowel schwa was present or absent in the first syllable. In Experiment 1, the words were consistently produced without schwa or produced in a variable manner (i.e., sometimes produced with and sometimes produced without schwa). In Experiment 2, words were always produced in a consistent manner, but an orthographic exposure phase was included in which words that were produced without schwa were either spelled with or without the letter . Results from naming and eye-tracking tasks suggest that both phonological variation and spelling-sound consistency influence the processing of spoken novel words. However, the influence of phonological variation outweighs the effect of spelling-sound consistency. Our findings therefore suggest that the influence of orthography on the processing of reduced word forms is relatively small.

Abstract

We meta‐analyzed the effectiveness of incidental second language word learning from spoken input. Our sample contained 105 effect sizes from 32 primary studies employing meaning‐focused word‐learning activities with 1,964 participants with typical cognitive functioning. The random‐effects meta‐analysis yielded a mean effect size of g = 1.05, reflecting generally large vocabulary gains from spoken input in meaning‐focused activities. A meta‐regression with three substantive and two methodological predictors also revealed that adult participants outperformed children in terms of word learning and that interactive learning tasks were more effective than noninteractive ones. Furthermore, learning scores were higher when measured with recognition than with recall tests. Methodologically, the use of a no‐input control group seemed to protect against an overestimation of learning effects, evidenced by smaller effect sizes. Finally, whether a pretest–posttest design was used did not influence effect sizes. All data and the analysis script are publicly available.

Abstract

Noticing the hole (NTH) occurs when speakers want to say something, but realise they do not know the right word(s). Such awareness of lacking knowledge supposedly facilitates the acquisition of the unknown word(s) from later input (Swain, 1993). We tested this claim by experimentally inducing NTH in a second language (L2) for some participants (experimental), but not others (control). Then, in a price comparison game, all participants were exposed to spoken L2 input containing the to-be-learned words. They were unaware of taking part in an L2 study. Post-tests showed that participants who had noticed holes in their vocabulary had indeed learned more words compared to participants who had not. This held both for the experimental group as well as those participants in the control group who later reported to have noticed holes. Thus, when we become aware of vocabulary holes, the first step to improve our vocabulary is already taken.

Abstract

Since the 1990s, the field of sign language typology has shown that sign languages exhibit typological variation at all relevant levels of linguistic description. These initial typological comparisons were heavily skewed toward the urban sign languages of developed countries, mostly in the Western world. This review reports on the recent contributions made by rural signing varieties, that is, sign languages that have evolved in village communities, often in developing countries, due to a high incidence of deafness. With respect to a number of structural properties, rural sign languages fit into previously established typological classifications. However, they also exhibit unique and typologically marked features that challenge received views on possible sign languages. At the same time, the shared features of geographically dispersed rural signing varieties provide a unique window into the social dynamics that may shape the structures of modern human languages.

Abstract

Signed utterances are densely packed with pointing signs, reaching a frequency of one in six signs in spontaneous conversations (de Vos, 2012; Johnston, 2013a; Morford & MacFarlane, 2003). These pointing signs attain a wide range of functions and are formally highly diversified. Based on corpus analysis of spontaneous pointing signs in Kata Kolok, a rural signing variety of Bali, this paper argues that the full meaning potentials of pointing signs come about through the integration of a varied set of linguistic and extralinguistic cues. Taking this hybrid nature of point- ing phenomena into account, it is argued that pointing signs may become an intrinsic aspect of sign language grammars through two mechanisms: morphemization and syntactic integration. Although not entailed in this research, this approach could implicate that some highly systema- tized pointing systems of speaking communities may to a degree be grammatical as well.

Abstract

In spoken interactions, interlocutors carefully plan and time their utterances, minimising gaps and overlaps between consecutive turns. Cross-linguistic comparison has indicated that spoken languages vary only minimally in terms of turn-timing, and language acquisition research has shown pre-linguistic vocal turn-taking in the first half year of life. These observations suggest that the turn-taking system may provide a fundamental basis for our linguistic capacities. The question remains however to what extent our capacity for rapid turn-taking is determined by modality constraints. The avoidance of overlapping turns could be motivated by the difficulty of hearing and speaking at the same time. If so, turn-taking in sign might show greater toleration for overlap. Alternatively, signed conversations may show a similar distribution of turn-timing as spoken languages, thus avoiding both gaps and overlaps. To address this question we look at turn-timing in question-answer sequences in spontaneous conversations of Sign Language of the Netherlands. The findings indicate that although there is considerable overlap in two or more signers' articulators in conversation, when proper allowance is made for onset preparation, post-utterance retraction and the intentional holding of signs for response, turn-taking latencies in sign look remarkably like those reported for spoken language. This is consistent with the possibility that, at least with regard to responses to questions, speakers and signers follow similar time courses in planning and producing their utterances in on-going conversation. This suggests that turn-taking systems may well be a shared cognitive infrastructure underlying all modern human languages, both spoken and signed.

