Publications

Displaying 301 - 400 of 925
  • Howe, L., Lawson, D. J., Davies, N. M., St Pourcain, B., Lewis, S. J., Smith, G. D., & Hemani, G. (2019). Genetic evidence for assortative mating on alcohol consumption in the UK Biobank. Nature Communications, 10: 5039. doi:10.1038/s41467-019-12424-x.

    Abstract

    Alcohol use is correlated within spouse-pairs, but it is difficult to disentangle effects of alcohol consumption on mate-selection from social factors or the shared spousal environment. We hypothesised that genetic variants related to alcohol consumption may, via their effect on alcohol behaviour, influence mate selection. Here, we find strong evidence that an individual’s self-reported alcohol consumption and their genotype at rs1229984, a missense variant in ADH1B, are associated with their partner’s self-reported alcohol use. Applying Mendelian randomization, we estimate that a unit increase in an individual’s weekly alcohol consumption increases partner’s alcohol consumption by 0.26 units (95% C.I. 0.15, 0.38; P = 8.20 × 10−6). Furthermore, we find evidence of spousal genotypic concordance for rs1229984, suggesting that spousal concordance for alcohol consumption existed prior to cohabitation. Although the SNP is strongly associated with ancestry, our results suggest some concordance independent of population stratification. Our findings suggest that alcohol behaviour directly influences mate selection.
  • Howe, L. J., Richardson, T. G., Arathimos, R., Alvizi, L., Passos-Bueno, M. R., Stanier, P., Nohr, E., Ludwig, K. U., Mangold, E., Knapp, M., Stergiakouli, E., St Pourcain, B., Smith, G. D., Sandy, J., Relton, C. L., Lewis, S. J., Hemani, G., & Sharp, G. C. (2019). Evidence for DNA methylation mediating genetic liability to non-syndromic cleft lip/palate. Epigenomics, 11(2), 133-145. doi:10.2217/epi-2018-0091.

    Abstract

    Aim: To determine if nonsyndromic cleft lip with or without cleft palate (nsCL/P) genetic risk variants influence liability to nsCL/P through gene regulation pathways, such as those involving DNA methylation. Materials & methods: nsCL/P genetic summary data and methylation data from four studies were used in conjunction with Mendelian randomization and joint likelihood mapping to investigate potential mediation of nsCL/P genetic variants. Results & conclusion: Evidence was found at VAX1 (10q25.3), LOC146880 (17q23.3) and NTN1 (17p13.1), that liability to nsCL/P and variation in DNA methylation might be driven by the same genetic variant, suggesting that genetic variation at these loci may increase liability to nsCL/P by influencing DNA methylation. Follow-up analyses using different tissues and gene expression data provided further insight into possible biological mechanisms.

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  • Hoymann, G. (2014). [Review of the book Bridging the language gap, Approaches to Herero verbal interaction as development practice in Namibia by Rose Marie Beck]. Journal of African languages and linguistics, 35(1), 130-133. doi:10.1515/jall-2014-0004.
  • Hubbard, R. J., Rommers, J., Jacobs, C. L., & Federmeier, K. D. (2019). Downstream behavioral and electrophysiological consequences of word prediction on recognition memory. Frontiers in Human Neuroscience, 13: 291. doi:10.3389/fnhum.2019.00291.

    Abstract

    When people process language, they can use context to predict upcoming information,
    influencing processing and comprehension as seen in both behavioral and neural
    measures. Although numerous studies have shown immediate facilitative effects
    of confirmed predictions, the downstream consequences of prediction have been
    less explored. In the current study, we examined those consequences by probing
    participants’ recognition memory for words after they read sets of sentences.
    Participants read strongly and weakly constraining sentences with expected or
    unexpected endings (“I added my name to the list/basket”), and later were tested on
    their memory for the sentence endings while EEG was recorded. Critically, the memory
    test contained words that were predictable (“list”) but were never read (participants
    saw “basket”). Behaviorally, participants showed successful discrimination between old
    and new items, but false alarmed to the expected-item lures more often than to new
    items, showing that predicted words or concepts can linger, even when predictions
    are disconfirmed. Although false alarm rates did not differ by constraint, event-related
    potentials (ERPs) differed between false alarms to strongly and weakly predictable words.
    Additionally, previously unexpected (compared to previously expected) endings that
    appeared on the memory test elicited larger N1 and LPC amplitudes, suggesting greater
    attention and episodic recollection. In contrast, highly predictable sentence endings that
    had been read elicited reduced LPC amplitudes during the memory test. Thus, prediction
    can facilitate processing in the moment, but can also lead to false memory and reduced
    recollection for predictable information.
  • Hubers, F., Cucchiarini, C., Strik, H., & Dijkstra, T. (2019). Normative data of Dutch idiomatic expressions: Subjective judgments you can bank on. Frontiers in Psychology, 10: 1075. doi:10.3389/fpsyg.2019.01075.

    Abstract

    The processing of idiomatic expressions is a topical issue in empirical research. Various factors have been found to influence idiom processing, such as idiom familiarity and idiom transparency. Information on these variables is usually obtained through norming studies. Studies investigating the effect of various properties on idiom processing have led to ambiguous results. This may be due to the variability of operationalizations of the idiom properties across norming studies, which in turn may affect the reliability of the subjective judgements. However, not all studies that collected normative data on idiomatic expressions investigated their reliability, and studies that did address the reliability of subjective ratings used various measures and produced mixed results. In this study, we investigated the reliability of subjective judgements, the relation between subjective and objective idiom frequency, and the impact of these dimensions on the participants’ idiom knowledge by collecting normative data of five subjective idiom properties (Frequency of Exposure, Meaning Familiarity, Frequency of Usage, Transparency, and Imageability) from 390 native speakers and objective corpus frequency for 374 Dutch idiomatic expressions. For reliability, we compared measures calculated in previous studies, with the D-coefficient, a metric taken from Generalizability Theory. High reliability was found for all subjective dimensions. One reliability metric, Krippendorff’s alpha, generally produced lower values, while similar values were obtained for three other measures (Cronbach’s alpha, Intraclass Correlation Coefficient, and the D-coefficient). Advantages of the D-coefficient are that it can be applied to unbalanced research designs, and to estimate the minimum number of raters required to obtain reliable ratings. Slightly higher coefficients were observed for so-called experience-based dimensions (Frequency of Exposure, Meaning Familiarity, and Frequency of Usage) than for content-based dimensions (Transparency and Imageability). In addition, fewer raters were required to obtain reliable ratings for the experience-based dimensions. Subjective and objective frequency appeared to be poorly correlated, while all subjective idiom properties and objective frequency turned out to affect idiom knowledge. Meaning Familiarity, Subjective and Objective Frequency of Exposure, Frequency of Usage, and Transparency positively contributed to idiom knowledge, while a negative effect was found for Imageability. We discuss these relationships in more detail, and give methodological recommendations with respect to the procedures and the measure to calculate reliability.

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  • Huettig, F., & Pickering, M. (2019). Literacy advantages beyond reading: Prediction of spoken language. Trends in Cognitive Sciences, 23(6), 464-475. doi:10.1016/j.tics.2019.03.008.

    Abstract

    Literacy has many obvious benefits—it exposes the reader to a wealth of new information and enhances syntactic knowledge. However, we argue that literacy has an additional, often overlooked, benefit: it enhances people’s ability to predict spoken language thereby aiding comprehension. Readers are under pressure to process information more quickly than listeners, and reading provides excellent conditions, in particular a stable environment, for training the predictive system. It also leads to increased awareness of words as linguistic units, and more fine-grained phonological and additional orthographic representations, which sharpen lexical representations and facilitate predicted representations to be retrieved. Thus, reading trains core processes and representations involved in language prediction that are common to both reading and listening.
  • Huettig, F., & Guerra, E. (2019). Effects of speech rate, preview time of visual context, and participant instructions reveal strong limits on prediction in language processing. Brain Research, 1706, 196-208. doi:10.1016/j.brainres.2018.11.013.

    Abstract

    There is a consensus among language researchers that people can predict upcoming language. But do people always predict when comprehending language? Notions that “brains … are essentially prediction machines” certainly suggest so. In three eye-tracking experiments we tested this view. Participants listened to simple Dutch sentences (‘Look at the displayed bicycle’) while viewing four objects (a target, e.g. a bicycle, and three unrelated distractors). We used the identical visual stimuli and the same spoken sentences but varied speech rates, preview time, and participant instructions. Target nouns were preceded by definite gender-marked determiners, which allowed participants to predict the target object because only the targets but not the distractors agreed in gender with the determiner. In Experiment 1, participants had four seconds preview and sentences were presented either in a slow or a normal speech rate. Participants predicted the targets as soon as they heard the determiner in both conditions. Experiment 2 was identical except that participants were given only a one second preview. Participants predicted the targets only in the slow speech condition. Experiment 3 was identical to Experiment 2 except that participants were explicitly told to predict. This led only to a small prediction effect in the normal speech condition. Thus, a normal speech rate only afforded prediction if participants had an extensive preview. Even the explicit instruction to predict the target resulted in only a small anticipation effect with a normal speech rate and a short preview. These findings are problematic for theoretical proposals that assume that prediction pervades cognition.
  • Huettig, F., Mishra, R. K., & Padakannaya, P. (2017). Editorial. Journal of Cultural Cognitive Science, 1( 1), 1. doi:10.1007/s41809-017-0006-2.
  • Huettig, F., & Mishra, R. K. (2014). How literacy acquisition affects the illiterate mind - A critical examination of theories and evidence. Language and Linguistics Compass, 8(10), 401-427. doi:10.1111/lnc3.12092.

    Abstract

    At present, more than one-fifth of humanity is unable to read and write. We critically examine experimental evidence and theories of how (il)literacy affects the human mind. In our discussion we show that literacy has significant cognitive consequences that go beyond the processing of written words and sentences. Thus, cultural inventions such as reading shape general cognitive processing in non-trivial ways. We suggest that this has important implications for educational policy and guidance as well as research into cognitive processing and brain functioning.
  • Huisman, J. L. A., Majid, A., & Van Hout, R. (2019). The geographical configuration of a language area influences linguistic diversity. PLoS One, 14(6): e0217363. doi:10.1371/journal.pone.0217363.

    Abstract

    Like the transfer of genetic variation through gene flow, language changes constantly as a result of its use in human interaction. Contact between speakers is most likely to happen when they are close in space, time, and social setting. Here, we investigated the role of geographical configuration in this process by studying linguistic diversity in Japan, which comprises a large connected mainland (less isolation, more potential contact) and smaller island clusters of the Ryukyuan archipelago (more isolation, less potential contact). We quantified linguistic diversity using dialectometric methods, and performed regression analyses to assess the extent to which distance in space and time predict contemporary linguistic diversity. We found that language diversity in general increases as geographic distance increases and as time passes—as with biodiversity. Moreover, we found that (I) for mainland languages, linguistic diversity is most strongly related to geographic distance—a so-called isolation-by-distance pattern, and that (II) for island languages, linguistic diversity reflects the time since varieties separated and diverged—an isolation-by-colonisation pattern. Together, these results confirm previous findings that (linguistic) diversity is shaped by distance, but also goes beyond this by demonstrating the critical role of geographic configuration.
  • Hulten, A., Schoffelen, J.-M., Udden, J., Lam, N. H. L., & Hagoort, P. (2019). How the brain makes sense beyond the processing of single words – An MEG study. NeuroImage, 186, 586-594. doi:10.1016/j.neuroimage.2018.11.035.

    Abstract

    Human language processing involves combinatorial operations that make human communication stand out in the animal kingdom. These operations rely on a dynamic interplay between the inferior frontal and the posterior temporal cortices. Using source reconstructed magnetoencephalography, we tracked language processing in the brain, in order to investigate how individual words are interpreted when part of sentence context. The large sample size in this study (n = 68) allowed us to assess how event-related activity is associated across distinct cortical areas, by means of inter-areal co-modulation within an individual. We showed that, within 500 ms of seeing a word, the word's lexical information has been retrieved and unified with the sentence context. This does not happen in a strictly feed-forward manner, but by means of co-modulation between the left posterior temporal cortex (LPTC) and left inferior frontal cortex (LIFC), for each individual word. The co-modulation of LIFC and LPTC occurs around 400 ms after the onset of each word, across the progression of a sentence. Moreover, these core language areas are supported early on by the attentional network. The results provide a detailed description of the temporal orchestration related to single word processing in the context of ongoing language.

