Publications

Abstract

The rise of molecular genetics is having a pervasive influence in a wide variety of fields, including research into neurodevelopmental disorders like dyslexia, speech and language impairments, and autism. There are many studies underway which are attempting to determine the roles of genetic factors in the aetiology of these disorders. Beyond the obvious implications for diagnosis, treatment and understanding, success in these efforts promises to shed light on the links between genes and aspects of cognition and behaviour. However, the deceptive simplicity of finding correlations between genetic and phenotypic variation has led to a common misconception that there exist straightforward linear relationships between specific genes and particular behavioural and/or cognitive outputs. The problem is exacerbated by the adoption of an abstract view of the nature of the gene, without consideration of molecular, developmental or ontogenetic frameworks. To illustrate the limitations of this perspective, I select two cases from recent research into the genetic underpinnings of neurodevelopmental disorders. First, I discuss the proposal that dyslexia can be dissected into distinct components specified by different genes. Second, I review the story of the FOXP2 gene and its role in human speech and language. In both cases, adoption of an abstract concept of the gene can lead to erroneous conclusions, which are incompatible with current knowledge of molecular and developmental systems. Genes do not specify behaviours or cognitive processes; they make regulatory factors, signalling molecules, receptors, enzymes, and so on, that interact in highly complex networks, modulated by environmental influences, in order to build and maintain the brain. I propose that it is necessary for us to fully embrace the complexity of biological systems, if we are ever to untangle the webs that link genes to cognition.

Abstract

The human capacity to acquire complex language seems to be without parallel in the natural world. The origins of this remarkable trait have long resisted adequate explanation, but advances in fields that range from molecular genetics to cognitive neuroscience offer new promise. Here we synthesize recent developments in linguistics, psychology and neuroimaging with progress in comparative genomics, gene-expression profiling and studies of developmental disorders. We argue that language should be viewed not as a wholesale innovation, but as a complex reconfiguration of ancestral systems that have been adapted in evolutionarily novel ways.

Abstract

Electrophysiological studies consistently find N400 effects of semantic incongruity in non-native written language comprehension. Typically these N400 effects are later than N400 effects in native comprehension, suggesting that semantic processing in one’s second language (L2) may be delayed compared to one’s first language (L1). In this study we were firstly interested in replicating the semantic incongruity effect using natural auditory speech, which poses strong demands on the speed of processing. Secondly, we wished to investigate whether a possible delay in semantic processing might be due to bilinguals accessing lexical items from both their L1 and L2 (a more extensive lexical search). We recorded EEG from 30 Dutch-English bilinguals who listened to English sentences � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � ��� � � in which the sentence-final word was: (1) semantically fitting, (2) semantically incongruent, (3) initially congruent: semantically incongruent, but sharing initial phonemes with the most probable sentence completion within the L2, (4) semantically incongruent, but sharing initial phonemes with the L1 translation equivalent of the most probable sentence completion. We found an N400 effect in each of the semantically incongruent conditions. This N400 effect was significantly delayed to L2 words that were initially congruent with the sentence context. We found no effect of initial overlap with L1 translation equivalents. Taken together these findings firstly demonstrate that non-native listeners are sensitive to semantic incongruity in natural speech, secondly indicate that semantic integration in non-native listening can start on the basis of word initial phonemes, and finally suggest that during L2 sentence processing listeners do not access the L1 lexicon.

Abstract

Partway along the vast waterways of Brazil's middle Rio Negro, upstream from urban Manaus and downstream from the ethnographically famous Northwest Amazon region, is the town of Castanheiro, whose inhabitants skillfully negotiate a space between the polar extremes of 'traditional' and 'acculturated.' This paper takes an ethnographic look at the non-polarizing terms that these rural Amazonian people use for talking about cultural change. While popular and academic discourses alike have often framed cultural change in the Amazon as a linear process, Amazonian discourse provides resources for describing change as situated in shifting fields of knowledge of the social and physical environments, better capturing its non-linear complexity and ambiguity.

Abstract

This paper examines code and style shifting during sales transactions based on two market case studies from highland Ecuador. Bringing together ideas of linguistic economy with work on stylistic variation and ethnohistorical research on Andean markets, I study bartering, market calls and sales pitches to show how sellers create stylistic performances distinguished by contrasts of code, register and poetic features. The interaction of the symbolic value of language with the economic values of the market presents a place to examine the relationship between discourse and the material world.

