Publications

Abstract

Background Various CACNA1A missense mutations cause familial hemiplegic migraine type 1 (FHM1), a rare monogenic subtype of migraine with aura. FHM1 mutation R192Q is associated with pure hemiplegic migraine, whereas the S218L mutation causes hemiplegic migraine, cerebellar ataxia, seizures, and mild head trauma-induced brain edema. Transgenic knock-in (KI) migraine mouse models were generated that carried either the FHM1 R192Q or the S218L mutation and were shown to exhibit increased CaV2.1 channel activity. Here we investigated their cerebellar and caudal cortical transcriptome. Methods Caudal cortical and cerebellar RNA expression profiles from mutant and wild-type mice were studied using microarrays. Respective brain regions were selected based on their relevance to migraine aura and ataxia. Relevant expression changes were further investigated at RNA and protein level by quantitative polymerase chain reaction (qPCR) and/or immunohistochemistry, respectively. Results Expression differences in the cerebellum were most pronounced in S218L mice. Particularly, tyrosine hydroxylase, a marker of delayed cerebellar maturation, appeared strongly upregulated in S218L cerebella. In contrast, only minimal expression differences were observed in the caudal cortex of either mutant mice strain. Conclusion Despite pronounced consequences of migraine gene mutations at the neurobiological level, changes in cortical RNA expression in FHM1 migraine mice compared to wild-type are modest. In contrast, pronounced RNA expression changes are seen in the cerebellum of S218L mice and may explain their cerebellar ataxia phenotype

Abstract

This study reports general and language-specific patterns in phoneme identification. In a series of phoneme monitoring experiments, Castilian Spanish, Catalan, Dutch, English, and Polish listeners identified vowel, fricative, and stop consonant targets that are phonemic in all these languages, embedded in nonsense words. Fricatives were generally identified more slowly than vowels, while the speed of identification for stop consonants was highly dependent on the onset of the measurements. Moreover, listeners' response latencies and accuracy in detecting a phoneme correlated with the number of categories within that phoneme's class in the listener's native phoneme repertoire: more native categories slowed listeners down and decreased their accuracy. We excluded the possibility that this effect stems from differences in the frequencies of occurrence of the phonemes in the different languages. Rather, the effect of the number of categories can be explained by general properties of the perception system, which cause language-specific patterns in speech processing.

Abstract

Genome-wide association study results have yielded evidence for the association of common genetic variants with crude measures of completed educational attainment in adults. Whilst informative, these results do not inform as to the mechanism of these effects or their presence at earlier ages and where educational performance is more routinely and more precisely assessed. Single nucleotide polymorphisms exhibiting genome-wide significant associations with adult educational attainment were combined to derive an unweighted allele score in 5,979 and 6,145 young participants from the Avon Longitudinal Study of Parents and Children with key stage 3 national curriculum test results (SATS results) available at age 13 to 14 years in English and mathematics respectively. Standardised (z-scored) results for English and mathematics showed an expected relationship with sex, with girls exhibiting an advantage over boys in English (0.433 SD (95%CI 0.395, 0.470), p<10-10) with more similar results (though in the opposite direction) in mathematics (0.042 SD (95%CI 0.004, 0.080), p = 0.030). Each additional adult educational attainment increasing allele was associated with 0.041 SD (95%CI 0.020, 0.063), p = 1.79×10-04 and 0.028 SD (95%CI 0.007, 0.050), p = 0.01 increases in standardised SATS score for English and mathematics respectively. Educational attainment is a complex multifactorial behavioural trait which has not had heritable contributions to it fully characterised. We were able to apply the results from a large study of adult educational attainment to a study of child exam performance marking events in the process of learning rather than realised adult end product. Our results support evidence for common, small genetic contributions to educational attainment, but also emphasise the likely lifecourse nature of this genetic effect. Results here also, by an alternative route, suggest that existing methods for child examination are able to recognise early life variation likely to be related to ultimate educational attainment.

