Publications

Abstract

Mutations of the epidermal growth factor receptor (EGFR) gene are found at a relatively high frequency in glioma, with the most common being the de2-7 EGFR (or EGFRvIII). This mutation arises from an in-frame deletion of exons 2–7, which removes 267 amino acids from the extracellular domain of the receptor. Despite being unable to bind ligand, the de2-7 EGFR is constitutively active at a low level. Transfection of human glioma cells with the de2-7 EGFR has little effect in vitro, but when grown as tumor xenografts this mutated receptor imparts a dramatic growth advantage. We have now mapped the phosphorylation pattern of de2-7 EGFR, both in vivo and in vitro, using a panel of antibodies unique to the different phosphorylated tyrosine residues. Phosphorylation of de2-7 EGFR was detected constitutively at all tyrosine sites surveyed both in vitro and in vivo, including tyrosine 845, a known target in the wild-type EGFR for src kinase. There was a substantial upregulation of phosphorylation at every tyrosine residue of the de2-7 EGFR when cells were grown in vivo compared to the receptor isolated from cells cultured in vitro. Upregulation of phosphorylation could be mimicked in vitro by the addition of specifi c components of the ECM such as collagen via an integrin-dependent mechanism. Since this increase in in vivo phosphorylation enhances de2-7 EGFR signaling, this observation explains why the growth enhancement mediated by de2-7 EGFR is largely restricted to the in vivo environment. In a second set of experiments we analyzed the interaction between EGFRvIII and ErbB2. Co-expression of these proteins in NR6 cells, a mouse fi broblast line devoid of ErbB family members, dramatically enhanced in vivo tumorigenicity of these cells compared to cells expressing either protein alone. Detailed analysis of these xenografts demonstrated that EGFRvIII could heterodimerize and transphosphorylate the ErbB2. Since both EGFRvIII and ErbB2 are commonly expressed at gliomas, this data suggests that the co-expression of these two proteins may enhance glioma tumorigenicity.

Abstract

Retaining detailed representations of unstressed syllables is a logical prerequisite for infants' use of probabilistic phonotactics to segment iambic words from fluent speech. The head-turn preference study was used to investigate the nature of English- learners' representations of iambic word onsets. Fifty-four 10.5-month-olds were familiarized to passages containing the nonsense iambic word forms ginome and tupong. Following familiarization, infants were either tested on familiar (ginome and tupong) or near-familiar (pinome and bupong) versus unfamiliar (kidar and mafoos) words. Infants in the familiar test group (familiar vs. unfamiliar) oriented significantly longer to familiar than unfamiliar test items, whereas infants in the near-familiar test group (near-familiar vs. unfamiliar) oriented equally long to near-familiar and unfamiliar test items. Our results provide evidence that infants retain fairly detailed representations of unstressed syllables and therefore support the hypothesis that infants use phonotactic cues to find words in fluent speech.

Abstract

It is an important feature of the human sentence production system that semantic and syntactic processes may overlap in time and do not proceed strictly serially. That is, the process of building the syntactic form of an utterance does not always wait until the complete semantic content for that utterance has been decided upon. On the contrary, speakers will often start pronouncing the first words of a sentence while still working on further details of its semantic content. An important advantage is memory economy. Semantic and syntactic fragments do not have to occupy working memory until complete semantic and syntactic structures for an utterance have been computed. Instead, each semantic and syntactic fragment is processed as soon as possible and is kept in working memory for a minimum period of time. This raises the question of how the sentence production system can maintain syntactic coherence across syntactic fragments. Presumably there are processes of "syntactic bookkeeping" which (1) store in working memory those syntactic properties of a fragmentary sentence which are needed to eliminate ungrammatical continuations, and (2) check whether a prospective continuation is indeed compatible with the sentence constructed so far. In reaction time experiments where subjects described, under time pressure, simple static pictures of an action performed by an actor, the second aspect of syntactic bookkeeping could be demonstrated. This evidence is used for modelling bookkeeping processes as part of a computational sentence generator which aims at simulating the syntactic operations people carry out during spontaneous speech.