Abstract

The human brain supports acquisition mechanisms that extract structural regularities implicitly from experience without the induction of an explicit model. It has been argued that the capacity to generalize to new input is based on the acquisition of abstract representations, which reflect underlying structural regularities in the input ensemble. In this study, we explored the outcome of this acquisition mechanism, and to this end, we investigated the neural correlates of artificial syntactic classification using event-related functional magnetic resonance imaging. The participants engaged once a day during an 8-day period in a short-term memory acquisition task in which consonant-strings generated from an artificial grammar were presented in a sequential fashion without performance feedback. They performed reliably above chance on the grammaticality classification tasks on days 1 and 8 which correlated with a corticostriatal processing network, including frontal, cingulate, inferior parietal, and middle occipital/occipitotemporal regions as well as the caudate nucleus. Part of the left inferior frontal region (BA 45) was specifically related to syntactic violations and showed no sensitivity to local substring familiarity. In addition, the head of the caudate nucleus correlated positively with syntactic correctness on day 8 but not day 1, suggesting that this region contributes to an increase in cognitive processing fluency.

Abstract

Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstream of the gene LRRTM1 (Leucine-rich repeat transmembrane neuronal 1) with a quantitative measure of human handedness in a set of dyslexic siblings, when the haplotype was inherited paternally (P=0.00002). While we were unable to find this effect in an epidemiological set of twin-based sibships, we did find that the same haplotype is overtransmitted paternally to individuals with schizophrenia/schizoaffective disorder in a study of 1002 affected families (P=0.0014). We then found direct confirmatory evidence that LRRTM1 is an imprinted gene in humans that shows a variable pattern of maternal downregulation. We also showed that LRRTM1 is expressed during the development of specific forebrain structures, and thus could influence neuronal differentiation and connectivity. This is the first potential genetic influence on human handedness to be identified, and the first putative genetic effect on variability in human brain asymmetry. LRRTM1 is a candidate gene for involvement in several common neurodevelopmental disorders, and may have played a role in human cognitive and behavioral evolution.

Abstract

We present a computational model that provides a unified account of inference, coherence, and disambiguation. It simulates how the build-up of coherence in text leads to the knowledge-based resolution of referential ambiguity. Possible interpretations of an ambiguity are represented by centers of gravity in a high-dimensional space. The unresolved ambiguity forms a vector in the same space. This vector is attracted by the centers of gravity, while also being affected by context information and world knowledge. When the vector reaches one of the centers of gravity, the ambiguity is resolved to the corresponding interpretation. The model accounts for reading time and error rate data from experiments on ambiguous pronoun resolution and explains the effects of context informativeness, anaphor type, and processing depth. It shows how implicit causality can have an early effect during reading. A novel prediction is that ambiguities can remain unresolved if there is insufficient disambiguating information.

Abstract

Disruptions of the human FOXP2 gene cause problems with articulation of complex speech sounds, accompanied by impairment in many aspects of language ability. The FOXP2/Foxp2 transcription factor is highly similar in humans and mice, and shows a complex conserved expression pattern, with high levels in neuronal subpopulations of the cortex, striatum, thalamus, and cerebellum. In the present study we generated mice in which loxP sites flank exons 12-14 of Foxp2; these exons encode the DNA-binding motif, a key functional domain. We demonstrate that early global Cre-mediated recombination yields a null allele, as shown by loss of the loxP-flanked exons at the RNA level and an absence of Foxp2 protein. Homozygous null mice display severe motor impairment, cerebellar abnormalities and early postnatal lethality, consistent with other Foxp2 mutants. When crossed to transgenic lines expressing Cre protein in a spatially and/or temporally controlled manner, these conditional mice will provide new insights into the contributions of Foxp2 to distinct neural circuits, and allow dissection of roles during development and in the mature brain.

