Publications

Displaying 301 - 400 of 475
  • Postema, M. (2021). Left-right asymmetry of the human brain: Associations with neurodevelopmental disorders and genetic factors. PhD Thesis, Radboud University Nijmegen, Nijmegen.
  • Postema, M., Hoogman, M., Ambrosino, S., Asherson, P., Banaschewski, T., Bandeira, C. E., Baranov, A., Bau, C. H. D., Baumeister, S., Baur-Streubel, R., Bellgrove, M. A., Biederman, J., Bralten, J., Brandeis, D., Brem, S., Buitelaar, J. K., Busatto, G. F., Castellanos, F. X., Cercignani, M., Chaim-Avancini, T. M. and 85 morePostema, M., Hoogman, M., Ambrosino, S., Asherson, P., Banaschewski, T., Bandeira, C. E., Baranov, A., Bau, C. H. D., Baumeister, S., Baur-Streubel, R., Bellgrove, M. A., Biederman, J., Bralten, J., Brandeis, D., Brem, S., Buitelaar, J. K., Busatto, G. F., Castellanos, F. X., Cercignani, M., Chaim-Avancini, T. M., Chantiluke, K. C., Christakou, A., Coghill, D., Conzelmann, A., Cubillo, A. I., Cupertino, R. B., De Zeeuw, P., Doyle, A. E., Durston, S., Earl, E. A., Epstein, J. N., Ethofer, T., Fair, D. A., Fallgatter, A. J., Faraone, S. V., Frodl, T., Gabel, M. C., Gogberashvili, T., Grevet, E. H., Haavik, J., Harrison, N. A., Hartman, C. A., Heslenfeld, D. J., Hoekstra, P. J., Hohmann, S., Høvik, M. F., Jernigan, T. L., Kardatzki, B., Karkashadze, G., Kelly, C., Kohls, G., Konrad, K., Kuntsi, J., Lazaro, L., Lera-Miguel, S., Lesch, K.-P., Louza, M. R., Lundervold, A. J., Malpas, C. B., Mattos, P., McCarthy, H., Namazova-Baranova, L., Nicolau, R., Nigg, J. T., Novotny, S. E., Oberwelland Weiss, E., O'Gorman Tuura, R. L., Oosterlaan, J., Oranje, B., Paloyelis, Y., Pauli, P., Picon, F. A., Plessen, K. J., Ramos-Quiroga, J. A., Reif, A., Reneman, L., Rosa, P. G. P., Rubia, K., Schrantee, A., Schweren, L. J. S., Seitz, J., Shaw, P., Silk, T. J., Skokauskas, N., Soliva Vila, J. C., Stevens, M. C., Sudre, G., Tamm, L., Tovar-Moll, F., Van Erp, T. G. M., Vance, A., Vilarroya, O., Vives-Gilabert, Y., Von Polier, G. G., Walitza, S., Yoncheva, Y. N., Zanetti, M. V., Ziegler, G. C., Glahn, D. C., Jahanshad, N., Medland, S. E., ENIGMA ADHD Working Group, Thompson, P. M., Fisher, S. E., Franke, B., & Francks, C. (2021). Analysis of structural brain asymmetries in Attention-Deficit/Hyperactivity Disorder in 39 datasets. Journal of Child Psychology and Psychiatry, 62(10), 1202-1219. doi:10.1111/jcpp.13396.

    Abstract

    Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here we performed the largest-ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.
    Methods: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modelling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.
    Results: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t=2.1, P=0.04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t=2.7, P=0.01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.
    Conclusion: Prior studies of altered structural brain asymmetry in ADHD were likely under-powered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

    Additional information

    jcpp13396-sup-0001-supinfo.pdf
  • Pouw, W., Dingemanse, M., Motamedi, Y., & Ozyurek, A. (2021). A systematic investigation of gesture kinematics in evolving manual languages in the lab. Cognitive Science, 45(7): e13014. doi:10.1111/cogs.13014.