Abstract

When you compare the behavior of two different age groups which are trying to master the same sensori-motor or cognitive skill, you are likely to discover varying learning routes: different stages, different intervals between stages, or even different orderings of stages. Such heterogeneous learning trajectories may be caused by at least six different types of factors: (1) Initial state: the kinds and levels of skills the learners have available at the onset of the learning episode. (2) Learning mechanisms: rule-based, inductive, connectionist, parameter setting, and so on. (3) Input and feedback characteristics: learning stimuli, information about success and failure. (4) Information processing mechanisms: capacity limitations, attentional biases, response preferences. (5) Energetic variables: motivation, emotional reactions. (6) Final state: the fine-structure of kinds and levels of subskills at the end of the learning episode. This applies to language acquisition as well. First and second language learners probably differ on all six factors. Nevertheless, the debate between advocates and opponents of the Fundamental Difference Hypothesis concerning L1 and L2 acquisition have looked almost exclusively at the first two factors. Those who believe that L1 learners have access to Universal Grammar whereas L2 learners rely on language processing strategies, postulate different learning mechanisms (UG parameter setting in L1, more general inductive strategies in L2 learning). Pienemann opposes this view and, based on his Processability Theory, argues that L1 and L2 learners start out from different initial states: they come to the grammar learning task with different structural hypotheses (SOV versus SVO as basic word order of German).

Abstract

Remarques sur les facteurs intervenant dans le processus de formulation des énoncés.

Abstract

The psychology of language as developed by Wilhelm Wundt in his fundamental work Die Sprache (1900) has a strongly mentalistic character. The dominating positions held by behaviorism in psychology and structuralism in linguistics have overruled Wundt’s language theory to the effect that it has remained relatively unknown. This situation has changed recently under the influence of transformational linguistics and cognitive psychology. The paper discusses how Wundt applied the basic psychological concepts of apperception and association to language behavior, in particular to the construction and production of sentences during unprepared speech. The final part of the paper is devoted to the work, published in 1917, of the Dutch linguistic scholar Jacques van Ginneken, who elaborated Wundt’s ideas towards an explanation of some syntactic phenomena during the language acquisition of children.

Abstract

A series of experiments is reported in which subjects describe simple visual scenes by means of both sentential and non-sentential responses. The data support the following statements about the lexicalization (word finding) process. (1) Words used by speakers in overt naming or sentence production responses are selected by a sequence of two lexical retrieval processes, the first yielding abstract pre-phonological items (Ll -items), the second one adding their phonological shapes (L2-items). (2) The selection of several Ll-items for a multi-word utterance can take place simultaneously. (3) A monitoring process is watching the output of Ll-lexicalization to check if it is in keeping with prevailing constraints upon utterance format. (4) Retrieval of the L2-item which corresponds with a given LI-item waits until the Ld-item has been checked by the monitor, and all other Ll-items needed for the utterance under construction have become available. A coherent picture of the lexicalization process begins to emerge when these characteristics are brought together with other empirical results in the area of naming and sentence production, e.g., picture naming reaction times (Seymour, 1979), speech errors (Garrett, 1980), and word order preferences (Bock, 1982).

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

Previous work has shown that Dutch listeners use prosodic information in the speech signal to optimise morphological processing: Listeners are sensitive to prosodic differences between a noun stem realised in isolation and a noun stem realised as part of a plural form (in which the stem is followed by an unstressed syllable). The present study, employing a lexical decision task, provides an additional demonstration of listeners' sensitivity to prosodic cues in the stem. This sensitivity is shown for two languages that differ in morphological productivity: Dutch and English. The degree of morphological productivity does not correlate with listeners' sensitivity to prosodic cues in the stem, but it is reflected in differential sensitivities to the word-specific log odds ratio of encountering an unshortened stem (i.e., a stem in isolation) versus encountering a shortened stem (i.e., a stem followed by a suffix consisting of one or more unstressed syllables). In addition to being sensitive to the prosodic cues themselves, listeners are also sensitive to the probabilities of occurrence of these prosodic cues.