Abstract

Discourse markers (DMs) are linguistic elements that index different relations and coherence between units of talk (Schiffrin, Deborah, 1987. Discourse Markers. Cambridge University Press, Cambridge). Most research on the development of these forms has focused on conversations rather than narratives and furthermore has not directly compared children's use of DMs to adult usage. This study examines the development of three DMs (şey ‘uuhh’, yani ‘I mean’, işte ‘y’know’) that mark interactional levels of discourse in oral Turkish narratives in 60 Turkish children (3-, 5- and 9-year-olds) and 20 Turkish-speaking adults. The results show that the frequency and functions of DMs change with age. Children learn şey, which mainly marks exchange level structures, earliest. However, yani and işte have multi-functions such as marking both information states and participation frameworks and are consequently learned later. Children also use DMs with different functions than adults. Overall, the results show that learning to use interactional DMs in narratives is complex and goes beyond age 9, especially for multi-functional DMs that index an interplay of discourse coherence at different levels.

Abstract

Segmentation (and, indeed, definition) of the human body in Kuuk Thaayorre (a Paman language of Cape York Peninsula, Australia) is in some respects typologically unusual, while at other times it conforms to cross-linguistic patterns. The process of deriving complex body part terms from monolexemic items is revealing of metaphorical associations between parts of the body. Associations between parts of the body and entities and phenomena in the broader environment are evidenced by the ubiquity of body part terms (in their extended uses) throughout Thaayorre speech. Understanding the categorisation of the body is therefore prerequisite to understanding the Thaayorre language and worldview.

Abstract

The Error-Related Negativity (ERN) is a component of the event-related brain potential (ERP) that is associated with action monitoring and error detection. The present study addressed the question whether or not an ERN occurs after verbal error detection, e.g., during phoneme monitoring.We obtained an ERN following verbal errors which showed a typical decrease in amplitude under severe time pressure. This result demonstrates that the functioning of the verbal self-monitoring system is comparable to other performance monitoring, such as action monitoring. Furthermore, we found that participants made more errors in phoneme monitoring under time pressure than in a control condition. This may suggest that time pressure decreases the amount of resources available to a capacity-limited self-monitor thereby leading to more errors.

Abstract

The aim of this paper is to explore whether indexing terms for an audiovisual program can be derived from contextual texts automatically. For this we apply natural-language processing techniques to contextual texts of two Dutch TV-programs. We use a Dutch domain thesaurus to derive possible metadata. This possible metadata is ranked by an algorithm which uses the relations of the thesaurus. We evaluate the results by comparing them to human made descriptions.

Abstract

Irrelevant speech effect (ISE) is defined as a decrement in visually presented digit-list short-term memory performance due to exposure to irrelevant auditory material. Perhaps the most successful theoretical explanation of the effect is the changing state hypothesis. This hypothesis explains the effect in terms of confusion between amodal serial order cues, and represents a view based on the interference caused by the processing of similar order information of the visual and auditory materials. An alternative view suggests that the interference occurs as a consequence of the similarity between the visual and auditory contents of the stimuli. An important argument for the former view is the observation that ISE is almost exclusively observed in tasks that require memory for serial order. However, most short-term memory tasks require that both item and order information be retained in memory. An ideal task to investigate the sensitivity of maintenance of serial order to irrelevant speech would be one that calls upon order information but not item information. One task that is particularly suited to address this issue is serial recognition. In a typical serial recognition task, a list of items is presented and then probed by the same list in which the order of two adjacent items has been transposed. Due to the re-presentation of the encoding string, serial recognition requires primarily the serial order to be maintained while the content of the presented items is deemphasized. In demonstrating a highly significant ISE of changing versus steady-state auditory items in a serial recognition task, the present finding lends support for and extends previous empirical findings suggesting that irrelevant speech has the potential to interfere with the coding of the order of the items to be memorized.

Abstract

Using parametric and nonparametric techniques, our study investigated the presence of single locus and pairwise effects between 20 markers of the Genetic Analysis Workshop 15 (GAW15) North American Rheumatoid Arthritis Consortium (NARAC) candidate gene data set (Problem 2), analyzing 463 independent patients and 855 controls. Specifically, our work examined the correspondence between logistic regression (LR) analysis of single-locus and pairwise interaction effects, and random forest (RF) single and joint importance measures. For this comparison, we selected small but stable RFs (500 trees), which showed strong correlations (r~0.98) between their importance measures and those by RFs grown on 5000 trees. Both RF importance measures captured most of the LR single-locus and pairwise interaction effects, while joint importance measures also corresponded to full LR models containing main and interaction effects. We furthermore showed that RF measures were particularly sensitive to data imputation. The most consistent pairwise effect on rheumatoid arthritis was found between two markers within MAP3K7IP2/SUMO4 on 6q25.1, although LR and RFs assigned different significance levels. Within a hypothetical two-stage design, pairwise LR analysis of all markers with significant RF single importance would have reduced the number of possible combinations in our small data set by 61%, whereas joint importance measures would have been less efficient for marker pair reduction. This suggests that RF single importance measures, which are able to detect a wide range of interaction effects and are computationally very efficient, might be exploited as pre-screening tool for larger association studies. Follow-up analysis, such as by LR, is required since RFs do not indicate highrisk genotype combinations.

