Publications

Abstract

Research on pattern perception and rule learning, grounded in formal language theory (FLT) and using artificial grammar learning paradigms, has exploded in the last decade. This approach marries empirical research conducted by neuroscientists, psychologists and ethologists with the theory of computation and FLT, developed by mathematicians, linguists and computer scientists over the last century. Of particular current interest are comparative extensions of this work to non-human animals, and neuroscientific investigations using brain imaging techniques. We provide a short introduction to the history of these fields, and to some of the dominant hypotheses, to help contextualize these ongoing research programmes, and finally briefly introduce the papers in the current issue.

Abstract

Event-related potentials (ERPs) provide a window into how the brain is processing language. Here, we propose a theory that argues that ERPs such as the N400 and P600 arise as side effects of an error-based learning mechanism that explains linguistic adaptation and language learning. We instantiated this theory in a connectionist model that can simulate data from three studies on the N400 (amplitude modulation by expectancy, contextual constraint, and sentence position), five studies on the P600 (agreement, tense, word category, subcategorization and garden-path sentences), and a study on the semantic P600 in role reversal anomalies. Since ERPs are learning signals, this account explains adaptation of ERP amplitude to within-experiment frequency manipulations and the way ERP effects are shaped by word predictability in earlier sentences. Moreover, it predicts that ERPs can change over language development. The model provides an account of the sensitivity of ERPs to expectation mismatch, the relative timing of the N400 and P600, the semantic nature of the N400, the syntactic nature of the P600, and the fact that ERPs can change with experience. This approach suggests that comprehension ERPs are related to sentence production and language acquisition mechanisms

Abstract

No abstract is available for this article

Abstract

Understanding the progression of neurological diseases is vital for accurate and early diagnosis and treatment planning. We introduce a new characterization of disease progression, which describes the disease as a series of events, each comprising a significant change in patient state. We provide novel algorithms to learn the event ordering from heterogeneous measurements over a whole patient cohort and demonstrate using combined imaging and clinical data from familial-Alzheimer's and Huntington's disease cohorts. Results provide new detail in the progression pattern of these diseases, while confirming known features, and give unique insight into the variability of progression over the cohort. The key advantage of the new model and algorithms over previous progression models is that they do not require a priori division of the patients into clinical stages. The model and its formulation extend naturally to a wide range of other diseases and developmental processes and accommodate cross-sectional and longitudinal input data.

Abstract

Previous research on the effect of perturbed auditory feedback in speech production has focused on two types of responses. In the short term, speakers generate compensatory motor commands in response to unexpected perturbations. In the longer term, speakers adapt feedforward motor programmes in response to feedback perturbations, to avoid future errors. The current study investigated the relation between these two types of responses to altered auditory feedback. Specifically, it was hypothesised that consistency in previous feedback perturbations would influence whether speakers adapt their feedforward motor programmes. In an altered auditory feedback paradigm, formant perturbations were applied either across all trials (the consistent condition) or only to some trials, whereas the others remained unperturbed (the inconsistent condition). The results showed that speakers’ responses were affected by feedback consistency, with stronger speech changes in the consistent condition compared with the inconsistent condition. Current models of speech-motor control can explain this consistency effect. However, the data also suggest that compensation and adaptation are distinct processes, which are not in line with all current models.

Abstract

A spelling disorder that received much attention recently is the so-called graphemic buffer impairment. Caramazza et al. (1987) presented the first systematic case study of a patient with this disorder. Miceli & Capasso (2006) provide an extensive overview of the relevant literature. This article adds to the literature by describing a Dutch case, i.e. patient BM. We demonstrate how specific features of Dutch and Dutch orthography interact with the graphemic buffer impairment. In addition, we paid special attention to the influence of grapheme position on the patient’s spelling accuracy. For this we used, in contrast with most of the previous literature, the proportional accountability method described in Machtynger & Shallice (2009). We show that by using this method the underlying error distribution can be more optimally captured than with classical methods. The result of this analysis replicates two distributions that have been previously reported in the literature. Finally, attention will be paid to the role of phonology in the described disorder.

Abstract

Kleefstra syndrome (KS) is a neurodevelopmental disorder caused by mutations in the histone methyltransferase EHMT1. To study the impact of decreased EHMT1 function in human cells, we generated excitatory cortical neurons from induced pluripotent stem (iPS) cells derived from KS patients. Neuronal networks of patient-derived cells exhibit network bursting with a reduced rate, longer duration, and increased temporal irregularity compared to control networks. We show that these changes are mediated by upregulation of NMDA receptor (NMDAR) subunit 1 correlating with reduced deposition of the repressive H3K9me2 mark, the catalytic product of EHMT1, at the GRIN1 promoter. In mice EHMT1 deficiency leads to similar neuronal network impairments with increased NMDAR function. Finally, we rescue the KS patient-derived neuronal network phenotypes by pharmacological inhibition of NMDARs. Summarized, we demonstrate a direct link between EHMT1 deficiency and NMDAR hyperfunction in human neurons, providing a potential basis for more targeted therapeutic approaches for KS.

Abstract

Disruptions of the FOXP2 gene cause a speech and language disorder involving difficulties in sequencing orofacial movements. FOXP2 is expressed in cortico-striatal and cortico-cerebellar circuits important for fine motor skills, and affected individuals show abnormalities in these brain regions. We selectively disrupted Foxp2 in the cerebellar Purkinje cells, striatum or cortex of mice and assessed the effects on skilled motor behaviour using an operant lever-pressing task. Foxp2 loss in each region impacted behaviour differently, with striatal and Purkinje cell disruptions affecting the variability and the speed of lever-press sequences, respectively. Mice lacking Foxp2 in Purkinje cells showed a prominent phenotype involving slowed lever pressing as well as deficits in skilled locomotion. In vivo recordings from Purkinje cells uncovered an increased simple spike firing rate and decreased modulation of firing during limb movements. This was caused by increased intrinsic excitability rather than changes in excitatory or inhibitory inputs. Our findings show that Foxp2 can modulate different aspects of motor behaviour in distinct brain regions, and uncover an unknown role for Foxp2 in the modulation of Purkinje cell activity that severely impacts skilled movements.

Abstract

Mutations in the human FOXP2 gene cause impaired speech development and linguistic deficits, which have been best characterised in a large pedigree called the KE family. The encoded protein is highly conserved in many vertebrates and is expressed in homologous brain regions required for sensorimotor integration and motor-skill learning, in particular corticostriatal circuits. Independent studies in multiple species suggest that the striatum is a key site of FOXP2 action. Here, we used in vivo recordings in awake-behaving mice to investigate the effects of the KE-family mutation on the function of striatal circuits during motor-skill learning. We uncovered abnormally high ongoing striatal activity in mice carrying an identical mutation to that of the KE family. Furthermore, there were dramatic alterations in striatal plasticity during the acquisition of a motor skill, with most neurons in mutants showing negative modulation of firing rate, starkly contrasting with the predominantly positive modulation seen in control animals. We also observed striking changes in the temporal coordination of striatal firing during motor-skill learning in mutants. Our results indicate that FOXP2 is critical for the function of striatal circuits in vivo, which are important not only for speech but also for other striatal-dependent skills.

Abstract

Achieving linguistic proficiency requires identifying words from speech, and discovering the constraints that govern the way those words are used. In a recent study of non-adjacent dependency learning, Frost and Monaghan (2016) demonstrated that learners may perform these tasks together, using similar statistical processes - contrary to prior suggestions. However, in their study, non-adjacent dependencies were marked by phonological cues (plosive-continuant-plosive structure), which may have influenced learning. Here, we test the necessity of these cues by comparing learning across three conditions; fixed phonology, which contains these cues, varied phonology, which omits them, and shapes, which uses visual shape sequences to assess the generality of statistical processing for these tasks. Participants segmented the sequences and generalized the structure in both auditory conditions, but learning was best when phonological cues were present. Learning was around chance on both tasks for the visual shapes group, indicating statistical processing may critically differ across domains.

Abstract

High frequency words have been suggested to benefit both speech segmentation and grammatical categorization of the words around them. Despite utilizing similar information, these tasks are usually investigated separately in studies examining learning. We determined whether including high frequency words in continuous speech could support categorization when words are being segmented for the first time. We familiarized learners with continuous artificial speech comprising repetitions of target words, which were preceded by high-frequency marker words. Crucially, marker words distinguished targets into 2 distributionally defined categories. We measured learning with segmentation and categorization tests and compared performance against a control group that heard the artificial speech without these marker words (i.e., just the targets, with no cues for categorization). Participants segmented the target words from speech in both conditions, but critically when the marker words were present, they influenced acquisition of word-referent mappings in a subsequent transfer task, with participants demonstrating better early learning for mappings that were consistent (rather than inconsistent) with the distributional categories. We propose that high-frequency words may assist early grammatical categorization, while speech segmentation is still being learned.

Abstract

Sleep plays an important role in neural reorganisation which underpins memory consolidation. The gradual replacement of
hippocampal binding of new memories with intracortical connections helps to link new memories to existing knowledge. This process appears to be faster for memories which fit more easily into existing schemas. Here we seek to investigate whether this more rapid consolidation of schema-conformant information is facilitated by
sleep, and the neural basis of this process.

Abstract

In many languages the future is in front and the past behind, but in some cultures (like Aymara) the past is in front. Is it possible to find this mapping as an alternative conceptualization of time in other cultures? If so, what are the factors that affect its choice out of the set of available alternatives? In a paper and pencil task, participants placed future or past events either in front or behind a character (a schematic head viewed from above). A sample of 24 Islamic participants (whose language also places the future in front and the past behind) tended to locate the past event in the front box more often than Spanish participants. This result might be due to the greater cultural value assigned to tradition in Islamic culture. The same pattern was found in a sample of Spanish elders (N = 58), what may support that conclusion. Alternatively, the crucial factor may be the amount of attention paid to the past. In a final study, young Spanish adults (N = 200) who had just answered a set of questions about their past showed the past-in-front pattern, whereas questions about their future exacerbated the future-in-front pattern. Thus, the attentional explanation was supported: attended events are mapped to front space in agreement with the experiential connection between attending and seeing. When attention is paid to the past, it tends to occupy the front location in spite of available alternative mappings in the language-culture.

