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 mapped the phosphorylation pattern of de2-7 EGFR, both in vivo and in vitro, using a panel of antibodies specific for different phosphorylated tyrosine residues. Phosphorylation of de2-7 EGFR was detected constitutively at all tyrosine sites surveyed 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 yrosine 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 at tyrosine 845 could be stimulated in vitro by the addition of specific components of the ECM via an integrindependent mechanism. These observations may partially explain why the growth enhancement mediated by de2-7 EGFR is largely restricted to the in vivo environment

Abstract

In early Dutch learner varieties, there is no evidence of finiteness being a functional category. There is no V2nd: no correlation between inflectional morphology and movement. Initially, learners express the illocutive function of finiteness through the use of illocutive markers, with the non-use of an illocutive marker expressing the default illocutive function of assertion. Illocutive markers are functioning as adjuncts with scope over the predicate. Illocutive markers become re-analysed as functional elements.The driving force is the acquisition of the auxiliary verbs that occur with past participles. It leads to a reanalysis of illocutive markers as two separate elements: an auxiliary verb and a scope adverb. The (modal) auxiliary carries illocutive function. Lexical verb-argument structure (including the external argument) occurs within the domain of the auxiliary verb. The predicate as the focus constituent occurs within the domain of a scope adverb. This reanalysis establishes a position for the external argument within the domain of AUX. The acquisition of AUX causes the acquisition of a (hierarchical) structure with a complement as a constituent which represents an underlying verb-argument structure, a predicate as the domain of elements that are in focus, and an external (specifier) position as a landing site for elements with topic function.

Abstract

We outline an algorithm capable of generating varied but natural sounding sequences of argument NPs in subordinate clauses of German, a semi-free word order language. In order to attain the right level of output flexibility, the algorithm considers (1) the relevant lexical properties of the head verb (not only transitivity type but also reflexivity, thematic relations expressed by the NPs, etc.), and (2) the animacy and definiteness values of the arguments, and their length. The relevant statistical data were extracted from the NEGRA–II treebank and from hand-coded features for animacy and definiteness. The algorithm maps the relevant properties onto “primary” versus “secondary” placement options in the generator. The algorithm is restricted in that it does not take into account linear order determinants related to the sentence’s information structure and its discourse context (e.g. contrastiveness). These factors may modulate the above preferences or license “tertiary” linear orders beyond the primary and secondary options considered here.

Abstract

Human speakers often produce sentences incrementally. They can start speaking having in mind only a fragmentary idea of what they want to say, and while saying this they refine the contents underlying subsequent parts of the utterance. This capability imposes a number of constraints on the design of a syntactic processor. This paper explores these constraints and evaluates some recent computational sentence generators from the perspective of incremental production.

Abstract

Listeners cannot recognize highly reduced word forms in isolation, but they can do so when these forms are presented in context (Ernestus, Baayen, & Schreuder, 2002). This suggests that not all possible surface forms of words have equal status in the mental lexicon. The present study shows that the reduced forms are linked to the canonical representations in the mental lexicon, and that these latter representations induce reconstruction processes. Listeners restore suffixes that are partly or completely missing in reduced word forms. A series of phoneme-monitoring experiments reveals the nature of this restoration: the basis for suffix restoration is mainly phonological in nature, but orthography has an influence as well.

Abstract

This dissertation investigates two seemingly contradictory properties of the speech perception system. On the one hand, listeners are extremely sensitive to the fine phonetic details in the speech signal. These subtle acoustic cues can reduce the temporal ambiguity between words that show initial segmental overlap, and can guide lexical activation. On the other hand, comprehension does not seem to be hampered at all by the drastic reductions that typically occur in casual speech. Complete segments, and sometimes even complete syllables, may be missing, but comprehension is seemingly unaffected. This thesis aims at elucidating how words are represented and accessed in the mental lexicon, by investigating these contradictory phenomena for the domain of morphology

Abstract

Drozd's critique of Crain & Thornton's (C&T) (1998) book Investigations in Universal Grammar (IUG) raises many issues concerning theory and experimental design within generative approaches to language acquisition. I focus here on one of the strongest theoretical claims of the Modularity Matching Model (MMM): continuity of processing. For reasons different to Drozd, I argue that the assumption is tenuous. Furthermore, I argue that the focus of the MMM and the methodological prescriptions contained in IUG are too narrow to capture language acquisition.

Abstract

Pauses during continuous speech, particularly those that occur within clauses, are thought to reflect the planning of forthcoming verbal output. We used functional Magnetic Resonance Imaging (fMRI) to examine their neural correlates. Six volunteers were scanned while describing seven Rorschach inkblots, producing 3 min of speech per inkblot. In an event-related design, the level of blood oxygenation level dependent (BOLD) contrast during brief speech pauses (mean duration 1.3 s, SD 0.3 s) during overt speech was contrasted with that during intervening periods of articulation. We then examined activity associated with pauses that occurred within clauses and pauses that occurred between grammatical junctions. Relative to articulation during speech, pauses were associated with activation in the banks of the left superior temporal sulcus (BA 39/22), at the temporoparietal junction. Continuous speech was associated with greater activation bilaterally in the inferior frontal (BA 44/45), middle frontal (BA 8) and anterior cingulate (BA 24) gyri, the middle temporal sulcus (BA 21/22), the occipital cortex and the cerebellum. Left temporal activation was evident during pauses that occurred within clauses but not during pauses at grammatical junctions. In summary, articulation during continuous speech involved frontal, temporal and cerebellar areas, while pausing was associated with activity in the left temporal cortex, especially when this occurred within a clause. The latter finding is consistent with evidence that within-clause pauses are a correlate of speech planning and in particular lexical retrieval.