Abstract

Metaphors occur frequently in literary texts. Deliberate Metaphor Theory (DMT; e.g., Steen, 2017) proposes that metaphors that serve a communicative function as metaphor are radically different from metaphors that do not have this function. We investigated differences in processing between deliberate and non-deliberate metaphors, compared to non-metaphorical words in literary reading. Using the Deliberate Metaphor Identification Procedure (Reijnierse et al., 2018), we identified metaphors in two literary stories. Then, eye-tracking was used to investigate participants’ (N = 72) reading behavior. Deliberate metaphors were read slower than non-deliberate metaphors, and both metaphor types were read slower than non-metaphorical words. Differences were controlled for several psycholinguistic variables. Differences in reading behavior were related to individual differences in reading experience and absorption and appreciation of the story. These results are in line with predictions from DMT and underline the importance of distinguishing between metaphor types in the experimental study of literary reading.

Abstract

The present study investigated the interplay between selective inhibition (the ability to suppress specific competing responses) and nonselective inhibition (the ability to suppress any inappropriate response) during single word production. To this end, we combined two well-established research paradigms: the picture-word interference task and the stop-signal task. Selective inhibition was assessed by instructing participants to name target pictures (e.g., dog) in the presence of semantically related (e.g., cat) or unrelated (e.g., window) distractor words. Nonselective inhibition was tested by occasionally presenting a visual stop-signal, indicating that participants should withhold their verbal response. The stop-signal was presented early (250 ms) aimed at interrupting the lexical selection stage, and late (325 ms) to influence the word-encoding stage of the speech production process. We found longer naming latencies for pictures with semantically related distractors than with unrelated distractors (semantic interference effect). The results further showed that, at both delays, stopping latencies (i.e., stop-signal RTs) were prolonged for naming pictures with semantically related distractors compared to pictures with unrelated distractors. Taken together, our findings suggest that selective and nonselective inhibition, at least partly, share a common inhibitory mechanism during different stages of the speech production process.

Abstract

Understanding the genetic basis of airflow obstruction and smoking behaviour is key to determining the pathophysiology of chronic obstructive pulmonary disease (COPD). We used UK Biobank data to study the genetic causes of smoking behaviour and lung health.

Abstract

Using event-related potentials (ERPs), this study examines how trait information inferred from behaviors is associated with person names. In linguistic discourses, person names were associated with descriptions of either positive or negative behaviors. In a subsequent explicit evaluation task, the previously described person names were presented in isolation, and the participants were asked to judge the emotional valence of these names. We found that the names associated with positive descriptions elicited a larger positivity in the ERP than the names associated with negative descriptions. The results indicate that the emotional valence of person names attached to person perception can be dynamically influenced by short descriptions of the target person, probably due to trait inference based on the provided behavioral descriptions

Abstract

Readers and listeners actively predict upcoming words during language processing. These predictions might serve to support the unification of incoming words into sentence context and thus rely on interactions between areas in the language network. In the current magnetoencephalography study, participants read sentences that varied in contextual constraints so that the predictability of the sentence-final words was either high or low. Before the sentence-final words, we observed stronger alpha power suppression for the highly compared with low constraining sentences in the left inferior frontal cortex, left posterior temporal region, and visual word form area. Importantly, the temporal and visual word form area alpha power correlated negatively with left frontal gamma power for the highly constraining sentences. We suggest that the correlation between alpha power decrease in temporal language areas and left prefrontal gamma power reflects the initiation of an anticipatory unification process in the language network.

Abstract

Using magnetoencephalography, the current study examined gamma activity associated with language prediction. Participants read high- and low-constraining sentences in which the final word of the sentence was either expected or unexpected. Although no consistent gamma power difference induced by the sentence-final words was found between the expected and unexpected conditions, the correlation of gamma power during the prediction and activation intervals of the sentence-final words was larger when the presented words matched with the prediction compared with when the prediction was violated or when no prediction was available. This suggests that gamma magnitude relates to the match between predicted and perceived words. Moreover, the expected words induced activity with a slower gamma frequency compared with that induced by unexpected words. Overall, the current study establishes that prediction is related to gamma power correlations and a slowing of the gamma frequency.

Abstract

The blocked cyclic naming paradigm has been increasingly employed to investigate the mechanisms underlying spoken word production. Semantic homogeneity typically elicits longer naming latencies than heterogeneity; however, it is debated whether competitive lexical selection or incremental learning underlies this effect. The current study manipulated both semantic and phonological homogeneity and used behavioural and electrophysiological measurements to provide evidence that can distinguish between the two accounts. Results show that naming latencies are longer in semantically homogeneous blocks, but shorter in phonologically homogeneous blocks, relative to heterogeneity. The semantic factor significantly modulates electrophysiological waveforms from 200 ms and the phonological factor from 350 ms after picture presentation. A positive component was demonstrated in both manipulations, possibly reflecting a task-related top-down bias in performing blocked cyclic naming. These results provide novel insights into the neural correlates of blocked cyclic naming and further contribute to the understanding of spoken word production.