Abstract

Several studies report an association between REM Sleep Behavior Disorder (RBD) and neurodegenerative diseases, in particular synucleinopathies. Interestingly, the onset of RBD precedes the development of neurodegeneration by several years. This review and meta-analysis aims to establish the rate of conversion of RBD into neurodegenerative diseases. Longitudinal studies were searched from the PubMed, Web of Science, and SCOPUS databases. Using random-effect modeling, we performed a meta-analysis on the rate of RBD conversions into neurodegeneration. Furthermore, we fitted a Kaplan-Meier analysis and compared the differences between survival curves of different diseases with log-rank tests. The risk for developing neurodegenerative diseases was 33.5% at five years follow-up, 82.4% at 10.5 years and 96.6% at 14 years. The average conversion rate was 31.95% after a mean duration of follow-up of 4.75 ± 2.43 years. The majority of RBD patients converted to Parkinson's Disease (43%), followed by Dementia with Lewy Bodies (25%). The estimated risk for RBD patients to develop a neurodegenerative disease over a long-term follow-up is more than 90%. Future studies should include control group for the evaluation of REM sleep without atonia as marker for neurodegeneration also in non-clinical population and target RBD as precursor of neurodegeneration to develop protective trials.

Abstract

Large-scale graph data in real-world applications is often not static but dynamic,
i. e., new nodes and edges appear over time. Current graph convolution approaches
are promising, especially, when all the graph’s nodes and edges are available dur-
ing training. When unseen nodes and edges are inserted after training, it is not
yet evaluated whether up-training or re-training from scratch is preferable. We
construct an experimental setup, in which we insert previously unseen nodes and
edges after training and conduct a limited amount of inference epochs. In this
setup, we compare adapting pretrained graph neural networks against retraining
from scratch. Our results show that pretrained models yield high accuracy scores
on the unseen nodes and that pretraining is preferable over retraining from scratch.
Our experiments represent a first step to evaluate and develop truly online variants
of graph neural networks.

Abstract

Many contemporary texts include shortcuts, such as cu or phones4u. The aim of this study was to investigate how the meanings of shortcuts are retrieved. A primed lexical decision paradigm was used with shortcuts and the corresponding words as primes. The target word was associatively related to the meaning of the whole prime (cu/see you – goodbye), to a component of the prime (cu/see you – look), or unrelated to the prime. In Experiment 1, primes were presented for 57 ms. For both word and shortcut primes, responses were faster to targets preceded by whole-related than by unrelated primes. No priming from component-related primes was found. In Experiment 2, the prime duration was 1000 ms. The priming effect seen in Experiment 1 was replicated. Additionally, there was priming from component-related word primes, but not from component-related shortcut primes. These results indicate that the meanings of shortcuts can be retrieved without translating them first into corresponding words.

Abstract

Learning to read a second language (L2) can pose a great challenge for children who have already been struggling to read in their first language (L1). Moreover, it is not clear whether, to what extent, and under what circumstances L1 reading difficulty increases the risk of L2 reading difficulty. This study investigated Chinese (L1) and English (L2) reading skills in a large representative sample of 1,824 Chinese–English bilingual children in Grades 4 and 5 from both urban and rural schools in Beijing. We examined the prevalence of reading difficulty in Chinese only (poor Chinese readers, PC), English only (poor English readers, PE), and both Chinese and English (poor bilingual readers, PB) and calculated the co-occurrence, that is, the chances of becoming a poor reader in English given that the child was already a poor reader in Chinese. We then conducted a multinomial logistic regression analysis and compared the prevalence of PC, PE, and PB between children in Grade 4 versus Grade 5, in urban versus rural areas, and in boys versus girls. Results showed that compared to girls, boys demonstrated significantly higher risk of PC, PE, and PB. Meanwhile, compared to the 5th graders, the 4th graders demonstrated significantly higher risk of PC and PB. In addition, children enrolled in the urban schools were more likely to become better second language readers, thus leading to a concerning rural–urban gap in the prevalence of L2 reading difficulty. Finally, among these Chinese–English bilingual children, regardless of sex and school location, poor reading skill in Chinese significantly increased the risk of also being a poor English reader, with a considerable and stable co-occurrence of approximately 36%. In sum, this study suggests that despite striking differences between alphabetic and logographic writing systems, L1 reading difficulty still significantly increases the risk of L2 reading difficulty. This indicates the shared meta-linguistic skills in reading different writing systems and the importance of understanding the universality and the interdependent relationship of reading between different writing systems. Furthermore, the male disadvantage (in both L1 and L2) and the urban–rural gap (in L2) found in the prevalence of reading difficulty calls for special attention to disadvantaged populations in educational practice.

Abstract

Previous research shows conflicting findings for the effect of font readability on comprehension and memory for language. It has been found that—perhaps counterintuitively–a hard to read font can be beneficial for language comprehension, especially for difficult language. Here we test how font readability influences the subjective experience of poetry reading. In three experiments we tested the influence of poem difficulty and font readability on the subjective experience of poems. We specifically predicted that font readability would have opposite effects on the subjective experience of easy versus difficult poems. Participants read poems which could be more or less difficult in terms of conceptual or structural aspects, and which were presented in a font that was either easy or more difficult to read. Participants read existing poems and subsequently rated their subjective experience (measured through four dependent variables: overall liking, perceived flow of the poem, perceived topic clarity, and perceived structure). In line with previous literature we observed a Poem Difficulty x Font Readability interaction effect for subjective measures of poetry reading. We found that participants rated easy poems as nicer when presented in an easy to read font, as compared to when presented in a hard to read font. Despite the presence of the interaction effect, we did not observe the predicted opposite effect for more difficult poems. We conclude that font readability can influence reading of easy and more difficult poems differentially, with strongest effects for easy poems.

Abstract

The effortfulness hypothesis implies that difficulty in decoding the surface form, as in the case of age-related sensory limitations or background noise, consumes the attentional resources that are then unavailable for semantic integration in language comprehension. Because ageing is associated with sensory declines, degrading of the surface form by a noisy background can pose an extra challenge for older adults. In two experiments, this hypothesis was tested in a self-paced moving window paradigm in which younger and older readers' online allocation of attentional resources to surface decoding and semantic integration was measured as they read sentences embedded in varying levels of visual noise. When visual noise was moderate (Experiment 1), resource allocation among young adults was unaffected but older adults allocated more resources to decode the surface form at the cost of resources that would otherwise be available for semantic processing; when visual noise was relatively intense (Experiment 2), both younger and older participants allocated more attention to the surface form and less attention to semantic processing. The decrease in attentional allocation to semantic integration resulted in reduced recall of core ideas in both experiments, suggesting that a less organized semantic representation was constructed in noise. The greater vulnerability of older adults at relatively low levels of noise is consistent with the effortfulness hypothesis.

Abstract

It is a common finding across languages that young children have problems in understanding patient-initial sentences. We used Tagalog, a verb-initial language with a reliable voice-marking system and highly frequent patient voice constructions, to test the predictions of several accounts that have been proposed to explain this difficulty: the frequency account, the Competition Model, and the incremental processing account. Study 1 presents an analysis of Tagalog child-directed speech, which showed that the dominant argument order is agent-before-patient and that morphosyntactic markers are highly valid cues to thematic role assignment. In Study 2, we used a combined self-paced listening and picture verification task to test how Tagalog-speaking adults and 5- and 7-year-old children process reversible transitive sentences. Results showed that adults performed well in all conditions, while children’s accuracy and listening times for the first noun phrase indicated more difficulty in interpreting patient-initial sentences in the agent voice compared to the patient voice. The patient voice advantage is partly explained by both the frequency account and incremental processing account.

Abstract

Print Friendly XML Gebre, Binyam Gebrekidan, Max Planck Institute for Psycholinguistics, The Netherlands, binyamgebrekidan.gebre [at] mpi.nl Wittenburg, Peter, Max Planck Institute for Psycholinguistics, The Netherlands, peter.wittenburg [at] mpi.nl Introduction Many gesture and sign language researchers manually annotate video recordings to systematically categorize, analyze and explain their observations. The number and kinds of annotations are so diverse and unpredictable that any attempt at developing non-adaptive automatic annotation systems is usually less effective. The trend in the literature has been to develop models that work for average users and for average scenarios. This approach has three main disadvantages. First, it is impossible to know beforehand all the patterns that could be of interest to all researchers. Second, it is practically impossible to find enough training examples for all patterns. Third, it is currently impossible to learn a model that is robustly applicable across all video quality-recording variations.

Abstract

Automatic annotation of gesture strokes is important for many gesture and sign language researchers. The unpredictable diversity of human gestures and video recording conditions require that we adopt a more adaptive case-by-case annotation model. In this paper, we present a work-in progress annotation model that allows a user to a) track hands/face b) extract features c) distinguish strokes from non-strokes. The hands/face tracking is done with color matching algorithms and is initialized by the user. The initialization process is supported with immediate visual feedback. Sliders are also provided to support a user-friendly adjustment of skin color ranges. After successful initialization, features related to positions, orientations and speeds of tracked hands/face are extracted using unique identifiable features (corners) from a window of frames and are used for training a learning algorithm. Our preliminary results for stroke detection under non-ideal video conditions are promising and show the potential applicability of our methodology.

Abstract

The way the human brain represents speech in memory is still unknown. An obvious characteristic of speech is its evolvement over time.
During speech processing, neural oscillations are modulated by the temporal properties of the acoustic speech signal, but also acquired
knowledge on the temporal structure of language influences speech perception-related brain activity. This suggests that speech could be
represented in the temporal domain, a form of representation that the brain also uses to encode autobiographic memories. Empirical
evidence for such a memory code is lacking. We investigated the nature of speech memory representations using direct cortical recordings
in the left perisylvian cortex during delayed sentence reproduction in female and male patients undergoing awake tumor surgery.
Our results reveal that the brain endogenously represents speech in the temporal domain. Temporal pattern similarity analyses revealed
that the phase of frontotemporal low-frequency oscillations, primarily in the beta range, represents sentence identity in working memory.
The positive relationship between beta power during working memory and task performance suggests that working memory
representations benefit from increased phase separation.

