Publications

Abstract

Theeffects of spatial filtering in functional magnetic resonance imaging were investigated by reevaluating the data of a previous study of episodic memory encoding at 2 × 2 × 4-mm3 resolution with use of a SPM99 analysis involving a Gaussian kernel of 8-mm full width at half maximum. In addition, a multisubject analysis of activated regions was performed by normalizing the functional images to an approximate Talairach brain atlas. In individual subjects, spatial filtering merged activations in anatomically separated brain regions. Moreover, small foci of activated pixels which originated from veins became blurred and hence indistinguishable from parenchymal responses. The multisubject analysis resulted in activation of the hippocampus proper, a finding which could not be confirmed by the activation maps obtained at high resolution. It is concluded that the validity of multisubject fMRI analyses can be considerably improved by first analyzing individual data sets at optimum resolution to assess the effects of spatial filtering and minimize the risk of signal contamination by macroscopically visible vessels.

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

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

Languages, like molecules, document evolutionary history. Darwin(1) observed that evolutionary change in languages greatly resembled the processes of biological evolution: inheritance from a common ancestor and convergent evolution operate in both. Despite many suggestions(2-4), few attempts have been made to apply the phylogenetic methods used in biology to linguistic data. Here we report a parsimony analysis of a large language data set. We use this analysis to test competing hypotheses - the "express-train''(5) and the "entangled-bank''(6,7) models - for the colonization of the Pacific by Austronesian-speaking peoples. The parsimony analysis of a matrix of 77 Austronesian languages with 5,185 lexical items produced a single most-parsimonious tree. The express-train model was converted into an ordered geographical character and mapped onto the language tree. We found that the topology of the language tree was highly compatible with the express-train model.

Abstract

To study the time course of sentence formulation, we monitored the eye movements of speakers as they described simple events. The similarity between speakers' initial eye movements and those of observers performing a nonverbal event-comprehension task suggested that response-relevant information was rapidly extracted from scenes, allowing speakers to select grammatical subjects based on comprehended events rather than salience. When speaking extemporaneously, speakers began fixating pictured elements less than a second before naming them within their descriptions, a finding consistent with incremental lexical encoding. Eye movements anticipated the order of mention despite changes in picture orientation, in who-did-what-to-whom, and in sentence structure. The results support Wundt's theory of sentence production.

Abstract

In this study, event-related brain potential ffects of speech processing are obtained and compared to similar effects in sentence reading. In two experiments sentences were presented that contained three different types of grammatical violations. In one experiment sentences were presented word by word at a rate of four words per second. The grammatical violations elicited a Syntactic Positive Shift (P600/SPS), 500 ms after the onset of the word that rendered the sentence ungrammatical. The P600/SPS consisted of two phases, an early phase with a relatively equal anterior-posterior distribution and a later phase with a strong posterior distribution. We interpret the first phase as an indication of structural integration complexity, and the second phase as an indication of failing parsing operations and/or an attempt at reanalysis. In the second experiment the same syntactic violations were presented in sentences spoken at a normal rate and with normal intonation. These violations elicited a P600/SPS with the same onset as was observed for the reading of these sentences. In addition two of the three violations showed a preceding frontal negativity, most clearly over the left hemisphere.

Abstract

In this study, event-related brain potential effects of speech processing are obtained and compared to similar effects insentence reading. In two experiments spoken sentences were presented with semantic violations in sentence-signal or mid-sentence positions. For these violations N400 effects were obtained that were very similar to N400 effects obtained in reading. However, the N400 effects in speech were preceded by an earlier negativity (N250). This negativity is not commonly observed with written input. The early effect is explained as a manifestation of a mismatch between the word forms expected on the basis of the context, and the actual cohort of activated word candidates that is generated on the basis of the speech signal.

