Publications

Abstract

The murine homologue of the human chloride channel gene, CLCN5, defects in which are responsible for Dent disease, has been cloned and characterized. We isolated the entire coding region of mouse Clcn5 cDNA and approximately 45 kb of genomic sequence embracing the gene. To study its transcriptional control, the 5' upstream sequences of the mouse Clcn5 gene were cloned into a luciferase reporter vector. Deletion analysis of 1.5 kb of the 5' flanking sequence defined an active promoter region within 128 bp of the putative transcription start site, which is associated with a TATA motif but lacks a CAAT consensus. Within this sequence, there is a motif with homology to a purine-rich sequence responsible for the kidney-specific promoter activity of the rat CLC-K1 gene, another member of the chloride-channel gene family expressed in kidney. An enhancer element that confers a 10- to 20-fold increase in the promoter activity of the mouse Clcn5 gene was found within the first intron. The organization of the human CLCN5 and mouse Clcn5 gene structures is highly conserved, and the sequence of the murine protein is 98% similar to that of human, with its highest expression seen in the kidney. This study thus provides the first identification of the transcriptional control region of, and the basis for an understanding of the regulatory mechanism that controls, this kidney-specific, chloride-channel gene.

Abstract

The medial temporal lobe (MTL) is crucial for declarative memory formation, but the function of its subcomponents in associative memory formation remains controversial. Most functional imaging studies on this topic are based on a stepwise approach comparing a condition with and one without associative encoding. Extending this approach we applied additionally a parametric analysis by varying the amount of associative memory formation. We found a hippocampal subsequent memory effect of almost similar magnitude regardless of the amount of associations formed. By contrast, subsequent memory effects in rhinal and parahippocampal cortices were parametrically and positively modulated by the amount of associations formed. Our results indicate that the parahippocampal region supports associative memory formation as tested here and the hippocampus adds a general mnemonic operation. This pattern of results might suggest a new interpretation. Instead of having either a fixed division of labor between the hippocampus (associative memory formation) and the rhinal cortex (non-associative memory formation) or a functionally unitary MTL system, in which all substructures are contributing to memory formation in a similar way, we propose that the location where associations are formed within the MTL depends on the kind of associations bound: If visual single-dimension associations, as used here, can already be integrated within the parahippocampal region, the hippocampus might add a general purpose mnemonic operation only. In contrast, if associations have to be formed across widely distributed neocortical representations, the hippocampus may provide a binding operation in order to establish a coherent memory.

Abstract

This paper presents electrophysiological data on the on-line processing of open- and closed-class words in patients with Broca’s aphasia with agrammatic comprehension. Event-related brain potentials were recorded from the scalp when Broca patients and nonaphasic control subjects were visually presented with a story in which the words appeared one at a time on the screen. Separate waveforms were computed for open- and closed-class words. The non-aphasic control subjects showed clear differences between the processing of open- and closed-class words in an early (210-375 ms) and a late (400-700 ms) time-window.The early electrophysiological differences reflect the first manifestation of the availability of word-category information from the mental lexicon. The late differences presumably relate to post-lexical semantic and syntactic processing. In contrast to the control subjects, the Broca patients showed no early vocabulary class effect and only a limited late effect. The results suggest that an important factor in the agrammatic comprehension deficit of Broca’s aphasics is a delayed and/or incomplete availability of word-class information.

Abstract

The current article proposes a new theory of infant pointing involving multiple layers of intentionality and shared intentionality. In the context of this theory, evidence is presented for a rich interpretation of prelinguistic communication, that is, one that posits that when 12-month-old infants point for an adult they are in some sense trying to influence her mental states. Moreover, evidence is also presented for a deeply social view in which infant pointing is best understood—on many levels and in many ways—as depending on uniquely human skills and motivations for cooperation and shared intentionality (e.g., joint intentions and attention with others). Children's early linguistic skills are built on this already existing platform of prelinguistic communication.

Abstract

We investigated whether non-native listeners can exploit phonetic detail in recognizing potentially ambiguous utterances, as native listeners can [6, 7, 8, 9, 10]. Due to the phenomenon of intrusive /r/, the English phrase extra ice may sound like extra rice. A production study indicates that the intrusive /r/ can be distinguished from the onset /r/ in rice, as it is phonetically weaker. In two cross-modal identity priming studies, however, we found no conclusive evidence that Dutch learners of English are able to make use of this difference. Instead, auditory primes such as extra rice and extra ice with onset and intrusive /r/s activate both types of targets such as ice and rice. This supports the notion of spurious lexical activation in L2 perception.