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

Acquiring the sounds of a language involves learning to recognize distributional patterns present in the input. We show that among adult learners, this distributional learning of auditory categories (which are conceived of here as probability density functions in a multidimensional space) is constrained by the salience of the dimensions that form the axes of this perceptual space. Only with a particular ratio of variation in the perceptual dimensions was category learning driven by the distributional properties of the input.

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

This paper outlines some reasons for why gestures are relevant to the study of SLA. First, given cross-cultural and cross-linguistic gestural repertoires, gestures can be treated as part of what learners can acquire in a target language. Gestures can therefore be studied as a developing system in their own right both in L2 production and comprehension. Second, because of the close link between gestures, language, and speech, learners' gestures as deployed in L2 usage and interaction can offer valuable insights into the processes of acquisition, such as the handling of expressive difficulties, the influence of the first language, interlanguage phenomena, and possibly even into planning and processing difficulties. As a form of input to learners and to their interlocutors alike, finally, gestures also play a potential role for comprehension and learning.

Abstract

The papers in this volume explore the cognitive neuroscience of second language acquisition from the perspectives of critical/sensitive periods, maturational effects, individual differences, neural regions involved, and processing characteristics. The research methodologies used include functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and event related potentials (ERP). Questions addressed include: Which brain areas are reliably activated in second language processing? Are they the same or different from those activated in first language acquisition and use? What are the behavioral consequences of individual differences among brains? What are the consequences of anatomical and physiological differences, learner proficiency effects, critical/sensitive periods? What role does degeneracy, in which two different neural systems can produce the same behavioral output, play? What does it mean that learners' brains respond to linguistic distinctions that cannot be recognized or produced yet? The studies in this volume provide initial answers to all of these questions.

Abstract

This study investigates whether addressees visually attend to speakers’ gestures in interaction and whether attention is modulated by changes in social setting and display size. We compare a live face-to-face setting to two video conditions. In all conditions, the face dominates as a fixation target and only a minority of gestures draw fixations. The social and size parameters affect gaze mainly when combined and in the opposite direction from the predicted with fewer gestures fixated on video than live. Gestural holds and speakers’ gaze at their own gestures reliably attract addressees’ fixations in all conditions. The attraction force of holds is unaffected by changes in social and size parameters, suggesting a bottom-up response, whereas speaker-fixated gestures draw significantly less attention in both video conditions, suggesting a social effect for overt gaze-following and visual joint attention. The study provides and validates a video-based paradigm enabling further experimental but ecologically valid explorations of cross-modal information processing.

Abstract

The production of cohesive discourse, especially maintained reference, poses problems for early second language (L2) speakers. This paper considers a communicative account of overexplicit L2 discourse by focusing on the interdependence between spoken and gestural cohesion, the latter being expressed by anchoring of referents in gesture space. Specifically, this study investigates whether overexplicit maintained reference in speech (lexical noun phrases [NPs]) and gesture (anaphoric gestures) constitutes an interactional communication strategy. We examine L2 speech and gestures of 16 Dutch learners of French retelling stories to addressees under two visibility conditions. The results indicate that the overexplicit properties of L2 speech are not motivated by interactional strategic concerns. The results for anaphoric gestures are more complex. Although their presence is not interactionally

Abstract

Since listeners usually look at the speaker's face, gestural information has to be absorbed through peripheral visual perception. In the literature, it has been suggested that listeners look at gestures under certain circumstances: 1) when the articulation of the gesture is peripheral; 2) when the speech channel is insufficient for comprehension; and 3) when the speaker him- or herself indicates that the gesture is worthy of attention. The research here reported employs eye tracking techniques to study the perception of gestures in face-to-face interaction. The improved control over the listener's visual channel allows us to test the validity of the above claims. We present preliminary findings substantiating claims 1 and 3, and relate them to theoretical proposals in the literature and to the issue of how visual and cognitive attention are related.

