Publications

Abstract

Humans associate abstract words with physical stimulus dimensions, such as linking upward locations with positive concepts (e.g., happy = up). These associations manifest both via subjective reports of associations and on objective performance metrics. Humans also report subjective associations between colours and abstract words (e.g., joy is linked to yellow). Here we tested whether such associations manifest on objective task performance, even when not task-relevant. Across three experiments, participants were presented with abstract words in physical colours that were either congruent with previously-reported subjective word-colour associations (e.g., victory in red and unhappy in blue), or were incongruent (e.g., victory in blue and unhappy in red). In Experiment 1, participants' task was to identify the valence of words. This congruency manipulation systematically affected objective task performance. In Experiment 2, participants completed two blocks, a valence-identification and a colour-identification task block. Both tasks produced congruency effects on performance, however, the results of the colour identification block could have reflected learning effects (i.e., associating the more common congruent colour with the word). This issue was rectified in Experiment 3, whereby participants completed the same two tasks as Experiment 2, but now matched congruent and incongruent pairs were used for both tasks. Again, both tasks produced reliable congruency effects. Item analyses in each experiment revealed that these effects demonstrated a degree of item specificity. Overall, there was clear evidence that at least some abstract word-colour pairings can systematically affect behaviour.

Abstract

When language abilities in aphasia are assessed in clinical and research settings, the standard practice is to examine each language of a multilingual person separately. But many multilingual individuals, with and without aphasia, mix their languages regularly when they communicate with other speakers who share their languages. We applied a novel approach to scoring language production of a multilingual person with aphasia. Our aim was to discover whether the assessment outcome would differ meaningfully when we count accurate responses in only the target language of the assessment session versus when we apply a translanguaging framework, that is, count all accurate responses, regardless of the language in which they were produced. The participant is a Farsi-German-English speaking woman with chronic moderate aphasia. We examined the participant’s performance on two picture-naming tasks, an answering wh-question task, and an elicited narrative task. The results demonstrated that scores in English, the participant’s third-learned and least-impaired language did not differ between the two scoring methods. Performance in German, the participant’s moderately impaired second language benefited from translanguaging-based scoring across the board. In Farsi, her weakest language post-CVA, the participant’s scores were higher under the translanguaging-based scoring approach in some but not all of the tasks. Our findings suggest that whether a translanguaging-based scoring makes a difference in the results obtained depends on relative language abilities and on pragmatic constraints, with additional influence of the linguistic distances between the languages in question.

Abstract

Background: While persons with aphasia (PwA) are often dichotomised as fluent or nonfluent, agreement that fluency is not an all-or-nothing construct has led to the use of continuous variables as a way to quantify fluency, such as multi-dimensional rating scales, speech rate, and utterance length. Though these measures are often used in research, they provide little information about the underlying fluency deficit.
Aim: The aim of the study was to identify how well commonly used continuous measures of fluency capture variability in spontaneous speech variables at lexical, grammatical, and speech production levels. Methods & Procedures: Speech samples of 254 English-speaking PwA from the AphasiaBank database were analyzed to examine the distributions of four continuous measures of fluency: the WAB-R fluency scale, utterance length, retracing, and speech rate. Linear regression was used to identify spontaneous speech predictors contributing to each fluency outcome measure.
Outcomes & Results: All the outcome measures reflected the influence of multiple underlying dimensions, although the predictors varied. The WAB-R fluency scale, speech rate, and retracing were influenced by measures of grammatical competence, lexical retrieval, and speech production, whereas utterance length was influenced only by measures of grammatical competence and lexical retrieval. The strongest predictor of WAB-R fluency was aphasia severity, whereas the strongest predictor for all other fluency proxy measures was grammatical complexity.
Conclusions: Continuous measures allow a variety of ways to objectively quantify speech fluency; however, they reflect superficial manifestations of fluency that may be affected by multiple underlying deficits. Furthermore, the deficits underlying different measures vary, which may reduce the reliability of fluency diagnoses. Capturing these differences at the individual level is critical to accurate diagnosis and appropriately targeted therapy.

Abstract

Our aim in the present study is to measure neural correlates during spontaneous interactive sentence production. We present a novel approach using the word-by-word technique from improvisational theatre, in which two speakers jointly produce one sentence. This paradigm allows the assessment of behavioural aspects, such as turn-times, and electrophysiological responses, such as event-related-potentials (ERPs). Twenty-five participants constructed a cued but spontaneous four-word German sentence together with a confederate, taking turns for each word of the sentence. In 30% of the trials, the confederate uttered an unexpected gender-marked article. To complete the sentence in a meaningful way, the participant had to detect the violation and retrieve and utter a new fitting response. We found significant increases in response times after unexpected words and – despite allowing unscripted language production and naturally varying speech material – successfully detected significant N400 and P600 ERP effects for the unexpected word. The N400 EEG activity further significantly predicted the response time of the subsequent turn. Our results show that combining behavioural and neuroscientific measures of verbal interactions while retaining sufficient experimental control is possible, and that this combination provides promising insights into the mechanisms of spontaneous spoken dialogue.

Abstract

The aim of this study was to investigate whether early-English education benefits the perception
of English phonetic contrasts that are known to be perceptually confusable for Dutch
native speakers, comparing Dutch pupils who were enrolled in an early-English programme
at school from the age of four with pupils in a mainstream programme with English instruction
from the age of 11, and English-Dutch early bilingual children. Children were 4-5-yearolds
(start of primary school), 8-9-year-olds, or 11-12-year-olds (end of primary school).
Children were tested on four contrasts that varied in difficulty: /b/-/s/ (easy), /k/-/ɡ/ (intermediate),
/f/-/θ/ (difficult), /ε/-/æ/ (very difficult). Bilingual children outperformed the two other
groups on all contrasts except /b/-/s/. Early-English pupils did not outperform mainstream
pupils on any of the contrasts. This shows that early-English education as it is currently
implemented is not beneficial for pupils’ perception of non-native contrasts.

Abstract

This doctoral dissertation investigated the learning of auditory categories by applying insights from child language learning, visual category learning and phonetic categorization by adults. The experiments in chapter 2 concern supervised learning of multidimensional non-speech categories varying in two dimensions: duration and a non speech analogue of formant frequency. In experiment 1, one dimension of variation determined category membership, variation in the other dimension was irrelevant. Listeners quickly learned to categorize according to this distinction. In experiment 2, both dimensions needed to be combined to categorize correctly. Performance was much lower, but most listeners succeeded in this task. However, in a maintenance phase without feedback or distributional information, listeners reverted to a unidimensional solution. In a maintenance phase with distributional information, listeners did use both dimensions correctly, arguing for the importance of distributional information in (auditory) category acquisition. In chapter 3, the listeners had to classify the same categories, but without feedback. In experiment 1, listeners succeeded to discover the relevant dimension of variation (and ignore the irrelevant one) without feedback. Much of this learning was lost in the maintenance phase, especially for the dimension formant frequency. With two relevant dimensions (Experiment 2), listeners were not able to learn to use both dimensions and reverted to a unidimensional solution. Chapter 4 applied the paradigms of chapter 2 and 3 to the learning of speech categories. Spanish native listeners learned Dutch vowel contrast with one relevant dimension of variation. With feedback, learning was swift, although was not well maintained without feedback or distributional information. Without feedback, Spanish listeners reverted to the dimensions best known in their native phonology, formant frequency, even when distributional information pointed to duration. The results are discussed in chapter 5. The implications for models of speech acquisition are discussed.

Abstract

Distributional learning is almost certainly involved in the human acquisition of phonetic categories. Because speech is inherently a multidimensional signal, learning phonetic categories entails multidimensional learning. Yet previous studies of auditory category learning have shown poor maintenance of learned multidimensional categories. Two experiments explored ways to improve maintenance: by increasing the costs associated with applying a unidimensional strategy; by providing additional information about the category structures; and by giving explicit instructions on how to categorize. Only with explicit instructions were categorization strategies maintained in a maintenance phase without supervision or distributional information.

Abstract

In recent years, the influence of alpha (7–13 Hz) phase on visual processing has received a lot of attention. Magneto‐/encephalography (M/EEG) studies showed that alpha phase indexes visual excitability and task performance. Studies with transcranial alternating current stimulation (tACS) aim to modulate oscillations and causally impact task performance. Here, we applied right occipital tACS (O2 location) to assess the functional role of alpha phase in a series of experiments. We presented visual stimuli at different pre‐determined, experimentally controlled, phases of the entraining tACS signal, hypothesizing that this should result in an oscillatory pattern of visual performance in specifically left hemifield detection tasks. In experiment 1, we applied 10 Hz tACS and used separate psychophysical staircases for six equidistant tACS‐phase conditions, obtaining contrast thresholds for detection of visual gratings in left or right hemifield. In experiments 2 and 3, tACS was at EEG‐based individual peak alpha frequency. In experiment 2, we measured detection rates for gratings with (pseudo‐)fixed contrast. In experiment 3, participants detected brief luminance changes in a custom‐built LED device, at eight equidistant alpha phases. In none of the experiments did the primary outcome measure over phase conditions consistently reflect a one‐cycle sinusoid. However, post hoc analyses of reaction times (RT) suggested that tACS alpha phase did modulate RT for specifically left hemifield targets in both experiments 1 and 2 (not measured in experiment 3). This observation requires future confirmation, but is in line with the idea that alpha phase causally gates visual inputs through cortical excitability modulation.

Abstract

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson’s disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.