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

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

Drawings of objects were presented in series of 54 each to 14 German speaking subjects with the tasks to indicate by button presses a) whether the grammatical gender of an object name was masculine ("der") or feminine ("die") and b) whether the depicted object was man-made or nature-made. The magnetoencephalogram (MEG) was recorded with a whole-head neuromagnetometer and task-specific patterns of brain activity were determined in the source space (Minimum Norm Estimates, MNE). A left-temporal focus of activity 150-275 ms after stimulus onset in the gender decision compared to the semantic classification task was discussed as indicating the retrieval of syntactic information, while a more expanded left hemispheric activity in the gender relative to the semantic task 300-625 ms after stimulus onset was discussed as indicating phonological encoding. A predominance of activity in the semantic task was observed over right fronto-central region 150-225 ms after stimulus-onset, suggesting that semantic and syntactic processes are prominent in this stage of lexical selection.

Abstract

When a sentence such as The model embraced the designer and the photographer laughed is read, the noun phrase the photographer is temporarily ambiguous: It can be either one of the objects of embraced (NP-coordination) or the subject of a new, conjoined sentence (S-coordination). It has been shown for a number of languages, including Dutch (the language used in this study), that readers prefer NP-coordination over S-coordination, at least in isolated sentences. In the present paper, it will be suggested that NP-coordination is preferred because it is the simpler of the two options in terms of topic-structure; in NP-coordinations there is only one topic, whereas S-coordinations contain two. Results from off-line (sentence completion) and online studies (a self-paced reading and an eye tracking experiment) support this topic-structure explanation. The processing difficulty associated with S-coordinated sentences disappeared when these sentences followed contexts favoring a two-topic continuation. This finding establishes topic-structure as an important factor in online sentence processing.

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

Dutch-learning and English-learning 9-month-olds were tested, using the Headturn Preference Procedure, for their ability to segment Dutch words with strong/weak stress patterns from fluent Dutch speech. This prosodic pattern is highly typical for words of both languages. The infants were familiarized with pairs of words and then tested on four passages, two that included the familiarized words and two that did not. Both the Dutch- and the English-learning infants gave evidence of segmenting the targets from the passages, to an equivalent degree. Thus, English-learning infants are able to extract words from fluent speech in a language that is phonetically different from English. We discuss the possibility that this cross-language segmentation ability is aided by the similarity of the typical rhythmic structure of Dutch and English words.

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

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

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

The authors report six implicit priming experiments that examined the production of inflected forms. Participants produced words out of small sets in response to prompts. The words differed in form or shared word-initial segments, which allowed for preparation. In constant inflectional sets, the words had the same number of inflectional suffixes, whereas in variable sets the number of suffixes differed. In the experiments, preparation effects were obtained, which were larger in the constant than in the variable sets. Control experiments showed that this difference in effect was not due to syntactic class or phonological form per se. The results are interpreted in terms of a slot-and-filler model of word production, in which inflectional frames, on the one hand, and stems and affixes, on the other hand, are independently spelled out on the basis of an abstract morpho-syntactic specification of the word, which is followed by morpheme-to-frame association.

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

Language processing is influenced by multiple sources of information. We examined whether the performance in simultaneous interpreting would be improved when providing two sources of information, the auditory speech as well as corresponding lip-movements, in comparison to presenting the auditory speech alone. Although there was an improvement in sentence recognition when presented with visible speech, there was no difference in performance between these two presentation conditions when bilinguals simultaneously interpreted from English to German or from English to Spanish. The reason why visual speech did not contribute to performance could be the presentation of the auditory signal without noise (Massaro, 1998). This hypothesis should be tested in the future. Furthermore, it should be investigated if an effect of visible speech can be found for other contexts, when visual information could provide cues for emotions, prosody, or syntax.

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

In this study, we use the association between various measures of the morphological family and decision latencies to reveal the way in which the components of Dutch and English compounds are processed. The results show that for constituents of concatenated compounds in both languages, a position-related token count of the morphological family plays a role, whereas English open compounds show an effect of a type count, similar to the effect of family size for simplex words. When Dutch compounds are written with an artificial space, they reveal no effect of type count, which shows that the differential effect for the English open compounds is not superficial. The final experiment provides converging evidence for the lexical consequences of the space in English compounds. Decision latencies for English simplex words are better predicted from counts of the morphological family that include concatenated and hyphenated but not open family members.