Abstract

In principle mutational records make it possible to estimate frequencies of disease alleles (q) for autosomal recessive disorders using a novel approach based on the calculation of the Homozygosity Index (HI), i.e., the proportion of homozygous patients, which is complementary to the proportion of compound heterozygous patients P(CH). In other words, the rarer the disorder, the higher will be the HI and the lower will be the P(CH). To test this hypothesis we used mutational records of individuals affected with Familial Mediterranean Fever (FMF) and Phenylketonuria (PKU), born to either consanguineous or apparently unrelated parents from six population samples of the Mediterranean region. Despite the unavailability of precise values of the inbreeding coefficient for the general population, which are needed in the case of apparently unrelated parents, our estimates of q are very similar to those of previous descriptive epidemiological studies. Finally, we inferred from simulation studies that the minimum sample size needed to use this approach is 25 patients either with unrelated or first cousin parents. These results show that the HI can be used to produce a ranking order of allele frequencies of autosomal recessive disorders, especially in populations with high rates of consanguineous marriages.

Abstract

Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562–3468). We observed a genome-wide significant effect (p < 1 × 10−8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 × 10−9), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 × 10−8). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 × 10−8) and with all the cognitive traits tested (p = 3.07 × 10−8), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p ~ [10−5–10−7]) and negatively associated with ADHD PRS (p ~ [10−8−10−17]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.

Abstract

Recognizing the speech acts in our interlocutors’ utterances is a crucial prerequisite for conversation. However, it is not a trivial task given that the form and content of utterances is frequently underspecified for this level of meaning. In the present study we investigate participants’ competence in categorizing speech acts in such action-underspecific sentences and explore the time-course of speech act inferencing using a self-paced reading paradigm. The results demonstrate that participants are able to categorize the speech acts with very high accuracy, based on limited context and without any prosodic information. Furthermore, the results show that the exact same sentence is processed differently depending on the speech act it performs, with reading times starting to differ already at the first word. These results indicate that participants are very good at “getting” the speech acts, opening up a new arena for experimental research on action recognition in conversation.

Abstract

Patterns formed by reaction-diffusion mechanisms are crucial for the development or sustenance of most organisms in nature. Patterns include dynamic waves, but are more often found as static distributions, such as animal skin patterns. Yet, a simplistic biological model system to reproduce and quantitatively investigate static reaction-diffusion patterns has been missing so far. Here, we demonstrate that the Escherichia coli MM system, known for its oscillatory behavior between the cell poles, is under certain conditions capable of transitioning to quasi-stationary protein distributions on membranes closely resembling Turing patterns. We systematically titrated both proteins, MinD and MinE, and found that removing all purification tags and linkers from the N-terminus of MinE was critical for static patterns to occur. At small bulk heights, dynamic patterns dominate, such as in rod-shaped microcompartments. We see implications of this work for studying pattern formation in general, but also for creating artificial gradients as downstream cues in synthetic biology applications.

Abstract

Interactive models of language production predict that it should be possible to observe long-distance interactions; effects that arise at one level of processing influence multiple subsequent stages of representation and processing. We examine the hypothesis that disruptions arising in nonform-based levels of planning—specifically, lexical selection—should modulate articulatory processing. A novel automatic phonetic analysis method was used to examine productions in a paradigm yielding both general disruptions to formulation processes and, more specifically, overt errors during lexical selection. This analysis method allowed us to examine articulatory disruptions at multiple levels of analysis, from whole words to individual segments. Baseline performance by young adults was contrasted with young speakers’ performance under time pressure (which previous work has argued increases interaction between planning and articulation) and performance by older adults (who may have difficulties inhibiting nontarget representations, leading to heightened interactive effects). The results revealed the presence of interactive effects. Our new analysis techniques revealed these effects were strongest in initial portions of responses, suggesting that speech is initiated as soon as the first segment has been planned. Interactive effects did not increase under response pressure, suggesting interaction between planning and articulation is relatively fixed. Unexpectedly, lexical selection disruptions appeared to yield some degree of facilitation in articulatory processing (possibly reflecting semantic facilitation of target retrieval) and older adults showed weaker, not stronger interactive effects (possibly reflecting weakened connections between lexical and form-level representations).

Abstract

Chicks can convey information about their needs with calls. But it is still unknown if there are any universal need indicators in chick vocalizations. Previous studies have shown that in some species vocal activity and/or temporal-frequency variables of calls are related to the chick state, whereas other studies did not confirm it. Here, we tested experimentally whether vocal activity and temporal-frequency variables of calls change with cooling. We studied 10 human-raised
Siberian crane (Grus leucogeranus) chicks at 3–15 days of age. We found that the cooled chicks produced calls higher in fundamental
frequency and power variables, longer in duration and at a higher calling rate than in the control chicks. However, we did not find
significant changes in level of entropy and occurrence of non-linear phenomena in chick calls recorded during the experimental cooling. We suggest that the level of vocal activity is a universal indicator of need for warmth in precocial and semi-precocial birds (e.g. cranes), but not in altricial ones. We also assume that coding of needs via temporal-frequency variables of calls is typical in species whose adults could not confuse their chicks with other chicks. Siberian cranes stay on separate territories during their breeding season, so parents do not need to check individuality of their offspring in the home area. In this case, all call characteristics are available for other purposes and serve to communicate chicks’ vital needs.

Abstract

Adopting the paradigm of a study conducted with chimpanzees, Pan troglodytes (Melis et al. 2006, Journal of Comparative Psychology, 120, 154–162), we investigated orang-utans', Pongo pygmaeus, understanding of others' visual perspectives. More specifically, we examined whether orang-utans would adjust their behaviour in a way that prevents a human competitor from seeing them steal a piece of food. In the task, subjects had to reach through one of two opposing Plexiglas tunnels in order to retrieve a food reward. Both rewards were also physically accessible to a human competitor sitting opposite the subject. Subjects always had the possibility of reaching one piece of food that was outside the human's line of sight. This was because either the human was oriented to one, but not the other, reward or because one tunnel was covered by an opaque barrier and the other remained transparent. In the situation in which the human was oriented towards one reward, the orang-utans successfully avoided the tunnel that the competitor was facing. If one tunnel was covered, they marginally preferred to reach through the opaque versus the transparent tunnel. However, they did so frequently after initially inspecting the transparent tunnel (then switching to the opaque one). Considering only the subjects' initial inspections, they chose randomly between the opaque and transparent tunnel, indicating that their final decision to reach was probably driven by a more egocentric behavioural rule. Overall the results suggest that orang-utans have a limited understanding of others' perspectives, relying mainly on cues from facial and bodily orientation and egocentric rules when making such judgements.

Abstract

This study examined electrophysiological correlates of sentence comprehension of native-accented and foreign-accented
speech in a second language (L2), for sentences produced in a foreign accent different from that associated with the listeners’
L1. Bilingual speaker-listeners process different accents in their L2 conversations, but the effects on real-time L2 sentence
comprehension are unknown. Dutch–English bilinguals listened to native American-English accented sentences and foreign
(and for them unfamiliarly-accented) Chinese-English accented sentences while EEG was recorded. Behavioral sentence
comprehension was highly accurate for both native-accented and foreign-accented sentences. ERPs showed different patterns
for L2 grammar and semantic processing of native- and foreign-accented speech. For grammar, only native-accented speech
elicited an Nref. For semantics, both native- and foreign-accented speech elicited an N400 effect, but with a delayed onset
across both accent conditions. These findings suggest that the way listeners comprehend native- and foreign-accented
sentences in their L2 depends on their familiarity with the accent.

Abstract

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.

Abstract

Partisan gerrymandering poses a threat to democracy. Moreover, the complexity of the districting task may exceed human capacities. One potential solution is using computational models to automate the districting process by optimizing objective and open criteria, such as how spatially compact districts are. We formulated one such model that minimised pairwise distance between voters within a district. Using US Census Bureau data, we confirmed our prediction that the difference in compactness between the computed and actual districts would be greatest for states that are large and, therefore, difficult for humans to properly district given their limited capacities. The computed solutions highlighted differences in how humans and machines solve this task with machine solutions more fully optimised and displaying emergent properties not evident in human solutions. These results suggest a division of labour in which humans debate and formulate districting criteria whereas machines optimise the criteria to draw the district boundaries. We discuss how criteria can be expanded beyond notions of compactness to include other factors, such as respecting municipal boundaries, historic communities, and relevant legislation.

Abstract

PURPOSE: Time spent in "sports/outdoor activity" has shown a negative association with incident myopia during childhood. We investigated the association of incident myopia with time spent outdoors and physical activity separately. METHODS: Participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) were assessed by noncycloplegic autorefraction at ages 7, 10, 11, 12, and 15 years, and classified as myopic (≤-1 diopters) or as emmetropic/hyperopic (≥-0.25 diopters) at each visit (N = 4,837-7,747). Physical activity at age 11 years was measured objectively using an accelerometer, worn for 1 week. Time spent outdoors was assessed via a parental questionnaire administered when children were aged 8-9 years. Variables associated with incident myopia were examined using Cox regression. RESULTS: In analyses using all available data, both time spent outdoors and physical activity were associated with incident myopia, with time outdoors having the larger effect. The results were similar for analyses restricted to children classified as either nonmyopic or emmetropic/hyperopic at age 11 years. Thus, for children nonmyopic at age 11, the hazard ratio (95% confidence interval, CI) for incident myopia was 0.66 (0.47-0.93) for a high versus low amount of time spent outdoors, and 0.87 (0.76-0.99) per unit standard deviation above average increase in moderate/vigorous physical activity. CONCLUSION: Time spent outdoors was predictive of incident myopia independently of physical activity level. The greater association observed for time outdoors suggests that the previously reported link between "sports/outdoor activity" and incident myopia is due mainly to its capture of information relating to time outdoors rather than physical activity.