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    1-s2.0-S1053811918321165-mmc1.pdf
  • Hulten, A., Karvonen, L., Laine, M., & Salmelin, R. (2014). Producing speech with a newly learned morphosyntax and vocabulary: An MEG study. Journal of Cognitive Neuroscience, 26(8), 1721-1735. doi:10.1162/jocn_a_00558.
  • Hustá, C., Dalmaijer, E., Belopolsky, A., & Mathôt, S. (2019). The pupillary light response reflects visual working memory content. Journal of Experimental Psychology: Human Perception and Performance, 45(11), 1522-1528. doi:10.1037/xhp0000689.

    Abstract

    Recent studies have shown that the pupillary light response (PLR) is modulated by higher cognitive functions, presumably through activity in visual sensory brain areas. Here we use the PLR to test the involvement of sensory areas in visual working memory (VWM). In two experiments, participants memorized either bright or dark stimuli. We found that pupils were smaller when a prestimulus cue indicated that a bright stimulus should be memorized; this reflects a covert shift of attention during encoding of items into VWM. Crucially, we obtained the same result with a poststimulus cue, which shows that internal shifts of attention within VWM affect pupil size as well. Strikingly, the effect of VWM content on pupil size was most pronounced immediately after the poststimulus cue, and then dissipated. This suggests that a shift of attention within VWM momentarily activates an "active" memory representation, but that this representation quickly transforms into a "hidden" state that does not rely on sensory areas.

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    Supplementary_xhp0000689.docx
  • Iacozza, S., Meyer, A. S., & Lev-Ari, S. (2019). How in-group bias influences source memory for words learned from in-group and out-group speakers. Frontiers in Human Neuroscience, 13: 308. doi:10.3389/fnhum.2019.00308.

    Abstract

    Individuals rapidly extract information about others’ social identity, including whether or not they belong to their in-group. Group membership status has been shown to affect how attentively people encode information conveyed by those others. These findings are highly relevant for the field of psycholinguistics where there exists an open debate on how words are represented in the mental lexicon and how abstract or context-specific these representations are. Here, we used a novel word learning paradigm to test our proposal that the group membership status of speakers also affects how speaker-specific representations of novel words are. Participants learned new words from speakers who either attended their own university (in-group speakers) or did not (out-group speakers) and performed a task to measure their individual in-group bias. Then, their source memory of the new words was tested in a recognition test to probe the speaker-specific content of the novel lexical representations and assess how it related to individual in-group biases. We found that speaker group membership and participants’ in-group bias affected participants’ decision biases. The stronger the in-group bias, the more cautious participants were in their decisions. This was particularly applied to in-group related decisions. These findings indicate that social biases can influence recognition threshold. Taking a broader scope, defining how information is represented is a topic of great overlap between the fields of memory and psycholinguistics. Nevertheless, researchers from these fields tend to stay within the theoretical and methodological borders of their own field, missing the chance to deepen their understanding of phenomena that are of common interest. Here we show how methodologies developed in the memory field can be implemented in language research to shed light on an important theoretical issue that relates to the composition of lexical representations.

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  • Iacozza, S., Costa, A., & Duñabeitia, J. A. (2017). What do your eyes reveal about your foreign language? Reading emotional sentences in a native and foreign language. PLoS One, 12(10): e0186027. doi:10.1371/journal.pone.0186027.

    Abstract

    Foreign languages are often learned in emotionally neutral academic environments which differ greatly from the familiar context where native languages are acquired. This difference in learning contexts has been argued to lead to reduced emotional resonance when confronted with a foreign language. In the current study, we investigated whether the reactivity of the sympathetic nervous system in response to emotionally-charged stimuli is reduced in a foreign language. To this end, pupil sizes were recorded while reading aloud emotional sentences in the native or foreign language. Additionally, subjective ratings of emotional impact were provided after reading each sentence, allowing us to further investigate foreign language effects on explicit emotional understanding. Pupillary responses showed a larger effect of emotion in the native than in the foreign language. However, such a difference was not present for explicit ratings of emotionality. These results reveal that the sympathetic nervous system reacts differently depending on the language context, which in turns suggests a deeper emotional processing when reading in a native compared to a foreign language.

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    pone.0186027.s001.docx
  • Indefrey, P., & Levelt, W. J. M. (1999). A meta-analysis of neuroimaging experiments on word production. Neuroimage, 7, 1028.
  • Indefrey, P., Sahin, H., & Gullberg, M. (2017). The expression of spatial relationships in Turkish-Dutch bilinguals. Bilingualism: Language and Cognition, 20(3), 473-493. doi:10.1017/S1366728915000875.

    Abstract

    We investigated how two groups of Turkish-Dutch bilinguals and two groups of monolingual speakers of the two languages described static topological relations. The bilingual groups differed with respect to their first (L1) and second (L2) language proficiencies and a number of sociolinguistic factors. Using an elicitation tool that covers a wide range of topological relations, we first assessed the extensions of different spatial expressions (topological relation markers, TRMs) in the Turkish and Dutch spoken by monolingual speakers. We then assessed differences in the use of TRMs between the two bilingual groups and monolingual speakers. In both bilingual groups, differences compared to monolingual speakers were mainly observed for Turkish. Dutch-dominant bilinguals showed enhanced congruence between translation-equivalent Turkish and Dutch TRMs. Turkish-dominant bilinguals extended the use of a topologically neutral locative marker. Our results can be interpreted as showing different bilingual optimization strategies (Muysken, 2013) in bilingual speakers who live in the same environment but differ with respect to L2 onset, L2 proficiency, and perceived importance of the L1.
  • Indefrey, P. (1999). Some problems with the lexical status of nondefault inflection. Behavioral and Brain Sciences, 22(6), 1025. doi:10.1017/S0140525X99342229.

    Abstract

    Clahsen's characterization of nondefault inflection as based exclusively on lexical entries does not capture the full range of empirical data on German inflection. In the verb system differential effects of lexical frequency seem to be input-related rather than affecting morphological production. In the noun system, the generalization properties of -n and -e plurals exceed mere analogy-based productivity.
  • Indefrey, P. (2014). Time course of word production does not support a parallel input architecture. Language, Cognition and Neuroscience, 29(1), 33-34. doi:10.1080/01690965.2013.847191.

    Abstract

    Hickok's enterprise to unify psycholinguistic and motor control models is highly stimulating. Nonetheless, there are problems of the model with respect to the time course of neural activation in word production, the flexibility for continuous speech, and the need for non-motor feedback.

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  • Ioumpa, K., Graham, S. A., Clausner, T., Fisher, S. E., Van Lier, R., & Van Leeuwen, T. M. (2019). Enhanced self-reported affect and prosocial behaviour without differential physiological responses in mirror-sensory synaesthesia. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences, 374: 20190395. doi:10.1098/rstb.2019.0395.

    Abstract

    Mirror-sensory synaesthetes mirror the pain or touch that they observe in other people on their own bodies. This type of synaesthesia has been associated with enhanced empathy. We investigated whether the enhanced empathy of people with mirror-sensory synesthesia influences the experience of situations involving touch or pain and whether it affects their prosocial decision making. Mirror-sensory synaesthetes (N = 18, all female), verified with a touch-interference paradigm, were compared with a similar number of age-matched control individuals (all female). Participants viewed arousing images depicting pain or touch; we recorded subjective valence and arousal ratings, and physiological responses, hypothesizing more extreme reactions in synaesthetes. The subjective impact of positive and negative images was stronger in synaesthetes than in control participants; the stronger the reported synaesthesia, the more extreme the picture ratings. However, there was no evidence for differential physiological or hormonal responses to arousing pictures. Prosocial decision making was assessed with an economic game assessing altruism, in which participants had to divide money between themselves and a second player. Mirror-sensory synaesthetes donated more money than non-synaesthetes, showing enhanced prosocial behaviour, and also scored higher on the Interpersonal Reactivity Index as a measure of empathy. Our study demonstrates the subjective impact of mirror-sensory synaesthesia and its stimulating influence on prosocial behaviour.

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  • Ito, A., Martin, A. E., & Nieuwland, M. S. (2017). How robust are prediction effects in language comprehension? Failure to replicate article-elicited N400 effects. Language, Cognition and Neuroscience, 32, 954-965. doi:10.1080/23273798.2016.1242761.

    Abstract

    Current psycholinguistic theory proffers prediction as a central, explanatory mechanism in language
    processing. However, widely-replicated prediction effects may not mean that prediction is
    necessary in language processing. As a case in point, C. D. Martin et al. [2013. Bilinguals reading
    in their second language do not predict upcoming words as native readers do.
    Journal of
    Memory and Language, 69
    (4), 574

    588. doi:10.1016/j.jml.2013.08.001] reported ERP evidence for
    prediction in native- but not in non-native speakers. Articles mismatching an expected noun
    elicited larger negativity in the N400 time window compared to articles matching the expected
    noun in native speakers only. We attempted to replicate these findings, but found no evidence
    for prediction irrespective of language nativeness. We argue that pre-activation of phonological
    form of upcoming nouns, as evidenced in article-elicited effects, may not be a robust
    phenomenon. A view of prediction as a necessary computation in language comprehension
    must be re-evaluated.
  • Ito, A., Martin, A. E., & Nieuwland, M. S. (2017). On predicting form and meaning in a second language. Journal of Experimental Psychology: Learning, Memory, and Cognition, 43(4), 635-652. doi:10.1037/xlm0000315.

    Abstract

    We used event-related potentials (ERP) to investigate whether Spanish−English bilinguals preactivate form and meaning of predictable words. Participants read high-cloze sentence contexts (e.g., “The student is going to the library to borrow a . . .”), followed by the predictable word (book), a word that was form-related (hook) or semantically related (page) to the predictable word, or an unrelated word (sofa). Word stimulus onset synchrony (SOA) was 500 ms (Experiment 1) or 700 ms (Experiment 2). In both experiments, all nonpredictable words elicited classic N400 effects. Form-related and unrelated words elicited similar N400 effects. Semantically related words elicited smaller N400s than unrelated words, which however, did not depend on cloze value of the predictable word. Thus, we found no N400 evidence for preactivation of form or meaning at either SOA, unlike native-speaker results (Ito, Corley et al., 2016). However, non-native speakers did show the post-N400 posterior positivity (LPC effect) for form-related words like native speakers, but only at the slower SOA. This LPC effect increased gradually with cloze value of the predictable word. We do not interpret this effect as necessarily demonstrating prediction, but rather as evincing combined effects of top-down activation (contextual meaning) and bottom-up activation (form similarity) that result in activation of unseen words that fit the context well, thereby leading to an interpretation conflict reflected in the LPC. Although there was no evidence that non-native speakers preactivate form or meaning, non-native speakers nonetheless appear to use bottom-up and top-down information to constrain incremental interpretation much like native speakers do.
  • Ito, A., Martin, A. E., & Nieuwland, M. S. (2017). Why the A/AN prediction effect may be hard to replicate: A rebuttal to DeLong, Urbach & Kutas (2017). Language, Cognition and Neuroscience, 32(8), 974-983. doi:10.1080/23273798.2017.1323112.
  • Iyer, S., Sam, F. S., DiPrimio, N., Preston, G., Verheijen, J., Murthy, K., Parton, Z., Tsang, H., Lao, J., Morava, E., & Perlstein, E. O. (2019). Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG. Disease models & mechanisms, 12(11): UNSP dmm040584. doi:10.1242/dmm.040584.

    Abstract

    Phosphomannomutase 2 deficiency, or PMM2-CDG, is the most common congenital disorder of glycosylation and affects over 1000 patients globally. There are no approved drugs that treat the symptoms or root cause of PMM2-CDG. To identify clinically actionable compounds that boost human PMM2 enzyme function, we performed a multispecies drug repurposing screen using a novel worm model of PMM2-CDG, followed by PMM2 enzyme functional studies in PMM2-CDG patient fibroblasts. Drug repurposing candidates from this study, and drug repurposing candidates from a previously published study using yeast models of PMM2-CDG, were tested for their effect on human PMM2 enzyme activity in PMM2-CDG fibroblasts. Of the 20 repurposing candidates discovered in the worm-based phenotypic screen, 12 were plant-based polyphenols. Insights from structure-activity relationships revealed epalrestat, the only antidiabetic aldose reductase inhibitor approved for use in humans, as a first-in-class PMM2 enzyme activator. Epalrestat increased PMM2 enzymatic activity in four PMM2-CDG patient fibroblast lines with genotypes R141H/F119L, R141H/E139K, R141H/N216I and R141H/F183S. PMM2 enzyme activity gains ranged from 30% to 400% over baseline, depending on genotype. Pharmacological inhibition of aldose reductase by epalrestat may shunt glucose from the polyol pathway to glucose-1,6-bisphosphate, which is an endogenous stabilizer and coactivator of PMM2 homodimerization. Epalrestat is a safe, oral and brain penetrant drug that was approved 27 years ago in Japan to treat diabetic neuropathy in geriatric populations. We demonstrate that epalrestat is the first small molecule activator ofPMM2 enzyme activity with the potential to treat peripheral neuropathy and correct the underlying enzyme deficiency in a majority of pediatric and adult PMM2-CDG patients.