Abstract

The present study compared the role of metrical stress in comprehension and production of three-year-old children with a familial risk of dyslexia with that of normally developing children. A visual fixation task with stress (mis-)matches in bisyllabic words, as well as a non-word repetition task with bisyllabic targets were presented to the control and at-risk children. Results show that the at-risk group is less sensitive to stress mismatches in word recognition than the control group. Correct production of metrical stress patterns did not differ significantly between the groups, but the percentages of phonemes produced correctly were lower for the at-risk than the control group. The findings indicate that processing of metrical stress patterns is not impaired in at-risk children, but that the at-risk group cannot exploit metrical stress in word recognition

Abstract

In this paper we investigate acoustic differences between vowels in syllables that do or do not carry lexical stress. In doing so, we concentrated on segmental acoustic phonetic features that are conventionally assumed to differ between stressed and unstressed syllables, viz. Duration, Energy and Spectral Tilt. The speech material in this study differs from the type of material used in previous research: instead of specially constructed sentences we used phonetically rich sentences from the Dutch POLYPHONE corpus. Most of the Duration, Energy and Spectral Tilt features that we used in the investigation show statistically significant differences for the population means of stressed and unstressed vowels. However, it also appears that the distributions overlap to such an extent that automatic detection of stressed and unstressed syllables yields correct classifications of 72.6% at best. It is argued that this result is due to the large variety in the ways in which the abstract linguistic feature `lexical stress' is realized in the acoustic speech signal. Our findings suggest that a lexical stress detector has little use for a single pass decoder in an automatic speech recognition (ASR) system, but could still play a useful role as an additional knowledge source in a multi-pass decoder.

Abstract

An event-related brain potentials experiment was carried out to examine the interplay of referential and structural factors during sentence processing in discourse. Subjects read (Dutch) sentences beginning like “David told the girl that … ” in short story contexts that had introduced either one or two referents for a critical singular noun phrase (“the girl”). The waveforms showed that within 280 ms after onset of the critical noun the reader had already determined whether the noun phrase had a unique referent in earlier discourse. Furthermore, this referential information was immediately used in parsing the rest of the sentence, which was briefly ambiguous between a complement clause (“ … that there would be some visitors”) and a relative clause (“ … that had been on the phone to hang up”). A consistent pattern of P600/SPS effects elicited by various subsequent disambiguations revealed that a two-referent discourse context had led the parser to initially pursue the relative-clause alternative to a larger extent than a one-referent context. Together, the results suggest that during the processing of sentences in discourse, structural and referential sources of information interact on a word-by-word basis.

Abstract

An introductory study of the perception of stochastically specified events is reported. The initial problem was to determine whether the perceiver can split visual input data of this kind into random and determined components. The inability of subjects to do so with the stimulus material used (a filmlike sequence of dot patterns), led to the more general question of how subjects code this kind of visual material. To meet the difficulty of defining the subjects' responses, two experiments were designed. In both, patterns were presented as a rapid sequence of dots on a screen. The patterns were more or less disturbed by “noise,” i.e. the dots did not appear exactly at their proper places. In the first experiment the response was a rating on a semantic scale, in the second an identification from among a set of alternative patterns. The results of these experiments give some insight in the coding systems adopted by the subjects. First, noise appears to be detrimental to pattern recognition, especially to patterns with little spread. Second, this shows connections with the factors obtained from analysis of the semantic ratings, e.g. easily disturbed patterns show a large drop in the semantic regularity factor, when only a little noise is added.

Abstract

The electrophysiology of language comprehension has long been dominated by research on syntactic and semantic integration. However, to understand expressions like "he did it" or "the little girl", combining word meanings in accordance with semantic and syntactic constraints is not enough--readers and listeners also need to work out what or who is being referred to. We review our event-related brain potential research on the processes involved in establishing reference, and present a new experiment in which we examine when and how the implicit causality associated with specific interpersonal verbs affects the interpretation of a referentially ambiguous pronoun. The evidence suggests that upon encountering a singular noun or pronoun, readers and listeners immediately inspect their situation model for a suitable discourse entity, such that they can discriminate between having too many, too few, or exactly the right number of referents within at most half a second. Furthermore, our implicit causality findings indicate that a fragment like "David praised Linda because..." can immediately foreground a particular referent, to the extent that a subsequent "he" is at least initially construed as a syntactic error. In all, our brain potential findings suggest that referential processing is highly incremental, and not necessarily contingent upon the syntax. In addition, they demonstrate that we can use ERPs to relatively selectively keep track of how readers and listeners establish reference.