    Abstract

    Silent gestures consist of complex multi-articulatory movements but are now primarily studied through categorical coding of the referential gesture content. The relation of categorical linguistic content with continuous kinematics is therefore poorly understood. Here, we reanalyzed the video data from a gestural evolution experiment (Motamedi, Schouwstra, Smith, Culbertson, & Kirby, 2019), which showed increases in the systematicity of gesture content over time. We applied computer vision techniques to quantify the kinematics of the original data. Our kinematic analyses demonstrated that gestures become more efficient and less complex in their kinematics over generations of learners. We further detect the systematicity of gesture form on the level of thegesture kinematic interrelations, which directly scales with the systematicity obtained on semantic coding of the gestures. Thus, from continuous kinematics alone, we can tap into linguistic aspects that were previously only approachable through categorical coding of meaning. Finally, going beyond issues of systematicity, we show how unique gesture kinematic dialects emerged over generations as isolated chains of participants gradually diverged over iterations from other chains. We, thereby, conclude that gestures can come to embody the linguistic system at the level of interrelationships between communicative tokens, which should calibrate our theories about form and linguistic content.
  • Pouw, W., Wit, J., Bögels, S., Rasenberg, M., Milivojevic, B., & Ozyurek, A. (2021). Semantically related gestures move alike: Towards a distributional semantics of gesture kinematics. In V. G. Duffy (Ed.), Digital human modeling and applications in health, safety, ergonomics and risk management. human body, motion and behavior:12th International Conference, DHM 2021, Held as Part of the 23rd HCI International Conference, HCII 2021 (pp. 269-287). Berlin: Springer. doi:10.1007/978-3-030-77817-0_20.
  • Pouw, W., Proksch, S., Drijvers, L., Gamba, M., Holler, J., Kello, C., Schaefer, R. S., & Wiggins, G. A. (2021). Multilevel rhythms in multimodal communication. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences, 376: 20200334. doi:10.1098/rstb.2020.0334.

    Abstract

    It is now widely accepted that the brunt of animal communication is conducted via several modalities, e.g. acoustic and visual, either simultaneously or sequentially. This is a laudable multimodal turn relative to traditional accounts of temporal aspects of animal communication which have focused on a single modality at a time. However, the fields that are currently contributing to the study of multimodal communication are highly varied, and still largely disconnected given their sole focus on a particular level of description or their particular concern with human or non-human animals. Here, we provide an integrative overview of converging findings that show how multimodal processes occurring at neural, bodily, as well as social interactional levels each contribute uniquely to the complex rhythms that characterize communication in human and non-human animals. Though we address findings for each of these levels independently, we conclude that the most important challenge in this field is to identify how processes at these different levels connect.
  • Pouw, W., De Jonge-Hoekstra, L., Harrison, S. J., Paxton, A., & Dixon, J. A. (2021). Gesture-speech physics in fluent speech and rhythmic upper limb movements. Annals of the New York Academy of Sciences, 1491(1), 89-105. doi:10.1111/nyas.14532.

    Abstract

    Communicative hand gestures are often coordinated with prosodic aspects of speech, and salient moments of gestural movement (e.g., quick changes in speed) often co-occur with salient moments in speech (e.g., near peaks in fundamental frequency and intensity). A common understanding is that such gesture and speech coordination is culturally and cognitively acquired, rather than having a biological basis. Recently, however, the biomechanical physical coupling of arm movements to speech movements has been identified as a potentially important factor in understanding the emergence of gesture-speech coordination. Specifically, in the case of steady-state vocalization and mono-syllable utterances, forces produced during gesturing are transferred onto the tensioned body, leading to changes in respiratory-related activity and thereby affecting vocalization F0 and intensity. In the current experiment (N = 37), we extend this previous line of work to show that gesture-speech physics impacts fluent speech, too. Compared with non-movement, participants who are producing fluent self-formulated speech, while rhythmically moving their limbs, demonstrate heightened F0 and amplitude envelope, and such effects are more pronounced for higher-impulse arm versus lower-impulse wrist movement. We replicate that acoustic peaks arise especially during moments of peak-impulse (i.e., the beat) of the movement, namely around deceleration phases of the movement. Finally, higher deceleration rates of higher-mass arm movements were related to higher peaks in acoustics. These results confirm a role for physical-impulses of gesture affecting the speech system. We discuss the implications of
    gesture-speech physics for understanding of the emergence of communicative gesture, both ontogenetically and phylogenetically.