Abstract

Discussions about the adult L2 learning capacity often take as their starting point stages where considerable L2 knowledge has already been accumulated. This paper probes the absolute earliest stages of learning and investigates what lexical knowledge adult learners can extract from complex, continuous speech in an unknown language after minimal exposure and without any help. Dutch participants were exposed to naturalistic but controlled audiovisual input in Mandarin Chinese, in which item frequency and gestural highlighting were manipulated. The results from a word recognition task showed that adults are able to draw on frequency to recognize disyllabic words appearing only eight times in continuous speech. The findings from a sound-to-picture matching task revealed that the mapping of meaning to word form requires a combination of cues: disyllabic words accompanied by a gesture were correctly assigned meaning after eight encounters. Overall, the study suggests that the adult learning mechanism is a considerably more powerful than typically assumed in the SLA literature drawing on frequency, gestural cues and syllable structure. Even in the absence of pre-existing knowledge about cognates and sound system to bootstrap and boost learning, it deals efficiently with very little, very complex input.

Abstract

One of the features that distinguishes modern humans from our extinct relatives
and ancestors is a globular shape of the braincase [1-4]. As the endocranium
closely mirrors the outer shape of the brain, these differences might reflect
altered neural architecture [4,5]. However, in the absence of fossil brain tissue the
underlying neuroanatomical changes as well as their genetic bases remain
elusive. To better understand the biological foundations of modern human
endocranial shape, we turn to our closest extinct relatives, the Neandertals.
Interbreeding between modern humans and Neandertals has resulted in
introgressed fragments of Neandertal DNA in the genomes of present-day non-
Africans [6,7]. Based on shape analyses of fossil skull endocasts, we derive a
measure of endocranial globularity from structural magnetic resonance imaging
(MRI) scans of thousands of modern humans, and study the effects of
introgressed fragments of Neandertal DNA on this phenotype. We find that
Neandertal alleles on chromosomes 1 and 18 are associated with reduced
endocranial globularity. These alleles influence expression of two nearby genes,
UBR4 and PHLPP1, which are involved in neurogenesis and myelination,
respectively. Our findings show how integration of fossil skull data with archaic
genomics and neuroimaging can suggest developmental mechanisms that may
contribute to the unique modern human endocranial shape.

Abstract

“The most profound technologies are those that disappear. They weave themselves into the fabric of everyday life until they are indistinguishable from it.” (Weiser 1991, S. 94). – Die Behauptung stammt aus einem vielzitierten Text von Mark Weiser, ehemals Chief Technology Officer am berühmten Xerox Palo Alto Research Center (PARC), wo nicht nur einige bedeutende computertechnische Innovationen ihren Ursprung hatten, sondern auch grundlegende anthropologische Einsichten zum Umgang mit technischen Artefakten gewonnen wurden.1 In einem populärwissenschaftlichen Artikel mit dem Titel „The Computer for the 21st Century” entwarf Weiser 1991 die Vision einer Zukunft, in der wir nicht mehr mit einem einzelnen PC an unserem Arbeitsplatz umgehen – vielmehr seien wir in jedem Raum umgeben von hunderten elektronischer Vorrichtungen, die untrennbar in Alltagsgegenstände eingebettet und daher in unserer materiellen Umwelt gleichsam „verschwunden“ sind. Dabei ging es Weiser nicht allein um das ubiquitäre Phänomen, das in der Medientheorie als „Transparenz der Medien“ bekannt ist2 oder in allgemeineren Theorien der Alltagserfahrung als eine selbstverständliche Verwobenheit des Menschen mit den Dingen, die uns in ihrem Sinn vertraut und praktisch „zuhanden“ sind.3 Darüber hinaus zielte Weisers Vision darauf, unsere bereits existierende Umwelt durch computerlesbare Daten zu erweitern und in die Operationen eines solchen allgegenwärtigen Netzwerks alltägliche Praktiken gleichsam lückenlos zu integrieren: In der Welt, die Weiser entwirft, öffnen sich Türen für denjenigen, der ein bestimmtes elektronisches Abzeichen trägt, begrüßen Räume Personen, die sie betreten, mit Namen, passen sich Computerterminals an die Präferenzen individueller Nutzer an usw. (Weiser 1991, S. 99).

Abstract

“The most profound technologies are those that disappear. They weave themselves into the fabric of everyday life until they are indistinguishable from it.” (Weiser 1991, S. 94). – Die Behauptung stammt aus einem vielzitierten Text von Mark Weiser, ehemals Chief Technology Officer am berühmten Xerox Palo Alto Research Center (PARC), wo nicht nur einige bedeutende computertechnische Innovationen ihren Ursprung hatten, sondern auch grundlegende anthropologische Einsichten zum Umgang mit technischen Artefakten gewonnen wurden.1 In einem populärwissenschaftlichen Artikel mit dem Titel „The Computer for the 21st Century” entwarf Weiser 1991 die Vision einer Zukunft, in der wir nicht mehr mit einem einzelnen PC an unserem Arbeitsplatz umgehen – vielmehr seien wir in jedem Raum umgeben von hunderten elektronischer Vorrichtungen, die untrennbar in Alltagsgegenstände eingebettet und daher in unserer materiellen Umwelt gleichsam „verschwunden“ sind. Dabei ging es Weiser nicht allein um das ubiquitäre Phänomen, das in der Medientheorie als „Transparenz der Medien“ bekannt ist2 oder in allgemeineren Theorien der Alltagserfahrung als eine selbstverständliche Verwobenheit des Menschen mit den Dingen, die uns in ihrem Sinn vertraut und praktisch „zuhanden“ sind.3 Darüber hinaus zielte Weisers Vision darauf, unsere bereits existierende Umwelt durch computerlesbare Daten zu erweitern und in die Operationen eines solchen allgegenwärtigen Netzwerks alltägliche Praktiken gleichsam lückenlos zu integrieren: In der Welt, die Weiser entwirft, öffnen sich Türen für denjenigen, der ein bestimmtes elektronisches Abzeichen trägt, begrüßen Räume Personen, die sie betreten, mit Namen, passen sich Computerterminals an die Präferenzen individueller Nutzer an usw. (Weiser 1991, S. 99).

Abstract

The standard for the analysis of distorted voices is perceptual rating of read-out texts or spontaneous speech. Automatic voice evaluation, however, is usually done on stable sections of sustained vowels. In this paper, text-based and established vowel-based analysis are compared with respect to their ability to measure hoarseness and its subclasses. 73 hoarse patients (48.3±16.8 years) uttered the vowel /e/ and read the German version of the text “The North Wind and the Sun”. Five speech therapists and physicians rated roughness, breathiness, and hoarseness according to the German RBH evaluation scheme. The best human-machine correlations were obtained for measures based on the Cepstral Peak Prominence (CPP; up to |r | = 0.73). Support Vector Regression (SVR) on CPP-based measures and prosodic features improved the results further to r ≈0.8 and confirmed that automatic voice evaluation should be performed on a text recording.

Abstract

Geen andere soort dan homo sapiens heeft in de loop van zijn evolutionaire geschiedenis een communicatiesysteem ontwikkeld waarin een eindig aantal symbolen samen met een reeks van regels voor het combineren daarvan een oneindig aantal uitdrukkingen mogelijk maakt. Dit natuurlijke taalsysteem stelt leden van onze soort in staat gedachten een uiterlijke vorm te geven en uit te wisselen met de sociale groep en, door de uitvinding van schriftsystemen, met de gehele samenleving. Spraak en taal zijn effectieve middelen voor het behoud van sociale cohesie in samenlevingen waarvan de groepsgrootte en de complexe sociale organisatie van dien aard is dat dit niet langer kan door middel van ‘vlooien’, de wijze waarop onze genetische buren, de primaten van de oude wereld, sociale cohesie bevorderen [1,2].

Abstract

This study tests the recent claim that Broca’s aphasics are impaired in automatic lexical access, including the retrieval of word meaning. Subjects are required to perform a lexical decision on visually presented prime target pairs. Half of the word targets are preceded by a related word, half by an unrelated word. Primes and targets are presented with a long stimulus-onset-asynchrony (SOA) of 1400 msec and with a short SOA of 300 msec. Normal priming effects are observed in Broca’s aphasics for both SOAs. This result is discussed in the context of the claim that Broca’s aphasics suffer from an impairment in the automatic access of lexical–semantic information. It is argued that none of the current priming studies provides evidence supporting this claim, since with short SOAs priming effects have been reliably obtained in Broca’s aphasics. The results are more compatible with the claim that in many Broca’s aphasics the functional locus of their comprehension deficit is at the level of postlexical integration processes.

Abstract

In this contribution, the following four questions are discussed: (i) where is meaning?; (ii) what is meaning?; (iii) what is the meaning of mechanism?; (iv) what are the mechanisms of meaning? I will argue that meanings are in the head. Meanings have multiple facets, but minimally one needs to make a distinction between single word meanings (lexical meaning) and the meanings of multi-word utterances. The latter ones cannot be retrieved from memory, but need to be constructed on the fly. A mechanistic account of the meaning-making mind requires an analysis at both a functional and a neural level, the reason being that these levels are causally interdependent. I will show that an analysis exclusively focusing on patterns of brain activation lacks explanatory power. Finally, I shall present an initial sketch of how the dynamic interaction between temporo-parietal areas and inferior frontal cortex might instantiate the interpretation of linguistic utterances in the context of a multimodal setting and ongoing discourse information.