Abstract

We report a series of experiments examining the effects on word processing of insertion of an optional epenthetic vowel in word-final consonant clusters in Dutch. Such epenthesis turns film, for instance, into film. In a word-reversal task listeners treated words with and without epenthesis alike, as monosyllables, suggesting that the variant forms both activate the same canonical representation, that of a monosyllabic word without epenthesis. In both lexical decision and word spotting, response times to recognize words were significantly faster when epenthesis was present than when the word was presented in its canonical form without epenthesis. It is argued that addition of the epenthetic vowel makes the liquid consonants constituting the first member of a cluster more perceptible; a final phoneme-detection experiment confirmed that this was the case. These findings show that a transformed variant of a word, although it contacts the lexicon via the representation of the canonical form, can be more easily perceptible than that canonical form.

Abstract

Progesterone, or rather its neuroactive metabolite allopregnanolone, modulates amygdala activity and thereby influences anxiety. Cognition and, in particular, memory are also altered by allopregnanolone. In the present study, we investigated whether allopregnanolone modulates memory for biologically salient stimuli by influencing amygdala activity, which in turn may affect neural processes in other brain regions. A single progesterone dose was administered orally to healthy young women in a double-blind, placebo-controlled, crossover design, and participants were asked to memorize and recognize faces while undergoing functional magnetic resonance imaging. Progesterone decreased recognition accuracy without affecting reaction times. The imaging results show that the amygdala, hippocampus, and fusiform gyrus supported memory formation. Importantly, progesterone decreased responses to faces in the amygdala and fusiform gyrus duringmemoryencoding, whereas it increased hippocampal responses. The progesterone-induced decrease in neural activity in the amygdala and fusiform gyrus predicted the decrease in memory performance across subjects. However, progesterone did not modulate the differential activation between subsequently remembered and subsequently forgotten faces in these areas. A similar pattern of results was observed in the fusiform gyrus and prefrontal cortex during memory retrieval. These results suggest that allopregnanolone impairs memory by reducing the recruitment of those brain regions that support memory formation and retrieval. Given the important role of the amygdala in the modulation of memory, these results suggest that allopregnanolone alters memory by influencing amygdala activity, which in turn may affect memory processes in other brain regions

Abstract

This article addresses the issue of the different status that typology has in American linguistics as opposed to European linguistics. The historical roots of the difference lie in both structural and generative linguistics, in the contrasts between post-Bloomfieldian structuralism in the US vs. Praguean structuralism in Europe, and in the extent of the influence of generative grammar on the two continents.

Abstract

In two ERP experiments we investigated how and when the language comprehension system relates an incoming word to semantic representations of an unfolding local sentence and a wider discourse. In experiment 1, subjects were presented with short stories. The last sentence of these stories occasionally contained a critical word that, although acceptable in the local sentence context, was semantically anomalous with respect to the wider discourse (e.g., "Jane told the brother that he was exceptionally slow" in a discourse context where he had in fact been very quick). Relative to coherent control words (e.g., "quick"), these discourse-dependent semantic anomalies elicited a large N400 effect that began at about 200-250 ms after word onset. In experiment 2, the same sentences were presented without their original story context. Although the words that had previously been anomalous in discourse still elicited a slightly larger average N400 than the coherent words, the resulting N400 effect was much reduced, showing that the large effect observed in stories was related to the wider discourse. In the same experiment, single sentences that contained a clear local semantic anomaly elicited a standard sentence-dependent N400 effect (e.g., Kutas & Hillyard, 1980). The N400 effects elicited in discourse and in single sentences had the same time course, overall morphology, and scalp distribution. We argue that these findings are most compatible with models of language processing in which there is no fundamental distinction between the integration of a word in its local (sentence-level) and its global (discourse-level) semantic context.

Abstract

We review the implications of recent ERP evidence for when and how grammatical gender agreement constrains sentence parsing. In some theories of parsing, gender is assumed to immediately and categorically block gender-incongruent phrase structure alternatives from being pursued. In other theories, the parser initially ignores gender altogether. The ERP evidence we discuss suggests an intermediate position, in which grammatical gender does not immediately block gender-incongruent phrase structures from being considered, but is used to dispose of them shortly thereafter.