Abstract

A key strength of connectionist modelling is its ability to simulate both intact cognition and the behavioural effects of neural damage. We survey the literature, showing that models have been damaged in a variety of ways, e.g. by removing connections, by adding noise to connection weights, by scaling weights, by removing units and by adding noise to unit activations. While these different implementations of damage have often been assumed to be behaviourally equivalent, some theorists have made aetiological claims that rest on nonequivalence. They suggest that related deficits with different aetiologies might be accounted for by different forms of damage within a single model. We present two case studies that explore the effects of different forms of damage in two influential connectionist models, each of which has been applied to explain neuropsychological deficits. Our results indicate that the effect of simulated damage can indeed be sensitive to the way in which damage is implemented, particularly when the environment comprises subsets of items that differ in their statistical properties, but such effects are sensitive to relatively subtle aspects of the model’s training environment. We argue that, as a consequence, substantial methodological care is required if aetiological claims about simulated neural damage are to be justified, and conclude more generally that implementation assumptions, including those concerning simulated damage, must be fully explored when evaluating models of neurological deficits, both to avoid over-extending the explanatory power of specific implementations and to ensure that reported results are replicable.

Abstract

Gestures are often regarded as the most typical compensatory device used by language learners in communicative trouble. Yet gestural solutions to communicative problems have rarely been studied within any theory of second language use. The work pre­sented in this volume aims to account for second language learners’ strategic use of speech-associated gestures by combining a process-oriented framework for communi­cation strategies with a cognitive theory of gesture. Two empirical studies are presented. The production study investigates Swedish lear­ners of French and French learners of Swedish and their use of strategic gestures. The results, which are based on analyses of both individual and group behaviour, contradict popular opinion as well as theoretical assumptions from both fields. Gestures are not primarily used to replace speech, nor are they chiefly mimetic. Instead, learners use gestures with speech, and although they do exploit mimetic gestures to solve lexical problems, they also use more abstract gestures to handle discourse-related difficulties and metalinguistic commentary. The influence of factors such as proficiency, task, culture, and strategic competence on gesture use is discussed, and the oral and gestural strategic modes are compared. In the evaluation study, native speakers’ assessments of learners’ gestures, and the potential effect of gestures on evaluations of proficiency are analysed and discussed in terms of individual communicative style. Compensatory gestures function at multiple communicative levels. This has implica­tions for theories of communication strategies, and an expansion of the existing frameworks is discussed taking both cognitive and interactive aspects into account.

Abstract

What is the long‐term trajectory of semantic memory deficits in patients who have suffered structural brain damage? Memory is, per definition, a changing faculty. The traditional view is that after an initial recovery period, the mature human brain has little capacity to repair or reorganize. More recently, it has been suggested that the central nervous system may be more plastic with the ability to change in neural structure, connectivity, and function. The latter observations are, however, largely based on normal learning in healthy subjects. Here, we report a patient who suffered bilateral ventro‐medial damage after presumed herpes encephalitis in 1971. He was seen regularly in the eighties, and we recently had the opportunity to re‐assess his semantic memory deficits. On semantic category fluency, he showed a very clear category‐specific deficit performing better that control data on non‐living categories and significantly worse on living items. Recent testing showed that his impairments have remained unchanged for more than 40 years. We suggest cautiousness when extrapolating the concept of brain plasticity, as observed during normal learning, to plasticity in the context of structural brain damage.

Abstract

A central and influential idea among researchers of language is that our language faculty is organized according to Fregean compositionality, which states that the meaning of an utterance is a function of the meaning of its parts and of the syntactic rules by which these parts are combined. Since the domain of syntactic rules is the sentence, the implication of this idea is that language interpretation takes place in a two-step fashion. First, the meaning of a sentence is computed. In a second step, the sentence meaning is integrated with information from prior discourse, world knowledge, information about the speaker and semantic information from extra-linguistic domains such as co-speech gestures or the visual world. Here, we present results from recordings of event-related brain potentials that are inconsistent with this classical two-step model of language interpretation. Our data support a one-step model in which knowledge about the context and the world, concomitant information from other modalities, and the speaker are brought to bear immediately, by the same fast-acting brain system that combines the meanings of individual words into a message-level representation. Underlying the one-step model is the immediacy assumption, according to which all available information will immediately be used to co-determine the interpretation of the speaker's message. Functional magnetic resonance imaging data that we collected indicate that Broca's area plays an important role in semantic unification. Language comprehension involves the rapid incorporation of information in a 'single unification space', coming from a broader range of cognitive domains than presupposed in the standard two-step model of interpretation.

Abstract

Language is inherently multimodal. In spoken languages, combined spoken and visual signals (e.g., co-speech gestures) are an integral part of linguistic structure and language representation. This requires an extension of the parallel architecture, which needs to include the visual signals concomitant to speech. We present the evidence for the multimodality of language. In addition, we propose that distributional semantics might provide a format for integrating speech and co-speech gestures in a common semantic representation.

Abstract

Children’s 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 children’s songs in a playhouse. The playhouse is designed by the Noplica foundation (www.noplica.nl) to advance language learning through unsupervised play. We present data from three experiments that serve to scientifically proof the functionality of one game of the playhouse: the Energy Center. For this game, children move three hand-bikes mounted on a panel within the playhouse. Once the children cycle, a song starts playing that is accompanied by musical instruments. In our experiments, children executed a picture-selection task to evaluate whether they acquired new vocabulary from the songs presented during the game. Two of our experiments were run in the field, one at a Dutch and one at an Indian pre-school. The third experiment 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 the songs they heard. We will pick up upon these promising observations during future studies.

Abstract

Infants exploit acoustic boundaries to perceptually organize phrases in speech. This prosodic parsing ability is well‐attested and is a cornerstone to the development of speech perception and grammar. However, infants also receive linguistic input in child songs. This study provides evidence that infants parse songs into meaningful phrasal units and replicates previous research for speech. Six‐month‐old Dutch infants (n = 80) were tested in the song or speech modality in the head‐turn preference procedure. First, infants were familiarized to two versions of the same word sequence: One version represented a well‐formed unit, and the other contained a phrase boundary halfway through. At test, infants were presented two passages, each containing one version of the familiarized sequence. The results for speech replicated the previously observed preference for the passage containing the well‐formed sequence, but only in a more fine‐grained analysis. The preference for well‐formed phrases was also observed in the song modality, indicating that infants recognize phrase structure in song. There were acoustic differences between stimuli of the current and previous studies, suggesting that infants are flexible in their processing of boundary cues while also providing a possible explanation for differences in effect sizes.

Abstract

In an ERP experiment we investigated how the recruitment and integration of world knowledge information relate to the integration of information within a current discourse context. Participants were presented with short discourse contexts which were followed by a sentence that contained a critical word that was correct or incorrect based on general world knowledge and the supporting discourse context, or was more or less acceptable based on the combination of general world knowledge and the specific local discourse context. Relative to the critical word in the correct world knowledge sentences following a neutral discourse, all other critical words elicited an N400 effect that began at about 300 ms after word onset. However, the magnitude of the N400 effect varied in a way that suggests an interaction between world knowledge and discourse context. The results indicate that both world knowledge and discourse context have an effect on sentence interpretation, but neither overrides the other.

Abstract

Written language comprehension at the word and the sentence level was analysed by the combination of spatial and temporal analysis of functional magnetic resonance imaging (fMRI). Spatial analysis was performed via general linear modelling (GLM). Concerning the temporal analysis, local differences in neurovascular coupling may confound a direct comparison of blood oxygenation level-dependent (BOLD) response estimates between regions. To avoid this problem, we parametrically varied linguistic task demands and compared only task-induced within-region BOLD response differences across areas. We reasoned that, in a hierarchical processing system, increasing task demands at lower processing levels induce delayed onset of higher-level processes in corresponding areas. The flow of activation is thus reflected in the size of task-induced delay increases. We estimated BOLD response delay and duration for each voxel and each participant by fitting a model function to the event-related average BOLD response. The GLM showed increasing activations with increasing linguistic demands dominantly in the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG). The combination of spatial and temporal analysis allowed a functional differentiation of IFG subregions involved in written language comprehension. Ventral IFG region (BA 47) and STG subserve earlier processing stages than two dorsal IFG regions (BA 44 and 45). This is in accordance with the assumed early lexical semantic and late syntactic processing of these regions and illustrates the complementary information provided by spatial and temporal fMRI data analysis of the same data set.

Abstract

Rheumatoid arthritis is the most common systematic autoimmune disease and its etiology is believed to have both strong genetic and environmental components. We demonstrate the utility of including genetic and clinical phenotypes as covariates within a linkage analysis framework to search for rheumatoid arthritis susceptibility loci. The raw genotypes of 1302 affected relative pairs were combined from four large family-based samples (North American Rheumatoid Arthritis Consortium, United Kingdom, European Consortium on Rheumatoid Arthritis Families, and Canada). The familiality of the clinical phenotypes was assessed. The affected relative pairs were subjected to autosomal multipoint affected relative-pair linkage analysis. Covariates were included in the linkage analysis to take account of heterogeneity within the sample. Evidence of familiality was observed with age at onset (p <} 0.001) and rheumatoid factor (RF) IgM (p {< 0.001), but not definite erosions (p = 0.21). Genome-wide significant evidence for linkage was observed on chromosome 6. Genome-wide suggestive evidence for linkage was observed on chromosomes 13 and 20 when conditioning on age at onset, chromosome 15 conditional on gender, and chromosome 19 conditional on RF IgM after allowing for multiple testing of covariates.