Abstract

Twenty American English listeners identified gated fragments of all 2288 possible English within-word and cross-word diphones, providing a total of 538 560 phoneme categorizations. The results show orderly uptake of acoustic information in the signal and provide a view of where information about segments occurs in time. Information locus depends on each speech sound’s identity and phonological features. Affricates and diphthongs have highly localized information so that listeners’ perceptual accuracy rises during a confined time range. Stops and sonorants have more distributed and gradually appearing information. The identity and phonological features (e.g., vowel vs consonant) of the neighboring segment also influences when acoustic information about a segment is available. Stressed vowels are perceived significantly more accurately than unstressed vowels, but this effect is greater for lax vowels than for tense vowels or diphthongs. The dataset charts the availability of perceptual cues to segment identity across time for the full phoneme repertoire of English in all attested phonetic contexts.

Abstract

Previous studies have shown that spoken-language processing is inhibited by violation of obligatory regressive assimilation. Weber (2001) replicated this inhibitory effect in a phoneme-monitoring study examining regressive place assimilation of nasals, but found facilitation for violation of progressive assimilation. German listeners detected the velar fricative [x] more quickly when fricative assimilation was violated (e.g., *[bIxt] or *[blInx@n]) than when no violation occurred (e.g., [baxt] or [blu:x@n]). It was argued that a combination of two factors caused facilitation:(1) progressive assimilation creates different restrictions for the monitoring target than regressive assimilation does, and (2) the sequences violating assimilation (e.g., *[Ix]) are novel for German listeners and therefore facilitate fricative detection (novel popout). The present study tested progressive assimilation violation in non-novel sequences using the palatal fricative [C]. Stimuli either violated fricative assimilation (e.g., *[ba:C@l ]) or did not (e.g., [bi: C@l ]). This manipulation does not create novel sequences: sequences like *[a:C] can occur across word boundaries, while *[Ix] cannot. No facilitation was found. However, violation also did not significantly inhibit processing. The results confirm that facilitation depends on the combination of progressive assimilation with novelty of the sequence.

Abstract

Recent brain potential research into first versus second language (L1 vs. L2) processing revealed striking responses to morphosyntactic features absent in the mother tongue. The aim of the present study was to establish whether the presence of comparable morphosyntactic features in L1 leads to more similar electrophysiological L1 and L2 profiles. ERPs were acquired while German-English bilinguals and native speakers of English read sentences. Some sentences were meaningful and well formed, whereas others contained morphosyntactic or semantic violations in the final word. In addition to the expected P600 component, morphosyntactic violations in L2 but not L1 led to an enhanced N400. This effect may suggest either that resolution of morphosyntactic anomalies in L2 relies on the lexico-semantic system or that the weaker/slower morphological mechanisms in L2 lead to greater sentence wrap-up difficulties known to result in N400 enhancement.

Abstract

Two cross-modal priming experiments examined two questions about word recognition in foreign-accented speech: Does accent adaptation occur only for genuine accents markers, and does adaptation depend on language experience? We compared recognition of words spoken with canonical, genuinely-accented and arbitrarily-accented vowels. In Experiment 1, an Italian speaker pronounced vowels in English prime words canonically, or by lengthening /ɪ/ as in a genuine Italian accent (*/tri:k/ for trick), or by arbitrarily shortening /i:/ (*/trɪt/ for treat). Lexical-decision times to subsequent visual target words showed different priming effects in three listener groups. Monolingual native English listeners recognized variants with lengthened but not shortened vowels. Bilingual nonnative Italian-English listeners, who could not reliably distinguish vowel length, recognized both variants. Bilingual nonnative Dutch-English listeners also recognized both variants. In Experiment 2, bilingual Dutch-English listeners recognized Dutch words with genuinely- and arbitrarily-accented vowels (spoken by a native Italian with lengthened and shortened vowels respectively), but recognized words with canonical vowels more easily than words with accented vowels. These results suggest that adaptation to genuine accent markers arises for monolingual and bilingual listeners alike and can occur in native and nonnative languages, but that bilinguals can adapt to arbitrary accent markers better than monolinguals.