Abstract

Two experimental results often reported in support of perceptual interpretations concerning the influence of set on perception are critically examined: (a) the relation between word frequency and recognition threshold, and (b) the so-called compromise reactions between set and stimulus, Alter elimination of certain methodological artifacts (e.g., introduction of a temporal forced-choice method instead of the ascending-limits method), both phenomena disappear; the influence of set on perception appears to be wholly a matter of response bias.

Abstract

Written information is often of limited accessibility to deaf people who use sign language. The eSign project was undertaken as a response to the need for technologies enabling efficient production and distribution over the Internet of sign language content. By using an avatar-independent scripting notation for signing gestures and a client-side web browser plug-in to translate this notation into motion data for an avatar, we achieve highly efficient delivery of signing, while avoiding the inflexibility of video or motion capture. Tests with members of the deaf community have indicated that the method can provide an acceptable quality of signing.

Abstract

Speech is structured into parts by syntactic and prosodic breaks. In locally syntactic ambiguous sentences, the detection of a syntactic break necessarily follows detection of a corresponding prosodic break, making an investigation of the immediate interplay of syntactic and prosodic information impossible when studying sentences in isolation. This problem can be solved, however, by embedding sentences in a discourse context that induces the expectation of either the presence or the absence of a syntactic break right at a prosodic break. Event-related potentials (ERPs) were compared to acoustically identical sentences in these different contexts. We found in two experiments that the closure positive shift, an ERP component known to be elicited by prosodic breaks, was reduced in size when a prosodic break was aligned with a syntactic break. These results establish that the brain matches prosodic information against syntactic information immediately.

Abstract

Children must possess some ability to process input in a meaningful manner to acquire language. The present study reports on data from an experiment investigating 3- to 5-year-old English-speaking children's understanding of restrictive relative clauses manipulated for embeddedness and focus. The results of the study showed that English-speaking children acquire right-branching before center-embedded structures. Comparisons made with data from Portuguese-speaking children suggest general-cognitive and language-specific constraints on development, and with respect to English, a “clause expansion” approach to processing in development

Abstract

This paper reports on two studies investigating children's and adults' processing of sentences containing ambiguity of prepositional phrase (PP) attachment. Study 1 used corpus data to investigate whether cues argued to be used by adults to resolve PP-attachment ambiguities are available in child-directed speech. Study 2 was an on-line reaction time study investigating the role of lexical and referential biases in syntactic ambiguity resolution by children and adults. Forty children (mean age 8;4) and 37 adults listened to V-NP-PP sentences containing temporary ambiguity of PP-attachment. The sentences were manipulated for (i) verb semantics, (ii) the definiteness of the object NP, and (iii) PP-attachment site. The children and adults did not differ qualitatively from each other in their resolution of the ambiguity. A verb semantics by attachment interaction suggested that different attachment analyses were pursued depending on the semantics of the verb. There was no influence of the definiteness of the object NP in either children's or adults' parsing preferences. The findings from the on-line task matched up well with the corpus data, thus identifying a role for the input in the development of parsing strategies.

Abstract

We present the results from four studies, two corpora and two experimental, which suggest that English- and German-speaking children (3;1–4;9 years) use multiple constraints to process and produce object relative clauses. Our two corpora studies show that children produce object relatives that reflect the distributional and discourse regularities of the input. Specifically, the results show that when children produce object relatives they most often do so with (a) an inanimate head noun, and (b) a pronominal relative clause subject. Our experimental findings show that children use these constraints to process and produce this construction type. Moreover, when children were required to repeat the object relatives they most often use in naturalistic speech, the subject-object asymmetry in processing of relative clauses disappeared. We also report cross-linguistic differences in children's rate of acquisition which reflect properties of the input language. Overall, our results suggest that children are sensitive to the same constraints on relative clause processing as adults.