Abstract

Syntactic parsers and generators need highquality grammars of coordination and coordinate ellipsis—structures that occur very frequently but are much less well understood theoretically than many other domains of grammar. Modern grammars of coordinate ellipsis are based nearly exclusively on linguistic judgments (intuitions). The extent to which grammar rules based on this type of empirical evidence generate all and only the structures in text corpora, is unknown. As part of a project on the development of a grammar and a generator for coordinate ellipsis in German, we undertook an extensive exploration of the TIGER treebank—a syntactically annotated corpus of about 50,000 newspaper sentences. We report (1) frequency data for the various patterns of coordinate ellipsis, and (2) several rarely (but regularly) occurring ‘fringe deviations’ from the intuition-based rules for several ellipsis types. This information can help improve parser and generator performance.

Abstract

The potential of sentence generators as engines in Intelligent Computer-Assisted Language Learning and teaching (ICALL) software has hardly been explored. We sketch the prototype of COMPASS, a system that supports integrated writing and grammar curricula for 10 to 14 year old elementary or secondary schoolers. The system enables first- or second-language teachers to design controlled writing exercises, in particular of the “sentence combining” variety. The system includes facilities for error diagnosis and on-line feedback. Syntactic structures built by students or system can be displayed as easily understood phrase-structure or dependency trees, adapted to the student’s level of grammatical knowledge. The heart of the system is a specially designed generator capable of lexically guided sentence generation, of generating syntactic paraphrases, and displaying syntactic structures visually.

Abstract

There is evidence that the process of executing a planned utterance involves the use of both preceding-context and top-down cues. Utterance-initial words are cued only by the top-down plan. In contrast, non-initial words are cued both by top-down cues and preceding-context cues. Co-existence of both cue types raises the question of how they interact during learning. We argue that this interaction is competitive: items that tend to be preceded by predictive preceding-context cues are harder to activate from the plan without this predictive context. A novel computational model of this competition is developed. The model is tested on a corpus of repetition disfluencies and shown to account for the influences on patterns of restarts during production. In particular, this model predicts a novel Initiation Effect: following an interruption, speakers re-initiate production from words that tend to occur in utterance-initial position, even when they are not initial in the interrupted utterance.

Abstract

The representations generated by many mod-
els of language (word embeddings, recurrent
neural networks and transformers) correlate
to brain activity recorded while people read.
However, these decoding results are usually
based on the brain’s reaction to syntactically
and semantically sound language stimuli. In
this study, we asked: how does an LSTM (long
short term memory) language model, trained
(by and large) on semantically and syntac-
tically intact language, represent a language
sample with degraded semantic or syntactic
information? Does the LSTM representation
still resemble the brain’s reaction? We found
that, even for some kinds of nonsensical lan-
guage, there is a statistically significant rela-
tionship between the brain’s activity and the
representations of an LSTM. This indicates
that, at least in some instances, LSTMs and the
human brain handle nonsensical data similarly.

Abstract

This thesis elaborates on a methodological approach to reliably infer cognitive preferences in an extinct evolutionary ancestor of modern humans. In attempts to understand cognitive evolution, humans have been compared to capuchin monkeys, tamarins, and chimpanzees to name but a few. But comparisons between humans and one other, maybe even distantly related primate, as interesting as they might be, will not tell us anything about an evolutionary ancestor to humans. To put it bluntly: None of the living primates, not even chimpanzees, are a human ancestor. With that in mind, we can still use a comparative approach to gain information about our evolutionary ancestors, as long as we are careful about whom we compare with whom. If a certain trait exists in all genera of a phylogenetic clade, it was most likely present in their common ancestor. The great apes are such a clade (Pongo, Gorilla, Pan and Homo). It follows that, if members of all great ape genera shared a particular cognitive preference or ability, it is most likely part of the evolutionary inheritance of the clade at least ever since their last common ancestor, and therefore also an evolutionarily old, inherited cognitive default in humans. This thesis contains studies comparing all 4 extant Hominid genera, including humans of 4 different age-groups and 2 different cultures. Results show that all great apes do indeed share some cognitive preferences, which they most likely inherited from an evolutionary ancestor. Additionally, human cognitive preferences can change away from such an inherited predisposition given ontogenetic factors, and are at least in part variably adaptable to cultural circumstance.

Abstract

Preregistration, the act of specifying a research plan in advance, is becoming more common in scientific research. Infant researchers contend with unique problems that might make preregistration particularly challenging. Infants are a hard‐to‐reach population, usually yielding small sample sizes, they can only complete a limited number of trials, and they can be excluded based on hard‐to‐predict complications (e.g., parental interference, fussiness). In addition, as effects themselves potentially change with age and population, it is hard to calculate an a priori effect size. At the same time, these very factors make preregistration in infant studies a valuable tool. A priori examination of the planned study, including the hypotheses, sample size, and resulting statistical power, increases the credibility of single studies and adds value to the field. Preregistration might also improve explicit decision making to create better studies. We present an in‐depth discussion of the issues uniquely relevant to infant researchers, and ways to contend with them in preregistration and study planning. We provide recommendations to researchers interested in following current best practices.

Abstract

Background
Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations.

Methods
In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708–58,630) using maternal reports on 76 items assessing children’s motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests.

Results
We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items rg range = − 0.27–0.78), ADHD (items rg range = − 0.40–1), and schizophrenia (items rg range = − 0.24–0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other.

Conclusions
These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs.

Abstract

The present article on executive control addresses the issue of the locus of the Stroop effect by examining neurophysiological components marking conflict monitoring, interference suppression, and conflict resolution. Our goal was to provide an overview of a series of determining neurophysiological findings including neural source reconstruction data on distinct executive control processes and sub-processes involved in the Stroop task. Consistently, a fronto-central N2 component is found to reflect conflict monitoring processes, with its main neural generator being the anterior cingulate cortex (ACC). Then, for cognitive control tasks that involve a linguistic component like the Stroop task, the N2 is followed by a centro-posterior N400 and subsequently a late sustained potential (LSP). The N400 is mainly generated by the ACC and the prefrontal cortex (PFC) and is thought to reflect interference suppression, whereas the LSP plausibly reflects conflict resolution processes. The present overview shows that ERP constitute a reliable methodological tool for tracing with precision the time course of different executive processes and sub-processes involved in experimental tasks involving a cognitive conflict. Future research should shed light on the fine-grained mechanisms of control respectively involved in linguistic and non-linguistic tasks.

Abstract

Speakers and listeners usually interact in larger discourses than single words or even single sentences. The goal of the present study was to identify the neural bases reflecting how the mental representation of the situation denoted in a multi-sentence discourse (situation model) is constructed and shared between speakers and listeners. An fMRI study using a variant of the ambiguous text paradigm was designed. Speakers (n=15) produced ambiguous texts in the scanner and listeners (n=27) subsequently listened to these texts in different states of ambiguity: preceded by a highly informative, intermediately informative or no title at all. Conventional BOLD activation analyses in listeners, as well as inter-subject correlation analyses between the speakers’ and the listeners’ hemodynamic time courses were performed. Critically, only the processing of disambiguated, coherent discourse with an intelligible situation model representation involved (shared) activation in bilateral lateral parietal and medial prefrontal regions. This shared spatiotemporal pattern of brain activation between the speaker and the listener suggests that the process of memory retrieval in medial prefrontal regions and the binding of retrieved information in the lateral parietal cortex constitutes a core mechanism underlying the communication of complex conceptual representations.

Abstract

Visual context facilitates perception, but how this is neurally implemented remains unclear. One example of contextual facilitation is found in reading, where letters are more easily identified when embedded in a word. Bottom-up models explain this word advantage as a post-perceptual decision bias, while top-down models propose that word contexts enhance perception itself. Here, we arbitrate between these accounts by presenting words and nonwords and probing the representational fidelity of individual letters using functional magnetic resonance imaging. In line with top-down models, we find that word contexts enhance letter representations in early visual cortex. Moreover, we observe increased coupling between letter information in visual cortex and brain activity in key areas of the reading network, suggesting these areas may be the source of the enhancement. Our results provide evidence for top-down representational enhancement in word recognition, demonstrating that word contexts can modulate perceptual processing already at the earliest visual regions.

Abstract

Rare disruptions of the transcription factor FOXP1 are implicated in a human neurodevelopmental disorder characterized by autism and/or intellectual disability with prominent problems in speech and language abilities. Avian orthologues of this transcription factor are evolutionarily conserved and highly expressed in specific regions of songbird brains, including areas associated with vocal production learning and auditory perception. Here, we investigated possible contributions of FoxP1 to song discrimination and auditory perception in juvenile and adult female zebra finches. They received lentiviral knockdowns of FoxP1 in one of two brain areas involved in auditory stimulus processing, HVC (proper name) or CMM (caudomedial mesopallium). Ninety-six females, distributed over different experimental and control groups were trained to discriminate between two stimulus songs in an operant Go/Nogo paradigm and subsequently tested with an array of stimuli. This made it possible to assess how well they recognized and categorized altered versions of training stimuli and whether localized FoxP1 knockdowns affected the role of different features during discrimination and categorization of song. Although FoxP1 expression was significantly reduced by the knockdowns, neither discrimination of the stimulus songs nor categorization of songs modified in pitch, sequential order of syllables or by reversed playback were affected. Subsequently, we analyzed the full dataset to assess the impact of the different stimulus manipulations for cue weighing in song discrimination. Our findings show that zebra finches rely on multiple parameters for song discrimination, but with relatively more prominent roles for spectral parameters and syllable sequencing as cues for song discrimination.