Abstract

In this Review, I propose a multiple-network view for the neurobiological basis of distinctly human language skills. A much more complex picture of interacting brain areas emerges than in the classical neurobiological model of language. This is because using language is more than single-word processing, and much goes on beyond the information given in the acoustic or orthographic tokens that enter primary sensory cortices. This requires the involvement of multiple networks with functionally nonoverlapping contributions

Abstract

Child songs are a great source for linguistic learning. Here we explore whether children can acquire novel words in a second language by playing a game featuring child songs in a playhouse. We present data from three studies that serve as scientific proof for the functionality of one game of the playhouse: the Energy Center. For this game, three hand-bikes were mounted on a panel. When children start moving the hand-bikes, child songs start playing simultaneously. Once the children produce enough energy with the hand-bikes, the songs are additionally accompanied with the sounds of musical instruments. In our studies, children executed a picture-selection task to evaluate whether they acquired new vocabulary from the songs presented during the game. Two of our studies were run in the field, one at a Dutch and one at an Indian pre-school. The third study features data from a more controlled laboratory setting. Our results partly confirm that the Energy Center is a successful means to support vocabulary acquisition in a second language. More research with larger sample sizes and longer access to the Energy Center is needed to evaluate the overall functionality of the game. Based on informal observations at our test sites, however, we are certain that children do pick up linguistic content from the songs during play, as many of the children repeat words and phrases from songs they heard. We will pick up upon these promising observations during future studies

Abstract

A series of articles by Ross (1995, 2001, 2005) use pronoun sim- ilarities to gauge relatedness between various Papuan microgroups, arguing that the similarities could not be the result of chance or bor- rowing. I argue that a more appropriate manner of calculating chance gives a signicantly dierent result: when cross-comparing a pool of languages the prospects for chance matches of rst and second person pronouns are very good. Using pronoun form data from over 3000 lan- guages and over 300 language families inside and outside New Guinea, I show that there is, nevertheless, a tendency for Papuan pronouns to use certain consonants more often in 1P and 2P SG forms than in the rest of the world. This could reect an underlying family. An alter- native explanation is the established Papuan areal feature of having a small consonant inventory, which results in a higher functional load on the remaining consonants, which is, in turn, reected in the enhanced popularity of certain consonants in pronouns of those languages. A test of surface forms (i.e., non-reconstructed forms) favours the latter explanation.

Abstract

Speech production studies have shown that phonological unit initially used to fill the metrical frame during phonological encoding is language specific, that is, a phoneme for English and Dutch, an atonal syllable for Mandarin Chinese, and a mora for Japanese. However, only a few studies chronometrically investigated speech production in Korean, and they obtained mixed results. Korean is particularly interesting as there might be both phonemic and syllabic influences during phonological encoding. The purpose of this study is to further examine the initial phonological preparation unit in Korean, employing a masked priming task (Experiment 1) and a phonological Stroop task (Experiment 2). The results showed that significant onset (and onset-plus, that is, consonant-vowel [CV]) effects were found in both experiments, but there was no compelling evidence for a prominent role for the syllable. When the prime words were presented in three different forms related to the targets, namely, without any change, with re-syllabified codas, and with nasalised codas, there were no significant differences in facilitation among the three forms. Alternatively, it is also possible that participants may not have had sufficient time to process the primes up to the point that re-syllabification or nasalisation could have been carried out. In addition, the results of a Stroop task demonstrated that the onset phoneme effect was not driven by any orthographic influence. These findings suggest that the onset segment and not the syllable is the initial (or proximate) phonological unit used in the segment-to-frame encoding process during speech planning in Korean.

Abstract

This study investigated whether a shadowing task can provide insights in the nature of reduction processes that are typical of casual speech. We focused on the shortening and presence versus absence of schwa and /t/ in Dutch past participles. Results showed that the absence of these segments was affected by the same variables as their shortening, suggesting that absence mostly resulted from extreme gradient shortening. This contrasts with results based on recordings of spontaneous conversations. We hypothesize that this difference is due to non-casual fast speech elicited by a shadowing task.

Abstract

This paper examines the role of morphological structure in the reduced pronunciation of morphologically complex words by discussing and re-analyzing data from the literature. Acoustic reduction refers to the phenomenon that, in spontaneous speech, phonemes may be shorter or absent. We review studies investigating effects of the repetition of a morpheme, of whether a segment plays a crucial role in the identification of its morpheme, and of a word's morphological decomposability. We conclude that these studies report either no effects of morphological structure or effects that are open to alternative interpretations. Our analysis also reveals the need for a uniform definition of morphological decomposability. Furthermore, we examine whether the reduction of segments in morphologically complex words correlates with these segments' contribution to the identification of the whole word, and discuss previous studies and new analyses supporting this hypothesis. We conclude that the data show no convincing evidence that morphological structure conditions reduction, which contrasts with the expectations of several models of speech production and of morphological processing (e.g., weaver++ and dual-route models). The data collected so far support psycholinguistic models which assume that all morphologically complex words are processed as complete units.

Abstract

Many learners of a foreign language (L2) struggle to correctly pronounce newly-learned speech sounds, yet many others achieve this with apparent ease. Here we explored how a training study of learning complex consonant clusters at the very onset of the L2 acquisition can inform us about L2 learning in general and individual differences in particular. To this end, adult Dutch native speakers were trained on Slovak words with complex consonant clusters (e.g., pstruh /pstrux/‘trout’, štvrť /ʃtvrc/ ‘quarter’) using auditory and orthographic input. In the same session following training, participants were tested on a battery of L2 perception and production tasks. The battery of L2 tests was repeated twice more with one week between each session. In the first session, an additional battery of control tests was used to test participants’ native language (L1) skills. Overall, in line with some previous research, participants showed only weak learning effects across the L2 perception tasks. However, there were considerable individual differences across all L2 tasks, which remained stable across sessions. Only two participants showed overall high L2 production performance that fell within 2 standard deviations of the mean ratings obtained for an L1 speaker. The mispronunciation detection task was the only perception task which significantly predicted production performance in the final session. We conclude by discussing several recommendations for future L2 learning studies.

Abstract

We used eyetracking, perceptual discrimination, and production tasks to examine the influences of perceptual similarity and linguistic experience on word recognition in nonnative (L2) speech. Eye movements to printed words were tracked while German and Dutch learners of English heard words containing one of three pronunciation variants (/t/, /s/, or /f/) of the interdental fricative /θ/. Irrespective of whether the speaker was Dutch or German, looking preferences for target words with /θ/ matched the preferences for producing /s/ variants in German speakers and /t/ variants in Dutch speakers (as determined via the production task), while a control group of English participants showed no such preferences. The perceptually most similar and most confusable /f/ variant (as determined via the discrimination task) was never preferred as a match for /θ/. These results suggest that linguistic experience with L2 pronunciations facilitates recognition of variants in an L2, with effects of frequency outweighing effects of perceptual similarity.

Abstract

How do native listeners process grammatical errors that are frequent in non-native speech? We investigated whether the neural correlates of syntactic processing are modulated by speaker identity. ERPs to gender agreement errors in sentences spoken by a native speaker were compared with the same errors spoken by a non-native speaker. In line with previous research, gender violations in native speech resulted in a P600 effect (larger P600 for violations in comparison with correct sentences), but when the same violations were produced by the non-native speaker with a foreign accent, no P600 effect was observed. Control sentences with semantic violations elicited comparable N400 effects for both the native and the non-native speaker, confirming no general integration problem in foreign-accented speech. The results demonstrate that the P600 is modulated by speaker identity, extending our knowledge about the role of speaker's characteristics on neural correlates of speech processing.

Abstract

Feedback has been shown to be effective in shifting attention across perceptual cues to a phonological contrast in speech perception (Francis, Baldwin & Nusbaum, 2000). However, the learning mechanisms behind this process remain obscure. We compare the predictions of supervised error-driven learning (Rescorla & Wagner, 1972) and reinforcement learning (Sutton & Barto, 1998) using computational simulations. Supervised learning predicts downweighting of an informative cue when the learner receives evidence that it is no longer informative. In contrast, reinforcement learning suggests that a reduction in cue weight requires positive evidence for the informativeness of an alternative cue. Experimental evidence supports the latter prediction, implicating reinforcement learning as the mechanism behind the effect of feedback on cue weighting in speech perception. Native English listeners were exposed to either bimodal or unimodal VOT distributions spanning the unaspirated/aspirated boundary (bear/pear). VOT is the primary cue to initial stop voicing in English. However, lexical feedback in training indicated that VOT was no longer predictive of voicing. Reduction in the weight of VOT was observed only when participants could use an alternative cue, F0, to predict voicing. Frequency distributions had no effect on learning. Overall, the results suggest that attention shifting in learning the phonetic cues to phonological categories is accomplished using simple reinforcement learning principles that also guide the choice of actions in other domains.

Abstract

Previous studies have linked the low expression variant of a variable number of tandem repeat polymorphism in the monoamine oxidase A gene (MAOA‐L) to the risk for impulsivity and aggression, brain developmental abnormalities, altered cortico‐limbic circuit function, and an exaggerated neural serotonergic tone. However, the neurobiological effects of this variant on human brain network architecture are incompletely understood. We studied healthy individuals and used multimodal neuroimaging (sample size range: 219–284 across modalities) and network‐based statistics (NBS) to probe the specificity of MAOA‐L‐related connectomic alterations to cortical‐limbic circuits and the emotion processing domain. We assessed the spatial distribution of affected links across several neuroimaging tasks and data modalities to identify potential alterations in network architecture. Our results revealed a distributed network of node links with a significantly increased connectivity in MAOA‐L carriers compared to the carriers of the high expression (H) variant. The hyperconnectivity phenotype primarily consisted of between‐lobe (“anisocoupled”) network links and showed a pronounced involvement of frontal‐temporal connections. Hyperconnectivity was observed across functional magnetic resonance imaging (fMRI) of implicit emotion processing (pFWE = .037), resting‐state fMRI (pFWE = .022), and diffusion tensor imaging (pFWE = .044) data, while no effects were seen in fMRI data of another cognitive domain, that is, spatial working memory (pFWE = .540). These observations are in line with prior research on the MAOA‐L variant and complement these existing data by novel insights into the specificity and spatial distribution of the neurogenetic effects. Our work highlights the value of multimodal network connectomic approaches for imaging genetics.