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  • Janse, E., & Jesse, A. (2014). Working memory affects older adults’ use of context in spoken-word recognition. Quarterly Journal of Experimental Psychology, 67, 1842-1862. doi:10.1080/17470218.2013.879391.

    Abstract

    Many older listeners report difficulties in understanding speech in noisy situations. Working memory and other cognitive skills may modulate, however, older listeners’ ability to use context information to alleviate the effects of noise on spoken-word recognition. In the present study, we investigated whether working memory predicts older adults’ ability to immediately use context information in the recognition of words embedded in sentences, presented in different listening conditions. In a phoneme-monitoring task, older adults were asked to detect as fast and as accurately as possible target phonemes in sentences spoken by a target speaker. Target speech was presented without noise, with fluctuating speech-shaped noise, or with competing speech from a single distractor speaker. The gradient measure of contextual probability (derived from a separate offline rating study) mainly affected the speed of recognition, with only a marginal effect on detection accuracy. Contextual facilitation was modulated by older listeners’ working memory and age across listening conditions. Working memory and age, as well as hearing loss, were also the most consistent predictors of overall listening performance. Older listeners’ immediate benefit from context in spoken-word recognition thus relates to their ability to keep and update a semantic representation of the sentence content in working memory.

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  • Janssen, C., Segers, E., McQueen, J. M., & Verhoeven, L. (2019). Comparing effects of instruction on word meaning and word form on early literacy abilities in kindergarten. Early Education and Development, 30(3), 375-399. doi:10.1080/10409289.2018.1547563.

    Abstract

    Research Findings: The present study compared effects of explicit instruction on and practice with the phonological form of words (form-focused instruction) versus explicit instruction on and practice with the meaning of words (meaning-focused instruction). Instruction was given via interactive storybook reading in the kindergarten classroom of children learning Dutch. We asked whether the 2 types of instruction had different effects on vocabulary development and 2 precursors of reading ability—phonological awareness and letter knowledge—and we examined effects on these measures of the ability to learn new words with minimal acoustic-phonetic differences. Learners showed similar receptive target-word vocabulary gain after both types of instruction, but learners who received form-focused vocabulary instruction showed more gain in semantic knowledge of target vocabulary, phonological awareness, and letter knowledge than learners who received meaning-focused vocabulary instruction. Level of ability to learn pairs of words with minimal acoustic-phonetic differences predicted gain in semantic knowledge of target vocabulary and in letter knowledge in the form-focused instruction group only. Practice or Policy: A focus on the form of words during instruction appears to have benefits for young children learning vocabulary.
  • Janssen, R., Moisik, S. R., & Dediu, D. (2019). The effects of larynx height on vowel production are mitigated by the active control of articulators. Journal of Phonetics, 74, 1-17. doi:10.1016/j.wocn.2019.02.002.

    Abstract

    The influence of larynx position on vowel articulation is an important topic in understanding speech production, the present-day distribution of linguistic diversity and the evolution of speech and language in our lineage. We introduce here a realistic computer model of the vocal tract, constructed from actual human MRI data, which can learn, using machine learning techniques, to control the articulators in such a way as to produce speech sounds matching as closely as possible to a given set of target vowels. We systematically control the vertical position of the larynx and we quantify the differences between the target and produced vowels for each such position across multiple replications. We report that, indeed, larynx height does affect the accuracy of reproducing the target vowels and the distinctness of the produced vowel system, that there is a “sweet spot” of larynx positions that are optimal for vowel production, but that nevertheless, even extreme larynx positions do not result in a collapsed or heavily distorted vowel space that would make speech unintelligible. Together with other lines of evidence, our results support the view that the vowel space of human languages is influenced by our larynx position, but that other positions of the larynx may also be fully compatible with speech.

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  • Janssen, C., Segers, E., McQueen, J. M., & Verhoeven, L. (2017). Transfer from implicit to explicit phonological abilities in first and second language learners. Bilingualism: Language and Cognition, 20(4), 795-812. doi:10.1017/S1366728916000523.

    Abstract

    Children's abilities to process the phonological structure of words are important predictors of their literacy development. In the current study, we examined the interrelatedness between implicit (i.e., speech decoding) and explicit (i.e., phonological awareness) phonological abilities, and especially the role therein of lexical specificity (i.e., the ability to learn to recognize spoken words based on only minimal acoustic-phonetic differences). We tested 75 Dutch monolingual and 64 Turkish–Dutch bilingual kindergartners. SEM analyses showed that speech decoding predicted lexical specificity, which in turn predicted rhyme awareness in the first language learners but phoneme awareness in the second language learners. Moreover, in the latter group there was an impact of the second language: Dutch speech decoding and lexical specificity predicted Turkish phonological awareness, which in turn predicted Dutch phonological awareness. We conclude that language-specific phonological characteristics underlie different patterns of transfer from implicit to explicit phonological abilities in first and second language learners.
  • Jesse, A., & McQueen, J. M. (2014). Suprasegmental lexical stress cues in visual speech can guide spoken-word recognition. Quarterly Journal of Experimental Psychology, 67, 793-808. doi:10.1080/17470218.2013.834371.

    Abstract

    Visual cues to the individual segments of speech and to sentence prosody guide speech recognition. The present study tested whether visual suprasegmental cues to the stress patterns of words can also constrain recognition. Dutch listeners use acoustic suprasegmental cues to lexical stress (changes in duration, amplitude, and pitch) in spoken-word recognition. We asked here whether they can also use visual suprasegmental cues. In two categorization experiments, Dutch participants saw a speaker say fragments of word pairs that were segmentally identical but differed in their stress realization (e.g., 'ca-vi from cavia "guinea pig" vs. 'ka-vi from kaviaar "caviar"). Participants were able to distinguish between these pairs from seeing a speaker alone. Only the presence of primary stress in the fragment, not its absence, was informative. Participants were able to distinguish visually primary from secondary stress on first syllables, but only when the fragment-bearing target word carried phrase-level emphasis. Furthermore, participants distinguished fragments with primary stress on their second syllable from those with secondary stress on their first syllable (e.g., pro-'jec from projector "projector" vs. 'pro-jec from projectiel "projectile"), independently of phrase-level emphasis. Seeing a speaker thus contributes to spoken-word recognition by providing suprasegmental information about the presence of primary lexical stress.
  • Jones, G., & Rowland, C. F. (2017). Diversity not quantity in caregiver speech: Using computational modeling to isolate the effects of the quantity and the diversity of the input on vocabulary growth. Cognitive Psychology, 98, 1-21. doi:10.1016/j.cogpsych.2017.07.002.

    Abstract

    Children who hear large amounts of diverse speech learn language more quickly than children who do not. However, high correlations between the amount and the diversity of the input in speech samples makes it difficult to isolate the influence of each. We overcame this problem by controlling the input to a computational model so that amount of exposure to linguistic input (quantity) and the quality of that input (lexical diversity) were independently manipulated. Sublexical, lexical, and multi-word knowledge were charted across development (Study 1), showing that while input quantity may be important early in learning, lexical diversity is ultimately more crucial, a prediction confirmed against children’s data (Study 2). The model trained on a lexically diverse input also performed better on nonword repetition and sentence recall tests (Study 3) and was quicker to learn new words over time (Study 4). A language input that is rich in lexical diversity outperforms equivalent richness in quantity for learned sublexical and lexical knowledge, for well-established language tests, and for acquiring words that have never been encountered before.
  • Jongman, S. R. (2017). Sustained attention ability affects simple picture naming. Collabra: Psychology, 3(1): 17. doi:10.1525/collabra.84.

    Abstract

    Sustained attention has previously been shown as a requirement for language production. However, this is mostly evident for difficult conditions, such as a dual-task situation. The current study provides corroborating evidence that this relationship holds even for simple picture naming. Sustained attention ability, indexed both by participants’ reaction times and individuals’ hit rate (the proportion of correctly detected targets) on a digit discrimination task, correlated with picture naming latencies. Individuals with poor sustained attention were consistently slower and their RT distributions were more positively skewed when naming pictures compared to individuals with better sustained attention. Additionally, the need to sustain attention was manipulated by changing the speed of stimulus presentation. Research has suggested that fast event rates tax sustained attention resources to a larger degree than slow event rates. However, in this study the fast event rate did not result in increased difficulty, neither for the picture naming task nor for the sustained attention task. Instead, the results point to a speed-accuracy trade-off in the sustained attention task (lower accuracy but faster responses in the fast than in the slow event rate), and to a benefit for faster rates in the picture naming task (shorter naming latencies with no difference in accuracy). Performance on both tasks was largely comparable, supporting previous findings that sustained attention is called upon during language production
  • Jongman, S. R., Roelofs, A., Scheper, A., & Meyer, A. S. (2017). Picture naming in typically developing and language impaired children: The role of sustained attention. International Journal of Language & Communication Disorders, 52(3), 323-333. doi:10.1111/1460-6984.12275.

    Abstract

    Children with specific language impairment (SLI) have problems not only with language performance but also with sustained attention, which is the ability to maintain alertness over an extended period of time. Although there is consensus that this ability is impaired with respect to processing stimuli in the auditory perceptual modality, conflicting evidence exists concerning the visual modality.
    Aims

    To address the outstanding issue whether the impairment in sustained attention is limited to the auditory domain, or if it is domain-general. Furthermore, to test whether children's sustained attention ability relates to their word-production skills.
    Methods & Procedures

    Groups of 7–9 year olds with SLI (N = 28) and typically developing (TD) children (N = 22) performed a picture-naming task and two sustained attention tasks, namely auditory and visual continuous performance tasks (CPTs).
    Outcomes & Results

    Children with SLI performed worse than TD children on picture naming and on both the auditory and visual CPTs. Moreover, performance on both the CPTs correlated with picture-naming latencies across developmental groups.
    Conclusions & Implications

    These results provide evidence for a deficit in both auditory and visual sustained attention in children with SLI. Moreover, the study indicates there is a relationship between domain-general sustained attention and picture-naming performance in both TD and language-impaired children. Future studies should establish whether this relationship is causal. If attention influences language, training of sustained attention may improve language production in children from both developmental groups.
  • Jongman, S. R., & Meyer, A. S. (2017). To plan or not to plan: Does planning for production remove facilitation from associative priming? Acta Psychologica, 181, 40-50. doi:10.1016/j.actpsy.2017.10.003.

    Abstract

    Theories of conversation propose that in order to have smooth transitions from one turn to the next, speakers already plan their response while listening to their interlocutor. Moreover, it has been argued that speakers align their linguistic representations (i.e. prime each other), thereby reducing the processing costs associated with concurrent listening and speaking. In two experiments, we assessed how identity and associative priming from spoken words onto picture naming were affected by a concurrent speech planning task. In a baseline (no name) condition, participants heard prime words that were identical, associatively related, or unrelated to target pictures presented two seconds after prime onset. Each prime was accompanied by a non-target picture and followed by its recorded name. The participant did not name the non-target picture. In the plan condition, the participants first named the non-target picture, instead of listening to the recording, and then the target. In Experiment 1, where the plan- and no-plan conditions were tested between participants, priming effects of equal strength were found in the plan and no-plan condition. In Experiment 2, where the two conditions were tested within participants, the identity priming effect was maintained, but the associative priming effect was only seen in the no-plan but not in the plan condition. In this experiment, participant had to decide at the onset of each trial whether or not to name the non-target picture, rendering the task more complex than in Experiment 1. These decision processes may have interfered with the processing of the primes. Thus, associative priming can take place during speech planning, but only if the cognitive load is not too high.
  • Jordens, P., & Bittner, D. (2017). Developing interlanguage: Driving forces in children learning Dutch and German. IRAL, 55(4), 365-392. doi:10.1515/iral-2017-0147.