NEW & NOTEWORTHY In humans, mutations of the transcription factor FoxP1 are implicated in speech and language problems. In songbirds, FoxP1 has been linked to male song learning and female preference strength. We found that FoxP1 knockdowns in female HVC and caudomedial mesopallium (CMM) did not alter song discrimination or categorization based on spectral and temporal information. However, this large dataset allowed to validate different cue weights for spectral over temporal information for song recognition.

Abstract

Timing is an essential parameter influencing many behaviours. A previous study demonstrated a high sensitivity of a phocid, the harbour seal (Phoca vitulina), in discriminating time intervals. In the present study, we compared the harbour seal’s timing abilities with the timing abilities of an otariid, the South African fur seal (Arctocephalus pusillus pusillus). This comparison seemed essential as phocids and otariids differ in many respects and might, thus, also differ regarding their timing abilities. We determined time difference thresholds for sub- and suprasecond time intervals marked by a white circle on a black background displayed for a specific time interval on a monitor using a staircase method. Contrary to our expectation, the timing abilities of the fur seal and the harbour seal were comparable. Over a broad range of time intervals, 0.8–7 s in the fur seal and 0.8–30 s in the harbour seal, the difference thresholds followed Weber’s law. In this range, both animals could discriminate time intervals differing only by 12 % and 14 % on average. Timing might, thus be a fundamental cue for pinnipeds in general to be used in various contexts, thereby complementing information provided by classical sensory systems. Future studies will help to clarify if timing is indeed involved in foraging decisions or the estimation of travel speed or distance.

Abstract

Polymorphisms in the apolipoprotein E (APOE) gene have been associated with individual differences in cognition, brain structure and brain function. For example, the ε4 allele has been associated with cognitive and brain impairment in old age and increased risk of dementia, while the ε2 allele has been claimed to be neuroprotective. According to the ‘antagonistic pleiotropy’ hypothesis, these polymorphisms have different effects across the lifespan, with ε4, for example, postulated to confer benefits on cognitive and brain functions earlier in life. In this stage 2 of the Registered Report – https://osf.io/bufc4, we report the results from the cognitive and brain measures in the Cambridge Centre for Ageing and Neuroscience cohort (www.cam-can.org). We investigated the antagonistic pleiotropy hypothesis by testing for allele-by-age interactions in approximately 600 people across the adult lifespan (18–88 years), on six outcome variables related to cognition, brain structure and brain function (namely, fluid intelligence, verbal memory, hippocampal grey-matter volume, mean diffusion within white matter and resting-state connectivity measured by both functional magnetic resonance imaging and magnetoencephalography). We found no evidence to support the antagonistic pleiotropy hypothesis. Indeed, Bayes factors supported the null hypothesis in all cases, except for the (linear) interaction between age and possession of the ε4 allele on fluid intelligence, for which the evidence for faster decline in older ages was ambiguous. Overall, these pre-registered analyses question the antagonistic pleiotropy of APOE polymorphisms, at least in healthy adults.

Abstract

This paper reports on findings from an elicited production task with German 5-year-old children, investigating their use of intonation to mark information status of discourse referents. In line with findings for adults, new referents were preferably marked by H* and L+H*; textually given referents were mainly deaccented. Accessible referents (whose first mentions were less recent) were mostly accented, and predominantly also realised with H* and L+H*, showing children’s sensitivity to recency of mention. No evidence for the consistent use of a special ‘accessibility accent’ H+L* (as has been proposed for adult German) was found.

Abstract

While rhythm can facilitate and enhance many aspects of behavior, its evolutionary trajectory in vocal communication systems remains enigmatic. We can trace evolutionary processes by investigating rhythmic abilities in different species, but research to date has largely focused on songbirds and primates. We present evidence that cetaceans—whales, dolphins, and porpoises—are a missing piece of the puzzle for understanding why rhythm evolved in vocal communication systems. Cetaceans not only produce rhythmic vocalizations but also exhibit behaviors known or thought to play a role in the evolution of different features of rhythm. These behaviors include vocal learning abilities, advanced breathing control, sexually selected vocal displays, prolonged mother–infant bonds, and behavioral synchronization. The untapped comparative potential of cetaceans is further enhanced by high interspecific diversity, which generates natural ranges of vocal and social complexity for investigating various evolutionary hypotheses. We show that rhythm (particularly isochronous rhythm, when sounds are equally spaced in time) is prevalent in cetacean vocalizations but is used in different contexts by baleen and toothed whales. We also highlight key questions and research areas that will enhance understanding of vocal rhythms across taxa. By coupling an infraorder-level taxonomic assessment of vocal rhythm production with comparisons to other species, we illustrate how broadly comparative research can contribute to a more nuanced understanding of the prevalence, evolution, and possible functions of rhythm in animal communication.

Abstract

We argue, based on a study of brain responses to speech sound differences in Japanese, that memory encoding of functional speech sounds-phonemes-are highly abstract. As an example, we provide evidence for a theory where the consonants/p t k b d g/ are not only made up of symbolic features but are underspecified with respect to voicing or laryngeal features, and that languages differ with respect to which feature value is underspecified. In a previous study we showed that voiced stops are underspecified in English [Hestvik, A., & Durvasula, K. (2016). Neurobiological evidence for voicing underspecification in English. Brain and Language], as shown by asymmetries in Mismatch Negativity responses to /t/ and /d/. In the current study, we test the prediction that the opposite asymmetry should be observed in Japanese, if voiceless stops are underspecified in that language. Our results confirm this prediction. This matches a linguistic architecture where phonemes are highly abstract and do not encode actual physical characteristics of the corresponding speech sounds, but rather different subsets of abstract distinctive features.

Abstract

Objective
Determining the genetic basis of speech disorders provides insight into the neurobiology of
human communication. Despite intensive investigation over the past 2 decades, the etiology of
most speech disorders in children remains unexplained. To test the hypothesis that speech
disorders have a genetic etiology, we performed genetic analysis of children with severe speech
disorder, specifically childhood apraxia of speech (CAS).
Methods
Precise phenotyping together with research genome or exome analysis were performed on
children referred with a primary diagnosis of CAS. Gene coexpression and gene set enrichment
analyses were conducted on high-confidence gene candidates.
Results
Thirty-four probands ascertained for CAS were studied. In 11/34 (32%) probands, we identified
highly plausible pathogenic single nucleotide (n = 10; CDK13, EBF3, GNAO1, GNB1,
DDX3X, MEIS2, POGZ, SETBP1, UPF2, ZNF142) or copy number (n = 1; 5q14.3q21.1 locus)
variants in novel genes or loci for CAS. Testing of parental DNA was available for 9 probands
and confirmed that the variants had arisen de novo. Eight genes encode proteins critical for
regulation of gene transcription, and analyses of transcriptomic data found CAS-implicated
genes were highly coexpressed in the developing human brain.
Conclusion
We identify the likely genetic etiology in 11 patients with CAS and implicate 9 genes for the first
time. We find that CAS is often a sporadic monogenic disorder, and highly genetically heterogeneous.
Highly penetrant variants implicate shared pathways in broad transcriptional
regulation, highlighting the key role of transcriptional regulation in normal speech development.
CAS is a distinctive, socially debilitating clinical disorder, and understanding its
molecular basis is the first step towards identifying precision medicine approaches.

Abstract

Contemporary accounts of anticipatory language processing assume that individuals predict upcoming information at multiple levels of representation. Research investigating language-mediated anticipatory eye gaze typically assumes that linguistic input restricts the domain of subsequent reference (visual target objects). Here, we explored the converse case: Can visual input restrict the dynamics of anticipatory language processing? To this end, we recorded participants’ eye movements as they listened to sentences in which an object was predictable based on the verb’s selectional restrictions (“The man peels a banana”). While listening, participants looked at different types of displays: The target object (banana) was either present or it was absent. On target-absent trials, the displays featured objects that had a similar visual shape as the target object (canoe) or objects that were semantically related to the concepts invoked by the target (monkey). Each trial was presented in a long preview version, where participants saw the displays for approximately 1.78 seconds before the verb was heard (pre-verb condition), and a short preview version, where participants saw the display approximately 1 second after the verb had been heard (post-verb condition), 750 ms prior to the spoken target onset. Participants anticipated the target objects in both conditions. Importantly, robust evidence for predictive looks to objects related to the (absent) target objects in visual shape and semantics was found in the post-verb but not in the pre-verb condition. These results suggest that visual information can restrict language-mediated anticipatory gaze and delineate theoretical accounts of predictive processing in the visual world.

Abstract

Previous studies have shown that during comprehension readers activate words beyond the unfolding sentence. An open question concerns the mechanisms underlying this behavior. One proposal is that readers mentally simulate the described event and activate related words that might be referred to as the discourse further unfolds. Another proposal is that activation between words spreads in an automatic, associative fashion. The empirical support for these proposals is mixed. Therefore, theoretical accounts differ with regard to how much weight they place on the contributions of these sources to sentence comprehension. In the present study, we attempted to assess the contributions of event simulation and lexical associations to discourse reading, using event-related brain potentials (ERPs). Participants read target words, which were preceded by associatively related words either appearing in a coherent discourse event (Experiment 1) or in sentences that did not form a coherent discourse event (Experiment 2). Contextually unexpected target words that were associatively related to the described events elicited a reduced N400 amplitude compared to contextually unexpected target words that were unrelated to the events (Experiment 1). In Experiment 2, a similar but reduced effect was observed. These findings support the notion that during discourse reading event simulation and simple word associations jointly contribute to language comprehension by activating words that are beyond contextually congruent sentence continuations.