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

In the first, critical part of this study, a small sample of simple German sentences with their empirically determined pitch contours is used to demonstrate the incorrectness of numerous currently hold views of German sentence intonation. In the second, more constructive part, several interrogative sentence types are analysed and an attempt is made to show that intonation, besides other functions, indicates the permantently changing 'thematic score' in on-going discourse as well as certain validity claims.

Abstract

This study addresses the supralexical inferential processes underlying wellformedness judgements and latencies for a specic sublexical unit that appears in Dutch compounds, the interfix. Production studies have shown that the selection of interfixes in novel Dutch compounds and the speed of
this selection is primarily determined by the distribution of interfixes in existing compounds that share the left constituent with the target compound, i.e. the ‘‘left constituent family’’. In this paper, we consider the question whether constituent families also affect wellformedness decisions of novel as well as existing Dutch compounds in comprehension. We visually presented compounds containing interfixes that were either in line with the bias of the left constituent family or not. In the case of existing compounds, we also presented variants with replaced interfixes. As in production, the bias of the left constituent family emerged as a crucial predictor for both acceptance rates and response latencies. This result supports the hypothesis that, as in production, constituent families are (co-)activated in comprehension. We argue that this co-activation is part of a supralexical inferential process, and we discuss how our data might be interpreted within sublexical and supralexical theories of morphological processing.

Abstract

This study addresses the possibility that interfixes in multiconstituent nominal compounds in German and Dutch are functional as markers of immediate constituent structure.We report a lexical statistical survey of interfixation in the lexicons of German and Dutch which shows that all interfixes of German and one interfix of Dutch are significantly more likely to appear at the major constituent boundary than expected under chance conditions. A series of experiments provides evidence that speakers of German and Dutch are sensitive to the probabilistic cues to constituent structure provided by the interfixes. Thus, our data provide evidence that probability is part and parcel of grammatical competence.

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

Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS. We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups. Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error. Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.

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

How can one conceive of the neuronal implementation of the processing model we proposed in our target article? In his commentary (Pulvermüller 1999, reprinted here in this issue), Pulvermüller makes various proposals concerning the underlying neural mechanisms and their potential localizations in the brain. These proposals demonstrate the compatibility of our processing model and current neuroscience. We add further evidence on details of localization based on a recent meta-analysis of neuroimaging studies of word production (Indefrey & Levelt 2000). We also express some minor disagreements with respect to Pulvermüller’s interpretation of the “lemma” notion, and concerning his neural modeling of phonological code retrieval. Branigan & Pickering discuss important aspects of syntactic encoding, which was not the topic of the target article. We discuss their well-taken proposal that multiple syntactic frames for a single verb lemma are represented as independent nodes, which can be shared with other verbs, such as accounting for syntactic priming in speech production. We also discuss how, in principle, the alternative multiple-frame-multiplelemma account can be tested empirically. The available evidence does not seem to support that account.

Abstract

During the second half of the 19th century, the psychology of language was invented as a discipline for the sole purpose of explaining the evolution of spoken language. These efforts culminated in Wilhelm Wundt’s monumental Die Sprache of 1900, which outlined the psychological mechanisms involved in producing utterances and considered how these mechanisms could have evolved. Wundt assumes that articulatory movements were originally rather arbitrary concomitants of larger, meaningful expressive bodily gestures. The sounds such articulations happened to produce slowly acquired the meaning of the gesture as a whole, ultimately making the gesture superfluous. Over a century later, gestural theories of language origins still abound. I argue that such theories are unlikely and wasteful, given the biological, neurological and genetic evidence.

Abstract

Linguistic skills are primarily tuned to the proper conduct of conversation. The innate ability to converse has provided species with a capacity to share moods, attitudes, and information of almost any kind, to assemble knowledge and skills, to plan coordinated action, to educate its offspring, in short, to create and transmit culture. In conversation the interlocutors are involved in negotiating meaning. Speaking is most complex cognitive-motor skill. It involves the conception of an intention, the selection of information whose expression will make that intention recognizable, the selection of appropriate words, the construction of a syntactic framework, the retrieval of the words’ sound forms, and the computation of an articulatory plan for each word and for the utterance as a whole. The question where communicative intentions come from is a psychodynamic question rather than a psycholinguistic one. Speaking is a form of social action, and it is in the context of action that intentions, goals, and subgoals develop.

Abstract

The first, theoretical part of this paper sketches a framework for phonological encoding in which the speaker successively generates phonological syllables in connected speech. The final stage of this process, phonetic encoding, consists of accessing articulatory gestural scores for each of these syllables in a "mental syllabary". The second, experimental part studies various predictions derived from this theory. The main finding is a syllable frequency effect: words ending in a high-frequent syllable are named faster than words ending in a low-frequent syllable. As predicted, this syllable frequency effect is independent of and additive to the effect of word frequency on naming latency. The effect, moreover, is not due to the complexity of the word-final syllable. In the General Discussion, the syllabary model is further elaborated with respect to phonological underspecification and activation spreading. Alternative accounts of the empirical findings in terms of core syllables and demisyllables are considered.