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

The central issue of this study concerns the claim that the processing of gender agreement in online sentence comprehension is a syntactic rather than a conceptual/semantic process. This claim was tested for the grammatical gender agreement in Dutch between the definite article and the noun. Subjects read sentences in which the definite article and the noun had the same gender and sentences in which the gender agreement was violated, While subjects read these sentences, their electrophysiological activity was recorded via electrodes placed on the scalp. Earlier research has shown that semantic and syntactic processing events manifest themselves in different event-related brain potential (ERP) effects. Semantic integration modulates the amplitude of the so-called N400.The P600/SPS is an ERP effect that is more sensitive to syntactic processes. The violation of grammatical gender agreement was found to result in a P600/SPS. For violations in sentence-final position, an additional increase of the N400 amplitude was observed. This N400 effect is interpreted as resulting from the consequence of a syntactic violation for the sentence-final wrap-up. The overall pattern of results supports the claim that the on-line processing of gender agreement information is not a content driven but a syntactic-form driven process.

Abstract

Silent reading and reading aloud of German words and pseudowords were used in a PET study using (15O)butanol to examine the neural correlates of reading and of the phonological conversion of legal letter strings, with or without meaning.
The results of 11 healthy, right-handed volunteers in the age range of 25 to 30 years showed activation of the lingual gyri during silent reading in comparison with viewing a fixation cross. Comparisons between the reading of words and pseudowords suggest the involvement of the middle temporal gyri in retrieving both the phonological and semantic code for words. The reading of pseudowords activates the left inferior frontal gyrus, including the ventral part of Broca’s area, to a larger extent than the reading of words. This suggests that this area might be involved in the sublexical conversion of orthographic input strings into phonological output codes. (Pre)motor areas were found to be activated during both silent reading and reading aloud. On the basis of the obtained activation patterns, it is hypothesized that the articulation of high-frequency syllables requires the retrieval of their concomitant articulatory gestures from the SMA and that the articulation of lowfrequency syllables recruits the left medial premotor cortex.

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

We explore the nature of the oscillatory dynamics in the EEG of subjects reading sentences that contain a semantic violation. More specifically, we examine whether increases in theta (≈3–7 Hz) and gamma (around 40 Hz) band power occur in response to sentences that were either semantically correct or contained a semantically incongruent word (semantic violation). ERP results indicated a classical N400 effect. A wavelet-based time-frequency analysis revealed a theta band power increase during an interval of 300–800 ms after critical word onset, at temporal electrodes bilaterally for both sentence conditions, and over midfrontal areas for the semantic violations only. In the gamma frequency band, a predominantly frontal power increase was observed during the processing of correct sentences. This effect was absent following semantic violations. These results provide a characterization of the oscillatory brain dynamics, and notably of both theta and gamma oscillations, that occur during language comprehension.

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

Many current sentence generators lack the ability to compute elliptical versions of coordinated clauses in accordance with the rules for Gapping, Forward and Backward Conjunction Reduction, and SGF (Subject Gap in clauses with Finite/ Fronted verb). We describe a module (implemented in JAVA, with German and Dutch as target languages) that takes non-elliptical coordinated clauses as input and returns all reduced versions licensed by coordinative ellipsis. It is loosely based on a new psycholinguistic theory of coordinative ellipsis proposed by Kempen. In this theory, coordinative ellipsis is not supposed to result from the application of declarative grammar rules for clause formation but from a procedural component that interacts with the sentence generator and may block the overt expression of certain constituents.

Abstract

We describe a generation-oriented workbench for the Performance Grammar (PG) formalism, highlighting the treatment of certain word order and movement constraints in Dutch and German. PG enables a simple and uniform treatment of a heterogeneous collection of linear order phenomena in the domain of verb constructions (variably known as Cross-serial Dependencies, Verb Raising, Clause Union, Extraposition, Third Construction, Particle Hopping, etc.). The central data structures enabling this feature are clausal “topologies”: one-dimensional arrays associated with clauses, whose cells (“slots”) provide landing sites for the constituents of the clause. Movement operations are enabled by unification of lateral slots of topologies at adjacent levels of the clause hierarchy. The PGW generator assists the grammar developer in testing whether the implemented syntactic knowledge allows all and only the well-formed permutations of constituents.