    Abstract

    Spontaneous language learning both in children learning their mother tongue and in adults learning a second language shows that language development proceeds in a stage-wise manner. Given that a developmental stage is defined as a coherent linguistic system, utterances of language learners can be accounted for in terms of what (Selinker, Larry. 1972. Interlanguage. International Review of Applied Linguistics 10. 209-231) referred to with the term Interlanguage. This paper is a study on the early interlanguage systems of children learning Dutch and German as their mother tongue. The present child learner systems, so it is claimed, are coherent lexical systems based on types of verb-argument structure that are either agentive (as in Dutch: kannie bal pakke 'cannot ball get', or German: mag nich nase putzen 'like not nose clean') or non-agentive (as in Dutch: popje valt bijna 'doll falls nearly', or in German: ente fällt 'duck falls'). At this lexical stage, functional morphology (e. g. morphological finiteness, tense), function words (e. g. auxiliary verbs, determiners) and word order variation are absent. For these typically developing children, both in Dutch and in German, it is claimed that developmental progress is driven by the acquisition of the formal properties of topicalization. It is, furthermore, argued that this feature seems to serve as the driving force in the instantiation of the functional, i. e. informational linguistic properties of the target-language system
  • Junge, C., & Cutler, A. (2014). Early word recognition and later language skills. Brain sciences, 4(4), 532-559. doi:10.3390/brainsci4040532.

    Abstract

    Recent behavioral and electrophysiological evidence has highlighted the long-term importance for language skills of an early ability to recognize words in continuous speech. We here present further tests of this long-term link in the form of follow-up studies conducted with two (separate) groups of infants who had earlier participated in speech segmentation tasks. Each study extends prior follow-up tests: Study 1 by using a novel follow-up measure that taps into online processing, Study 2 by assessing language performance relationships over a longer time span than previously tested. Results of Study 1 show that brain correlates of speech segmentation ability at 10 months are positively related to 16-month-olds’ target fixations in a looking-while-listening task. Results of Study 2 show that infant speech segmentation ability no longer directly predicts language profiles at the age of five. However, a meta-analysis across our results and those of similar studies (Study 3) reveals that age at follow-up does not moderate effect size. Together, the results suggest that infants’ ability to recognize words in speech certainly benefits early vocabulary development; further observed relationships of later language skills to early word recognition may be consequent upon this vocabulary size effect.
  • Junge, C., Cutler, A., & Hagoort, P. (2014). Successful word recognition by 10-month-olds given continuous speech both at initial exposure and test. Infancy, 19(2), 179-193. doi:10.1111/infa.12040.

    Abstract

    Most words that infants hear occur within fluent speech. To compile a vocabulary, infants therefore need to segment words from speech contexts. This study is the first to investigate whether infants (here: 10-month-olds) can recognize words when both initial exposure and test presentation are in continuous speech. Electrophysiological evidence attests that this indeed occurs: An increased extended negativity (word recognition effect) appears for familiarized target words relative to control words. This response proved constant at the individual level: Only infants who showed this negativity at test had shown such a response, within six repetitions after first occurrence, during familiarization.
  • Kakimoto, N., Shimamoto, H., Kitisubkanchana, J., Tsujimoto, T., Senda, Y., Iwamoto, Y., Verdonschot, R. G., Hasegawa, Y., & Murakami, S. (2019). T2 relaxation times of the retrodiscal tissue in patients with temporomandibular joint disorders and in healthy volunteers: A comparative study. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 128(3), 311-318. doi:10.1016/j.oooo.2019.02.005.

    Abstract

    Objective. The aims of this study were to compare the temporomandibular joint (TMJ) retrodiscal tissue T2 relaxation times between patients with temporomandibular disorders (TMDs) and asymptomatic volunteers and to assess the diagnostic potential of this approach.
    Study Design. Patients with TMD (n = 173) and asymptomatic volunteers (n = 17) were examined by using a 1.5-T magnetic resonance scanner. The imaging protocol consisted of oblique sagittal, T2-weighted, 8-echo fast spin echo sequences in the closed mouth position. Retrodiscal tissue T2 relaxation times were obtained. Additionally, disc location and reduction, disc configuration, joint effusion, osteoarthritis, and bone edema or osteonecrosis were classified using MRI scans. The T2 relaxation times of each group were statistically compared.
    Results. Retrodiscal tissue T2 relaxation times were significantly longer in patient groups than in asymptomatic volunteers (P < .01). T2 relaxation times were significantly longer in all of the morphologic categories. The most important variables affecting retrodiscal tissue T2 relaxation times were disc configuration, joint effusion, and osteoarthritis.
    Conclusion. Retrodiscal tissue T2 relaxation times of patients with TMD were significantly longer than those of healthy volunteers. This finding may lead to the development of a diagnostic marker to aid in the early detection of TMDs.
  • Kamermans, K. L., Pouw, W., Mast, F. W., & Paas, F. (2019). Reinterpretation in visual imagery is possible without visual cues: A validation of previous research. Psychological Research, 83(6), 1237-1250. doi:10.1007/s00426-017-0956-5.

    Abstract

    Is visual reinterpretation of bistable figures (e.g., duck/rabbit figure) in visual imagery possible? Current consensus suggests that it is in principle possible because of converging evidence of quasi-pictorial functioning of visual imagery. Yet, studies that have directly tested and found evidence for reinterpretation in visual imagery, allow for the possibility that reinterpretation was already achieved during memorization of the figure(s). One study resolved this issue, providing evidence for reinterpretation in visual imagery (Mast and Kosslyn, Cognition 86:57-70, 2002). However, participants in that study performed reinterpretations with aid of visual cues. Hence, reinterpretation was not performed with mental imagery alone. Therefore, in this study we assessed the possibility of reinterpretation without visual support. We further explored the possible role of haptic cues to assess the multimodal nature of mental imagery. Fifty-three participants were consecutively presented three to be remembered bistable 2-D figures (reinterpretable when rotated 180 degrees), two of which were visually inspected and one was explored hapticly. After memorization of the figures, a visually bistable exemplar figure was presented to ensure understanding of the concept of visual bistability. During recall, 11 participants (out of 36; 30.6%) who did not spot bistability during memorization successfully performed reinterpretations when instructed to mentally rotate their visual image, but additional haptic cues during mental imagery did not inflate reinterpretation ability. This study validates previous findings that reinterpretation in visual imagery is possible.
  • Kamermans, K. L., Pouw, W., Fassi, L., Aslanidou, A., Paas, F., & Hostetter, A. B. (2019). The role of gesture as simulated action in reinterpretation of mental imagery. Acta Psychologica, 197, 131-142. doi:10.1016/j.actpsy.2019.05.004.

    Abstract

    In two experiments, we examined the role of gesture in reinterpreting a mental image. In Experiment 1, we found that participants gestured more about a figure they had learned through manual exploration than about a figure they had learned through vision. This supports claims that gestures emerge from the activation of perception-relevant actions during mental imagery. In Experiment 2, we investigated whether such gestures have a causal role in affecting the quality of mental imagery. Participants were randomly assigned to gesture, not gesture, or engage in a manual interference task as they attempted to reinterpret a figure they had learned through manual exploration. We found that manual interference significantly impaired participants' success on the task. Taken together, these results suggest that gestures reflect mental imaginings of interactions with a mental image and that these imaginings are critically important for mental manipulation and reinterpretation of that image. However, our results suggest that enacting the imagined movements in gesture is not critically important on this particular task.
  • Kaufhold, S. P., & Van Leeuwen, E. J. C. (2019). Why intergroup variation matters for understanding behaviour. Biology Letters, 15(11): 20190695. doi:10.1098/rsbl.2019.0695.

    Abstract

    Intergroup variation (IGV) refers to variation between different groups of the same species. While its existence in the behavioural realm has been expected and evidenced, the potential effects of IGV are rarely considered in studies that aim to shed light on the evolutionary origins of human socio-cognition, especially in our closest living relatives—the great apes. Here, by taking chimpanzees as a point of reference, we argue that (i) IGV could plausibly explain inconsistent research findings across numerous topics of inquiry (experimental/behavioural studies on chimpanzees), (ii) understanding the evolutionary origins of behaviour requires an accurate assessment of species' modes of behaving across different socio-ecological contexts, which necessitates a reliable estimation of variation across intraspecific groups, and (iii) IGV in the behavioural realm is increasingly likely to be expected owing to the progressive identification of non-human animal cultures. With these points, and by extrapolating from chimpanzees to generic guidelines, we aim to encourage researchers to explicitly consider IGV as an explanatory variable in future studies attempting to understand the socio-cognitive and evolutionary determinants of behaviour in group-living animals.
  • Kavaklioglu, T., Guadalupe, T., Zwiers, M., Marquand, A. F., Onnink, M., Shumskaya, E., Brunner, H., Fernandez, G., Fisher, S. E., & Francks, C. (2017). Structural asymmetries of the human cerebellum in relation to cerebral cortical asymmetries and handedness. Brain Structure and Function, 22, 1611-1623. doi:10.1007/s00429-016-1295-9.

    Abstract

    There is evidence that the human cerebellum is involved not only in motor control but also in other cognitive functions. Several studies have shown that language-related activation is lateralized toward the right cerebellar hemisphere in most people, in accordance with leftward cerebral cortical lateralization for language and a general contralaterality of cerebral–cerebellar activations. In terms of behavior, hand use elicits asymmetrical activation in the cerebellum, while hand preference is weakly associated with language lateralization. However, it is not known how, or whether, these functional relations are reflected in anatomy. We investigated volumetric gray matter asymmetries of cerebellar lobules in an MRI data set comprising 2226 subjects. We tested these cerebellar asymmetries for associations with handedness, and for correlations with cerebral cortical anatomical asymmetries of regions important for language or hand motor control, as defined by two different automated image analysis methods and brain atlases, and supplemented with extensive visual quality control. No significant associations of cerebellar asymmetries to handedness were found. Some significant associations of cerebellar lobular asymmetries to cerebral cortical asymmetries were found, but none of these correlations were greater than 0.14, and they were mostly method-/atlas-dependent. On the basis of this large and highly powered study, we conclude that there is no overt structural manifestation of cerebellar functional lateralization and connectivity, in respect of hand motor control or language laterality
  • Keller, K. L., Fritz, R. S., Zoubek, C. M., Kennedy, E. H., Cronin, K. A., Rothwell, E. S., & Serfass, T. L. (2014). Effects of transport on fecal glucocorticoid levels in captive-bred cotton-top tamarins (Saguinus oedipus). Journal of the Pennsylvania Academy of Science, 88(2), 84-88.

    Abstract

    The relocation of animals can induce stress when animals are placed in novel environmental conditions. The movement of captive animals among facilities is common, especially for non-human primates used in research. The stress response begins with the activation of the hypothalamic-pituitary-adrenal (HPA) axis which results in the release of glucocorticoid hormones (GC), which at chronic levels could lead to deleterious physiological effects. There is a substantial body of data concerning GC levels affecting reproduction, and rank and aggression in primates. However, the effect of transport has received much less attention. Fecal samples from eight (four male and four female) captive-bred cotton-top tamarins (Saguinus oedipus) were collected at four different time points (two pre-transport and two post-transport). The fecal samples were analyzed using an immunoassay to determine GC levels. A repeated measures analysis of variance (ANOVA) demonstrated that GC levels differed among transport times (p = 0.009), but not between sexes (p = 0.963). Five of the eight tamarins exhibited an increase in GC levels after transport. Seven of the eight tamarins exhibited a decrease in GC levels from three to six days post-transport to three weeks post-transport. Most values returned to pre-transport levels after three weeks. The results indicate that these tamarins experienced elevated GC levels following transport, but these increases were of short duration. This outcome would suggest that the negative effects of elevated GC levels were also of short duration.
  • Kelly, B., Wigglesworth, G., Nordlinger, R., & Blythe, J. (2014). The acquisition of polysynthetic languages. Language and Linguistics Compass, 8, 51-64. doi:10.1111/lnc3.12062.