Abstract

Gestures that accompany speech are known to be tightly coupled with speech production. However little is known about the cognitive processes that underlie this link. Previous cross-linguistic research has provided preliminary evidence for online interaction between the two systems based on the systematic co-variation found between how different languages syntactically package Manner and Path information of a motion event and how gestures represent Manner and Path. Here we elaborate on this finding by testing whether speakers within the same language gesturally express Manner and Path differently according to their online choice of syntactic packaging of Manner and Path, or whether gestural expression is pre-determined by a habitual conceptual schema congruent with the linguistic typology. Typologically congruent and incongruent syntactic structures for expressing Manner and Path (i.e., in a single clause or multiple clauses) were elicited from English speakers. We found that gestural expressions were determined by the online choice of syntactic packaging rather than by a habitual conceptual schema. It is therefore concluded that speech and gesture production processes interface online at the conceptual planning phase. Implications of the findings for models of speech and gesture production are discussed

Abstract

In a way, the entire history of linguistic thought from the Antiquity to present days is a series of variations on two key themes: 1. In a certain sense, language and cognition are the same, and 2. In a certain sense, all languages are the same. What varies is the way in which “in a certain sense” is spelled out. Interpretations oscillate between radical positions such as the idea that thinking without speaking is impossible to the idea that it is just language which vexes our cognition and hence makes it rather impossible, and similarly between the idea that all differences between natural languages are nothing but irrelevant variations in the “vox”, the “external form” to the idea that it our thought is massively shaped by the particular structural features of the language we happen to speak. It is remarkable how little agreement has been reached on these issues after more than 2500 years of discussion. This, it is argued, has mainly two reasons: (a) The entire argument is largely confined to a few lexical and morphological properties of human languages, and (b) the discussion is rarely based on empirical research on “language at work” - how do we manage to solve those many little tasks for which human languages are designed in the first place.

Abstract

The German Perfekt has two quite different temporal readings, as illustrated by the two possible continuations of the sentence Peter hat gearbeitet in i, ii, respectively: (i) Peter hat gearbeitet und ist müde. Peter has worked and is tired. (ii) Peter hat gearbeitet und wollte nicht gestört werden. Peter has worked and wanted not to be disturbed. The first reading essentially corresponds to the English present perfect; the second can take a temporal adverbial with past time reference ('yesterday at five', 'when the phone rang', and so on), and an English translation would require a past tense ('Peter worked/was working'). This article shows that the Perfekt has a uniform temporal meaning that results systematically from the interaction of its three components-finiteness marking, auxiliary and past participle-and that the two readings are the consequence of a structural ambiguity. This analysis also predicts the properties of other participle constructions, in particular the passive in German.

Abstract

Chinese has a number of particles such as le, guo, zai and zhe that add a particular aspectual value to the verb to which they are attached. There have been many characterisations of this value in the literature. In this paper, we review several existing influential accounts of these particles, including those in Li and Thompson (1981), Smith (1991), and Mangione and Li (1993). We argue that all these characterisations are intuitively plausible, but none of them is precise.We propose that these particles serve to mark which part of the sentence''s descriptive content is asserted, and that their aspectual value is a consequence of this function. We provide a simple and precise definition of the meanings of le, guo, zai and zhe in terms of the relationship between topic time and time of situation, and show the consequences of their interaction with different verb expressions within thisnew framework of interpretation.

Abstract

Language acquisition is the transition between the language faculty, with which we are born as a part of our genetic endowment, to the mastery of one or more linguistic systems. There is a plethora of findings about this process; but these findings still do not form a coherent picture of the principles which underlie this process. There are at least six reasons for this situation. First, there is an enormous variability in the conditions under which this process occurs. Second, the learning capacity does not remain constant over time. Third, the process extends over many years and is therefore hard to study. Fourth, especially the investigation of the meaning side is problem-loaded. Fifth, many skills and types of knowledge must be learned in a more or less synchronised way. And sixth, our understanding of the functioning of linguistic systems is still very limited. Nevertheless, there are a few overarching results, three of which are discussed here: (1) There are salient differences between child and adult learners: While children normally end up with perfect mastery of the language to be learned, this is hardly ever the case for adults. On the hand, it could be shown for each linguistic property examined so far, that adults are in principle able to learn it up to perfection. So, adults can learn everything perfectly well, they just don’t. (2) Within childhood, age of onset plays no essential role for ultimate attainment. (3) Children care much more for formal correctness than adults - they are just better in mimicking existing systems. It is argued that age does not affect the „construction capacity”- the capacity to build up linguistic systems - but the „copying faculty”, i.e., the faculty to imitate an existing system.