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

Comparatively little is known about the inherited primate background underlying human cognition, the human cognitive “wild-type.” Yet it is possible to trace the evolution of human cognitive abilities and tendencies by contrasting the skills of our nearest cousins, not just chimpanzees, but all the extant great apes, thus showing what we are likely to have inherited from the common ancestor [1]. By looking at human infants early in cognitive development, we can also obtain insights into native cognitive biases in our species [2]. Here, we focus on spatial memory, a central cognitive domain. We show, first, that all nonhuman great apes and 1-year-old human infants exhibit a preference for place over feature strategies for spatial memory. This suggests the common ancestor of all great apes had the same preference. We then examine 3-year-old human children and find that this preference reverses. Thus, the continuity between our species and the other great apes is masked early in human ontogeny. These findings, based on both phylogenetic and ontogenetic contrasts, open up the prospect of a systematic evolutionary psychology resting upon the cladistics of cognitive preferences.

Abstract

Current approaches to human cognition often take a strong nativist stance based on Western adult performance, backed up where possible by neonate and infant research and almost never by comparative research across the Hominidae. Recent research suggests considerable cross-cultural differences in cognitive strategies, including relational thinking, a domain where infant research is impossible because of lack of cognitive maturation. Here, we apply the same paradigm across children and adults of different cultures and across all nonhuman great ape genera. We find that both child and adult spatial cognition systematically varies with language and culture but that, nevertheless, there is a clear inherited bias for one spatial strategy in the great apes. It is reasonable to conclude, we argue, that language and culture mask the native tendencies in our species. This cladistic approach suggests that the correct perspective on human cognition is neither nativist uniformitarian nor ‘‘blank slate’’ but recognizes the powerful impact that language and culture can have on our shared primate cognitive biases.

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

Interrogative structures such as ‘Could you pass the salt? and ‘Couldn’t you pass the salt?’ can be used for making requests. A study of such pairs within a conversation analytic framework suggests that these are not used interchangeably, and that they have different impacts on the interaction. Focusing on Danish interactions between elderly care recipients and their home help assistants, I demonstrate how the care recipient displays different degrees of stance towards whether she is entitled to make a request or not, depending on whether she formats her request as a positive or a negative interrogative. With a positive interrogative request, the care recipient orients to her request as one she is not entitled to make. This is underscored by other features, such as the use of mitigating devices and the choice of verb. When accounting for this type of request, the care recipient ties the request to the specific situation she is in, at the moment in which the request is produced. In turn, the home help assistant orients to the lack of entitlement by resisting the request. With a negative interrogative request, the care recipient, in contrast, orients to her request as one she is entitled to make. This is strengthened by the choice of verb and the lack of mitigating devices. When such requests are accounted for, the requested task is treated as something that should be routinely performed, and hence as something the home help assistant has neglected to do. In turn, the home help assistant orients to the display of entitlement by treating the request as unproblematic, and by complying with it immediately.

Abstract

Longitudinally collected VOT data from an early English-Italian bilingual who became increasingly English-dominant was analyzed. Stops in English were always produced with significantly longer VOT than in Italian. However, the speaker did not show any significant change in the VOT production in either language over time, despite the clear dominance of English in his every day language use later in his life. The results indicate that – unlike L2 learners – early bilinguals may remain unaffected by language use with respect to phonetic realization.

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

When faced with the noun phrase (NP) versus sentence (S) coordination ambiguity as in, for example, The thief shot the jeweller and the cop hellip, readers prefer the reading with NP-coordination (e.g., "The thief shot the jeweller and the cop yesterday") over one with two conjoined sentences (e.g., "The thief shot the jeweller and the cop panicked"). A corpus study is presented showing that NP-coordinations are produced far more often than S-coordinations, which in frequency-based accounts of parsing might be taken to explain the NP-coordination preference. In addition, we describe an eye-tracking experiment investigating S-coordinated sentences such as Jasper sanded the board and the carpenter laughed, where the poor thematic fit between carpenter and sanded argues against NP-coordination. Our results indicate that information regarding poor thematic fit was used rapidly, but not without leaving some residual processing difficulty. This is compatible with claims that thematic information can reduce but not completely eliminate garden-path effects.