Abstract

Humans differ widely in their navigational abilities. Studies have shown that self-reports on navigational abilities are good predictors of performance on navigation tasks in real and virtual environments. The caudate nucleus and medial temporal lobe regions have been suggested to subserve different navigational strategies. The ability to use different strategies might underlie navigational ability differences. This study examines the anatomical correlates of self-reported navigational ability in both gray and white matter. Local gray matter volume was compared between a group (N = 134) of good and bad navigators using voxel-based morphometry (VBM), as well as regional volumes. To compare between good and bad navigators, we also measured white matter anatomy using diffusion tensor imaging (DTI) and looked at fractional anisotropy (FA) values. We observed a trend toward higher local GM volume in right anterior parahippocampal/rhinal cortex for good versus bad navigators. Good male navigators showed significantly higher local GM volume in right hippocampus than bad male navigators. Conversely, bad navigators showed increased FA values in the internal capsule, the white matter bundle closest to the caudate nucleus and a trend toward higher local GM volume in the caudate nucleus. Furthermore, caudate nucleus regional volume correlated negatively with navigational ability. These convergent findings across imaging modalities are in line with findings showing that the caudate nucleus and the medial temporal lobes are involved in different wayfinding strategies. Our study is the first to show a link between self-reported large-scale navigational abilities and different measures of brain anatomy.

Abstract

A combination of Southern blot analysis on a panel of tumor-derived somatic cell hybrids and fluorescence in situ hybridization techniques was used to map YACs, cosmids and DNA markers from the Xp11.2 region relative to the X chromosome breakpoint of the renal cell carcinoma-associated t(X;1)(p11;q21). The position of the breakpoint could be determined as follows: Xcen-OATL2-DXS146-DXS255-SYP-t(X;1)-TFE 3-OATL1-Xpter. Fluorescence in situ hybridization experiments using TFE3-containing YACs and cosmids revealed split signals indicating that the corresponding DNA inserts span the breakpoint region. Subsequent Southern blot analysis showed that a 2.3-kb EcoRI fragment which is present in all TFE3 cosmids identified, hybridizes to aberrant restriction fragments in three independent t(X;1)-positive renal cell carcinoma DNAs. The breakpoints in these tumors are not the same, but map within a region of approximately 6.5 kb. Through preparative gel electrophoresis an (X;1) chimaeric 4.4-kb EcoRI fragment could be isolated which encompasses the breakpoint region present on der(X). Preliminary characterization of this fragment revealed the presence of a 150-bp region with a strong homology to the 5' end of the mouse TFE3 cDNA in the X-chromosome part, and a 48-bp segment in the chromosome 1-derived part identical to the 5' end of a known EST (accession number R93849). These observations suggest that a fusion gene is formed between the two corresponding genes in t(X;1)(p11;q21)-positive papillary renal cell carcinomas.

Abstract

Studies on metacognition have shown that participants can report on their performance on a wide range of perceptual, memory and behavioral tasks. We know little, however, about the ability to report on one's attentional focus. The degree and direction of somatosensory attention can, however, be readily discerned through suppression of alpha band frequencies in EEG/MEG produced by the somatosensory cortex. Such top-down attentional modulations of cortical excitability have been shown to result in better discrimination performance and decreased response times. In this study we asked whether the degree of attentional focus is also accessible for subjective report, and whether such evaluations correspond to the amount of somatosensory alpha activity. In response to auditory cues participants maintained somatosensory attention to either their left or right hand for intervals varying randomly between 5 and 32seconds, while their brain activity was recorded with MEG. Trials were terminated by a probe sound, to which they reported their level of attention on the cued hand right before probe-onset. Using a beamformer approach, we quantified the alpha activity in left and right somatosensory regions, one second before the probe. Alpha activity from contra- and ipsilateral somatosensory cortices for high versus low attention trials were compared. As predicted, the contralateral somatosensory alpha depression correlated with higher reported attentional focus. Finally, alpha activity two to three seconds before the probe-onset was correlated with attentional focus. We conclude that somatosensory attention is indeed accessible to metacognitive awareness.

Abstract

This contribution emphasizes the role of multimedia data not only for archiving languages but also for creating opportunities for innovative analyses. In the case at hand, video material was collected as part of the documentation of Akhoe Haiom, a Khoisan language spoken in northern Namibia. The multimedia documentation project brought together linguistic and anthropological work to highlight connections between specialized domains, namely kinship terminology, interrogatives and reciprocals. These connections would have gone unnoticed or undocumented in more conventional modes of language description. It is suggested that such an approach may be particularly appropriate for the documentation of endangered languages since it directs the focus of attention away from isolated traits of languages towards more complex practices of communication that are also frequently threatened with extinction.