Abstract

Objectives: To investigate the time resolution of different methods for the computation of event-related desynchronization/synchronization (ERD/ERS), including one based on Hilbert transform. Methods: In order to better understand the time resolution of ERD/ERS, which is a function of factors such as the exact computation method, the frequency under study, the number of trials, and the sampling frequency, we simulated sudden changes in oscillation amplitude as well as very short and closely spaced events. Results: Hilbert-based ERD yields very similar results to ERD integrated over predefined time intervals (block ERD), if the block length is half the period length of the studied frequency. ERD predicts the onset of a change in oscillation amplitude with an error margin of only 10–30 ms. On the other hand, the time the ERD response needs to climb to its full height after a sudden change in oscillation amplitude is quite long, i.e. between 200 and 500 ms. With respect to sensitivity to short oscillatory events, the ratio between sampling frequency and electroencephalographic frequency band plays a major role. Conclusions: (1) The optimal time interval for the computation of block ERD is half a period of the frequency under investigation. (2) Due to the slow impulse response, amplitude effects in the ERD may in reality be caused by duration differences. (3) Although ERD based on the Hilbert transform does not yield any significant advantages over classical ERD in terms of time resolution, it has some important practical advantages.

Abstract

Does the naming of clocks always require conceptual preparation? To examine this question, speakers were presented with analog and digital clocks that had to be named in Dutch using either a relative (e.g., “quarter to four”) or an absolute (e.g., “three forty-five”) clock time expression format. Naming latencies showed evidence of conceptual preparation when speakers produced relative time expressions to analog and digital clocks, but not when they used absolute time expressions. These findings indicate that conceptual mediation is not always mandatory for telling time, but instead depends on clock time expression format, supporting a multiple-route account of Dutch clock time naming.

Abstract

* Kristiansen, M., Deriziotis, P. These authors contributed equally to this work.* - The mechanism of cell death in prion disease is unknown but is associated with the production of a misfolded conformer of the prion protein. We report that disease-associated prion protein specifically inhibits the proteolytic β subunits of the 26S proteasome. Using reporter substrates, fluorogenic peptides, and an activity probe for the β subunits, this inhibitory effect was demonstrated in pure 26S proteasome and three different cell lines. By challenge with recombinant prion and other amyloidogenic proteins, we demonstrate that only the prion protein in a nonnative β sheet conformation inhibits the 26S proteasome at stoichiometric concentrations. Preincubation with an antibody specific for aggregation intermediates abrogates this inhibition, consistent with an oligomeric species mediating this effect. We also present evidence for a direct relationship between prion neuropathology and impairment of the ubiquitin-proteasome system (UPS) in prion-infected UPS-reporter mice. Together, these data suggest a mechanism for intracellular neurotoxicity mediated by oligomers of misfolded prion protein.

Abstract

Only relatively recently have theories of speech production concerned themselves with the part idioms and other multi-word lexical items (MLIs) play in the processes of speech production. Two theories of speech production which attempt to account for the accessing of idioms in speech production are those of Cutting and Bock (1997) and superlemma theory (Sprenger, 2003; Sprenger, Levelt, & Kempen, 2006). Much of the data supporting theories of speech production comes either from time course experiments or from slips of the tongue (Bock & Levelt, 1994). The latter are of two kinds: experimentally induced (Baars, 1992) or naturally observed (Fromkin, 1980). Cutting and Bock use experimentally induced speech errors while Sprenger et al. use time course experiments. The missing data type that has a bearing on speech production involving MLIs is that of naturally occurring slips. In this study the impact of data taken from naturally observed slips involving English and Dutch MLIs are brought to bear on these theories. The data are taken initially from a corpus of just over 1000 naturally observed English slips involving MLIs (the Tuggy corpus). Our argument proceeds as follows. First we show that slips occur independent of whether or not there are MLIs involved. In other words, speech production proceeds in certain of its aspects as though there were no MLI present. We illustrate these slips from the Tuggy data. Second we investigate the predictions of superlemma theory. Superlemma theory (Sprenger et al., 2006) accounts for the selection of MLIs and how their properties enter processes of speech production. It predicts certain activation patterns dependent on a MLI being selected. Each such pattern might give rise to slips of the tongue. This set of predictions is tested against the Tuggy data. Each of the predicted activation patterns yields a significant number of slips. These findings are therefore compatible with a view of MLIs as single units in so far as their activation by lexical concepts goes. However, the theory also predicts that some slips are likely not to occur. We confirm that such slips are not present in the data. These findings are further corroborated by reference a second smaller dataset of slips involving Dutch MLIs (the Kempen corpus). We then use slips involving irreversible binomials to distinguish between the predictions of superlemma theory which are supported by slips involving irreversible binomials and the Cutting and Bock model's predictions for slips involving these MLIs which are not