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

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

In the visual world paradigm, participants are more likely to fixate a visual referent that has some semantic relationship with a heard word, than they are to fixate an unrelated referent [Cooper, R. M. (1974). The control of eye fixation by the meaning of spoken language. A new methodology for the real-time investigation of speech perception, memory, and language processing. Cognitive Psychology, 6, 813–839]. Here, this method is used to examine the psychological validity of models of high-dimensional semantic space. The data strongly suggest that these corpus-based measures of word semantics predict fixation behavior in the visual world and provide further evidence that language-mediated eye movements to objects in the concurrent visual environment are driven by semantic similarity rather than all-or-none categorical knowledge. The data suggest that the visual world paradigm can, together with other methodologies, converge on the evidence that may help adjudicate between different theoretical accounts of the psychological semantics.

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

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

This article presents the results of a meta-analysis of 30 hemodynamic experiments comparing first language (L1) and second language (L2) processing in a range of tasks. The results suggest that reliably stronger activation during L2 processing is found (a) only for task-specific subgroups of L2 speakers and (b) within some, but not all regions that are also typically activated in native language processing. A tentative interpretation based on the functional roles of frontal and temporal regions is suggested.

Abstract

This volume is a harvest of articles from the first conference in a series on the cognitive neuroscience of language. The first conference focused on the cognitive neuroscience of second language acquisition (henceforth SLA). It brought together experts from as diverse fields as second language acquisition, bilingualism, cognitive neuroscience, and neuroanatomy. The articles and discussion articles presented here illustrate state-of-the-art findings and represent a wide range of theoretical approaches to classic as well as newer SLA issues. The theoretical themes cover age effects in SLA related to the so-called Critical Period Hypothesis and issues of ultimate attainment and focus both on age effects pertaining to childhood and to aging. Other familiar SLA topics are the effects of proficiency and learning as well as issues concerning the difference between the end product and the process that yields that product, here discussed in terms of convergence and degeneracy. A topic more related to actual usage of a second language once acquired concerns how multilingual speakers control and regulate their two languages.

Abstract

Clahsen's characterization of nondefault inflection as based exclusively on lexical entries does not capture the full range of empirical data on German inflection. In the verb system differential effects of lexical frequency seem to be input-related rather than affecting morphological production. In the noun system, the generalization properties of -n and -e plurals exceed mere analogy-based productivity.

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

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

Research has shown that Broca’s and Wernicke’s aphasic patients show different impairments in auditory lexical processing. The results of an experiment with form-overlapping primes showed an inhibitory effect of form-overlap for control adults and a weak inhibition trend for Broca’s aphasic patients, but a facilitatory effect of form-overlap was found for Wernicke’s aphasic participants. This suggests that Wernicke’s aphasic patients are mainly impaired in suppression of once-activated word candidates and selection of one winning candidate, which may be related to their problems in auditory language comprehension.

Abstract

In everyday life people have to deal with tasks such as finding a novel path to a certain goal location, finding one’s way back, finding a short cut, or making a detour. In all of these tasks people acquire route knowledge. For finding the same way back they have to remember locations of objects like buildings and additionally direction changes. In three experiments using recognition tasks as well as conscious and unconscious spatial priming paradigms memory processes underlying wayfinding behaviour were investigated. Participants learned a route through a virtual environment with objects either placed at intersections (i.e., decision points) where another route could be chosen or placed along the route (non-decision points). Analyses indicate first that objects placed at decision points are recognized faster than other objects. Second, they indicate that the direction in which a route is travelled is represented only at locations that are relevant for wayfinding (e.g., decision points). The results point out the efficient way in which memory for object location and memory for route direction interact.

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

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

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.

Abstract

There is evidence for cognitive as well as neural plasticity across the adult life span, although aging is associated with certain constraints on plasticity. In the current paper, we argue that the age-related reduction in cognitive plasticity may be due to (a) deficits in general processing resources, and (b) failure to engage in task-relevant cognitive operations. Memory-training research suggests that age-related processing deficits (e.g., executive functions, speed) hinder older adults from utilizing mnemonic techniques as efficiently as the young, and that this age difference is reflected by diminished frontal activity during mnemonic use. Additional constraints on memory plasticity in old age are related to difficulties that are specific to the task, such as creating visual images, as well as in binding together the information to be remembered. These deficiencies are paralleled by reduced activity in occipito-parietal and medial–temporal regions, respectively. Future attempts to optimize intervention-related gains in old age should consider targeting both general processing and task-specific origins of age-associated reductions in cognitive plasticity.