    Additional information

    data and analyses
  • Preisig, B., Riecke, L., Sjerps, M. J., Kösem, A., Kop, B. R., Bramson, B., Hagoort, P., & Hervais-Adelman, A. (2021). Selective modulation of interhemispheric connectivity by transcranial alternating current stimulation influences binaural integration. Proceedings of the National Academy of Sciences of the United States of America, 118(7): e2015488118. doi:10.1073/pnas.2015488118.

    Abstract

    Brain connectivity plays a major role in the encoding, transfer, and
    integration of sensory information. Interregional synchronization
    of neural oscillations in the γ-frequency band has been suggested
    as a key mechanism underlying perceptual integration. In a recent
    study, we found evidence for this hypothesis showing that the
    modulation of interhemispheric oscillatory synchrony by means of
    bihemispheric high-density transcranial alternating current stimulation
    (HD-TACS) affects binaural integration of dichotic acoustic features.
    Here, we aimed to establish a direct link between oscillatory
    synchrony, effective brain connectivity, and binaural integration.
    We experimentally manipulated oscillatory synchrony (using bihemispheric
    γ-TACS with different interhemispheric phase lags) and
    assessed the effect on effective brain connectivity and binaural integration
    (as measured with functional MRI and a dichotic listening
    task, respectively). We found that TACS reduced intrahemispheric
    connectivity within the auditory cortices and antiphase (interhemispheric
    phase lag 180°) TACS modulated connectivity between the
    two auditory cortices. Importantly, the changes in intra- and interhemispheric
    connectivity induced by TACS were correlated with
    changes in perceptual integration. Our results indicate that γ-band
    synchronization between the two auditory cortices plays a functional
    role in binaural integration, supporting the proposed role
    of interregional oscillatory synchrony in perceptual integration.
  • Pronina, M., Hübscher, I., Holler, J., & Prieto, P. (2021). Interactional training interventions boost children’s expressive pragmatic abilities: Evidence from a novel multidimensional testing approach. Cognitive Development, 57: 101003. doi:10.1016/j.cogdev.2020.101003.

    Abstract

    This study investigates the effectiveness of training preschoolers in order to enhance their social cognition and pragmatic skills. Eighty-three 3–4-year-olds were divided into three groups and listened to stories enriched with mental state terms. Then, whereas the control group engaged in non-reflective activities, the two experimental groups were guided by a trainer to reflect on mental states depicted in the stories. In one of these groups, the children were prompted to not only talk about these states but also “embody” them through prosodic and gestural cues. Results showed that while there were no significant effects on Theory of Mind, emotion understanding, and mental state verb comprehension, the experimental groups significantly improved their pragmatic skill scores pretest-to-posttest. These results suggest that interactional interventions can contribute to preschoolers’ pragmatic development, demonstrate the value of the new embodied training, and highlight the importance of multidimensional testing for the evaluation of intervention effects.
  • Puebla, G., Martin, A. E., & Doumas, L. A. A. (2021). The relational processing limits of classic and contemporary neural network models of language processing. Language, Cognition and Neuroscience, 36(2), 240-254. doi:10.1080/23273798.2020.1821906.

    Abstract

    Whether neural networks can capture relational knowledge is a matter of long-standing controversy. Recently, some researchers have argued that (1) classic connectionist models can handle relational structure and (2) the success of deep learning approaches to natural language processing suggests that structured representations are unnecessary to model human language. We tested the Story Gestalt model, a classic connectionist model of text comprehension, and a Sequence-to-Sequence with Attention model, a modern deep learning architecture for natural language processing. Both models were trained to answer questions about stories based on abstract thematic roles. Two simulations varied the statistical structure of new stories while keeping their relational structure intact. The performance of each model fell below chance at least under one manipulation. We argue that both models fail our tests because they can't perform dynamic binding. These results cast doubts on the suitability of traditional neural networks for explaining relational reasoning and language processing phenomena.