Abstract

It has recently been shown that listeners use systematic differences in vowel length and intonation to resolve ambiguities between onset-matched simple words (Davis, Marslen-Wilson, & Gaskell, 2002; Salverda, Dahan, & McQueen, 2003). The present study shows that listeners also use prosodic information in the speech signal to optimize morphological processing. The precise acoustic realization of the stem provides crucial information to the listener about the morphological context in which the stem appears and attenuates the competition between stored inflectional variants. We argue that listeners are able to make use of prosodic information, even though the speech signal is highly variable within and between speakers, by virtue of the relative invariance of the duration of the onset. This provides listeners with a baseline against which the durational cues in a vowel and a coda can be evaluated. Furthermore, our experiments provide evidence for item-specific prosodic effects.

Abstract

In Dutch, high-frequency words with the suffix -lijk are often highly reduced in spontaneous unscripted speech. This study addressed socio-geographic variation in the reduction of such words against the backdrop of the variation in their use in written and spoken Dutch. Multivariate analyses of the frequencies with which the words were used in a factorially contrasted set of subcorpora revealed signi ficant variation involving the speaker's country, sex, and education level for spoken Dutch, and involving country and register for written Dutch. Acoustic analyses revealed that Dutch men reduced most often, while Flemish highly educated women reduced least. Two linguistic context effects emerged, one prosodic, and the other pertaining to the flow of information. Words in sentence final position showed less reduction, while words that were better predictable from the preceding word in the sentence(based on mutual information) tended to be reduced more often. The increased probability of reduction for forms that are more predictable in context, combined with the loss of the suffix in the more extremely reduced forms, suggests that highfrequency words in -lijk are undergoing a process of erosion that causes them to gravitate towards monomorphemic function words.

Abstract

This paper reports on an investigation of children's (aged 3;5–9;8) comprehension of sentences containing ambiguity of prepositional phrase (PP) attachment. Results from a picture selection study (N=90) showed that children use verb semantics and preposition type to resolve the ambiguity, with older children also showing sensitivity to the definiteness of the object NP as a cue to interpretation. Study 2 investigated three- and five-year-old children's (N=47) ability to override an instrumental interpretation of ambiguous PPs in order to process attributes of the referential scene. The results showed that while five-year-olds are capable of incorporating aspects of the referential scene into their interpretations, three-year-olds are not as successful. Overall, the results suggest that children are attuned very early to the lexico-semantic co-occurrences that have been shown to aid ambiguity resolution in adults, but that more diffuse cues to interpretation are used only later in development

Abstract

The previous literature has suggested that the hand movement in co-speech gestures and signs consists of a series of phases with qualitatively different dynamic characteristics. In this paper, we propose a syntagmatic rule system for movement phases that applies to both co-speech gestures and signs. Descriptive criteria for the rule system were developed for the analysis video-recorded continuous production of signs and gesture. It involves segmenting a stream of body movement into phases and identifying different phase types. Two human coders used the criteria to analyze signs and cospeech gestures that are produced in natural discourse. It was found that the criteria yielded good inter-coder reliability. These criteria can be used for the technology of automatic recognition of signs and co-speech gestures in order to segment continuous production and identify the potentially meaningbearing phase.

Abstract

Gesture is an integral part of face-to-face communication, and provides a rich area for cross-cultural comparison. “Locally-anchored spatial gestures” are gestures that are roughly oriented to the actual geographical direction of referents. For example, such gestures may point to a location or a thing, trace the shape of a path, or indicate the direction of a particular area. The goal of this task is to elicit locally-anchored spatial gestures across different cultures. The task follows an interview format, where one participant prompts another to talk in detail about a specific area that the main speaker knows well. The data can be used for additional purposes such as the investigation of demonstratives.

Abstract

During the last 25 years, second language acquisition (SLA) research hasmade considerable progress, but is still far from proving a solid basis for foreign language teaching, or from a general theory of SLA. In addition, its status within the linguistic disciplines is still very low. I argue this has not much to do with low empirical or theoretical standards in the field—in this regard, SLA research is fully competitive—but with a particular perspective on the acquisition process: SLA researches learners' utterances as deviations from a certain target, instead of genuine manifestations of underlying language capacity; it analyses them in terms of what they are not rather than what they are. For some purposes such a "target deviation perspective" makes sense, but it will not help SLA researchers to substantially and independently contribute to a deeper understanding of the structure and function of the human language faculty. Therefore, these findings will remain of limited interest to other scientists until SLA researchers consider learner varieties a normal, in fact typical, manifestation of this unique human capacity.