Abstract

Even before it became a common place to assume that “the Eskimo have a hundred words for snow” the languages of hunting and gathering people have played an important role in debates about linguistic relativity concerning geographical ontologies. Evidence from languages of hunter-gatherers has been used in radical relativist challenges to the overall notion of a comparative typology of generic natural forms and landscapes as terms of reference. It has been invoked to emphasize a personalized relationship between humans and the non-human world. It is against this background that this contribution discusses the landscape terminology of ≠Akhoe Hai//om, a Khoisan language spoken by “Bushmen” in Namibia. Landscape vocabulary is ubiquitous in ≠Akhoe Hai//om due to the fact that the landscape plays a critical role in directionals and other forms of “topographical gossip” and due to merges between landscape and group terminology. This system of landscape-cum-group terminology is outlined and related to the use of place names in the area.

Abstract

Understanding language always occurs within a situational context and, therefore, often implies combining streams of information from different domains and modalities. One such combination is that of spoken language and visual information, which are perceived together in a variety of ways during everyday communication. Here we investigate whether and how words and pictures differ in terms of their neural correlates when they are integrated into a previously built-up sentence context. This is assessed in two experiments looking at the time course (measuring event-related potentials, ERPs) and the locus (using functional magnetic resonance imaging, fMRI) of this integration process. We manipulated the ease of semantic integration of word and/or picture to a previous sentence context to increase the semantic load of processing. In the ERP study, an increased semantic load led to an N400 effect which was similar for pictures and words in terms of latency and amplitude. In the fMRI study, we found overlapping activations to both picture and word integration in the left inferior frontal cortex. Specific activations for the integration of a word were observed in the left superior temporal cortex. We conclude that despite obvious differences in representational format, semantic information coming from pictures and words is integrated into a sentence context in similar ways in the brain. This study adds to the growing insight that the language system incorporates (semantic) information coming from linguistic and extralinguistic domains with the same neural time course and by recruitment of overlapping brain areas.

Abstract

Language is often perceived together with visual information. This raises the question on how the brain integrates information conveyed in visual and/or linguistic format during spoken language comprehension. In this study we investigated the dynamics of semantic integration of visual and linguistic information by means of time-frequency analysis of the EEG signal. A modified version of the N400 paradigm with either a word or a picture of an object being semantically incongruous with respect to the preceding sentence context was employed. Event-Related Potential (ERP) analysis showed qualitatively similar N400 effects for integration of either word or picture. Time-frequency analysis revealed early specific decreases in alpha and gamma band power for linguistic and visual information respectively. We argue that these reflect a rapid context-based analysis of acoustic (word) or visual (picture) form information. We conclude that although full semantic integration of linguistic and visual information occurs through a common mechanism, early differences in oscillations in specific frequency bands reflect the format of the incoming information and, importantly, an early context-based detection of its congruity with respect to the preceding language context

Abstract

Left-handers are often excluded from study cohorts in neuroscience and neurogenetics in order to reduce variance in the data. However, recent investigations have shown that the inclusion or targeted recruitment of left-handers can be informative in studies on a range of topics, such as cerebral lateralization and the genetic underpinning of asymmetrical brain development. Left-handed individuals represent a substantial portion of the human population and therefore left-handedness falls within the normal range of human diversity; thus, it is important to account for this variation in our understanding of brain functioning. We call for neuroscientists and neurogeneticists to recognize the potential of studying this often-discarded group of research subjects.