    Abstract

    One of the major challenges in acquiring a language is being able to use morphology as an adult would, and thus, a considerable amount of acquisition research has focused on morphological production and comprehension. Most of this research, however, has focused on the acquisition of morphology in isolating languages, or languages (such as English) with limited inflectional morphology. The nature of the learning task is different, and potentially more challenging, when the child is learning a polysynthetic language – a language in which words are highly morphologically complex, expressing in a single word what in English takes a multi-word clause. To date, there has been no cross-linguistic survey of how children approach this puzzle and learn polysynthetic languages. This paper aims to provide such a survey, including a discussion of some of the general findings in the literature regarding the acquisition of polysynthetic systems
  • Kemp, J. P., Sayers, A., Paternoster, L., Evans, D. M., Deere, K., St Pourcain, B., Timpson, N. J., Ring, S. M., Lorentzon, M., Lehtimäki, T., Eriksson, J., Kähönen, M., Raitakari, O., Laaksonen, M., Sievänen, H., Viikari, J., Lyytikäinen, L.-P., Smith, G. D., Fraser, W. D., Vandenput, L. and 2 moreKemp, J. P., Sayers, A., Paternoster, L., Evans, D. M., Deere, K., St Pourcain, B., Timpson, N. J., Ring, S. M., Lorentzon, M., Lehtimäki, T., Eriksson, J., Kähönen, M., Raitakari, O., Laaksonen, M., Sievänen, H., Viikari, J., Lyytikäinen, L.-P., Smith, G. D., Fraser, W. D., Vandenput, L., Ohlsson, C., & Tobias, J. H. (2014). Does Bone Resorption Stimulate Periosteal Expansion? A Cross-Sectional Analysis of β-C-telopeptides of Type I Collagen (CTX), Genetic Markers of the RANKL Pathway, and Periosteal Circumference as Measured by pQCT. Journal of Bone and Mineral Research, 29(4), 1015-1024. doi:10.1002/jbmr.2093.

    Abstract

    We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β-C-telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMDC ). CTX and mid-tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (β=0.19 [0.13, 0.24]) (coefficient=SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMDC (β=-0.46 [-0.52,-0.40]) and cortical thickness [β=-0.11 (-0.18, -0.03)]. CTX was positively related to bone strength as reflected by the strength-strain index (SSI) (β=0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single-nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF-κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p<}0.05 cut-off) (n=2379). Subsequently, we performed a meta-analysis of associations between these SNPs and PC in ALSPAC (n=3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n=938), and the Young Finns Study (YFS) (n=1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (p{<0.05 cut-off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion.
  • Kemp, J. P., Medina-Gomez, C., Estrada, K., St Pourcain, B., Heppe, D. H. M., Warrington, N. M., Oei, L., Ring, S. M., Kruithof, C. J., Timpson, N. J., Wolber, L. E., Reppe, S., Gautvik, K., Grundberg, E., Ge, B., van der Eerden, B., van de Peppel, J., Hibbs, M. A., Ackert-Bicknell, C. L., Choi, K. and 13 moreKemp, J. P., Medina-Gomez, C., Estrada, K., St Pourcain, B., Heppe, D. H. M., Warrington, N. M., Oei, L., Ring, S. M., Kruithof, C. J., Timpson, N. J., Wolber, L. E., Reppe, S., Gautvik, K., Grundberg, E., Ge, B., van der Eerden, B., van de Peppel, J., Hibbs, M. A., Ackert-Bicknell, C. L., Choi, K., Koller, D. L., Econs, M. J., Williams, F. M. K., Foroud, T., Zillikens, M. C., Ohlsson, C., Hofman, A., Uitterlinden, A. G., Davey Smith, G., Jaddoe, V. W. V., Tobias, J. H., Rivadeneira, F., & Evans, D. M. (2014). Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment. PLoS Genetics, 10(6): e1004423. doi:10.1371/journal.pgen.1004423.

    Abstract

    Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.
  • Kempen, G. (1971). [Review of the book General Psychology by N. Dember and J.J. Jenkins]. Nijmeegs Tijdschrift voor Psychologie, 19, 132-133.
  • Kempen, G. (1999). Fiets en (centri)fuge. Onze Taal, 68, 88.
  • Kempen, G., & Harbusch, K. (2019). Mutual attraction between high-frequency verbs and clause types with finite verbs in early positions: Corpus evidence from spoken English, Dutch, and German. Language, Cognition and Neuroscience, 34(9), 1140-1151. doi:10.1080/23273798.2019.1642498.

    Abstract

    We report a hitherto unknown statistical relationship between the corpus frequency of finite verbs and their fixed linear positions (early vs. late) in finite clauses of English, Dutch, and German. Compared to the overall frequency distribution of verb lemmas in the corpora, high-frequency finite verbs are overused in main clauses, at the expense of nonfinite verbs. This finite versus nonfinite split of high-frequency verbs is basically absent from subordinate clauses. Furthermore, this “main-clause bias” (MCB) of high-frequency verbs is more prominent in German and Dutch (SOV languages) than in English (an SVO language). We attribute the MCB and its varying effect sizes to faster accessibility of high-frequency finite verbs, which (1) increases the probability for these verbs to land in clauses mandating early verb placement, and (2) boosts the activation of clause plans that assign verbs to early linear positions (in casu: clauses with SVO as opposed to SOV order).

    Additional information

    plcp_a_1642498_sm1530.pdf
  • Kempen, G. (1971). Het onthouden van eenvoudige zinnen met zijn en hebben als werkwoorden: Een experiment met steekwoordreaktietijden. Nijmeegs Tijdschrift voor Psychologie, 19, 262-274.
  • Kempen, G., & Kolk, H. (1986). Het voortbrengen van normale en agrammatische taal. Van Horen Zeggen, 27(2), 36-40.
  • Kempen, G. (1971). Opslag van woordbetekenissen in het semantisch geheugen. Nijmeegs Tijdschrift voor Psychologie, 19, 36-50.
  • Kempen, G. (2014). Prolegomena to a neurocomputational architecture for human grammatical encoding and decoding. Neuroinformatics, 12, 111-142. doi:10.1007/s12021-013-9191-4.

    Abstract

    The study develops a neurocomputational architecture for grammatical processing in language production and language comprehension (grammatical encoding and decoding, respectively). It seeks to answer two questions. First, how is online syntactic structure formation of the complexity required by natural-language grammars possible in a fixed, preexisting neural network without the need for online creation of new connections or associations? Second, is it realistic to assume that the seemingly disparate instantiations of syntactic structure formation in grammatical encoding and grammatical decoding can run on the same neural infrastructure? This issue is prompted by accumulating experimental evidence for the hypothesis that the mechanisms for grammatical decoding overlap with those for grammatical encoding to a considerable extent, thus inviting the hypothesis of a single “grammatical coder.” The paper answers both questions by providing the blueprint for a syntactic structure formation mechanism that is entirely based on prewired circuitry (except for referential processing, which relies on the rapid learning capacity of the hippocampal complex), and can subserve decoding as well as encoding tasks. The model builds on the “Unification Space” model of syntactic parsing developed by Vosse & Kempen (2000, 2008, 2009). The design includes a neurocomputational mechanism for the treatment of an important class of grammatical movement phenomena.
  • Kempen, G. (1984). Taaltechnologie voor het Nederlands: Vorderingen bij de bouw van een Nederlandstalig dialoog- en auteursysteem. Toegepaste Taalwetenschap in Artikelen, 19, 48-58.
  • Kempen, G., Konst, L., & De Smedt, K. (1984). Taaltechnologie voor het Nederlands: Vorderingen bij de bouw van een Nederlandstalig dialoog- en auteursysteem. Informatie, 26, 878-881.
  • Kempen, G. (1986). RIKS: Kennistechnologisch centrum voor bedrijfsleven en wetenschap. Informatie, 28, 122-125.
  • Kempen, G., & Huijbers, P. (1983). The lexicalization process in sentence production and naming: Indirect election of words. Cognition, 14(2), 185-209. doi:10.1016/0010-0277(83)90029-X.

    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).
  • Kempen, G. (1983). Wat betekent taalvaardigheid voor informatiesystemen? TNO project: Maandblad voor toegepaste wetenschappen, 11, 401-403.
  • Kendrick, K. H., & Holler, J. (2017). Gaze direction signals response preference in conversation. Research on Language and Social Interaction, 50(1), 12-32. doi:10.1080/08351813.2017.1262120.

    Abstract

    In this article, we examine gaze direction in responses to polar questions using both quantitative and conversation analytic (CA) methods. The data come from a novel corpus of conversations in which participants wore eye-tracking glasses to obtain direct measures of their eye movements. The results show that while most preferred responses are produced with gaze toward the questioner, most dispreferred responses are produced with gaze aversion. We further demonstrate that gaze aversion by respondents can occasion self-repair by questioners in the transition space between turns, indicating that the relationship between gaze direction and preference is more than a mere statistical association. We conclude that gaze direction in responses to polar questions functions as a signal of response preference. Data are in American, British, and Canadian English.

    Additional information

    hrls_a_1262120_sm9379.pdf
  • Kersten, R. W. J., Van Gastel, B. E., Shkaravska, O., Montenegro, M., & Van Eekelen, M. C. J. D. (2014). ResAna: a resource analysis toolset for (real-time) JAVA. Concurrency and Computing: Practice and Experience, 26, 2432-2455. doi:10.1002/cpe.3154.

    Abstract

    For real-time and embedded systems, limiting the consumption of time and memory resources is often an important part of the requirements. Being able to predict bounds on the consumption of such resources during the development process of the code can be of great value. In this paper, we focus mainly on memory-related bounds. Recent research results have advanced the state of the art of resource consumption analysis. In this paper, we present a toolset that makes it possible to apply these research results in practice for (real-time) systems enabling JAVA developers to analyse symbolic loop bounds, symbolic bounds on heap size and both symbolic and numeric bounds on stack size. We describe which theoretical additions were needed in order to achieve this. We give an overview of the capabilities of the RESANA (Radboud University Nijmegen, The Netherlands) toolset that is the result of this effort. The toolset can not only perform generally applicable analyses, but it also contains a part of the analysis that is dedicated to the developers' (real-time) virtual machine, such that the results apply directly to the actual development environment that is used in practice
  • Wu, Q., Kidd, E., & Goodhew, S. C. (2019). The spatial mapping of concepts in English and Mandarin. Journal of Cognitive Psychology, 31(7), 703-724. doi:10.1080/20445911.2019.1663354.

    Abstract

    English speakers have been shown to map abstract concepts in space, which occurs on both the vertical and horizontal dimensions. For example, words such as God are associated with up and right spatial locations, and words such as Satan with down and left. If the tendency to map concepts in space is a universal property of human cognition, then it is likely that such mappings may be at least partly culturally-specific, since many concepts are themselves language-specific and therefore cultural conventions. Here we investigated whether Mandarin speakers report spatial mapping of concepts, and how these mappings compare with English speakers (i.e. are words with the same meaning associated with the same spatial locations). Across two studies, results showed that both native English and Mandarin speakers reported spatial mapping of concepts, and that the distribution of mappings was highly similar for the two groups. Theoretical implications are discussed.
  • Kim, N., Brehm, L., & Yoshida, M. (2019). The online processing of noun phrase ellipsis and mechanisms of antecedent retrieval. Language, Cognition and Neuroscience, 34(2), 190-213. doi:10.1080/23273798.2018.1513542.

    Abstract

    We investigate whether grammatical information is accessed in processing noun phrase ellipsis (NPE) and other anaphoric constructions. The first experiment used an agreement attraction paradigm to reveal that ungrammatical plural verbs following NPE with an antecedent containing a plural modifier (e.g. Derek’s key to the boxes … and Mary’s_ probably *are safe in the drawer) show similar facilitation to non-elided NPs. The second experiment used the same paradigm to examine a coordination construction without anaphoric elements, and the third examined anaphoric one. Agreement attraction was not observed in either experiment, suggesting that processing NPE is different from processing non-anaphoric coordination constructions or anaphoric one. Taken together, the results indicate that the parser is sensitive to grammatical distinctions at the ellipsis site where it prioritises and retrieves the head at the initial stage of processing and retrieves the local noun within the modifier phrase only when it is necessary in parsing NPE.

    Additional information

    Kim_Brehm_Yoshida_2018sup.pdf
  • Kinoshita, S., Schubert, T., & Verdonschot, R. G. (2019). Allograph priming is based on abstract letter identities: Evidence from Japanese kana. Journal of Experimental Psychology: Learning, Memory, and Cognition, 45(1), 183-190. doi:10.1037/xlm0000563.