Abstract

- * indicates joint first authorship - Lexical access is a core component of word processing. In order to produce or comprehend a word, language users must access word forms in their mental lexicon. However, despite its involvement in both tasks, previous research has often studied lexical access in either production or comprehension alone. Therefore, it is unknown to which extent lexical access processes are shared across both tasks. Picture naming and auditory lexical decision are considered good tools for studying lexical access. Both of them are speeded tasks. Given these commonalities, another open question concerns the involvement of general cognitive abilities (e.g., processing speed) in both linguistic tasks. In the present study, we addressed these questions. We tested a large group of young adults enrolled in academic and vocational courses. Participants completed picture naming and auditory lexical decision tasks as well as a battery of tests assessing non-verbal processing speed, vocabulary, and non-verbal intelligence. Our results suggest that the lexical access processes involved in picture naming and lexical decision are related but less closely than one might have thought. Moreover, reaction times in picture naming and lexical decision depended as least as much on general processing speed as on domain-specific linguistic processes (i.e., lexical access processes).

Abstract

This resource contains data from 112 Dutch adults (18–29 years of age) who completed the Individual Differences in Language Skills test battery that included 33 behavioural tests assessing language skills and domain-general cognitive skills likely involved in language tasks. The battery included tests measuring linguistic experience (e.g. vocabulary size, prescriptive grammar knowledge), general cognitive skills (e.g. working memory, non-verbal intelligence) and linguistic processing skills (word production/comprehension, sentence production/comprehension). Testing was done in a lab-based setting resulting in high quality data due to tight monitoring of the experimental protocol and to the use of software and hardware that were optimized for behavioural testing. Each participant completed the battery twice (i.e., two test days of four hours each). We provide the raw data from all tests on both days as well as pre-processed data that were used to calculate various reliability measures (including internal consistency and test-retest reliability). We encourage other researchers to use this resource for conducting exploratory and/or targeted analyses of individual differences in language and general cognitive skills.

Abstract

Using language requires access to domain-specific linguistic representations, but also draws on domain-general cognitive skills. A key issue in current psycholinguistics is to situate linguistic processing in the network of human cognitive abilities. Here, we focused on spoken word recognition and used an individual differences approach to examine the links of scores in word recognition tasks with scores on tasks capturing effects of linguistic experience, general processing speed, working memory, and non-verbal reasoning. 281 young native speakers of Dutch completed an extensive test battery assessing these cognitive skills. We used psychometric network analysis to map out the direct links between the scores, that is, the unique variance between pairs of scores, controlling for variance shared with the other scores. The analysis revealed direct links between word recognition skills and processing speed. We discuss the implications of these results and the potential of psychometric network analysis for studying language processing and its embedding in the broader cognitive system.

Abstract

We introduce the Individual Differences in Language Skills (IDLaS-NL) web platform, which enables users to run studies on individual differences in Dutch language skills via the internet. IDLaS-NL consists of 35 behavioral tests, previously validated in participants aged between 18 and 30 years. The platform provides an intuitive graphical interface for users to select the tests they wish to include in their research, to divide these tests into different sessions and to determine their order. Moreover, for standardized administration the platform
provides an application (an emulated browser) wherein the tests are run. Results can be retrieved by mouse click in the graphical interface and are provided as CSV-file output via email. Similarly, the graphical interface enables researchers to modify and delete their study configurations. IDLaS-NL is intended for researchers, clinicians, educators and in general anyone conducting fundaental research into language and general cognitive skills; it is not intended for diagnostic purposes. All platform services are free of charge. Here, we provide a
description of its workings as well as instructions for using the platform. The IDLaS-NL platform can be accessed at www.mpi.nl/idlas-nl.

Abstract

Objective: To evaluate cognitive outcome in adult survivors of bacterial meningitis. Methods: Data from three prospective multicentre studies were pooled and reanalysed, involving 155 adults surviving bacterial meningitis (79 after pneumococcal and 76 after meningococcal meningitis) and 72 healthy controls. Results: Cognitive impairment was found in 32% of patients and this proportion was similar for survivors of pneumococcal and meningococcal meningitis. Survivors of pneumococcal meningitis performed worse on memory tasks (p<0.001) and tended to be cognitively slower than survivors of meningococcal meningitis (p = 0.08). We found a diffuse pattern of cognitive impairment in which cognitive speed played the most important role. Cognitive performance was not related to time since meningitis; however, there was a positive association between time since meningitis and self-reported physical impairment (p<0.01). The frequency of cognitive impairment and the numbers of abnormal test results for patients with and without adjunctive dexamethasone were similar. Conclusions: Adult survivors of bacterial meningitis are at risk of cognitive impairment, which consists mainly of cognitive slowness. The loss of cognitive speed is stable over time after bacterial meningitis; however, there is a significant improvement in subjective physical impairment in the years after bacterial meningitis. The use of dexamethasone was not associated with cognitive impairment.

Abstract

Stroke is common, and its consequent brain damage can cause various cognitive impairments. Associations between where and how much brain lesion damage a patient has suffered, and the particular impairments that injury has caused (lesion-symptom associations) offer potentially compelling insights into how the brain implements cognition.1 A better understanding of those associations can also fill a gap in current stroke medicine by helping us to predict how individual patients might recover from post-stroke impairments.2 Most recent work in this area employs machine learning models trained with data from stroke patients whose mid-to-long-term outcomes are known.2-4 These machine learning models are tested by predicting new outcomes—typically scores on standardized tests of post-stroke impairment—for patients whose data were not used to train the model. Traditionally, these validation results have been shared in peer-reviewed publications describing the model and its training. But recently, and for the first time in this field (as far as we know), one of these pre-trained models has been made public—The Disconnectome Symptom Discoverer model (DSD) which draws its predictors from structural disconnection information inferred from stroke patients’ brain MRI.5

Here, we test the DSD model on wholly independent data, never seen by the model authors, before they published it. Specifically, we test whether its predictive performance is just as accurate as (i.e. not significantly worse than) that reported in the original (Washington University) dataset, when predicting new patients’ outcomes at a similar time post-stroke (∼1 year post-stroke) and also in another independent sample tested later (5+ years) post-stroke. A failure to generalize the DSD model occurs if it performs significantly better in the Washington data than in our data from patients tested at a similar time point (∼1 year post-stroke). In addition, a significant decrease in predictive performance for the more chronic sample would be evidence that lesion-symptom associations differ at ∼1 year post-stroke and >5 years post-stroke.

Abstract

Bats use a large repertoire of calls for social communication, which are often characterized by temporal amplitude and frequency modulations. As bats are considered to be among the few mammalian species capable of vocal learning, the perception of temporal sound modulations should be crucial for juvenile bats to develop social communication abilities. However, the post-natal development of auditory processing of temporal modulations has not been investigated in bats, so far. Here we use the minimally invasive technique of recording auditory brainstem responses to measure the envelope following response (EFR) to sinusoidally amplitude modulated noise (range of modulation frequencies: 11–130 Hz) in three juveniles (p8-p72) of the bat, Phyllostomus discolor. In two out of three animals, we show that although amplitude modulation processing is basically developed at p8, EFRs maturated further over a period of about two weeks until p33. Maturation of the EFR generally took longer for higher modulation frequencies (87–130 Hz) than for lower modulation frequencies (11–58 Hz).

Abstract

Speakers often use gesture to demonstrate how to perform actions—for example, they might show how to open the top of a jar by making a twisting motion above the jar. Yet it is unclear whether listeners learn as much from seeing such gestures as they learn from seeing actions that physically change the position of objects (i.e., actually opening the jar). Here, we examined participants' implicit and explicit understanding about a series of movements that demonstrated how to move a set of objects. The movements were either shown with actions that physically relocated each object or with gestures that represented the relocation without touching the objects. Further, the end location that was indicated for each object covaried with whether the object was grasped with one or two hands. We found that memory for the end location of each object was better after seeing the physical relocation of the objects, that is, after seeing action, than after seeing gesture, regardless of whether speech was absent (Experiment 1) or present (Experiment 2). However, gesture and action built similar implicit understanding of how a particular handgrasp corresponded with a particular end location. Although gestures miss the benefit of showing the end state of objects that have been acted upon, the data show that gestures are as good as action in building knowledge of how to perform an action.

Abstract

Many women diagnosed with a major depression continue or initiate antidepressant treatment during pregnancy. Both maternal stress and selective serotonin inhibitor (SSRI) antidepressant treatment during pregnancy have been associated with changes in offspring behavior, including increased anxiety and depressive-like behavior. Our aim was to investigate the effects of the SSRI fluoxetine (FLX), with and without the presence of a maternal depression, on affective behavior in male and female rat offspring. As reduced serotonin transporter (SERT) availability has been associated with altered behavioral outcome, both offspring with normal (SERT+/+) and reduced (SERT+/−) SERT expression were included. For our animal model of maternal depression, SERT+/− dams exposed to early life stress were used. Perinatal FLX treatment and early life stress in dams (ELSD) had sex- and genotype-specific effects on affective behavior in the offspring. In female offspring, perinatal FLX exposure interacted with SERT genotype to increase anxiety and depressive-like behavior in SERT+/+, but not SERT+/−, females. In male offspring, ELSD reduced anxiety and interacted with SERT genotype to decrease depressive-like behavior in SERT+/−, but not SERT+/+, males. Altogether, SERT+/+ female offspring appear to be more sensitive than SERT+/− females to the effects of perinatal FLX exposure, while SERT+/− male offspring appear more sensitive than SERT+/+ males to the effects of ELSD on affective behavior. Our data suggest a role for offspring SERT genotype and sex in FLX and ELSD-induced effects on affective behavior, thereby contributing to our understanding of the effects of perinatal SSRI treatment on offspring behavior later in life.