Abstract

As in the case of other non-English languages, the study of the acquisition of Turkish has mostly focused on aspects of grammatical morphology and syntax, largely neglecting the study of the effect of interactional factors on child morphosyntax. This paper reviews indications from past research that studying input and adult-child discourse can facilitate the study of the acquisition of morphosyntax in the Turkish language. It also provides some recent studies of Turkish child language on the relationship of child-directed speech to the early acquisition of morphosyntax, and on the pragmatic features of a certain kind of discourse form in child-directed speech called variation sets.

Abstract

This study explores the effects of informational redundancy, as carried by a word's morphological paradigmatic structure, on acoustic duration in read aloud speech. The hypothesis that the more predictable a linguistic unit is, the less salient its realization, was tested on the basis of the acoustic duration of interfixes in Dutch compounds in two datasets: One for the interfix -s- (1155 tokens) and one for the interfix -e(n)- (742 tokens). Both datasets show that the more probable the interfix is, given the compound and its constituents, the longer it is realized. These findings run counter to the predictions of information-theoretical approaches and can be resolved by the Paradigmatic Signal Enhancement Hypothesis. This hypothesis argues that whenever selection of an element from alternatives is probabilistic, the element's duration is predicted by the amount of paradigmatic support for the element: The most likely alternative in the paradigm of selection is realized longer.

Abstract

This study addressed prosodic effects on the duration of and amount of glottal vibration in German word-initial fricatives /f, v, z/ in assimilatory and non-assimilatory devoicing contexts. Fricatives following /small schwa/ (non-assimilation context) were longer and were produced with less glottal vibration after higher prosodic boundaries, reflecting domain-initial prosodic strengthening. After /t/ (assimilation context), lenis fricatives (/v, z/) were produced with less glottal vibration than after /small schwa/, due to assimilatory devoicing. This devoicing was especially strong across lower prosodic boundaries, showing the influence of prosodic structure on sandhi processes. Reduction in glottal vibration made lenis fricatives more fortis-like (/f, s/). Importantly, fricative duration, another major cue to the fortis-lenis distinction, was affected by initial lengthening, but not by assimilation. Hence, at smaller boundaries, fricatives were more devoiced (more fortis-like), but also shorter (more lenis-like). As a consequence, the fortis and lenis fricatives remained acoustically distinct in all prosodic and segmental contexts. Overall, /z/ was devoiced to a greater extent than /v/. Since /z/ does not have a fortis counterpart in word-initial position, these findings suggest that phonotactic restrictions constrain phonetic processes. The present study illuminates a complex interaction of prosody, sandhi processes, and phonotactics, yielding systematic phonetic cues to prosodic structure and phonological distinctions.