Abstract

Motor-related brain potentials were used to examine the time course of grammatical and phonological processes during noun phrase production in Dutch. In the experiments, participants named colored pictures using a no-determiner noun phrase. On half of the trials a syntactic-phonological classification task had to be performed before naming. Depending on the outcome of the classifications, a left or a right push-button response was given (go trials), or no push-button response was given (no-go trials). Lateralized readiness potentials (LRPs) were derived to test whether syntactic and phonological information affected the motor system at separate moments in time. The results showed that when syntactic information determined the response-hand decision, an LRP developed on no-go trials. However, no such effect was observed when phonological information determined response hand. On the basis of the data, it can be estimated that an additional period of at least 40 ms is needed to retrieve a word's initial phoneme once its lemma has been retrieved. These results provide evidence for the view that during speaking, grammatical processing precedes phonological processing in time.

Abstract

Over the past ten years Geographic Information Systems (GIS) have evolved from a highly specialised niche technology to one that is used daily by a wide range of people. This article describes geographic browsing of language archives, which provides intuitive exploration of resources and permits integration and correlation of information from different archives, even across different research disciplines. In order to facilitate both exploration and management of resources, digital language archives are organised according to criteria such as language name, research topic, project information, researchers, countries, or genres. A set of such criteria can form a tree-like classification scheme, such as in the MPI-IMDI archive, which in turn forms the main method of searching and querying the archive resources. Searching for information can be difficult for occasional users because effective use of these search-fields typically requires specialised knowledge. We assume that many non-specialist users of language resources will search by language name, language family, or geographic area, so that geographic navigation would offer a very powerful search method. We also assume that such users are familiar with maps, and that geographic browsing is more intuitive than browsing classification trees, so these users would prefer to start with a large scale map and then zoom in to find the data that interests them. Therefore, classification trees and geographic maps provide complementary methods for accessing language resources to meet the needs of different user groups. We selected Google Earth (GE) as a geographic browsing system and overlaid it with linguistic information. GE was chosen because it is available via the web, it has good navigation controls, it is familiar to many web users, and because the overlaid linguistic information can be formulated in XML, making it comparatively easy to interchange with other geographic systems.

Abstract

We previously discovered that mutations of the human FOXP2 gene cause a monogenic communication disorder, primarily characterized by difficulties in learning to make coordinated sequences of articulatory gestures that underlie speech. Affected people have deficits in expressive and receptive linguistic processing and display structural and/or functional abnormalities in cortical and subcortical brain regions. FOXP2 provides a unique window into neural processes involved in speech and language. In particular, its role as a transcription factor gene offers powerful functional genomic routes for dissecting critical neurogenetic mechanisms. Here, we employ chromatin immunoprecipitation coupled with promoter microarrays (ChIP-chip) to successfully identify genomic sites that are directly bound by FOXP2 protein in native chromatin of human neuron-like cells. We focus on a subset of downstream targets identified by this approach, showing that altered FOXP2 levels yield significant changes in expression in our cell-based models and that FOXP2 binds in a specific manner to consensus sites within the relevant promoters. Moreover, we demonstrate significant quantitative differences in target expression in embryonic brains of mutant mice, mediated by specific in vivo Foxp2-chromatin interactions. This work represents the first identification and in vivo verification of neural targets regulated by FOXP2. Our data indicate that FOXP2 has dual functionality, acting to either repress or activate gene expression at occupied promoters. The identified targets suggest roles in modulating synaptic plasticity, neurodevelopment, neurotransmission, and axon guidance and represent novel entry points into in vivo pathways that may be disturbed in speech and language disorders.

Abstract

Tzeltal, a Mayan language spoken in southern Mexico, exhibits allo-morphy of an unusual type. The vowel quality of the perfective suffix is determined by the number of syllables in the stem to which it is attaching. This paper presents previously unpublished data of this allomorphy and demonstrates that a syllable-count analysis of the phenomenon is the proper one. This finding is put in a more general context of segment-prosody interaction in allomorphy.