Abstract

CONTEXT Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. OBJECTIVE To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. DATA SOURCES Primary data. STUDY SELECTION Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DATA EXTRACTION Uniform statistical analysis scripts were run locally. Starting with 94 050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33 348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. DATA SYNTHESIS Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13 843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19 505) (P = .01). CONCLUSION These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

Abstract

Cultural transmission is a key component of human evolution. Two of humans' closest living relatives, chimpanzees and orangutans, have also been argued to transmit behavioral traditions across generations culturally [ [1], [2] and [3]], but how much the process might resemble the human process is still in large part unknown. One key phenomenon of human cultural transmission is majority-biased transmission: the increased likelihood for learners to end up not with the most frequent behavior but rather with the behavior demonstrated by most individuals. Here we show that chimpanzees and human children as young as 2 years of age, but not orangutans, are more likely to copy an action performed by three individuals, once each, than an action performed by one individual three times. The tendency to acquire the behaviors of the majority has been posited as key to the transmission of relatively safe, reliable, and productive behavioral strategies [ [4], [5], [6] and [7]] but has not previously been demonstrated in primates.

Abstract

Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences affecting these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic influences and low-frequency genetic variation. To understand these influences, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV+HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.

Abstract

Prediction in language has traditionally been studied using
simple designs in which neural responses to expected
and unexpected words are compared in a categorical
fashion. However, these designs have been contested
as being ‘prediction encouraging’, potentially exaggerating
the importance of prediction in language understanding.
A few recent studies have begun to address
these worries by using model-based approaches to probe
the effects of linguistic predictability in naturalistic stimuli
(e.g. continuous narrative). However, these studies
so far only looked at very local forms of prediction, using
models that take no more than the prior two words into
account when computing a word’s predictability. Here,
we extend this approach using a state-of-the-art neural
language model that can take roughly 500 times longer
linguistic contexts into account. Predictability estimates
fromthe neural network offer amuch better fit to EEG data
from subjects listening to naturalistic narrative than simpler
models, and reveal strong surprise responses akin to
the P200 and N400. These results show that predictability
effects in language are not a side-effect of simple designs,
and demonstrate the practical use of recent advances
in AI for the cognitive neuroscience of language.

Abstract

We used functional magnetic resonance imaging (fMRI) to investigate the neural basis of comprehension and perceptual learning of artificially degraded [noise vocoded (NV)] speech. Fifteen participants were scanned while listening to 6-channel vocoded words, which are difficult for naive listeners to comprehend, but can be readily learned with appropriate feedback presentations. During three test blocks, we compared responses to potentially intelligible NV words, incomprehensible distorted words and clear speech. Training sessions were interleaved with the test sessions and included paired presentation of clear then noise-vocoded words: a type of feedback that enhances perceptual learning. Listeners' comprehension of NV words improved significantly as a consequence of training. Listening to NV compared to clear speech activated left insula, and prefrontal and motor cortices. These areas, which are implicated in speech production, may play an active role in supporting the comprehension of degraded speech. Elevated activation in the precentral gyrus during paired clear-then-distorted presentations that enhance learning further suggests a role for articulatory representations of speech in perceptual learning of degraded speech.

Abstract

Learning to read is associated with the appearance of an orthographically sensitive brain region known as the visual word form area. It has been claimed that development of this area proceeds by impinging upon territory otherwise available for the processing of culturally relevant stimuli such as faces and houses. In a large-scale functional magnetic resonance imaging study of a group of individuals of varying degrees of literacy (from completely illiterate to highly literate), we examined cortical responses to orthographic and nonorthographic visual stimuli. We found that literacy enhances responses to other visual input in early visual areas and enhances representational similarity between text and faces, without reducing the extent of response to nonorthographic input. Thus, acquisition of literacy in childhood recycles existing object representation mechanisms but without destructive competition.

Abstract

We investigate the type of attention (domain-general or language-specific) used during
syntactic processing. We focus on syntactic priming: In this task, participants listen to a
sentence that describes a picture (prime sentence), followed by a picture the participants need
to describe (target sentence). We measure the proportion of times participants use the
syntactic structure they heard in the prime sentence to describe the current target sentence as a
measure of syntactic processing. Participants simultaneously conducted a motion-object
tracking (MOT) task, a task commonly used to tax domain-general attentional resources. We
manipulated the number of objects the participant had to track; we thus measured
participants’ ability to process syntax while their attention is not-, slightly-, or overly-taxed.
Performance in the MOT task was significantly worse when conducted as a dual-task
compared to as a single task. We observed an inverted U-shaped curve on priming magnitude
when conducting the MOT task concurrently with prime sentences (i.e., memory encoding),
but no effect when conducted with target sentences (i.e., memory retrieval). Our results
illustrate how, during the encoding of syntactic information, domain-general attention
differentially affects syntactic processing, whereas during the retrieval of syntactic
information domain-general attention does not influence syntactic processing

Abstract

Dialogue requires speakers to coordinate. According to the model of dialogue as joint action, interlocutors achieve this coordination by corepresenting their own and each other’s task share in a functionally equivalent manner. In two experiments, we investigated this corepresentation account using an interactive joint naming task in which pairs of participants took turns naming sets of objects on a shared display. Speaker A named the first, or the first and third object, and Speaker B named the second object. In control conditions, Speaker A named one, two, or all three objects and Speaker B remained silent. We recorded the timing of the speakers’ utterances and Speaker A’s eye movements. Interturn pause durations indicated that the speakers effectively coordinated their utterances in time. Speaker A’s speech onset latencies depended on the number of objects they named, but were unaffected by Speaker B’s naming task. This suggests speakers were not fully incorporating their partner’s task into their own speech planning. Moreover, Speaker A’s eye movements indicated that they were much less likely to attend to objects their partner named than to objects they named themselves. When speakers did inspect their partner’s objects, viewing times were too short to suggest that speakers were retrieving these object names as if they were planning to name the objects themselves. These results indicate that speakers prioritized planning their own responses over attending to their interlocutor’s task and suggest that effective coordination can be achieved without full corepresentation of the partner’s task.

Abstract

Multiple layers of visual (and vocal) signals, plus their different onsets and offsets, represent a significant semantic and temporal binding problem during face-to-face conversation.
Despite this complex unification process, multimodal messages appear to be processed faster than unimodal messages.

Multimodal gestalt recognition and multilevel prediction are proposed to play a crucial role in facilitating multimodal language processing.

The basis of the processing mechanisms involved in multimodal language comprehension is hypothesized to be domain general, coopted for communication, and refined with domain-specific characteristics.
A new, situated framework for understanding human language processing is called for that takes into consideration the multilayered, multimodal nature of language and its production and comprehension in conversational interaction requiring fast processing.

Abstract

Co-speech gestures are an integral part of human face-to-face communication, but little is known about how pragmatic factors influence our comprehension of those gestures. The present study investigates how different types of recipients process iconic gestures in a triadic communicative situation. Participants (N = 32) took on the role of one of two recipients in a triad and were presented with 160 video clips of an actor speaking, or speaking and gesturing. Crucially, the actor’s eye gaze was manipulated in that she alternated her gaze between the two recipients. Participants thus perceived some messages in the role of addressed recipient and some in the role of unaddressed recipient. In these roles, participants were asked to make judgements concerning the speaker’s messages. Their reaction times showed that unaddressed recipients did comprehend speaker’s gestures differently to addressees. The findings are discussed with respect to automatic and controlled processes involved in gesture comprehension.

Abstract

Background Reduced total brain volume is a consistent finding in children with Attention Deficit/Hyperactivity Disorder (ADHD). In order to get a better understanding of the neurobiology of ADHD, we take the first step in studying the dimensionality of current self-reported adult ADHD symptoms, by looking at its relation with total brain volume. Methodology/Principal Findings In a sample of 652 highly educated adults, the association between total brain volume, assessed with magnetic resonance imaging, and current number of self-reported ADHD symptoms was studied. The results showed an association between these self-reported ADHD symptoms and total brain volume. Post-hoc analysis revealed that the symptom domain of inattention had the strongest association with total brain volume. In addition, the threshold for impairment coincides with the threshold for brain volume reduction. Conclusions/Significance This finding improves our understanding of the biological substrates of self-reported ADHD symptoms, and suggests total brain volume as a target intermediate phenotype for future gene-finding in ADHD.

Abstract

Alcohol use is correlated within spouse-pairs, but it is difficult to disentangle effects of alcohol consumption on mate-selection from social factors or the shared spousal environment. We hypothesised that genetic variants related to alcohol consumption may, via their effect on alcohol behaviour, influence mate selection. Here, we find strong evidence that an individual’s self-reported alcohol consumption and their genotype at rs1229984, a missense variant in ADH1B, are associated with their partner’s self-reported alcohol use. Applying Mendelian randomization, we estimate that a unit increase in an individual’s weekly alcohol consumption increases partner’s alcohol consumption by 0.26 units (95% C.I. 0.15, 0.38; P = 8.20 × 10−6). Furthermore, we find evidence of spousal genotypic concordance for rs1229984, suggesting that spousal concordance for alcohol consumption existed prior to cohabitation. Although the SNP is strongly associated with ancestry, our results suggest some concordance independent of population stratification. Our findings suggest that alcohol behaviour directly influences mate selection.

Abstract

Aim: To determine if nonsyndromic cleft lip with or without cleft palate (nsCL/P) genetic risk variants influence liability to nsCL/P through gene regulation pathways, such as those involving DNA methylation. Materials & methods: nsCL/P genetic summary data and methylation data from four studies were used in conjunction with Mendelian randomization and joint likelihood mapping to investigate potential mediation of nsCL/P genetic variants. Results & conclusion: Evidence was found at VAX1 (10q25.3), LOC146880 (17q23.3) and NTN1 (17p13.1), that liability to nsCL/P and variation in DNA methylation might be driven by the same genetic variant, suggesting that genetic variation at these loci may increase liability to nsCL/P by influencing DNA methylation. Follow-up analyses using different tissues and gene expression data provided further insight into possible biological mechanisms.