Abstract

The KE family is a large three-generation pedigree in which half the members are affected with a severe speech and language disorder that is transmitted as an autosomal dominant monogenic trait. In previously published work, we localized the gene responsible (SPCH1) to a 5.6-cM region of 7q31 between D7S2459 and D7S643. In the present study, we have employed bioinformatic analyses to assemble a detailed BAC-/PAC-based sequence map of this interval, containing 152 sequence tagged sites (STSs), 20 known genes, and >7.75 Mb of completed genomic sequence. We screened the affected chromosome 7 from the KE family with 120 of these STSs (average spacing <100 kb), but we did not detect any evidence of a microdeletion. Novel polymorphic markers were generated from the sequence and were used to further localize critical recombination breakpoints in the KE family. This allowed refinement of the SPCH1 interval to a region between new markers 013A and 330B, containing ∼6.1 Mb of completed sequence. In addition, we have studied two unrelated patients with a similar speech and language disorder, who have de novo translocations involving 7q31. Fluorescence in situ hybridization analyses with BACs/PACs from the sequence map localized the t(5;7)(q22;q31.2) breakpoint in the first patient (CS) to a single clone within the newly refined SPCH1 interval. This clone contains the CAGH44 gene, which encodes a brain-expressed protein containing a large polyglutamine stretch. However, we found that the t(2;7)(p23;q31.3) breakpoint in the second patient (BRD) resides within a BAC clone mapping >3.7 Mb distal to this, outside the current SPCH1 critical interval. Finally, we investigated the CAGH44 gene in affected individuals of the KE family, but we found no mutations in the currently known coding sequence. These studies represent further steps toward the isolation of the first gene to be implicated in the development of speech and language.

Abstract

The present study investigates hemispheric specialisation in the use of space in communicative gestures. For this purpose, we investigate split-brain patients in whom spontaneous and distinct right hand gestures can only be controlled by the left hemisphere and vice versa, the left hand only by the right hemisphere. On this anatomical basis, we can infer hemispheric specialisation from the performances of the right and left hands. In contrast to left hand dyspraxia in tasks that require language processing, split-brain patients utilise their left hands in a meaningful way in visuo-constructive tasks such as copying drawings or block-design. Therefore, we conjecture that split-brain patients are capable of using their left hands for the communication of the content of visuo-spatial animations via gestural demonstration. On this basis, we further examine the use of space in communicative gestures by the right and left hands. McNeill and Pedelty (1995) noted for the split-brain patient N.G. that her iconic right hand gestures were exclusively displayed in the right personal space. The present study investigates systematically if there is indication for neglect of the left personal space in right hand gestures in split-brain patients.

Abstract

The present study investigates hemispheric specialisation in the use of space in communicative gestures. For this purpose, we investigate split-brain patients in whom spontaneous and distinct right hand gestures can only be controlled by the left hemisphere and vice versa, the left hand only by the right hemisphere. On this anatomical basis, we can infer hemispheric specialisation from the performances of the right and left hands. In contrast to left hand dyspraxia in tasks that require language processing, split-brain patients utilise their left hands in a meaningful way in visuo-constructive tasks such as copying drawings or block-design. Therefore, we conjecture that split-brain patients are capable of using their left hands for the communication of the content of visuo-spatial animations via gestural demonstration. On this basis, we further examine the use of space in communicative gestures by the right and left hands. McNeill and Pedelty (1995) noted for the split-brain patient N.G. that her iconic right hand gestures were exclusively displayed in the right personal space. The present study investigates systematically if there is indication for neglect of the left personal space in right hand gestures in split-brain patients.

Abstract

The temporal dynamics of processing morphologically complex words was investigated by recording event-related brain potentials (ERPs) when native Finnish-speakers performed a visual lexical decision task. Behaviorally, there is evidence that recognition of inflected nouns elicits a processing cost (i.e., longer reaction times and higher error rates) in comparison to matched monomorphemic words. We aimed to reveal whether the processing cost stems from decomposition at the early visual word form level or from recomposition at the later semantic–syntactic level. The ERPs showed no early effects for morphology, but revealed an interaction with word frequency at a late N400-type component, as well as a late positive component that was larger for inflected words. These results suggest that the processing cost stems mainly from the semantic–syntactic level. We also studied the features of the morphological decomposition route by investigating the recognition of pseudowords carrying real morphemes. The results showed no differences between inflected vs. uninflected pseudowords with a false stem, but differences in relation to those with a real stem, suggesting that a recognizable stem is needed to initiate the decomposition route.