Abstract

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

Abstract

Asperger Syndrome (AS) is a neurodevelopmental condition characterized by impairments in social interaction and communication, alongside the presence of unusually repetitive, restricted interests and stereotyped behaviour. Individuals with AS have no delay in cognitive and language development. It is a subset of Autism Spectrum Conditions (ASC), which are highly heritable and has a population prevalence of approximately 1%. Few studies have investigated the genetic basis of AS. To address this gap in the literature, we performed a genome-wide pooled DNA association study to identify candidate loci in 612 individuals (294 cases and 318 controls) of Caucasian ancestry, using the Affymetrix GeneChip Human Mapping version 6.0 array. We identified 11 SNPs that had a p-value below 1x10-5. These SNPs were independently genotyped in the same sample. Three of the SNPs (rs1268055, rs7785891 and rs2782448) were nominally significant, though none remained significant after Bonferroni correction. Two of our top three SNPs (rs7785891 and rs2782448) lie in loci previously implicated in ASC. However, investigation of the three SNPs in the ASC genome-wide association dataset from the Psychiatric Genomics Consortium indicated that these three SNPs were not significantly associated with ASC. The effect sizes of the variants were modest, indicating that our study was not sufficiently powered to identify causal variants with precision.

Abstract

Background: Several studies have investigated the effect of known adult body mass index (BMI) associated single nucleotide polymorphisms (SNPs) on BMI in childhood. There has been no genome-wide association study (GWAS) of BMI trajectories over childhood.
Methods: We conducted a GWAS meta-analysis of BMI trajectories from 1 to 17 years of age in 9377 children (77 967 measurements) from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Western Australian Pregnancy Cohort (Raine) Study. Genome-wide significant loci were examined in a further 3918 individuals (48 530 measurements) from Northern Finland. Linear mixed effects models with smoothing splines were used in each cohort for longitudinal modelling of BMI.
Results: A novel SNP, downstream from the FAM120AOS gene on chromosome 9, was detected in the meta-analysis of ALSPAC and Raine. This association was driven by a difference in BMI at 8 years (T allele of rs944990 increased BMI; PSNP = 1.52 × 10−8), with a modest association with change in BMI over time (PWald(Change) = 0.006). Three known adult BMI-associated loci (FTO, MC4R and ADCY3) and one childhood obesity locus (OLFM4) reached genome-wide significance (PWald < 1.13 × 10−8) with BMI at 8 years and/or change over time.
Conclusions: This GWAS of BMI trajectories over childhood identified a novel locus that warrants further investigation. We also observed genome-wide significance with previously established obesity loci, making the novel observation that these loci affected both the level and the rate of change in BMI. We have demonstrated that the use of repeated measures data can increase power to allow detection of genetic loci with smaller sample sizes.

Abstract

Exposure to high levels of environmental lead, or biomarker evidence of high body lead content, is associated with anaemia, developmental and neurological deficits in children, and increased mortality in adults. Adverse effects of lead still occur despite substantial reduction in environmental exposure. There is genetic variation between individuals in blood lead concentration but the polymorphisms contributing to this have not been defined. We measured blood or erythrocyte lead content, and carried out genome-wide association analysis, on population-based cohorts of adult volunteers from Australia and UK (N = 5433). Samples from Australia were collected in two studies, in 1993–1996 and 2002–2005 and from UK in 1991–1992. One locus, at ALAD on chromosome 9, showed consistent association with blood lead across countries and evidence for multiple independent allelic effects. The most significant single nucleotide polymorphism (SNP), rs1805313 (P = 3.91 × 10−14 for lead concentration in a meta-analysis of all data), is known to have effects on ALAD expression in blood cells but other SNPs affecting ALAD expression did not affect blood lead. Variants at 12 other loci, including ABO, showed suggestive associations (5 × 10−6 >} P {> 5 × 10−8). Identification of genetic polymorphisms affecting blood lead reinforces the view that genetic factors, as well as environmental ones, are important in determining blood lead levels. The ways in which ALAD variation affects lead uptake or distribution are still to be determined.

Abstract

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

Abstract

Induced pluripotent stem cell (iPSC) technology has emerged as an important tool in understanding, and potentially reversing, disease pathology. This is particularly true in the case of neurodegenerative diseases, in which the affected cell types are not readily accessible for study. Since the first descriptions of iPSC-based disease modelling, considerable advances have been made in understanding the aetiology and progression of a diverse array of neurodegenerative conditions, including Parkinson's disease and Alzheimer's disease. To date, however, relatively few studies have succeeded in using iPSCs to model the neurodegeneration observed in cerebellar ataxia. Given the distinct neurodevelopmental phenotypes associated with certain types of ataxia, iPSC-based models are likely to provide significant insights, not only into disease progression, but also to the development of early-intervention therapies. In this review, we describe the existing iPSC-based disease models of this heterogeneous group of conditions and explore the challenges associated with generating cerebellar neurons from iPSCs, which have thus far hindered the expansion of this research.

Abstract

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

Abstract

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

Abstract

Background

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

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

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

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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