Abstract

It has been hypothesised that nonsyndromic cleft lip/palate (nsCL/P) and cancer may share aetiological risk factors. Population studies have found inconsistent evidence for increased incidence of cancer in nsCL/P cases, but several genes (e.g.,CDH1,AXIN2) have been implicated in the aetiologies of both phenotypes. We aimed to evaluate shared genetic aetiology between nsCL/P and oral cavity/oropharyngeal cancers (OC/OPC), which affect similar anatomical regions. Using a primary sample of 5,048 OC/OPC cases and 5,450 controls of European ancestry and a replication sample of 750 cases and 336,319 controls from UK Biobank, we estimate genetic overlap using nsCL/P polygenic risk scores (PRS) with Mendelian randomization analyses performed to evaluate potential causal mechanisms. In the primary sample, we found strong evidence for an association between a nsCL/P PRS and increased odds of OC/OPC (per standard deviation increase in score, odds ratio [OR]: 1.09; 95% confidence interval [CI]: 1.04, 1.13;p = .000053). Although confidence intervals overlapped with the primary estimate, we did not find confirmatory evidence of an association between the PRS and OC/OPC in UK Biobank (OR 1.02; 95% CI: 0.95, 1.10;p = .55). Mendelian randomization analyses provided evidence that major nsCL/P risk variants are unlikely to influence OC/OPC. Our findings suggest possible shared genetic influences on nsCL/P and OC/OPC.

Abstract

Strong right-hand preference on the population level is a uniquely human feature, although its neural basis is still not clearly defined. Recent behavioural and neuroimaging literature suggests that hand preference may be related to the orchestrated function and size of fronto-parietal white matter tracts bilaterally. Lesions to these tracts induced during tumour resection may provide an opportunity to test this hypothesis. In the present study, a cohort of seventeen neurosurgical patients with left hemisphere brain tumours were recruited to investigate whether resection of certain white matter tracts affects the choice of hand selected for the execution of a goal-directed task (assembly of jigsaw puzzles). Patients performed the puzzles, but also tests for basic motor ability, selective attention and visuo-constructional ability, preoperatively and one month after surgery. An atlas-based disconnectome analysis was conducted to evaluate whether resection of tracts was significantly associated with changes in hand selection. Diffusion tractography was also used to dissect fronto-parietal tracts (the superior longitudinal fasciculus) and the corticospinal tract. Results showed a shift in hand selection despite the absence of any motor or cognitive deficits, which was significantly associated with frontal and parietal resections rather than other lobes. In particular, the shift in hand selection was significantly associated with the resection of dorsal rather than ventral fronto-parietal white matter connections. Dorsal white matter pathways contribute bilaterally to control of goal-directed hand movements. We show that unilateral lesions, that may unbalance the cooperation of the two hemispheres, can alter the choice of hand selected to accomplish movements.

Abstract

Common genetic variation has been associated with multiple symptoms in Autism Spectrum Disorder (ASD). However, our knowledge of shared genetic factor structures contributing to this highly heterogeneous neurodevelopmental condition is limited. Here, we developed a structural equation modelling framework to directly model genome-wide covariance across core and non-core ASD phenotypes, studying autistic individuals of European descent using a case-only design. We identified three independent genetic factors most strongly linked to language/cognition, behaviour and motor development, respectively, when studying a population-representative sample (N=5,331). These analyses revealed novel associations. For example, developmental delay in acquiring personal-social skills was inversely related to language, while developmental motor delay was linked to self-injurious behaviour. We largely confirmed the three-factorial structure in independent ASD-simplex families (N=1,946), but uncovered simplex-specific genetic overlap between behaviour and language phenotypes. Thus, the common genetic architecture in ASD is multi-dimensional and contributes, in combination with ascertainment-specific patterns, to phenotypic heterogeneity.

Abstract

Speakers of a language sometimes use particular constructions which violate prescriptive grammar rules. Despite their prescriptive ungrammaticality, they can occur rather frequently. One such example is the comparative construction in Dutch and similarly in German, where the equative particle is used in comparative constructions instead of the prescriptively correct comparative particle (Dutch beter als Jan and German besser wie Jan ‘lit. better as John’). From a theoretical linguist’s point of view, these so-called grammatical norm violations are perfectly grammatical, even though they are not part of the language’s prescriptive grammar. In a series of three experiments using sentence-matching and eye-tracking methodology, we investigated whether grammatical norm violations are processed as truly grammatical, as truly ungrammatical, or whether they fall in between these two. We hypothesized that the latter would be the case. We analyzed our data using linear mixed effects models in order to capture possible individual differences. The results of the sentence-matching experiments, which were conducted in both Dutch and German, showed that the grammatical norm violation patterns with ungrammatical sentences in both languages. Our hypothesis was therefore not borne out. However, using the more sensitive eye-tracking method on Dutch speakers only, we found that the ungrammatical alternative leads to higher reading times than the grammatical norm violation. We also found significant individual variation regarding this very effect. We furthermore replicated the processing difference between the grammatical norm violation and the prescriptively correct variant. In summary, we conclude that while the results of the more sensitive eye-tracking experiment suggest that grammatical norm violations are not processed on a par with ungrammatical sentences, the results of all three experiments clearly show that grammatical norm violations cannot be considered grammatical, either.

Abstract

Prescriptive grammar rules are taught in education, generally to ban the use of certain frequently encountered constructions in everyday language. This may lead to hypercorrection, meaning that the prescribed form in one construction is extended to another one in which it is in fact prohibited by prescriptive grammar. We discuss two such cases in Dutch: the hypercorrect use of the comparative particle dan ‘than’ in equative constructions, and the hypercorrect use of the accusative pronoun hen ‘them’ for a dative object. In two experiments, high school students of three educational levels were tested on their use of these hypercorrect forms (nexp1 = 162, nexp2 = 159). Our results indicate an overall large amount of hypercorrection across all levels of education, including pre-university level students who otherwise perform better in constructions targeted by prescriptive grammar rules. We conclude that while teaching prescriptive grammar rules to high school students seems to increase their use of correct forms in certain constructions, this comes at a cost of hypercorrection in others.

Abstract

Experiments 1 and 2 examined the time-course of retrieval of phonological, visual-shape and semantic knowledge as Dutch participants listened to sentences and looked at displays of four pictures. Given a sentence with beker, `beaker', for example, the display contained phonological (a beaver, bever), shape (a bobbin, klos), and semantic (a fork, vork) competitors. When the display appeared at sentence onset, fixations to phonological competitors preceded fixations to shape and semantic competitors. When display onset was 200 ms before (e.g.) beker, fixations were directed to shape and then semantic competitors, but not phonological competitors. In Experiments 3 and 4, displays contained the printed names of the previously-pictured entities; only phonological competitors were fixated preferentially. These findings suggest that retrieval of phonological, shape and semantic knowledge in the spoken-word and picture-recognition systems is cascaded, and that visual attention shifts are co-determined by the time-course of retrieval of all three knowledge types and by the nature of the information in the visual environment.

Abstract

Visual attention can be directed immediately, as a spoken word unfolds, towards conceptually related but nonassociated objects, even if they mismatch on other dimensions that would normally determine which objects in the scene were appropriate referents for the unfolding word (Huettig & Altmann, 2005). Here we demonstrate that the mapping between language and concurrent visual objects can also be mediated by visual-shape relations. On hearing "snake", participants directed overt attention immediately, within a visual display depicting four objects, to a picture of an electric cable, although participants had viewed the visual display with four objects for approximately 5 s before hearing the target word - sufficient time to recognize the objects for what they were. The time spent fixating the cable correlated significantly with ratings of the visual similarity between snakes in general and this particular cable. Importantly, with sentences contextually biased towards the concept snake, participants looked at the snake well before the onset of "snake", but they did not look at the visually similar cable until hearing "snake". Finally, we demonstrate that such activation can, under certain circumstances (e.g., during the processing of dominant meanings of homonyms), constrain the direction of visual attention even when it is clearly contextually inappropriate. We conclude that language-mediated attention can be guided by a visual match between spoken words and visual objects, but that such a match is based on lexical input and may not be modulated by contextual appropriateness.