Abstract

This commentary on Alario et al. (2002) addresses two issues: (1) Different from what the authors suggest, there are no theories of production claiming the phonological word to be the upper bound of advance planning before the onset of articulation; (2) Their picture naming study of word frequency effects on speech onset is inconclusive by lack of a crucial control, viz., of object recognition latency. This is a perennial problem in picture naming studies of word frequency and age of acquisition effects

Abstract

In this article, we present an account of developmental data regarding the acquisition of syllable types. The data come from a longitudinal corpus of phonetically transcribed speech of 12 children acquiring Dutch as their first language. A developmental order of acquisition of syllable types was deduced by aligning the syllabified data on a Guttman scale. This order could be analyzed as following from an initial ranking and subsequent rerankings in the grammar of the structural constraints ONSET, NO-CODA, *COMPLEX-O, and *COMPLEX-C; some local conjunctions of these constraints; and a faithfulness constraint FAITH. The syllable type frequencies in the speech surrounding the language learner are also considered. An interesting correlation is found between the frequencies and the order of development of the different syllable types.

Abstract

The present paper studies how, in deictic expressions, the temporal interdependency of speech and gesture is realized in the course of motor planning and execution. Two theoretical positions were compared. On the “interactive” view the temporal parameters of speech and gesture are claimed to be the result of feedback between the two systems throughout the phases of motor planning and execution. The alternative “ballistic” view, however, predicts that the two systems are independent during the phase of motor execution, the temporal parameters having been preestablished in the planning phase. In four experiments subjects were requested to indicate which of an array of referent lights was momentarily illuminated. This was done by pointing to the light and/or by using a deictic expression (this/that light). The temporal and spatial course of the pointing movement was automatically registered by means of a Selspot opto-electronic system. By analyzing the moments of gesture initiation and apex, and relating them to the moments of speech onset, it was possible to show that, for deictic expressions, the ballistic view is very nearly correct.

Abstract

It is quite normal for us to produce one or two million word tokens every year. Speaking is a dear occupation and producing words is at the core of it. Still, producing even a single word is a highly complex affair. Recently, Levelt, Roelofs, and Meyer (1999) reviewed their theory of lexical access in speech production, which dissects the word-producing mechanism as a staged application of various dedicated operations. The present paper begins by presenting a bird eye's view of this mechanism. We then square the complexity by asking how speakers control multiple access in generating simple utterances such as a table and a chair. In particular, we address two issues. The first one concerns dependency: Do temporally contiguous access procedures interact in any way, or do they run in modular fashion? The second issue concerns temporal alignment: How much temporal overlap of processing does the system tolerate in accessing multiple content words, such as table and chair? Results from picture-word interference and eye tracking experiments provide evidence for restricted cases of dependency as well as for constraints on the temporal alignment of access procedures.

Abstract

Li and Gleitman (Turning the tables: language and spatial reasoning. Cognition, in press) seek to undermine a large-scale cross-cultural comparison of spatial language and cognition which claims to have demonstrated that language and conceptual coding in the spatial domain covary (see, for example, Space in language and cognition: explorations in linguistic diversity. Cambridge: Cambridge University Press, in press; Language 74 (1998) 557): the most plausible interpretation is that different languages induce distinct conceptual codings. Arguing against this, Li and Gleitman attempt to show that in an American student population they can obtain any of the relevant conceptual codings just by varying spatial cues, holding language constant. They then argue that our findings are better interpreted in terms of ecologically-induced distinct cognitive styles reflected in language. Linguistic coding, they argue, has no causal effects on non-linguistic thinking – it simply reflects antecedently existing conceptual distinctions. We here show that Li and Gleitman did not make a crucial distinction between frames of spatial reference relevant to our line of research. We report a series of experiments designed to show that they have, as a consequence, misinterpreted the results of their own experiments, which are in fact in line with our hypothesis. Their attempts to reinterpret the large cross-cultural study, and to enlist support from animal and infant studies, fail for the same reasons. We further try to discern exactly what theory drives their presumption that language can have no cognitive efficacy, and conclude that their position is undermined by a wide range of considerations.