Abstract

We investigated 4- and 5-year-old children’s mapping strategies in a spatial task. Children were required to find a picture in an array of three identical cups after observing another picture being hidden in another array of three cups. The arrays were either aligned one behind the other in two rows or placed side by side forming one line. Moreover, children were rewarded for two different mapping strategies. Half of the children needed to choose a cup that held the same relative position as the rewarded cup in the other array; they needed to map left–left, middle–middle, and right–right cups together (aligned mapping), which required encoding and mapping of two relations (e.g., the cup left of the middle cup and left of the right cup). The other half needed to map together the cups that held the same relation to the table’s spatial features—the cups at the edges, the middle cups, and the cups in the middle of the table (landmark mapping)—which required encoding and mapping of one relation (e.g., the cup at the table’s edge). Results showed that children’s success was constellation dependent; performance was higher when the arrays were aligned one behind the other in two rows than when they were placed side by side. Furthermore, children showed a preference for landmark mapping over aligned mapping.

Abstract

When people process language, they can use context to predict upcoming information,
influencing processing and comprehension as seen in both behavioral and neural
measures. Although numerous studies have shown immediate facilitative effects
of confirmed predictions, the downstream consequences of prediction have been
less explored. In the current study, we examined those consequences by probing
participants’ recognition memory for words after they read sets of sentences.
Participants read strongly and weakly constraining sentences with expected or
unexpected endings (“I added my name to the list/basket”), and later were tested on
their memory for the sentence endings while EEG was recorded. Critically, the memory
test contained words that were predictable (“list”) but were never read (participants
saw “basket”). Behaviorally, participants showed successful discrimination between old
and new items, but false alarmed to the expected-item lures more often than to new
items, showing that predicted words or concepts can linger, even when predictions
are disconfirmed. Although false alarm rates did not differ by constraint, event-related
potentials (ERPs) differed between false alarms to strongly and weakly predictable words.
Additionally, previously unexpected (compared to previously expected) endings that
appeared on the memory test elicited larger N1 and LPC amplitudes, suggesting greater
attention and episodic recollection. In contrast, highly predictable sentence endings that
had been read elicited reduced LPC amplitudes during the memory test. Thus, prediction
can facilitate processing in the moment, but can also lead to false memory and reduced
recollection for predictable information.

Abstract

The processing of idiomatic expressions is a topical issue in empirical research. Various factors have been found to influence idiom processing, such as idiom familiarity and idiom transparency. Information on these variables is usually obtained through norming studies. Studies investigating the effect of various properties on idiom processing have led to ambiguous results. This may be due to the variability of operationalizations of the idiom properties across norming studies, which in turn may affect the reliability of the subjective judgements. However, not all studies that collected normative data on idiomatic expressions investigated their reliability, and studies that did address the reliability of subjective ratings used various measures and produced mixed results. In this study, we investigated the reliability of subjective judgements, the relation between subjective and objective idiom frequency, and the impact of these dimensions on the participants’ idiom knowledge by collecting normative data of five subjective idiom properties (Frequency of Exposure, Meaning Familiarity, Frequency of Usage, Transparency, and Imageability) from 390 native speakers and objective corpus frequency for 374 Dutch idiomatic expressions. For reliability, we compared measures calculated in previous studies, with the D-coefficient, a metric taken from Generalizability Theory. High reliability was found for all subjective dimensions. One reliability metric, Krippendorff’s alpha, generally produced lower values, while similar values were obtained for three other measures (Cronbach’s alpha, Intraclass Correlation Coefficient, and the D-coefficient). Advantages of the D-coefficient are that it can be applied to unbalanced research designs, and to estimate the minimum number of raters required to obtain reliable ratings. Slightly higher coefficients were observed for so-called experience-based dimensions (Frequency of Exposure, Meaning Familiarity, and Frequency of Usage) than for content-based dimensions (Transparency and Imageability). In addition, fewer raters were required to obtain reliable ratings for the experience-based dimensions. Subjective and objective frequency appeared to be poorly correlated, while all subjective idiom properties and objective frequency turned out to affect idiom knowledge. Meaning Familiarity, Subjective and Objective Frequency of Exposure, Frequency of Usage, and Transparency positively contributed to idiom knowledge, while a negative effect was found for Imageability. We discuss these relationships in more detail, and give methodological recommendations with respect to the procedures and the measure to calculate reliability.

Abstract

Literacy has many obvious benefits—it exposes the reader to a wealth of new information and enhances syntactic knowledge. However, we argue that literacy has an additional, often overlooked, benefit: it enhances people’s ability to predict spoken language thereby aiding comprehension. Readers are under pressure to process information more quickly than listeners, and reading provides excellent conditions, in particular a stable environment, for training the predictive system. It also leads to increased awareness of words as linguistic units, and more fine-grained phonological and additional orthographic representations, which sharpen lexical representations and facilitate predicted representations to be retrieved. Thus, reading trains core processes and representations involved in language prediction that are common to both reading and listening.

Abstract

There is a consensus among language researchers that people can predict upcoming language. But do people always predict when comprehending language? Notions that “brains … are essentially prediction machines” certainly suggest so. In three eye-tracking experiments we tested this view. Participants listened to simple Dutch sentences (‘Look at the displayed bicycle’) while viewing four objects (a target, e.g. a bicycle, and three unrelated distractors). We used the identical visual stimuli and the same spoken sentences but varied speech rates, preview time, and participant instructions. Target nouns were preceded by definite gender-marked determiners, which allowed participants to predict the target object because only the targets but not the distractors agreed in gender with the determiner. In Experiment 1, participants had four seconds preview and sentences were presented either in a slow or a normal speech rate. Participants predicted the targets as soon as they heard the determiner in both conditions. Experiment 2 was identical except that participants were given only a one second preview. Participants predicted the targets only in the slow speech condition. Experiment 3 was identical to Experiment 2 except that participants were explicitly told to predict. This led only to a small prediction effect in the normal speech condition. Thus, a normal speech rate only afforded prediction if participants had an extensive preview. Even the explicit instruction to predict the target resulted in only a small anticipation effect with a normal speech rate and a short preview. These findings are problematic for theoretical proposals that assume that prediction pervades cognition.

Abstract

The experimental investigation of language-mediated visual attention is a promising way to study the interaction of the cognitive systems involved in language, vision, attention, and memory. Here we highlight four challenges for a mechanistic account of this oculomotor behavior: the levels of representation at which language-derived and vision-derived representations are integrated; attentional mechanisms; types of memory; and the degree of individual and group differences. Central points in our discussion are (a) the possibility that local microcircuitries involving feedforward and feedback loops instantiate a common representational substrate of linguistic and non-linguistic information and attention; and (b) that an explicit working memory may be central to explaining interactions between language and visual attention. We conclude that a synthesis of further experimental evidence from a variety of fields of inquiry and the testing of distinct, non-student, participant populations will prove to be critical.

Abstract

Like the transfer of genetic variation through gene flow, language changes constantly as a result of its use in human interaction. Contact between speakers is most likely to happen when they are close in space, time, and social setting. Here, we investigated the role of geographical configuration in this process by studying linguistic diversity in Japan, which comprises a large connected mainland (less isolation, more potential contact) and smaller island clusters of the Ryukyuan archipelago (more isolation, less potential contact). We quantified linguistic diversity using dialectometric methods, and performed regression analyses to assess the extent to which distance in space and time predict contemporary linguistic diversity. We found that language diversity in general increases as geographic distance increases and as time passes—as with biodiversity. Moreover, we found that (I) for mainland languages, linguistic diversity is most strongly related to geographic distance—a so-called isolation-by-distance pattern, and that (II) for island languages, linguistic diversity reflects the time since varieties separated and diverged—an isolation-by-colonisation pattern. Together, these results confirm previous findings that (linguistic) diversity is shaped by distance, but also goes beyond this by demonstrating the critical role of geographic configuration.

Abstract

Human language processing involves combinatorial operations that make human communication stand out in the animal kingdom. These operations rely on a dynamic interplay between the inferior frontal and the posterior temporal cortices. Using source reconstructed magnetoencephalography, we tracked language processing in the brain, in order to investigate how individual words are interpreted when part of sentence context. The large sample size in this study (n = 68) allowed us to assess how event-related activity is associated across distinct cortical areas, by means of inter-areal co-modulation within an individual. We showed that, within 500 ms of seeing a word, the word's lexical information has been retrieved and unified with the sentence context. This does not happen in a strictly feed-forward manner, but by means of co-modulation between the left posterior temporal cortex (LPTC) and left inferior frontal cortex (LIFC), for each individual word. The co-modulation of LIFC and LPTC occurs around 400 ms after the onset of each word, across the progression of a sentence. Moreover, these core language areas are supported early on by the attentional network. The results provide a detailed description of the temporal orchestration related to single word processing in the context of ongoing language.

Abstract

Recent studies have shown that the pupillary light response (PLR) is modulated by higher cognitive functions, presumably through activity in visual sensory brain areas. Here we use the PLR to test the involvement of sensory areas in visual working memory (VWM). In two experiments, participants memorized either bright or dark stimuli. We found that pupils were smaller when a prestimulus cue indicated that a bright stimulus should be memorized; this reflects a covert shift of attention during encoding of items into VWM. Crucially, we obtained the same result with a poststimulus cue, which shows that internal shifts of attention within VWM affect pupil size as well. Strikingly, the effect of VWM content on pupil size was most pronounced immediately after the poststimulus cue, and then dissipated. This suggests that a shift of attention within VWM momentarily activates an "active" memory representation, but that this representation quickly transforms into a "hidden" state that does not rely on sensory areas.