    Abstract

    It is well-established that allographs like the uppercase and lowercase forms of the Roman alphabet (e.g., a and A) map onto the same "abstract letter identity," orthographic representations that are independent of the visual form. Consistent with this, in the allograph match task ("Are 'a' and 'A' the same letter?"), priming by a masked letter prime is equally robust for visually dissimilar prime-target pairs (e.g., d and D) and similar pairs (e.g., c and C). However, in principle this pattern of priming is also consistent with the possibility that allograph priming is purely phonological, based on the letter name. Because different allographic forms of the same letter, by definition, share a letter name, it is impossible to rule out this possibility a priori. In the present study, we investigated the influence of shared letter names by taking advantage of the fact that Japanese is written in two distinct writing systems, syllabic kana-that has two parallel forms, hiragana and katakana-and logographic kanji. Using the allograph match task, we tested whether a kanji prime with the same pronunciation as the target kana (e.g., both pronounced /i/) produces the same amount of priming as a kana prime in the opposite kana form (e.g.,). We found that the kana primes produced substantially greater priming than the phonologically identical kanji prime. which we take as evidence that allograph priming is based on abstract kana identity, not purely phonology.
  • Kinoshita, S., & Verdonschot, R. G. (2019). On recognizing Japanese katakana words: Explaining the reduced priming with hiragana and mixed-kana identity primes. Journal of Experimental Psychology: Human Perception and Performance, 45(11), 1513-1521. doi:10.1037/xhp0000692.

    Abstract

    The Japanese kana syllabary has 2 allographic forms, hiragana and katakana. As with other allographic variants like the uppercase and lowercase letters of the Roman alphabet, they show robust formindependent priming effects in the allograph match task (e.g., Kinoshita. Schubert. & Verdonschot, 2019). suggesting that they share abstract character-level representations. In direct contradiction, Perea. Nakayama, and Lupker (2017) argued that hiragana and katakana do not share character-level representations. based on their finding of reduced priming with identity prime containing a mix of hiragana and katakana (the mixed-kana prime) relative to the all-katakana identity prime in a lexical-decision task with loanword targets written in katakana. Here we sought to reconcile these seemingly contradictory claims, using mixed-kana. hiragana, and katakana primes in lexical decision. The mixed-kana prime and hiragana prime produced priming effects that are indistinguishable, and both were reduced in size relative to the priming effect produced by the katakana identity prime. Furthermore, this pattern was unchanged when the target was presented in hiragana. The findings are interpreted in terms of the assumption that the katakana format is specified in the orthographic representation of loanwords in Japanese readers. Implications of the account for the universality across writing systems is discussed.
  • Kirjavainen, M., Kidd, E., & Lieven, E. (2017). How do language-specific characteristics affect the acquisition of different relative clause types? Evidence from Finnish. Journal of Child Language, 44(1), 120-157. doi:10.1017/s0305000915000768.

    Abstract

    We report three studies (one corpus, two experimental) that investigated the acquisition of relative clauses (RCs) in Finnish-speaking children. Study 1 found that Finnish children's naturalistic exposure to RCs predominantly consists of non-subject relatives (i.e. oblique, object) which typically have inanimate head nouns. Study 2 tested children's comprehension of subject, object, and two types of oblique relatives. No difference was found in the children's performance on different structures, including a lack of previously widely reported asymmetry between subject and object relatives. However, children's comprehension was modulated by animacy of the head referent. Study 3 tested children's production of the same RC structures using sentence repetition. Again we found no subject–object asymmetry. The pattern of results suggested that distributional frequency patterns and the relative complexity of the relativizer contribute to the difficulty associated with particular RC structures.
  • Kirkham, J. A., & Kidd, E. (2017). The effect of Steiner, Montessori, and national curriculum education upon children's pretence and creativity. Journal of Creative Behavior, 51(1), 20-34. doi:10.1002/jocb.83.

    Abstract

    Pretence and creativity are often regarded as ubiquitous characteristics of childhood, yet not all education systems value or promote these attributes to the same extent. Different pedagogies and practices are evident within the UK National Curriculum, Steiner and Montessori schools. In this study, 20 children participated from each of these school systems (N = 60, aged 6;10–8;11) completing the test of creative thinking—drawing production (TCT-DP; K. K. Urban, & H. G. Jellen, 1996) and a pretend actions task (W. F. Overton & J. P. Jackson, 1973). Overall, Steiner pupils performed significantly higher on the TCT-DP than both the Montessori and National Curriculum pupils who performed similarly. Steiner pupils also performed significantly better on the pretend actions task than the Montessori pupils, but no other significant differences were found. Overall, there was also a significant positive correlation between pretence and creativity in the current sample, supporting previous research suggesting that these skills are related (e.g., A.S. Kaugars & S. W. Russ, 2009; P. Y. Mullineaux & L. F. Dilalla, 2009).
  • Kita, S., Alibali, M. W., & Chu, M. (2017). How Do Gestures Influence Thinking and Speaking? The Gesture-for-Conceptualization Hypothesis. Psychological Review, 124(3), 245-266. doi:10.1037/rev0000059.

    Abstract

    People spontaneously produce gestures during speaking and thinking. The authors focus here on gestures that depict or indicate information related to the contents of concurrent speech or thought (i.e., representational gestures). Previous research indicates that such gestures have not only communicative functions, but also self-oriented cognitive functions. In this article, the authors propose a new theoretical framework, the gesture-for-conceptualization hypothesis, which explains the self-oriented functions of representational gestures. According to this framework, representational gestures affect cognitive processes in 4 main ways: gestures activate, manipulate, package, and explore spatio-motoric information for speaking and thinking. These four functions are shaped by gesture's ability to schematize information, that is, to focus on a small subset of available information that is potentially relevant to the task at hand. The framework is based on the assumption that gestures are generated from the same system that generates practical actions, such as object manipulation; however, gestures are distinct from practical actions in that they represent information. The framework provides a novel, parsimonious, and comprehensive account of the self-oriented functions of gestures. The authors discuss how the framework accounts for gestures that depict abstract or metaphoric content, and they consider implications for the relations between self-oriented and communicative functions of gestures
  • Kita, S., Van Gijn, I., & Van Der Hulst, H. (2014). The non-linguistic status of the Symmetry Condition in signed languages: Evidence from a comparison of signs and speechaccompanying representational gestures. Sign language and linguistics, 17(2), 215-238.

    Abstract

    Since Battison (1978), it has been noted in many signed languages that the Symmetry Condition constrains the form of two-handed signs in which two hands move independently. The Condition states that the form features (e.g., the handshapes and movements) of the two hands are 'symmetrical'. The Symmetry Condition has been regarded in the literature as a part of signed language phonology. In this study, we examine the linguistic status of the Symmetry Condition by comparing the degree of symmetry in signs from Sign Language of the Netherlands and speech-accompanying representational gestures produced by Dutch speakers. Like signed language, such gestures use hand movements to express concepts, but they do not constitute a linguistic system in their own right. We found that the Symmetry Condition holds equally well for signs and spontaneous gestures. This indicates that this condition is a general cognitive constraint, rather than a constraint specific to language. We suggest that the Symmetry Condition is a manifestation of the mind having one active 'mental articulator' when expressing a concept with hand movements
  • De Kleijn, R., Wijnen, M., & Poletiek, F. H. (2019). The effect of context-dependent information and sentence constructions on perceived humanness of an agent in a Turing test. Knowledge-Based Systems, 163, 794-799. doi:10.1016/j.knosys.2018.10.006.

    Abstract

    In a Turing test, a judge decides whether their conversation partner is either a machine or human. What cues does the judge use to determine this? In particular, are presumably unique features of human language actually perceived as humanlike? Participants rated the humanness of a set of sentences that were manipulated for grammatical construction: linear right-branching or hierarchical center-embedded and their plausibility with regard to world knowledge.

    We found that center-embedded sentences are perceived as less humanlike than right-branching sentences and more plausible sentences are regarded as more humanlike. However, the effect of plausibility of the sentence on perceived humanness is smaller for center-embedded sentences than for right-branching sentences.

    Participants also rated a conversation with either correct or incorrect use of the context by the agent. No effect of context use was found. Also, participants rated a full transcript of either a real human or a real chatbot, and we found that chatbots were reliably perceived as less humanlike than real humans, in line with our expectation. We did, however, find individual differences between chatbots and humans.
  • Klein, W. (2017). Statt einer Einleitung: Brigitte Schlieben-Lange zum Gedenken. Zeitschrift für Literaturwissenschaft und Linguistik, 30(4), 5-10. doi:10.1007/BF03379240.
  • Klein, W., & Musan, R. (Eds.). (1999). Das deutsche Perfekt [Special Issue]. Zeitschrift für Literaturwissenschaft und Linguistik, (113).
  • Klein, W. (1986). Der Wahn vom Sprachverfall und andere Mythen. Zeitschrift für Literaturwissenschaft und Linguistik, 62, 11-28.
  • Klein, W. (1986). Einleitung. Zeitschrift für Literaturwissenschaft und Linguistik; Metzler, Stuttgart, 16(62), 9-10.
  • Klein, W. (1971). Eine kommentierte Bibliographie zur Computerlinguistik. Linguistische Berichte, (11), 101-134.
  • Klein, W. (2014). Is aspect time-relational? Commentary on the paper by Jürgen Bohnemeyer. Natural Language & Linguistic Theory, 32(3), 955-971. doi:10.1007/s11049-014-9240-1.

    Abstract

    Tense is traditionally assumed to express temporal relations between the time of the event and the moment of speech, whereas aspect expresses various views on one and the same event. In Klein (1994), it was argued that the intuitions which underlie this viewing metaphor can be made precise by a time-relational analysis as well. In his article “Aspect vs. relative tense: the case reopened”, Jürgen Bohnemeyer challenges one important point of this analysis, the equation of aspect and relative tense in the English perfect and in temporal forms of few other languages. In the present comment, it is argued that this is indeed a simplification, which does not speak, however, against a time-relational analysis of aspect in general. The main lines of such an analysis for the English perfect are sketched. It is shown that it naturally accounts for differences between the simple past and the present perfect, as well as for the oddity of constructions such as Einstein has visited Princeton or Ira has left yesterday at five.
  • Klein, M., Van Donkelaar, M., Verhoef, E., & Franke, B. (2017). Imaging genetics in neurodevelopmental psychopathology. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 174(5), 485-537. doi:10.1002/ajmg.b.32542.

    Abstract

    Neurodevelopmental disorders are defined by highly heritable problems during development and brain growth. Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), and intellectual disability (ID) are frequent neurodevelopmental disorders, with common comorbidity among them. Imaging genetics studies on the role of disease-linked genetic variants on brain structure and function have been performed to unravel the etiology of these disorders. Here, we reviewed imaging genetics literature on these disorders attempting to understand the mechanisms of individual disorders and their clinical overlap. For ADHD and ASD, we selected replicated candidate genes implicated through common genetic variants. For ID, which is mainly caused by rare variants, we included genes for relatively frequent forms of ID occurring comorbid with ADHD or ASD. We reviewed case-control studies and studies of risk variants in healthy individuals. Imaging genetics studies for ADHD were retrieved for SLC6A3/DAT1, DRD2, DRD4, NOS1, and SLC6A4/5HTT. For ASD, studies on CNTNAP2, MET, OXTR, and SLC6A4/5HTT were found. For ID, we reviewed the genes FMR1, TSC1 and TSC2, NF1, and MECP2. Alterations in brain volume, activity, and connectivity were observed. Several findings were consistent across studies, implicating, for example, SLC6A4/5HTT in brain activation and functional connectivity related to emotion regulation. However, many studies had small sample sizes, and hypothesis-based, brain region-specific studies were common. Results from available studies confirm that imaging genetics can provide insight into the link between genes, disease-related behavior, and the brain. However, the field is still in its early stages, and conclusions about shared mechanisms cannot yet be drawn.
  • Klein, W. (Ed.). (1983). Intonation [Special Issue]. Zeitschrift für Literaturwissenschaft und Linguistik, (49).
  • Klein, W. (Ed.). (1984). Textverständlichkeit - Textverstehen [Special Issue]. Zeitschrift für Literaturwissenschaft und Linguistik, (55).
  • Klein, W. (Ed.). (1986). Sprachverfall [Special Issue]. Zeitschrift für Literaturwissenschaft und Linguistik, (62).
  • Klein, W. (1999). Wie sich das deutsche Perfekt zusammensetzt. Zeitschrift für Literaturwissenschaft und Linguistik; Metzler, Stuttgart, (113), 52-85.
  • Klein, W. (1986). Über Ansehen und Wirkung der deutschen Sprachwissenschaft heute. Linguistische Berichte, 100, 511-520.
  • Klein, W. (1983). Vom Glück des Mißverstehens und der Trostlosigkeit der idealen Kommunikationsgemeinschaft. Zeitschrift für Literaturwissenschaft und Linguistik, 50, 128-140.
  • Klenova, A. V., Goncharova, M. V., Bragina, E. V., & Kashentseva, T. A. (2014). Vocal development and voice breaking in Demoiselle Cranes (Anthropoides virgo). Bioacoustics, 23, 247-265. doi:10.1080/09524622.2014.900648.