Abstract

While most people prefer to use their right hand to brush their teeth, throw a ball, or hold a tennis racket, left-handers prefer to use their left hand. This is the case for around 10 per cent of all people. There was a time (not so long ago) when left-handers were stigmatized in Western (and other) communities: it was considered a bad sign if you were left-handed, and left-handed children were often forced to write with their right hand. This is nonsensical: there is nothing wrong with being left-handed, and trying to write with the non-preferred hand is frustrating for almost everybody. As a matter of fact, science can learn from left-handers, and in this paper, we discuss how this may be the case. We review why some people are left-handed and others are not, how left-handers' brains differ from right-handers’, and why scientists study left-handedness in the first place

Abstract

Over recent years small submicroscopic DNA copy-number variants (CNVs) have been highlighted as an important source of variation in the human genome, human phenotypic diversity and disease susceptibility. Consequently, there is a pressing need for the development of methods that allow the efficient, accurate and cheap measurement of genomic copy number polymorphisms in clinical cohorts. We have developed a simple competitive PCR based method to determine DNA copy number which uses the entire genome of a single chimpanzee as a competitor thus eliminating the requirement for competitive sequences to be synthesized for each assay. This results in the requirement for only a single reference sample for all assays and dramatically increases the potential for large numbers of loci to be analysed in multiplex. In this study we establish proof of concept by accurately detecting previously characterized mutations at the PARK2 locus and then demonstrating the potential of quantitative interspecies competitive PCR (qicPCR) to accurately genotype CNVs in association studies by analysing chromosome 22q11 deletions in a sample of previously characterized patients and normal controls.

Abstract

Are listeners able to adapt to a foreign-accented speaker who has, as is often the case, an inconsistent accent? Two groups of native Dutch listeners participated in a cross-modal priming experiment, either in a consistent-accent condition (German-accented items only) or in an inconsistent-accent condition (German-accented and nativelike pronunciations intermixed). The experimental words were identical for both groups (words with vowel substitutions characteristic of German-accented speech); additional contextual words differed in accentedness (German-accented or nativelike words). All items were spoken by the same speaker: a German native who could produce the accented forms but could also pass for a Dutch native speaker. Listeners in the consistent-accent group were able to adapt quickly to the speaker (i.e., showed facilitatory priming for words with vocalic substitutions). Listeners in the inconsistent-accent condition showed adaptation to words with vocalic substitutions only in the second half of the experiment. These results indicate that adaptation to foreign-accented speech is rapid. Accent inconsistency slows listeners down initially, but a short period of additional exposure is enough for them to adapt to the speaker. Listeners can therefore tolerate inconsistency in foreign-accented speech.

Abstract

It is widely believed that human languages cannot encode odors. While this is true for English,
and other related languages, data from some non-Western languages challenge this
view. Maniq, a language spoken by a small population of nomadic hunter–gatherers in
southern Thailand, is such a language. It has a lexicon of over a dozen terms dedicated
to smell. We examined the semantics of these smell terms in 3 experiments (exemplar
listing, similarity judgment and off-line rating). The exemplar listing task confirmed that
Maniq smell terms have complex meanings encoding smell qualities. Analyses of the
similarity data revealed that the odor lexicon is coherently structured by two dimensions.
The underlying dimensions are pleasantness and dangerousness, as verified by the off-line
rating study. Ethnographic data illustrate that smell terms have detailed semantics tapping
into broader cultural constructs. Contrary to the widespread view that languages cannot
encode odors, the Maniq data show odor can be a coherent semantic domain, thus shedding
new light on the limits of language.

Abstract

In the present study, event-related brain potentials (ERP) were recorded to investigate the role of pitch accent and lexical tone in spoken discourse comprehension. Chinese was used as material to explore the potential difference in the nature and time course of brain responses to sentence meaning as indicated by pitch accent and to lexical meaning as indicated by tone. In both cases, the pitch contour of critical words was varied. The results showed that both inconsistent pitch accent and inconsistent lexical tone yielded N400 effects, and there was no interaction between them. The negativity evoked by inconsistent pitch accent had the some topography as that evoked by inconsistent lexical tone violation, with a maximum over central–parietal electrodes. Furthermore, the effect for the combined violations was the sum of effects for pure pitch accent and pure lexical tone violation. However, the effect for the lexical tone violation appeared approximately 90 ms earlier than the effect of the pitch accent violation. It is suggested that there might be a correspondence between the neural mechanism underlying pitch accent and lexical meaning processing in context. They both reflect the integration of the current information into a discourse context, independent of whether the current information was sentence meaning indicated by accentuation, or lexical meaning indicated by tone. In addition, lexical meaning was processed earlier than sentence meaning conveyed by pitch accent during spoken language processing.