Abstract

Children begin to talk at about age one. The vocabulary they need to do so must be built on perceptual evidence and, indeed, infants begin to recognize spoken words long before they talk. Most of the utterances infants hear, however, are continuous, without pauses between words, so constructing a vocabulary requires them to decompose continuous speech in order to extract the individual words. Here, we present electrophysiological evidence that 10-month-old infants recognize two-syllable words they have previously heard only in isolation when these words are presented anew in continuous speech. Moreover, they only need roughly the first syllable of the word to begin doing this. Thus, prelinguistic infants command a highly efficient procedure for segmentation and recognition of spoken words in the absence of an existing vocabulary, allowing them to tackle effectively the problem of bootstrapping a lexicon out of the highly variable, continuous speech signals in their environment.

Abstract

In various applications of forensic phonetics the question arises as to how far aural-perceptual speaker recognition performance is reliable. Therefore, it is necessary to examine the relationship between speaker recognition results and human perception/production abilities like musicality or speech sensitivity. In this study, performance in a speaker recognition experiment and a speech sensitivity test are correlated. The results show a moderately significant positive correlation between the two tasks. Generally, performance in the speaker recognition task was better than in the speech sensitivity test. Professionals in speech and singing yielded a more homogeneous correlation than non-experts. Training in speech as well as choir-singing seems to have a positive effect on performance in speaker recognition. It may be concluded, firstly, that in cases where the reliability of voice line-up results or the credibility of a testimony have to be considered, the speech sensitivity test could be a useful indicator. Secondly, the speech sensitivity test might be integrated into the canon of possible procedures for the accreditation of forensic phoneticians. Both tests may also be used in combination.

Abstract

Individuals affected with developmental disorders of speech and language have substantial difficulty acquiring expressive and/or receptive language in the absence of any profound sensory or neurological impairment and despite adequate intelligence and opportunity. Although studies of twins consistently indicate that a significant genetic component is involved, most families segregating speech and language deficits show complex patterns of inheritance, and a gene that predisposes individuals to such disorders has not been identified. We have studied a unique three-generation pedigree, KE, in which a severe speech and language disorder is transmitted as an autosomal-dominant monogenic trait. Our previous work mapped the locus responsible, SPCH1, to a 5.6-cM interval of region 7q31 on chromosome 7 (ref. 5). We also identified an unrelated individual, CS, in whom speech and language impairment is associated with a chromosomal translocation involving the SPCH1 interval. Here we show that the gene FOXP2, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, is directly disrupted by the translocation breakpoint in CS. In addition, we identify a point mutation in affected members of the KE family that alters an invariant amino-acid residue in the forkhead domain. Our findings suggest that FOXP2 is involved in the developmental process that culminates in speech and language

Abstract

This paper examines the language-specific aspect of the TIME PASSING IS MOTION metaphor and suggests that the temporal construal of time can be influenced by a person's second language. Ahrens and Huang (2002) have analyzed the source domain of MOTION for the TIME metaphor into two special cases. In the special case one, TIME PASSING is an object that moves towards an ego. For example, qimuokao kuai dao le "the final exam is approaching." In the special case two, TIME PASSING is a point (that a plural ego is attached to) that moves across a landscape. For example, women kuai dao qimuokao le "we are approaching the final exam." In addition, in English, the ego in the special case one faces the future while in Chinese, the ego faces the past. The current experiment hypothesizes that English influences the choice of the orientation of the ego in native Chinese speakers who speak English as the second language. 54 subjects are asked to switch the clock time one hour forward. Results show that native Chinese speakers living in the Chinese speaking country tend to move the clock one hour forward to the past (92%) while native Chinese speakers living in an English speaking country are less likely to do so (60%). This implies that the experience of English influences the conceptualization of time in Mandarin Chinese.