    Abstract

    The vocal development of cranes (Gruidae) has attracted scientific interest due to a
    special stage, so-called voice breaking. During voice breaking, chicks produce both
    adult low-frequency and juvenile high-frequency vocalizations. The triggers that affect voice breaking are unknown. For the first time, we study the vocal development of the Demoiselle Crane (Anthropoides virgo). We describe the age and possible drivers of
    the onset of voice breaking. We analyse the calls of 21 Demoiselle Crane chicks, and
    compare them with the calls of six adult birds, noting the day when adult low-frequency calls are first recorded as the day when voice breaking begins. The age of voice
    breaking onset does not depend on hatching date, clutch order or chick body mass. Thus, there is no correlation between body growth and the onset of voice breaking for individual Demoiselle Crane chicks. However, there is a strong relationship between body mass and voice breaking among different crane species. Demoiselle Cranes stop intense body growth at the age of 2 months and start voice breaking at 70 ^ 46 days. By way of comparison, Red-crowned Cranes finish the period of intense body growth at the age of 7 months and start voice breaking at 211 ^ 60 days. Thus, we show that the Demoiselle Crane has a sudden vocal development, similar to other crane species, and we suggest that the end of intense body growth is the trigger for the onset of voice breaking in cranes.
  • Klepp, A., Niccolai, V., Sieksmeyer, J., Arnzen, S., Indefrey, P., Schnitzler, A., & Biermann-Ruben, K. (2017). Body-part specific interactions of action verb processing with motor behaviour. Behavioural Brain Research, 328, 149-158. doi:10.1016/j.bbr.2017.04.002.

    Abstract

    The interaction of action-related language processing with actual movement is an indicator of the functional role of motor cortical involvement in language understanding. This paper describes two experiments using single action verb stimuli. Motor responses were performed with the hand or the foot. To test the double dissociation of language-motor facilitation effects within subjects, Experiments 1 and 2 used a priming procedure where both hand and foot reactions had to be performed in response to different geometrical shapes, which were preceded by action verbs. In Experiment 1, the semantics of the verbs could be ignored whereas Experiment 2 included semantic decisions. Only Experiment 2 revealed a clear double dissociation in reaction times: reactions were facilitated when preceded by verbs describing actions with the matching effector. In Experiment 1, by contrast, there was an interaction between verb-response congruence and a semantic variable related to motor features of the verbs. Thus, the double dissociation paradigm of semantic motor priming was effective, corroborating the role of the motor system in action-related language processing. Importantly, this effect was body part specific.

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  • Klingler, E., De la Rossa, A., Fièvre, S., Devaraju, K., Abe, P., & Jabaudon, D. (2019). A translaminar genetic logic for the circuit identity of intracortically projecting neurons. Current Biology, 29(2), 332-339. doi:10.1016/j.cub.2018.11.071.

    Abstract

    Neurons of the neocortex are organized into six radial layers, which have appeared at different times during evolution, with the superficial layers representing a more recent acquisition. Input to the neocortex predominantly reaches superficial layers (SL, i.e., layers (L) 2-4), while output is generated in deep layers (DL, i.e., L5-6) [1]. Intracortical connections, which bridge input and output pathways, are key components of cortical circuits because they allow the propagation and processing of information within the neocortex. Two main types of intracortically projecting neurons (ICPN) can be distinguished by their axonal features: L4 spiny stellate neurons (SSN) with short axons projecting locally within cortical columns [2, 3, 4, 5], and SL and DL long-range projection neurons, including callosally projecting neurons (CPNSL and CPNDL) [5, 6]. Here, we investigate the molecular hallmarks that distinguish SSN, CPNSL, and CPNDL and relate their transcriptional signatures with their output connectivity. Specifically, taking advantage of the presence of CPN in both SL and DL, we identify lamina-independent genetic hallmarks of a constant projection motif (i.e., interhemispheric projection). By performing unbiased transcriptomic comparisons between CPNSL, CPNDL and SSN, we provide specific molecular profiles for each of these populations and show that target identity supersedes laminar position in defining ICPN transcriptional diversity. Together, these findings reveal a projection-based organization of transcriptional programs across cortical layers, which we propose reflects conserved strategy to protect canonical circuit structure (and hence function) across a diverse range of neuroanatomies.

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  • Knudsen, B., Fischer, M., & Aschersleben, G. (2014). Development of Spatial Preferences for Counting and Picture Naming. Psychological Research, 79, 939-949. doi:10.1007/s00426-014-0623-z.

    Abstract

    The direction of object enumeration reflects children’s enculturation but previous work on the development of such spatial preferences has been inconsistent. Therefore, we documented directional preferences in finger counting, object counting, and picture naming for children (4 groups from 3 to 6 years, N = 104) and adults (N = 56). We found a right-side preference for finger counting in 3- to 6-year-olds and a left-side preference for counting objects and naming pictures by 6 years of age. Children were consistent in their special preferences when comparing object counting and picture naming, but not in other task pairings. Finally, spatial preferences were not related to cardinality comprehension. These results, together with other recent work, suggest a gradual development of spatial-numerical associations from early non-directional mappings into culturally constrained directional mappings.
  • Kochari, A., & Flecken, M. (2019). Lexical prediction in language comprehension: A replication study of grammatical gender effects in Dutch. Language, Cognition and Neuroscience, 34(2), 239-253. doi:10.1080/23273798.2018.1524500.

    Abstract

    An important question in predictive language processing is the extent to which prediction effects can reliably be measured on pre-nominal material (e.g. articles before nouns). Here, we present a large sample (N = 58) close replication of a study by Otten and van Berkum (2009). They report ERP modulations in relation to the predictability of nouns in sentences, measured on gender-marked Dutch articles. We used nearly identical materials, procedures, and data analysis steps. We fail to replicate the original effect, but do observe a pattern consistent with the original data. Methodological differences between our replication and the original study that could potentially have contributed to the diverging results are discussed. In addition, we discuss the suitability of Dutch gender-marked determiners as a test-case for future studies of pre-activation of lexical items.
  • Kong, X. (2014). Association between in-scanner head motion with cerebral white matter microstructure: a multiband diffusion-weighted MRI study. PeerJ, 2: e366. doi:10.7717/peerj.366.

    Abstract

    Diffusion-weighted Magnetic Resonance Imaging (DW-MRI) has emerged as the most popular neuroimaging technique used to depict the biological microstructural properties of human brain white matter. However, like other MRI techniques, traditional DW-MRI data remains subject to head motion artifacts during scanning. For example, previous studies have indicated that, with traditional DW-MRI data, head motion artifacts significantly affect the evaluation of diffusion metrics. Actually, DW-MRI data scanned with higher sampling rate are important for accurately evaluating diffusion metrics because it allows for full-brain coverage through the acquisition of multiple slices simultaneously and more gradient directions. Here, we employed a publicly available multiband DW-MRI dataset to investigate the association between motion and diffusion metrics with the standard pipeline, tract-based spatial statistics (TBSS). The diffusion metrics used in this study included not only the commonly used metrics (i.e., FA and MD) in DW-MRI studies, but also newly proposed inter-voxel metric, local diffusion homogeneity (LDH). We found that the motion effects in FA and MD seems to be mitigated to some extent, but the effect on MD still exists. Furthermore, the effect in LDH is much more pronounced. These results indicate that researchers shall be cautious when conducting data analysis and interpretation. Finally, the motion-diffusion association is discussed.
  • Kong, X., Song, Y., Zhen, Z., & Liu, J. (2017). Genetic Variation in S100B Modulates Neural Processing of Visual Scenes in Han Chinese. Cerebral Cortex, 27(2), 1326-1336. doi:10.1093/cercor/bhv322.

    Abstract

    Spatial navigation is a crucial ability for living. Previous animal studies have shown that the S100B gene is causally related to spatial navigation performance in mice. However, the genetic factors influencing human navigation and its neural substrates remain unclear. Here, we provided the first evidence that the S100B gene modulates neural processing of navigationally relevant scenes in humans. First, with a novel protocol, we demonstrated that the spatial pattern of S100B gene expression in postmortem brains was associated with brain activation pattern for spatial navigation in general, and for scene processing in particular. Further, in a large fMRI cohort of healthy adults of Han Chinese (N = 202), we found that S100B gene polymorphisms modulated scene selectivity in the retrosplenial cortex (RSC) and parahippocampal place area. Finally, the serum levels of S100B protein mediated the association between S100B gene polymorphism and scene selectivity in the RSC. Our study takes the first step toward understanding the neurogenetic mechanism of human spatial navigation and suggests a novel approach to discover candidate genes modulating cognitive functions.

    Additional information

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  • Kong, X., Wang, X., Pu, Y., Huang, L., Hao, X., Zhen, Z., & Liu, J. (2017). Human navigation network: The intrinsic functional organization and behavioral relevance. Brain Structure and Function, 222(2), 749-764. doi:10.1007/s00429-016-1243-8.

    Abstract

    Spatial navigation is a crucial ability for living. Previous work has revealed multiple distributed brain regions associated with human navigation. However, little is known about how these regions work together as a network (referred to as navigation network) to support flexible navigation. In a novel protocol, we combined neuroimaging meta-analysis, and functional connectivity and behavioral data from the same subjects. Briefly, we first constructed the navigation network for each participant, by combining a large-scale neuroimaging meta-analysis (with the Neurosynth) and resting-state functional magnetic resonance imaging. Then, we investigated multiple topological properties of the navigation networks, including small-worldness, modularity, and highly connected hubs. Finally, we explored the behavioral relevance of these intrinsic properties in a large sample of healthy young adults (N = 190). We found that navigation networks showed small-world and modular organization at global level. More importantly, we found that increased small-worldness and modularity of the navigation network were associated with better navigation ability. Finally, we found that the right retrosplenial complex (RSC) acted as one of the hubs in the navigation network, and that higher betweenness of this region correlated with better navigation ability, suggesting a critical role of the RSC in modulating the navigation network in human brain. Our study takes one of the first steps toward understanding the underlying organization of the navigation network. Moreover, these findings suggest the potential applications of the novel approach to investigating functionally meaningful networks in human brain and their relations to the behavioral impairments in the aging and psychiatric patients.
  • Kong, X., Zhen, Z., Li, X., Lu, H.-h., Wang, R., Liu, L., He, Y., Zang, Y., & Liu, J. (2014). Individual Differences in Impulsivity Predict Head Motion during Magnetic Resonance Imaging. PLoS One, 9(8): e104989. doi:10.1371/journal.pone.0104989.

    Abstract

    Magnetic resonance imaging (MRI) provides valuable data for understanding the human mind and brain disorders, but in-scanner head motion introduces systematic and spurious biases. For example, differences in MRI measures (e.g., network strength, white matter integrity) between patient and control groups may be due to the differences in their head motion. To determine whether head motion is an important variable in itself, or just simply a confounding variable, we explored individual differences in psychological traits that may predispose some people to move more than others during an MRI scan. In the first two studies, we demonstrated in both children (N  =  245) and adults (N  =  581) that head motion, estimated from resting-state functional MRI and diffusion tensor imaging, was reliably correlated with impulsivity scores. Further, the difference in head motion between children with attention deficit hyperactivity disorder (ADHD) and typically developing children was largely due to differences in impulsivity. Finally, in the third study, we confirmed the observation that the regression approach, which aims to deal with motion issues by regressing out motion in the group analysis, would underestimate the effect of interest. Taken together, the present findings provide empirical evidence that links in-scanner head motion to psychological traits.
  • Kong, X., Wang, X., Huang, L., Pu, Y., Yang, Z., Dang, X., Zhen, Z., & Liu, J. (2014). Measuring individual morphological relationship of cortical regions. Journal of Neuroscience Methods, 237, 103-107. doi:10.1016/j.jneumeth.2014.09.003.