    Additional information

    supplementary material
  • Räsänen, O., Seshadri, S., Lavechin, M., Cristia, A., & Casillas, M. (2021). ALICE: An open-source tool for automatic measurement of phoneme, syllable, and word counts from child-centered daylong recordings. Behavior Research Methods, 53, 818-835. doi:10.3758/s13428-020-01460-x.

    Abstract

    Recordings captured by wearable microphones are a standard method for investigating young children’s language environments. A key measure to quantify from such data is the amount of speech present in children’s home environments. To this end, the LENA recorder and software—a popular system for measuring linguistic input—estimates the number of adult words that children may hear over the course of a recording. However, word count estimation is challenging to do in a language-independent manner; the relationship between observable acoustic patterns and language-specific lexical entities is far from uniform across human languages. In this paper, we ask whether some alternative linguistic units, namely phone(me)s or syllables, could be measured instead of, or in parallel with, words in order to achieve improved cross-linguistic applicability and comparability of an automated system for measuring child language input. We discuss the advantages and disadvantages of measuring different units from theoretical and technical points of view. We also investigate the practical applicability of measuring such units using a novel system called Automatic LInguistic unit Count Estimator (ALICE) together with audio from seven child-centered daylong audio corpora from diverse cultural and linguistic environments. We show that language-independent measurement of phoneme counts is somewhat more accurate than syllables or words, but all three are highly correlated with human annotations on the same data. We share an open-source implementation of ALICE for use by the language research community, allowing automatic phoneme, syllable, and word count estimation from child-centered audio recordings.
  • Ravignani, A. (2021). Isochrony, vocal learning and the acquisition of rhythm and melody. Behavioral and Brain Sciences, 44: e88. doi:10.1017/S0140525X20001478.

    Abstract

    A cross-species perspective can extend and provide testable predictions for Savage et al.’s
    framework. Rhythm and melody, I argue, could bootstrap each other in the evolution of
    musicality. Isochrony may function as a temporal grid to support rehearsing and learning
    modulated, pitched vocalizations. Once this melodic plasticity is acquired, focus can shift back to refining rhythm processing and beat induction.
  • Ravignani, A., & De Boer, B. (2021). Joint origins of speech and music: Testing evolutionary hypotheses on modern humans. Semiotica, 239, 169-176. doi:10.1515/sem-2019-0048.

    Abstract

    How music and speech evolved is a mystery. Several hypotheses on their
    origins, including one on their joint origins, have been put forward but rarely
    tested. Here we report and comment on the first experiment testing the hypothesis
    that speech and music bifurcated from a common system. We highlight strengths
    of the reported experiment, point out its relatedness to animal work, and suggest
    three alternative interpretations of its results. We conclude by sketching a future
    empirical programme extending this work.
  • Raviv, L., De Heer Kloots, M., & Meyer, A. S. (2021). What makes a language easy to learn? A preregistered study on how systematic structure and community size affect language learnability. Cognition, 210: 104620. doi:10.1016/j.cognition.2021.104620.