Abstract

A main challenge for theories of embodied cognition is to understand the task dependency of embodied language processing. One possibility is that perceptual representations (e.g., typical colour of objects mentioned in spoken sentences) are not activated routinely but the influence of perceptual representation emerges only when context strongly supports their involvement in language. To explore this question, we tested the effects of colour representations during language processing in three visual- world eye-tracking experiments. On critical trials, participants listened to sentence- embedded words associated with a prototypical colour (e.g., ‘...spinach...’) while they inspected a visual display with four printed words (Experiment 1), coloured or greyscale line drawings (Experiment 2) and a ‘blank screen’ after a preview of coloured or greyscale line drawings (Experiment 3). Visual context always presented a word/object (e.g., frog) associated with the same prototypical colour (e.g. green) as the spoken target word and three distractors. When hearing spinach participants did not prefer the written word frog compared to other distractor words (Experiment 1). In Experiment 2, colour competitors attracted more overt attention compared to average distractors, but only for the coloured condition and not for greyscale trials. Finally, when the display was removed at the onset of the sentence, and in contrast to the previous blank-screen experiments with semantic competitors, there was no evidence of colour competition in the eye-tracking record (Experiment 3). These results fit best with the notion that the main role of perceptual representations in language processing is to contextualize language in the immediate environment.

Abstract

In the present paper we describe the Enhanced Literate Mind (ELM) hypothesis. As individuals learn to read and write, they are, from then on, exposed to extensive written-language input and become literate. We propose that acquisition and proficient processing of written language (‘literacy’) leads to, both, increased language knowledge as well as enhanced language and non-language (perceptual and cognitive) skills. We also suggest that all neurotypical native language users, including illiterate, low literate, and high literate individuals, share a Basic Language Cognition (BLC) in the domain of oral informal language. Finally, we discuss the possibility that the acquisition of ELM leads to some degree of ‘knowledge parallelism’ between BLC and ELM in literate language users, which has implications for empirical research on individual and situational differences in spoken language processing.

Abstract

We recently reported that refocusing attention between temporal and spatial tasks becomes more difficult with increasing age, which could impair daily activities such as driving (Callaghan et al., 2017). Here, we investigated the extent to which difficulties in refocusing attention extend to naturalistic settings such as simulated driving. A total of 118 participants in five age groups (18–30; 40–49; 50–59; 60–69; 70–91 years) were compared during continuous simulated driving, where they repeatedly switched from braking due to traffic ahead (a spatially focal yet temporally complex task) to reading a motorway road sign (a spatially more distributed task). Sequential-Task (switching) performance was compared to Single-Task performance (road sign only) to calculate age-related switch-costs. Electroencephalography was recorded in 34 participants (17 in the 18–30 and 17 in the 60+ years groups) to explore age-related changes in the neural oscillatory signatures of refocusing attention while driving. We indeed observed age-related impairments in attentional refocusing, evidenced by increased switch-costs in response times and by deficient modulation of theta and alpha frequencies. Our findings highlight virtual reality (VR) and Neuro-VR as important methodologies for future psychological and gerontological research.

Abstract

This chapter investigates the fit of genetic, phenotypic, and linguistic data to two well-known models of population history. The first of these models, termed the population fissions model, emphasizes population splitting, isolation, and independent evolution. It predicts that genetic and linguistic data will be perfectly tree-like. The second model, termed isolation by distance, emphasizes genetic exchange among geographically proximate populations. It predicts a monotonic decline in genetic similarity with increasing geographic distance. While these models are overly simplistic, deviations from them were expected to provide important insights into the population history of northern Island Melanesia. The chapter finds scant support for either model because the prehistory of the region has been so complex. Nonetheless, the genetic and linguistic data are consistent with an early radiation of proto-Papuan speakers into the region followed by a much later migration of Austronesian speaking peoples. While these groups subsequently experienced substantial genetic and cultural exchange, this exchange has been insufficient to erase this history of separate migrations.

Abstract

This paper reports on ongoing research on the role of various kinds of potential substrate languages in the development of the semantic structures of Ndyuka (Eastern Suriname Creole). A set of 100 senses of noun, verb, and other lexemes in Ndyuka were compared with senses of corresponding lexemes in three kinds of languages of the former Slave Coast and Gold Coast areas, and immediately adjoining hinterland: (a) Gbe languages; (b) other Kwa languages, specifically Akan and Ga; (c) non-Kwa Niger-Congo languages. The results of this process provide some evidence for the importance of the Gbe languages in the formation of the Suriname creoles, but also for the importance of other languages, and for the areal nature of some of the collocations studied, rendering specific identification of a single substrate source impossible and inappropriate. These results not only provide information about the role of Gbe and other languages in the formation of Ndyuka, but also give evidence for effects of substrate languages spoken by late arrivals some time after the "founders" of a given creole-speaking society. The conclusions are extrapolated beyond Suriname to creole genesis generally.

Abstract

An important issue in theories of word learning is how abstract or context-specific representations of novel words are. One aspect of this broad issue is how well learners maintain information about the source of novel words. We investigated whether listeners’ source memory was better for words learned from members of their in-group (students of their own university) than it is for words learned from members of an out-group (students from another institution). In the first session, participants saw 6 faces and learned which of the depicted students attended either their own or a different university. In the second session, they learned competing labels (e.g., citrus-peller and citrus-schiller; in English, lemon peeler and lemon stripper) for novel gadgets, produced by the in-group and out-group speakers. Participants were then tested for source memory of these labels and for the strength of their in-group bias, that is, for how much they preferentially process in-group over out-group information. Analyses of source memory accuracy demonstrated an interaction between speaker group membership status and participants’ in-group bias: Stronger in-group bias was associated with less accurate source memory for out-group labels than in-group labels. These results add to the growing body of evidence on the importance of social variables for adult word learning.

Abstract

Neurocognitive studies of language production have provided sufficient evidence on both the spatial and the temporal patterns of brain activation to allow tentative and in some cases not so tentative conclusions about function-structure relationships. This chapter reports meta-analysis results that identify reliable activation areas for a range of word, sentence, and narrative production tasks both in the native language and a second language. Based on a theoretically motivated analysis of language production tasks it is possible to specify relationships between brain areas and functional processing components of language production that could not have been derived from the data provided by any single task.

Abstract

Thesaurus alignment is important for efficient access to heterogeneous Cultural Heritage data. Current ontology alignment techniques provide solutions, but with limited value in practice, because the requirements from usage scenarios are rarely taken in account. In this paper, we start from particular requirements for book re-indexing and investigate possible ways of developing, deploying and evaluating thesaurus alignment techniques in this context. We then compare different aspects of this scenario with others from a more general perspective.

Abstract

The computations involved in statistical learning have long been debated. Here, we build on work suggesting that a basic memory process, chunking , may account for the processing of statistical regularities into larger units. Drawing on methods from the memory literature, we developed a novel paradigm to test statistical learning by leveraging a robust phenomenon observed in serial recall tasks: that short‐term memory is fundamentally shaped by long‐term distributional learning. In the statistically induced chunking recall (SICR) task, participants are exposed to an artificial language, using a standard statistical learning exposure phase. Afterward, they recall strings of syllables that either follow the statistics of the artificial language or comprise the same syllables presented in a random order. We hypothesized that if individuals had chunked the artificial language into word‐like units, then the statistically structured items would be more accurately recalled relative to the random controls. Our results demonstrate that SICR effectively captures learning in both the auditory and visual modalities, with participants displaying significantly improved recall of the statistically structured items, and even recall specific trigram chunks from the input. SICR also exhibits greater test–retest reliability in the auditory modality and sensitivity to individual differences in both modalities than the standard two‐alternative forced‐choice task. These results thereby provide key empirical support to the chunking account of statistical learning and contribute a valuable new tool to the literature.

Abstract

Many foundational questions in the psychology of music require cross-cultural approaches, yet the vast majority of work in the field to date has been conducted with Western participants and Western music. For cross-cultural research to thrive, it will require collaboration between people from different disciplinary backgrounds, as well as strategies for overcoming differences in assumptions, methods, and terminology. This position paper surveys the current state of the field and offers a number of concrete recommendations focused on issues involving ethics, empirical methods, and definitions of “music” and “culture.”

Abstract

Bioacoustics increasingly relies on large datasets and computational methods. The need to batch-process large amounts of data and the increased focus on algorithmic processing require software tools. To optimally assist in a bioacoustician’s workflow, software tools need to be as simple and effective as possible. Five years ago, the Python package Parselmouth was released to provide easy and intuitive access to all functionality in the Praat software. Whereas Praat is principally designed for phonetics and speech processing, plenty of bioacoustics studies have used its advanced acoustic algorithms. Here, we evaluate existing usage of Parselmouth and discuss in detail several studies which used the software library. We argue that Parselmouth has the potential to be used even more in bioacoustics research, and suggest future directions to be pursued with the help of Parselmouth.

Abstract

This study investigates how listeners cope with gradient forms of deletion of word-final /t/ when recognising words in a phonological context that makes /t/-deletion viable. A corpus study confirmed a high incidence of /t/-deletion in an /st#b/ context in Dutch. A discrimination study showed that differences between released /t/, unreleased /t/ and fully deleted /t/ in this specific /st#b/ context were salient. Two on-line experiments were carried out to investigate whether lexical activation might be affected by this form variation. Even though unreleased and released variants were processed equally fast by listeners, a detailed analysis of the unreleased condition provided evidence for gradient activation. Activating a target ending in /t/ is slowest for the most reduced variant because phonological context has to be taken into account. Importantly, activation for a target with /t/ in the absence of cues for /t/ is reduced if there is a surface-matching lexical competitor.

Abstract

In this study we investigated to what extent a meaningful sentence context facilitates spoken word processing in young and older listeners if listening is made taxing by time-compressing the speech. Even though elderly listeners have been shown to benefit more from sentence context in difficult listening conditions than young listeners, time compression of speech may interfere with semantic comprehension, particularly in older listeners because of cognitive slowing. The results of a target detection experiment showed that, unlike young listeners who showed facilitation by context at both rates, elderly listeners showed context facilitation at the intermediate, but not at the fastest rate. This suggests that semantic interpretation lags behind target identification.