Abstract

Neural structures change with age but there is no consensus on the exact processes involved. This study tested the hypothesis that white and grey matter in the language network changes during aging according to a “last in, first out” process. The fractional anisotropy (FA) of white matter and cortical thickness of grey matter were measured in 36 participants whose ages ranged from 55 to 79 years. Within the language network, the dorsal pathway connecting the mid-to-posterior superior temporal cortex (STC) and the inferior frontal cortex (IFC) was affected more by aging in both FA and thickness than the other dorsal pathway connecting the STC with the premotor cortex and the ventral pathway connecting the mid-to-anterior STC with the ventral IFC. These results were independently validated in a second group of 20 participants whose ages ranged from 50 to 73 years. The pathway that is most affected during aging matures later than the other two pathways (which are present at birth). The results are interpreted as showing that the neural structures which mature later are affected more than those that mature earlier, supporting the “last in, first out” theory.

Abstract

For most people, speech production is relatively effortless and error-free. Yet it has long been recognized that we need some type of control over what we are currently saying and what we plan to say. Precisely how we monitor our internal and external speech has been a topic of research interest for several decades. The predominant approach in psycholinguistics has assumed monitoring of both is accomplished via systems responsible for comprehending others' speech.

This special topic aimed to broaden the field, firstly by examining proposals that speech production might also engage more general systems, such as those involved in action monitoring. A second aim was to examine proposals for a production-specific, internal monitor. Both aims require that we also specify the nature of the representations subject to monitoring.

Abstract

Given the limited processing capabilities of the sensory system, it is essential that attended information is gated to downstream areas, whereas unattended information is blocked. While it has been proposed that alpha band (8–13 Hz) activity serves to route information to downstream regions by inhibiting neuronal processing in task-irrelevant regions, this hypothesis remains untested. Here we investigate how neuronal oscillations detected by electroencephalography in visual areas during working memory encoding serve to gate information reflected in the simultaneously recorded blood-oxygenation-level-dependent (BOLD) signals recorded by functional magnetic resonance imaging in downstream ventral regions. We used a paradigm in which 16 participants were presented with faces and landscapes in the right and left hemifields; one hemifield was attended and the other unattended. We observed that decreased alpha power contralateral to the attended object predicted the BOLD signal representing the attended object in ventral object-selective regions. Furthermore, increased alpha power ipsilateral to the attended object predicted a decrease in the BOLD signal representing the unattended object. We also found that the BOLD signal in the dorsal attention network inversely correlated with visual alpha power. This is the first demonstration, to our knowledge, that oscillations in the alpha band are implicated in the gating of information from the visual cortex to the ventral stream, as reflected in the representationally specific BOLD signal. This link of sensory alpha to downstream activity provides a neurophysiological substrate for the mechanism of selective attention during stimulus processing, which not only boosts the attended information but also suppresses distraction. Although previous studies have shown a relation between the BOLD signal from the dorsal attention network and the alpha band at rest, we demonstrate such a relation during a visuospatial task, indicating that the dorsal attention network exercises top-down control of visual alpha activity.

Abstract

The lexicons of many sign languages hold large proportions of “frozen” forms, viz. signs that are generally considered to have been formed productively (as classifier predicates), but that have diachronically undergone processes of lexicalisation. Nederlandse Gebarentaal (Sign Language of the Netherlands; henceforth: NGT) also has many of these signs (Van der Kooij 2002, Zwitserlood 2003). In contrast to the general view on “frozen” forms, a few researchers claim that these signs may be formed according to productive sign formation rules, notably Brennan (1990) for BSL, and Meir (2001, 2002) for ISL. Following these claims, I suggest an analysis of “frozen” NGT signs as morphologically complex, using the framework of Distributed Morphology. The signs in question are derived in a similar way as classifier predicates; hence their similar form (but diverging characteristics). I will indicate how and why the structure and use of classifier predicates and “frozen” forms differ. Although my analysis focuses on NGT, it may also be applicable to other sign languages.