    Abstract

    Cross-linguistic differences in morphological complexity could have important consequences for language learning. Specifically, it is often assumed that languages with more regular, compositional, and transparent grammars are easier to learn by both children and adults. Moreover, it has been shown that such grammars are more likely to evolve in bigger communities. Together, this suggests that some languages are acquired faster than others, and that this advantage can be traced back to community size and to the degree of systematicity in the language. However, the causal relationship between systematic linguistic structure and language learnability has not been formally tested, despite its potential importance for theories on language evolution, second language learning, and the origin of linguistic diversity. In this pre-registered study, we experimentally tested the effects of community size and systematic structure on adult language learning. We compared the acquisition of different yet comparable artificial languages that were created by big or small groups in a previous communication experiment, which varied in their degree of systematic linguistic structure. We asked (a) whether more structured languages were easier to learn; and (b) whether languages created by the bigger groups were easier to learn. We found that highly systematic languages were learned faster and more accurately by adults, but that the relationship between language learnability and linguistic structure was typically non-linear: high systematicity was advantageous for learning, but learners did not benefit from partly or semi-structured languages. Community size did not affect learnability: languages that evolved in big and small groups were equally learnable, and there was no additional advantage for languages created by bigger groups beyond their degree of systematic structure. Furthermore, our results suggested that predictability is an important advantage of systematic structure: participants who learned more structured languages were better at generalizing these languages to new, unfamiliar meanings, and different participants who learned the same more structured languages were more likely to produce similar labels. That is, systematic structure may allow speakers to converge effortlessly, such that strangers can immediately understand each other.
  • Rebuschat, P., Monaghan, P., & Schoetensack, C. (2021). Learning vocabulary and grammar from cross-situational statistics. Cognition, 206: 104475. doi:10.1016/j.cognition.2020.104475.

    Abstract

    Across multiple situations, child and adult learners are sensitive to co-occurrences between individual words and their referents in the environment, which provide a means by which the ambiguity of word-world mappings may be resolved (Monaghan & Mattock, 2012; Scott & Fisher, 2012; Smith & Yu, 2008; Yu & Smith, 2007). In three studies, we tested whether cross-situational learning is sufficiently powerful to support simultaneous learning the referents for words from multiple grammatical categories, a more realistic reflection of more complex natural language learning situations. In Experiment 1, adult learners heard sentences comprising nouns, verbs, adjectives, and grammatical markers indicating subject and object roles, and viewed a dynamic scene to which the sentence referred. In Experiments 2 and 3, we further increased the uncertainty of the referents by presenting two scenes alongside each sentence. In all studies, we found that cross-situational statistical learning was sufficiently powerful to facilitate acquisition of both vocabulary and grammar from complex sentence-to-scene correspondences, simulating the situations that more closely resemble the challenge facing the language learner.

    Additional information

    supplementary material
  • Redl, T. (2021). Masculine generic pronouns: Investigating the processing of an unintended gender cue. PhD Thesis, Radboud University Nijmegen, Nijmegen.
  • Redl, T., Frank, S. L., De Swart, P., & De Hoop, H. (2021). The male bias of a generically-intended masculine pronoun: Evidence from eye-tracking and sentence evaluation. PLoS One, 16(4): e0249309. doi:10.1371/journal.pone.0249309.

    Abstract

    Two experiments tested whether the Dutch possessive pronoun zijn ‘his’ gives rise to a gender inference and thus causes a male bias when used generically in sentences such as Everyone was putting on his shoes. Experiment 1 (N = 120, 48 male) was a conceptual replication of a previous eye-tracking study that had not found evidence of a male bias. The results of the current eye-tracking experiment showed the generically-intended masculine pronoun to trigger a gender inference and cause a male bias, but for male participants and in stereotypically neutral stereotype contexts only. No evidence for a male bias was thus found in stereotypically female and male context nor for female participants altogether. Experiment 2 (N = 80, 40 male) used the same stimuli as Experiment 1, but employed the sentence evaluation paradigm. No evidence of a male bias was found in Experiment 2. Taken together, the results suggest that the generically-intended masculine pronoun zijn ‘his’ can cause a male bias for male participants even when the referents are previously introduced by inclusive and grammatically gender-unmarked iedereen ‘everyone’. This male bias surfaces with eye-tracking, which taps directly into early language processing, but not in offline sentence evaluations. Furthermore, the results suggest that the intended generic reading of the masculine possessive pronoun zijn ‘his’ is more readily available for women than for men.

    Additional information

    data
  • Redolfi, M., Soares, S. M. P., Czypionka, A., & Kupisch, T. (2021). Experimental evidence for the interpretation of definite plural articles as markers of genericity – How Italian can help. Glossa: a journal of general linguistics, 6(1): 16. doi:10.5334/gjgl.1165.