Abstract

Successful navigation is facilitated by the presence of landmarks. Previous functional magnetic resonance imaging (fMRI) evidence indicated that the human parahippocampal gyrus automatically distinguishes between landmarks placed at navigationally relevant (decision points) and irrelevant locations (nondecision points). This storage of navigational relevance can provide a neural mechanism underlying successful navigation. However, an efficient wayfinding mechanism requires that important spatial information is learned quickly and maintained over time. The present study investigates whether the representation of navigational relevance is modulated by time and practice. Participants learned 2 film sequences through virtual mazes containing objects at decision and at nondecision points. One maze was shown one time, and the other maze was shown 3 times. Twenty-four hours after study, event-related fMRI data were acquired during recognition of the objects. The results showed that activity in the parahippocampal gyrus was increased for objects previously placed at decision points as compared with objects placed at nondecision points. The decision point effect was not modulated by the number of exposures to the mazes and independent of explicit memory functions. These findings suggest a persistent representation of navigationally relevant information, which is stable after only one exposure to an environment. These rapidly induced and long-lasting changes in object representation provide a basis for successful wayfinding.

Abstract

The human brain distinguishes between landmarks placed at navigationally relevant and irrelevant locations. However, to provide a successful wayfinding mechanism not only landmarks but also the routes between them need to be stored. We examined the neural representation of a memory for route direction and a memory for relevant landmarks. Healthy human adults viewed objects along a route through a virtual maze. Event-related functional magnetic resonance imaging (fMRI) data were acquired during a subsequent subliminal priming recognition task. Prime-objects either preceded or succeeded a target-object on a preciously learned route. Our results provide evidence that the parahippocampal gyri distinguish between relevant and irrelevant landmarks whereas the inferior parietal gyrus, the anterior cingulate gyrus as well as the right caudate nucleus are involved in the coding of route direction. These data show that separated memory systems store different spatial information. A memory for navigationally relevant object information and a memory for route direction exist.

Abstract

Bats possess extraordinary adaptations, including flight, echolocation, extreme longevity and unique immunity. High-quality genomes are crucial for understanding the molecular basis and evolution of these traits. Here we incorporated long-read sequencing and state-of-the-art scaffolding protocols1 to generate, to our knowledge, the first reference-quality genomes of six bat species (Rhinolophus ferrumequinum, Rousettus aegyptiacus, Phyllostomus discolor, Myotis myotis, Pipistrellus kuhlii and Molossus molossus). We integrated gene projections from our ‘Tool to infer Orthologs from Genome Alignments’ (TOGA) software with de novo and homology gene predictions as well as short- and long-read transcriptomics to generate highly complete gene annotations. To resolve the phylogenetic position of bats within Laurasiatheria, we applied several phylogenetic methods to comprehensive sets of orthologous protein-coding and noncoding regions of the genome, and identified a basal origin for bats within Scrotifera. Our genome-wide screens revealed positive selection on hearing-related genes in the ancestral branch of bats, which is indicative of laryngeal echolocation being an ancestral trait in this clade. We found selection and loss of immunity-related genes (including pro-inflammatory NF-κB regulators) and expansions of anti-viral APOBEC3 genes, which highlights molecular mechanisms that may contribute to the exceptional immunity of bats. Genomic integrations of diverse viruses provide a genomic record of historical tolerance to viral infection in bats. Finally, we found and experimentally validated bat-specific variation in microRNAs, which may regulate bat-specific gene-expression programs. Our reference-quality bat genomes provide the resources required to uncover and validate the genomic basis of adaptations of bats, and stimulate new avenues of research that are directly relevant to human health and disease

Abstract

Listeners use lexical knowledge to adjust their prelexical representations of speech sounds in response to the idiosyncratic pronunciations of particular speakers. We used an exposure-test paradigm to investigate whether this type of perceptual learning transfers across syllabic positions. No significant learning effect was found in Experiment 1, where exposure sounds were onsets and test sounds were codas. Experiments 2-4 showed that there was no learning even when both exposure and test sounds were onsets. But a trend was found when exposure sounds were codas and test sounds were onsets (Experiment 5). This trend was smaller than the robust effect previously found for the coda-to-coda case. These findings suggest that knowledge about idiosyncratic pronunciations may be position specific: Knowledge about how a speaker produces sounds in one position, if it can be acquired at all, influences perception of sounds in that position more strongly than of sounds in another position.

Abstract

Words repeated in the same voice are better recognized than when they are repeated in a different voice. Such findings have been taken as evidence for the storage of talker-specific lexical episodes. But results on perceptual learning suggest that talker-specific adjustments concern sublexical representations. This study thus investigates whether voice-specific repetition effects in auditory lexical decision are lexical or sublexical. The same critical set of items in Block 2 were, depending on materials in Block 1, either same-voice or different-voice word repetitions, new words comprising re-orderings of phonemes used in the same voice in Block 1, or new words with previously unused phonemes. Results show a benefit for words repeated by the same talker, and a smaller benefit for words consisting of phonemes repeated by the same talker. Talker-specific information thus appears to influence word recognition at multiple representational levels.

Abstract

Listeners use suprasegmental auditory lexical stress information to resolve the competition words engage in during spoken-word recognition. The present study investigated whether (a) visual speech provides lexical stress information, and, more importantly, (b) whether this visual lexical stress information is used to resolve lexical competition. Dutch word pairs that differ in the lexical stress realization of their first two syllables, but not segmentally (e.g., 'OCtopus' and 'okTOber'; capitals marking primary stress) served as auditory-only, visual-only, and audiovisual speech primes. These primes either matched (e.g., 'OCto-'), mismatched (e.g., 'okTO-'), or were unrelated to (e.g., 'maCHI-') a subsequent printed target (octopus), which participants had to make a lexical decision to. To the degree that visual speech contains lexical stress information, lexical decisions to printed targets should be modulated through the addition of visual speech. Results show, however, no evidence for a role of visual lexical stress information in audiovisual spoken-word recognition.

Abstract

Thematic roles characterise the functions of participants in events, but there is no agreement on how these roles are identified in the real world. In three experiments, we examined how role identification in push events is supported by the visual object-tracking system. Participants saw one to three push events in visual scenes with nine identical randomly moving circles. After a period of random movement, two circles from one of the push events and a foil object were given different colours and the participants had to identify their roles in the push with an active sentence, such as red pushed blue. It was found that the participants could track the agent and patient targets and generate descriptions that identified their roles at above chance levels, even under difficult conditions, such as when tracking multiple push events (Experiments 1–3), fixating their gaze (Experiment 1), performing a concurrent speeded-response task (Experiment 2), and when tracking objects that were temporarily invisible (Experiment 3). The results were consistent with previous findings of an average tracking capacity limit of four objects, individual differences in this capacity, and the use of attentional strategies. The studies demonstrated that thematic role information can be maintained when tracking the identity of visually identical objects, then used to map role fillers (e.g., the agent of a push event) into their appropriate sentence positions. This suggests that thematic role features are stored temporarily in the visual object-tracking system.

Abstract

We investigate differences of cerebral activation in 12 right-handed and left-handed participants, respectively, using a sentence-processing task. Functional MRI shows activation of left-frontal and inferior-parietal speech areas (BA 44, BA9, BA 40) in both groups, but a stronger bilateral activation in left-handers. Direct group comparison reveals a stronger activation in right-frontal cortex (BA 47, BA 6) and left cerebellum in left-handers. Laterality indices for the inferior-frontal cortex are less asymmetric in left-handers and are not related to the degree of handedness. Thus, our results show that sentence-processing induced enhanced activation involving a bilateral network in left-handed participants.

Abstract

Purpose: Factors affecting the efficacy of therapeutic monoclonal antibodies (mAb) directed to the epidermal growth factor receptor (EGFR) remain relatively unknown, especially in glioma. Experimental Design: We examined the efficacy of two EGFR-specific mAbs (mAbs 806 and 528) against U87MG-derived glioma xenografts expressing EGFR variants. Using this approach allowed us to change the form of the EGFR while keeping the genetic background constant. These variants included the de2-7 EGFR (or EGFRvIII), a constitutively active mutation of the EGFR expressed in glioma. Results: The efficacy of the mAbs correlated with EGFR number; however, the most important factor was receptor activation. Whereas U87MG xenografts expressing the de2-7 EGFR responded to therapy, those exhibiting a dead kinase de2-7 EGFR were refractory. A modified de2-7 EGFR that was kinase active but autophosphorylation deficient also responded, suggesting that these mAbs function in de2-7 EGFR–expressing xenografts by blocking transphosphorylation. Because de2-7 EGFR–expressing U87MG xenografts coexpress the wild-type EGFR, efficacy of the mAbs was also tested against NR6 xenografts that expressed the de2-7 EGFR in isolation. Whereas mAb 806 displayed antitumor activity against NR6 xenografts, mAb 528 therapy was ineffective, suggesting that mAb 528 mediates its antitumor activity by disrupting interactions between the de2-7 and wild-type EGFR. Finally, genetic disruption of Src in U87MG xenografts expressing the de2-7 EGFR dramatically enhanced mAb 806 efficacy. Conclusions: The effective use of EGFR-specific antibodies in glioma will depend on identifying tumors with activated EGFR. The combination of EGFR and Src inhibitors may be an effective strategy for the treatment of glioma.