Abstract

An event-related brain potential experiment was carried out to investigate on-line thematic role assignment during sentence–picture matching in patients with Broca's aphasia. Subjects were presented with a picture that was followed by an auditory sentence. The sentence either matched the picture or mismatched the visual information depicted. Sentences differed in complexity, and ranged from simple active semantically irreversible sentences to passive semantically reversible sentences. ERPs were recorded while subjects were engaged in sentence–picture matching. In addition, reaction time and accuracy were measured. Three groups of subjects were tested: Broca patients (N = 10), non-aphasic patients with a right hemisphere (RH) lesion (N = 8), and healthy aged-matched controls (N = 15). The results of this study showed that, in neurologically unimpaired individuals, thematic role assignment in the context of visual information was an immediate process. This in contrast to patients with Broca's aphasia who demonstrated no signs of on-line sensitivity to the picture–sentence mismatches. The syntactic contribution to the thematic role assignment process seemed to be diminished given the reduction and even absence of P600 effects. Nevertheless, Broca patients showed some off-line behavioral sensitivity to the sentence–picture mismatches. The long response latencies of Broca's aphasics make it likely that off-line response strategies were used.

Abstract

In a visual-world study, we examined spoken-wordrecognition in Spanish. Spanish listeners followed spoken instructions to click on pictures while their eye movements were monitored. When instructed to click on the picture of a door (puerta), they experienced interference from the picture of a pig (p u e r c o ). The same interference from phonologically related items was observed when the displays contained printed names or a combination of pictures with their names printed underneath, although the effect was strongest for displays with printed names. Implications of the finding that the interference effect can be induced with standard pictorial displays as well as with orthographic displays are discussed.

Abstract

Dichoptic mixtures of equiluminous components of different wavelengths were matched with a binocularly presented "monocular" mixture of appropriate chosen amounts of the same colour components. Stimuli were chosen from the region of 490-630 nm. Although satisfactory colour matches could be obtained, dichoptic mixtures differed from normal mixtures to a considerable extent. Midspectral stimuli tended to be more dominant in the dichoptic mixtures than either short or long wavelength stimuli. An attempt was made to describe the relation between monocular and dichoptic mixtures with one function containing a wavelength variable and an eye dominance parameter.

Abstract

Although generally studied in isolation, language and action often co-occur in everyday life. Here we investigated one particular form of simultaneous language and action, namely speech and gestures that speakers use in everyday communication. In a functional magnetic resonance imaging study, we identified the neural networks involved in the integration of semantic information from speech and gestures. Verbal and/or gestural content could be integrated easily or less easily with the content of the preceding part of speech. Premotor areas involved in action observation (Brodmann area [BA] 6) were found to be specifically modulated by action information "mismatching" to a language context. Importantly, an increase in integration load of both verbal and gestural information into prior speech context activated Broca's area and adjacent cortex (BA 45/47). A classical language area, Broca's area, is not only recruited for language-internal processing but also when action observation is integrated with speech. These findings provide direct evidence that action and language processing share a high-level neural integration system.

Abstract

Co-speech gestures embody a form of manual action that is tightly coupled to the language system. As such, the co-occurrence of speech and co-speech gestures is an excellent example of the interplay between language and action. There are, however, other ways in which language and action can be thought of as closely related. In this paper we will give an overview of studies in cognitive neuroscience that examine the neural underpinnings of links between language and action. Topics include neurocognitive studies of motor representations of speech sounds, action-related language, sign language and co-speech gestures. It will be concluded that there is strong evidence on the interaction between speech and gestures in the brain. This interaction however shares general properties with other domains in which there is interplay between language and action.

Abstract

Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions.

Abstract

Genome-wide association studies using thousands to hundreds of thousands of single nucleotide polymorphism (SNP) markers and region-wide association studies using a dense panel of SNPs are already in use to identify disease susceptibility genes and to predict disease risk in individuals. Because these tasks become increasingly important, three different data sets were provided for the Genetic Analysis Workshop 15, thus allowing examination of various novel and existing data mining methods for both classification and identification of disease susceptibility genes, gene by gene or gene by environment interaction. The approach most often applied in this presentation group was random forests because of its simplicity, elegance, and robustness. It was used for prediction and for screening for interesting SNPs in a first step. The logistic tree with unbiased selection approach appeared to be an interesting alternative to efficiently select interesting SNPs. Machine learning, specifically ensemble methods, might be useful as pre-screening tools for large-scale association studies because they can be less prone to overfitting, can be less computer processor time intensive, can easily include pair-wise and higher-order interactions compared with standard statistical approaches and can also have a high capability for classification. However, improved implementations that are able to deal with hundreds of thousands of SNPs at a time are required.