Abstract

The chronic fatigue syndrome (CFS) is a disabling disorder of unknown etiology. The symptomatology of CFS (central fatigue, impaired concentration, attention and memory) suggests that this disorder could be related to alterations at the level of the central nervous system. In this study, we have used an automated and unbiased morphometric technique to test whether CFS patients display structural cerebral abnormalities. We mapped structural cerebral morphology and volume in two cohorts of CFS patients (in total 28 patients) and healthy controls (in total 28 controls) from high-resolution structural magnetic resonance images, using voxel-based morphometry. Additionally, we recorded physical activity levels to explore the relation between severity of CFS symptoms and cerebral abnormalities. We observed significant reductions in global gray matter volume in both cohorts of CFS patients, as compared to matched control participants. Moreover, the decline in gray matter volume was linked to the reduction in physical activity, a core aspect of CFS. These findings suggest that the central nervous system plays a key role in the pathophysiology of CFS and point to a new objective and quantitative tool for clinical diagnosis of this disabling disorder.

Abstract

We have used implicit motor imagery to investigate the neural correlates of motor planning independently from actual movements. Subjects were presented with drawings of left or right hands and asked to judge the hand laterality, regardless of the stimulus rotation from its upright orientation. We paired this task with a visual imagery control task, in which subjects were presented with typographical characters and asked to report whether they saw a canonical letter or its mirror image, regardless of its rotation. We measured neurovascular activity with fast event-related fMRI, distinguishing responses parametrically related to motor imagery from responses evoked by visual imagery and other task-related phenomena. By quantifying behavioral and neurovascular correlates of imagery on a trial-by-trial basis, we could discriminate between stimulusrelated, mental rotation-related, and response-related neural activity. We found that specific portions of the posterior parietal and precentral cortex increased their activity as a function of mental rotation only during the motor imagery task. Within these regions, the parietal cortex was visually responsive, whereas the dorsal precentral cortex was not. Response- but not rotation-related activity was found around the left central sulcus (putative primary motor cortex) during both imagery tasks. Our study provides novel evidence on the topography and content of movement representations in the human brain. During intended action, the posterior parietal cortex combines somatosensory and visuomotor information, whereas the dorsal premotor cortex generates the actual motor plan, and the primary motor cortex deals with movement execution. We discuss the relevance of these results in the context of current models of action planning.

Abstract

This paper presents a new approach to functional magnetic resonance imaging (FMRI) data analysis. The main difference lies in the view of what comprises an observation. Here we treat the data from one scanning session (comprising t volumes, say) as one observation. This is contrary to the conventional way of looking at the data where each session is treated as t different observations. Thus instead of viewing the v voxels comprising the 3D volume of the brain as the variables, we suggest the usage of the vt hypervoxels comprising the 4D volume of the brain-over-session as the variables. A linear model is fitted to the 4D volumes originating from different sessions. Parameter estimation and hypothesis testing in this model can be performed with standard techniques. The hypothesis testing generates 4D statistical images (SIs) to which any relevant test statistic can be applied. In this paper we describe two test statistics, one voxel based and one cluster based, that can be used to test a range of hypotheses. There are several benefits in treating the data from each session as one observation, two of which are: (i) the temporal characteristics of the signal can be investigated without an explicit model for the blood oxygenation level dependent (BOLD) contrast response function, and (ii) the observations (sessions) can be assumed to be independent and hence inference on the 4D SI can be made by nonparametric or Monte Carlo methods. The suggested 4D approach is applied to FMRI data and is shown to accurately detect the expected signal

Abstract

The purpose of this study was to relate a psycholinguistic processing model of picture naming to the dynamics of cortical activation during picture naming. The activation was recorded from eight Dutch subjects with a whole-head neuromagnetometer. The processing model, based on extensive naming latency studies, is a stage model. In preparing a picture's name, the speaker performs a chain of specific operations. They are, in this order, computing the visual percept, activating an appropriate lexical concept, selecting the target word from the mental lexicon, phonological encoding, phonetic encoding, and initiation of articulation. The time windows for each of these operations are reasonably well known and could be related to the peak activity of dipole sources in the individual magnetic response patterns. The analyses showed a clear progression over these time windows from early occipital activation, via parietal and temporal to frontal activation. The major specific findings were that (1) a region in the left posterior temporal lobe, agreeing with the location of Wernicke's area, showed prominent activation starting about 200 msec after picture onset and peaking at about 350 msec, (i.e., within the stage of phonological encoding), and (2) a consistent activation was found in the right parietal cortex, peaking at about 230 msec after picture onset, thus preceding and partly overlapping with the left temporal response. An interpretation in terms of the management of visual attention is proposed.