Abstract

Individuals rapidly extract information about others’ social identity, including whether or not they belong to their in-group. Group membership status has been shown to affect how attentively people encode information conveyed by those others. These findings are highly relevant for the field of psycholinguistics where there exists an open debate on how words are represented in the mental lexicon and how abstract or context-specific these representations are. Here, we used a novel word learning paradigm to test our proposal that the group membership status of speakers also affects how speaker-specific representations of novel words are. Participants learned new words from speakers who either attended their own university (in-group speakers) or did not (out-group speakers) and performed a task to measure their individual in-group bias. Then, their source memory of the new words was tested in a recognition test to probe the speaker-specific content of the novel lexical representations and assess how it related to individual in-group biases. We found that speaker group membership and participants’ in-group bias affected participants’ decision biases. The stronger the in-group bias, the more cautious participants were in their decisions. This was particularly applied to in-group related decisions. These findings indicate that social biases can influence recognition threshold. Taking a broader scope, defining how information is represented is a topic of great overlap between the fields of memory and psycholinguistics. Nevertheless, researchers from these fields tend to stay within the theoretical and methodological borders of their own field, missing the chance to deepen their understanding of phenomena that are of common interest. Here we show how methodologies developed in the memory field can be implemented in language research to shed light on an important theoretical issue that relates to the composition of lexical representations.

Abstract

Being ostracized or excluded, even briefly and by strangers, is painful and threatens fundamental needs. Recent work by Zhong and Leonardelli (2008) found that excluded individuals perceive the room as cooler and that they desire warmer drinks. A perspective that many rely on in embodiment is the theoretical idea that people use metaphorical associations to understand social exclusion (see Landau, Meier, & Keefer, 2010). We suggest that people feel colder because they are colder. The results strongly support the idea that more complex metaphorical understandings of social relations are scaffolded onto literal changes in bodily temperature: Being excluded in an online ball tossing game leads to lower finger temperatures (Study 1), while the negative affect typically experienced after such social exclusion is alleviated after holding a cup of warm tea (Study 2). The authors discuss further implications for the interaction between body and social relations specifically, and for basic and cognitive systems in general.

Abstract

During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 × 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 × 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 × 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 × 10(-3) for 6q22 and 1.2 × 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.

Abstract

Stimulus-related changes in cerebral blood oxygenation were measured using high-resolution functional magnetic resonance imaging sequentially covering visual occipital areas in contiguous sections. During dynamic imaging, healthy subjects silently viewed pseudowords, single false fonts, or length-matched strings of the same false fonts. The paradigm consisted of a sixfold alternation of an activation and a control task. With pseudowords as activation vs single false fonts as control, responses were seen mainly in medial occipital cortex. These responses disappeared when pseudowords were alternated with false font strings as the control and reappeared when false font strings instead of pseudowords served as activation and were alternated with single false fonts. The string-length contrast alone, therefore, is sufficient to account for the activation pattern observed in medial visual cortex when word-like stimuli are contrasted with single characters.

Abstract

Infectious diseases exert a constant evolutionary pressure on the innate immunity genes. TLR4, an important member of the Toll-like receptors family, specifically recognizes conserved structures of various infectious pathogens. Two functional TLR4 polymorphisms, Asp299Gly and Thr399Ile, modulate innate host defense against infections, and their prevalence between various populations has been proposed to be influenced by local infectious pressures. If this assumption is true, strong local infectious pressures would lead to a homogeneous pattern of these ancient TLR4 polymorphisms in geographically close populations, while a weak selection or genetic drift may result in a diverse pattern. We evaluated TLR4 polymorphisms in 15 ethnic groups of Iran, to assess whether infections exerted selective pressures on different haplotypes containing these variants. The Iranian subpopulations displayed a heterogeneous pattern of TLR4 polymorphisms, comprising various percentages of Asp299Gly and Thr399Ile alone or in combination. The Iranian sample as a whole showed an intermediate mixed pattern when compared with commonly found patterns in Africa, Europe, Eastern Asia and Americas. These findings suggest a weak or absent selection pressure on TLR4 polymorphisms in the Middle-East, that does not support the assumption of an important role of these polymorphisms in the host defence against local pathogens.

Abstract

Mirror-sensory synaesthetes mirror the pain or touch that they observe in other people on their own bodies. This type of synaesthesia has been associated with enhanced empathy. We investigated whether the enhanced empathy of people with mirror-sensory synesthesia influences the experience of situations involving touch or pain and whether it affects their prosocial decision making. Mirror-sensory synaesthetes (N = 18, all female), verified with a touch-interference paradigm, were compared with a similar number of age-matched control individuals (all female). Participants viewed arousing images depicting pain or touch; we recorded subjective valence and arousal ratings, and physiological responses, hypothesizing more extreme reactions in synaesthetes. The subjective impact of positive and negative images was stronger in synaesthetes than in control participants; the stronger the reported synaesthesia, the more extreme the picture ratings. However, there was no evidence for differential physiological or hormonal responses to arousing pictures. Prosocial decision making was assessed with an economic game assessing altruism, in which participants had to divide money between themselves and a second player. Mirror-sensory synaesthetes donated more money than non-synaesthetes, showing enhanced prosocial behaviour, and also scored higher on the Interpersonal Reactivity Index as a measure of empathy. Our study demonstrates the subjective impact of mirror-sensory synaesthesia and its stimulating influence on prosocial behaviour.

Abstract

Phosphomannomutase 2 deficiency, or PMM2-CDG, is the most common congenital disorder of glycosylation and affects over 1000 patients globally. There are no approved drugs that treat the symptoms or root cause of PMM2-CDG. To identify clinically actionable compounds that boost human PMM2 enzyme function, we performed a multispecies drug repurposing screen using a novel worm model of PMM2-CDG, followed by PMM2 enzyme functional studies in PMM2-CDG patient fibroblasts. Drug repurposing candidates from this study, and drug repurposing candidates from a previously published study using yeast models of PMM2-CDG, were tested for their effect on human PMM2 enzyme activity in PMM2-CDG fibroblasts. Of the 20 repurposing candidates discovered in the worm-based phenotypic screen, 12 were plant-based polyphenols. Insights from structure-activity relationships revealed epalrestat, the only antidiabetic aldose reductase inhibitor approved for use in humans, as a first-in-class PMM2 enzyme activator. Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains ranged from 30% to 400% over baseline, depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations. We demonstrate that epalrestat is the first small molecule activator ofPMM2 enzyme activity with the potential to treat peripheral neuropathy and correct the underlying enzyme deficiency in a majority of pediatric and adult PMM2-CDG patients.

Abstract

Hereditary mixed polyposis syndrome (HMPS) is characterized by apparent autosomal dominant inheritance of multiple types of colorectal polyp, with colorectal carcinoma occurring in a high proportion of affected individuals. Here, we use genetic mapping, copy-number analysis, exclusion of mutations by high-throughput sequencing, gene expression analysis and functional assays to show that HMPS is caused by a duplication spanning the 3' end of the SCG5 gene and a region upstream of the GREM1 locus. This unusual mutation is associated with increased allele-specific GREM1 expression. Whereas GREM1 is expressed in intestinal subepithelial myofibroblasts in controls, GREM1 is predominantly expressed in the epithelium of the large bowel in individuals with HMPS. The HMPS duplication contains predicted enhancer elements; some of these interact with the GREM1 promoter and can drive gene expression in vitro. Increased GREM1 expression is predicted to cause reduced bone morphogenetic protein (BMP) pathway activity, a mechanism that also underlies tumorigenesis in juvenile polyposis of the large bowel.

Abstract

In this study, older adults monitored for pre-assigned target sounds in a target talker's speech in a quiet (no noise) condition and in a condition with competing-talker noise. The question was to which extent the impact of the competing-talker noise on performance could be predicted from individual hearing loss and from a cognitive measure of inhibitory abilities, i.e., a measure of Stroop interference. The results showed that the non-auditory measure of Stroop interference predicted the impact of distraction on performance, over and above the effect of hearing loss. This suggests that individual differences in inhibitory abilities among older adults relate to susceptibility to distracting speech.

Abstract

Microarrays provide a powerful analytical tool for the simultaneous detection of multiple pathogens. We developed diagnostic suspension microarrays for sensitive and specific detection of the biothreat pathogens Bacillus anthracis, Yersinia pestis, Francisella tularensis and Coxiella burnetii. Two assay chemistries for amplification and labeling were developed, one method using direct hybridization and the other using target-specific primer extension, combined with hybridization to universal arrays. Asymmetric PCR products for both assay chemistries were produced by using a multiplex asymmetric PCR amplifying 16 DNA signatures (16-plex). The performances of both assay chemistries were compared and their advantages and disadvantages are discussed. The developed microarrays detected multiple signature sequences and an internal control which made it possible to confidently identify the targeted pathogens and assess their virulence potential. The microarrays were highly specific and detected various strains of the targeted pathogens. Detection limits for the different pathogen signatures were similar or slightly higher compared to real-time PCR. Probit analysis showed that even a few genomic copies could be detected with 95% confidence. The microarrays detected DNA from different pathogens mixed in different ratios and from spiked or naturally contaminated samples. The assays that were developed have a potential for application in surveillance and diagnostics. © 2012 Janse et al.

Abstract

We investigated comprehension of and adaptation to speech in an unfamiliar accent in older adults. Participants performed a speeded sentence verification task for accented sentences: one group upon auditory-only presentation, and the other group upon audiovisual presentation. Our questions were whether audiovisual presentation would facilitate adaptation to the novel accent, and which cognitive and linguistic measures would predict adaptation. Participants were therefore tested on a range of background tests: hearing acuity, auditory verbal short-term memory, working memory, attention-switching control, selective attention, and vocabulary knowledge. Both auditory-only and audiovisual groups showed improved accuracy and decreasing response times over the course of the experiment, effectively showing accent adaptation. Even though the total amount of improvement was similar for the auditory-only and audiovisual groups, initial rate of adaptation was faster in the audiovisual group. Hearing sensitivity and short-term and working memory measures were associated with efficient processing of the novel accent. Analysis of the relationship between accent comprehension and the background tests revealed furthermore that selective attention and vocabulary size predicted the amount of adaptation over the course of the experiment. These results suggest that vocabulary knowledge and attentional abilities facilitate the attention-shifting strategies proposed to be required for perceptual learning.