    Abstract

    Background Although local features of brain morphology have been widely investigated in neuroscience, the inter-regional relations in brain morphology have rarely been investigated, especially not for individual participants. New method In this paper, we proposed a novel framework for investigating this relation based on an individual's magnetic resonance imaging (MRI) data. The key idea was to estimate the probability density function (PDF) of local morphological features within a brain region to provide a global description of this region. Then, the inter-regional relations were quantified by calculating the similarity of the PDFs for pairs of regions based on the Kullback–Leibler (KL) divergence. Results For illustration, we applied this approach to a pre-post intervention study to investigate the longitudinal changes in morphological relations after long-term sleep deprivation. The results suggest the potential application of this new method for studies on individual differences in brain structure. Comparison with existing methods The current method can be employed to estimate individual morphological relations between regions, which have been largely ignored by previous studies. Conclusions Our morphological relation metric, as a novel quantitative biomarker, can be used to investigate normal individual variability and even within-individual alterations/abnormalities in brain structure.
  • Kong, X., Huang, Y., Hu, S., & Liu, J. (2017). Sex-linked association between cortical scene selectivity and navigational ability. NeuroImage, 158, 397-405. doi:10.1016/j.neuroimage.2017.07.031.

    Abstract

    Spatial navigation is a crucial ability for living. Previous studies have shown that males are better at navigation than females, but little is known about the neural basis underlying the sex differences. In this study, we investigated whether cortical scene processing in three well-established scene-selective regions was sexually different, by examining sex differences in scene selectivity and its behavioral relevance to navigation. To do this, we used functional magnetic resonance imaging (fMRI) to scan the parahippocampal place area (PPA), retrosplenial complex (RSC), and occipital place area (OPA) in a large cohort of healthy young adults viewing navigationally relevant scenes (N = 202), and correlated their neural selectivity to scenes with their self-reported navigational ability. Behaviorally, we replicated the previous finding that males were better at navigation than females. Neurally, we found that the scene selectivity in the bilateral PPA, not in the RSC or OPA, was significantly higher in males than females. Such differences could not be explained by confounding factors including brain size and fMRI data quality. Importantly, males, not females, with stronger scene selectivity in the left PPA possessed better navigational ability. This brain-behavior association could not be accounted for by non-navigational abilities (i.e., intelligence and mental rotation ability). Overall, our study provides novel empirical evidence demonstrating sex differences in the brain activity, inviting further studies on sex differences in the neural network for spatial navigation.

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  • Konishi, M., Verdonschot, R. G., Shimabukuro, K., Nakamoto, T., Fujita, M., & Kakimoto, N. (2019). The effectiveness of mouthwashes in alleviating radiation-induced oral mucositis in head and neck cancer patients: A systematic review. Oral Radiology, 35(3), 207-223. doi:10.1007/s11282-018-0361-9.

    Abstract

    Objective The aim of the study was to perform a systematic literature search and meta-analysis to reveal the most effective mouthwash for head and neck cancer patients who are experiencing radiation therapy-induced mucositis. Methods Using two electronic databases, a literature search and data interpretation were systematically performed as follows: (i) problem specification, (ii) devising of a literature search plan, (iii) literature search and retrieval of publications, and (iv) meta-analysis and data interpretation. The main problem was specified as follows: what mouthwash is effective in alleviating oral mucositis for head and neck cancer patients who are undergoing radiotherapy? Results The literature search yielded 354 titles and abstracts. After reviewing the extracted literature, 25 publications met the inclusion criteria for this study and 17 of 25 were eventually evaluated in the meta-analysis. Conclusion The results of the meta-analysis indicated that the use of a mouthwash that includes anti-inflammatory properties contributes the most to alleviating oral mucositis in patients who are undergoing radiotherapy to treat head and neck cancer.
  • Konopka, A. E., & Meyer, A. S. (2014). Priming sentence planning. Cognitive Psychology, 73, 1-40. doi:10.1016/j.cogpsych.2014.04.001.

    Abstract

    Sentence production requires mapping preverbal messages onto linguistic structures. Because sentences are normally built incrementally, the information encoded in a sentence-initial increment is critical for explaining how the mapping process starts and for predicting its timecourse. Two experiments tested whether and when speakers prioritize encoding of different types of information at the outset of formulation by comparing production of descriptions of transitive events (e.g., A dog is chasing the mailman) that differed on two dimensions: the ease of naming individual characters and the ease of apprehending the event gist (i.e., encoding the relational structure of the event). To additionally manipulate ease of encoding, speakers described the target events after receiving lexical primes (facilitating naming; Experiment 1) or structural primes (facilitating generation of a linguistic structure; Experiment 2). Both properties of the pictured events and both types of primes influenced the form of target descriptions and the timecourse of formulation: character-specific variables increased the probability of speakers encoding one character with priority at the outset of formulation, while the ease of encoding event gist and of generating a syntactic structure increased the likelihood of early encoding of information about both characters. The results show that formulation is flexible and highlight some of the conditions under which speakers might employ different planning strategies.
  • Koppen, K., Ernestus, M., & Van Mulken, M. (2019). The influence of social distance on speech behavior: Formality variation in casual speech. Corpus Linguistics and Linguistic Theory, 15(1), 139-165. doi:10.1515/cllt-2016-0056.

    Abstract

    An important dimension of linguistic variation is formality. This study investigates the role of social distance between interlocutors. Twenty-five native Dutch speakers retold eight short films to confederates, who acted either formally or informally. Speakers were familiarized with the informal confederates, whereas the formal confederates remained strangers. Results show that the two types of interlocutors elicited different versions of the same stories. Formal interlocutors (large social distance) elicited lower articulation rates, and more nouns and prepositions, both indicators of explicit information. Speakers addressing interlocutors to whom social distance was small, however, provided more explicit information with an involved character (i.e. adjectives with subjective meanings). They also used the word and more often as a gap filler or as a way to keep the floor. Furthermore, they were more likely to laugh and to use more interjections, first-person pronouns and direct speech, which are all indicators of involvement, empathy and subjectivity.

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  • Kösem, A., Gramfort, A., & van Wassenhove, V. (2014). Encoding of event timing in the phase of neural oscillations. NeuroImage, 92, 274-284. doi:10.1016/j.neuroimage.2014.02.010.

    Abstract

    ime perception is a critical component of conscious experience. To be in synchrony with the environment, the brain must deal not only with differences in the speed of light and sound but also with its computational and neural transmission delays. Here, we asked whether the brain could actively compensate for temporal delays by changing its processing time. Specifically, can changes in neural timing or in the phase of neural oscillation index perceived timing? For this, a lag-adaptation paradigm was used to manipulate participants' perceived audiovisual (AV) simultaneity of events while they were recorded with magnetoencephalography (MEG). Desynchronized AV stimuli were presented rhythmically to elicit a robust 1 Hz frequency-tagging of auditory and visual cortical responses. As participants' perception of AV simultaneity shifted, systematic changes in the phase of entrained neural oscillations were observed. This suggests that neural entrainment is not a passive response and that the entrained neural oscillation shifts in time. Crucially, our results indicate that shifts in neural timing in auditory cortices linearly map participants' perceived AV simultaneity. To our knowledge, these results provide the first mechanistic evidence for active neural compensation in the encoding of sensory event timing in support of the emergence of time awareness.
  • Kösem, A., & Van Wassenhove, V. (2017). Distinct contributions of low and high frequency neural oscillations to speech comprehension. Language, Cognition and Neuroscience, 32(5), 536-544. doi:10.1080/23273798.2016.1238495.

    Abstract

    In the last decade, the involvement of neural oscillatory mechanisms in speech comprehension has been increasingly investigated. Current evidence suggests that low-frequency and high-frequency neural entrainment to the acoustic dynamics of speech are linked to its analysis. One crucial question is whether acoustical processing primarily modulates neural entrainment, or whether entrainment instead reflects linguistic processing. Here, we review studies investigating the effect of linguistic manipulations on neural oscillatory activity. In light of the current findings, we argue that theta (3–8 Hz) entrainment may primarily reflect the analysis of the acoustic features of speech. In contrast, recent evidence suggests that delta (1–3 Hz) and high-frequency activity (>40 Hz) are reliable indicators of perceived linguistic representations. The interdependence between low-frequency and high-frequency neural oscillations, as well as their causal role on speech comprehension, is further discussed with regard to neurophysiological models of speech processing
  • De Kovel, C. G. F., Meisler, M. H., Brilstra, E. H., van Berkestijn, F. M. C., van 't Slot, R., van Lieshout, S., Nijman, I. J., O'Brien, J. E., Hammer, M. F., Estacion, M., Waxman, S. G., Dib-Hajj, S. D., & Koeleman, B. P. C. (2014). Characterization of a de novo SCN8A mutation in a patient with epileptic encephalopathy. Epilepsy Research, 108(9), 1511-1518. doi:10.1016/j.eplepsyres.2014.08.020.

    Abstract

    Objective Recently, de novo SCN8A missense mutations have been identified as a rare dominant cause of epileptic encephalopathies. Functional studies on the first described case demonstrated gain-of-function effects of the mutation. We describe a novel de novo mutation of SCN8A in a patient with epileptic encephalopathy, and functional characterization of the mutant protein. Design Whole exome sequencing was used to discover the variant. We generated a mutant cDNA, transfected HEK293 cells, and performed Western blotting to assess protein stability. To study channel functional properties, patch-clamp experiments were carried out in transfected neuronal ND7/23 cells. Results The proband exhibited seizure onset at 6 months of age, diffuse brain atrophy, and more profound developmental impairment than the original case. The mutation p.Arg233Gly in the voltage sensing transmembrane segment D1S4 was present in the proband and absent in both parents. This mutation results in a temperature-sensitive reduction in protein expression as well as reduced sodium current amplitude and density and a relative increased response to a slow ramp stimulus, though this did not result in an absolute increased current at physiological temperatures. Conclusion The new de novo SCN8A mutation is clearly deleterious, resulting in an unstable protein with reduced channel activity. This differs from the gain-of-function attributes of the first SCN8A mutation in epileptic encephalopathy, pointing to heterogeneity of mechanisms. Since Nav1.6 is expressed in both excitatory and inhibitory neurons, a differential effect of a loss-of-function of Nav1.6 Arg223Gly on inhibitory interneurons may underlie the epilepsy phenotype in this patient.
  • De Kovel, C. G. F., Carrion Castillo, A., & Francks, C. (2019). A large-scale population study of early life factors influencing left-handedness. Scientific Reports, 9: 584. doi:10.1038/s41598-018-37423-8.

    Abstract

    Hand preference is a conspicuous variation in human behaviour, with a worldwide proportion of around 90% of people preferring to use the right hand for many tasks, and 10% the left hand. We used the large cohort of the UK biobank (~500,000 participants) to study possible relations between early life factors and adult hand preference. The probability of being left-handed was affected by the year and location of birth, likely due to cultural effects. In addition, hand preference was affected by birthweight, being part of a multiple birth, season of birth, breastfeeding, and sex, with each effect remaining significant after accounting for all others. Analysis of genome-wide genotype data showed that left-handedness was very weakly heritable, but shared no genetic basis with birthweight. Although on average left-handers and right-handers differed for a number of early life factors, all together these factors had only a minimal predictive value for individual hand preference.

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  • De Kovel, C. G. F., Lisgo, S., Karlebach, G., Ju, J., Cheng, G., Fisher, S. E., & Francks, C. (2017). Left-right asymmetry of maturation rates in human embryonic neural development. Biological Psychiatry, 82(3), 204-212. doi:10.1016/j.biopsych.2017.01.016.

    Abstract

    Background

    Left-right asymmetry is a fundamental organizing feature of the human brain, and neuro-psychiatric disorders such as schizophrenia sometimes involve alterations of brain asymmetry. As early as 8 weeks post conception, the majority of human fetuses move their right arms more than their left arms, but because nerve fibre tracts are still descending from the forebrain at this stage, spinal-muscular asymmetries are likely to play an important developmental role.
    Methods

    We used RNA sequencing to measure gene expression levels in the left and right spinal cords, and left and right hindbrains, of 18 post-mortem human embryos aged 4-8 weeks post conception. Genes showing embryonic lateralization were tested for an enrichment of signals in genome-wide association data for schizophrenia.
    Results

    The left side of the embryonic spinal cord was found to mature faster than the right side. Both sides transitioned from transcriptional profiles associated with cell division and proliferation at earlier stages, to neuronal differentiation and function at later stages, but the two sides were not in synchrony (p = 2.2 E-161). The hindbrain showed a left-right mirrored pattern compared to the spinal cord, consistent with the well-known crossing over of function between these two structures. Genes that showed lateralization in the embryonic spinal cord were enriched for association signals with schizophrenia (p = 4.3 E-05).
    Conclusions
    These are the earliest-stage left-right differences of human neural development ever reported. Disruption of the lateralised developmental programme may play a role in the genetic susceptibility to schizophrenia.

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