    Abstract

    In the Romance languages, definite plural articles (e.g., le rane ‘the frogs’) are generally ambiguous between a generic and a specific interpretation, and speakers must reconstruct the intended interpretation through the linguistic or extra-linguistic context. Following the “polar bear” paradigm implemented in Czypionka & Kupisch (2019)’s investigation on German, the goal of the present study is to check the suitability of their test on article semantics, by establishing to what extent native speakers of Italian interpret ambiguous definite plural DPs as generic or specific in the presence of a nonlinguistic picture context. We present judgment and reaction time data monitoring the preferred reading of sentences introduced by different kinds of noun phrases (e.g., Le rane/Queste rane/Le rane di solito sono verdi/gialle ‘The/These/Usually frogs are green/yellow’), while looking at pictures showing prototypical or non-prototypical properties (e.g., green vs. yellow frogs). Our results show that both possible interpretations of definite plural articles are routinely considered in Italian, despite the presence of a picture with specific referents, validating the “polar bear” paradigm as a suitable test of article semantics.
  • Reifegerste, J., Meyer, A. S., Zwitserlood, P., & Ullman, M. T. (2021). Aging affects steaks more than knives: Evidence that the processing of words related to motor skills is relatively spared in aging. Brain and Language, 218: 104941. doi:10.1016/j.bandl.2021.104941.

    Abstract

    Lexical-processing declines are a hallmark of aging. However, the extent of these declines may vary as a function of different factors. Motivated by findings from neurodegenerative diseases and healthy aging, we tested whether ‘motor-relatedness’ (the degree to which words are associated with particular human body movements) might moderate such declines. We investigated this question by examining data from three experiments. The experiments were carried out in different languages (Dutch, German, English) using different tasks (lexical decision, picture naming), and probed verbs and nouns, in all cases controlling for potentially confounding variables (e.g., frequency, age-of-acquisition, imageability). Whereas ‘non-motor words’ (e.g., steak) showed age-related performance decreases in all three experiments, ‘motor words’ (e.g., knife) yielded either smaller decreases (in one experiment) or no decreases (in two experiments). The findings suggest that motor-relatedness can attenuate or even prevent age-related lexical declines, perhaps due to the relative sparing of neural circuitry underlying such words.

    Additional information

    supplementary material
  • de Reus, K., Soma, M., Anichini, M., Gamba, M., de Heer Kloots, M., Lense, M., Bruno, J. H., Trainor, L., & Ravignani, A. (2021). Rhythm in dyadic interactions. Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences, 376: 20200337. doi:10.1098/rstb.2020.0337.

    Abstract

    This review paper discusses rhythmic dyadic interactions in social and sexual contexts. We report rhythmic interactions during communication within dyads, as found in humans, non-human primates, non-primate mammals, birds, anurans and insects. Based on the patterns observed, we infer adaptive explanations for the observed rhythm interactions and identify knowledge gaps. Across species, the social environment during ontogeny is a key factor in shaping adult signal repertoires and timing mechanisms used to regulate interactions. The degree of temporal coordination is influenced by the dynamic and strength of the dyadic interaction. Most studies of temporal structure in interactive signals mainly focus on one modality (acoustic and visual); we suggest more work should be performed on multimodal signals. Multidisciplinary approaches combining cognitive science, ethology and ecology should shed more light on the exact timing mechanisms involved. Taken together, rhythmic signalling behaviours are widespread and critical in regulating social interactions across taxa.
  • Rhie, A., McCarthy, S. A., Fedrigo, O., Damas, J., Formenti, G., Koren, S., Uliano-Silva, M., Chow, W., Fungtammasan, A., Kim, J., Lee, C., Ko, B. J., Chaisson, M., Gedman, G. L., Cantin, L. J., Thibaud-Nissen, F., Haggerty, L., Bista, I., Smith, M., Haase, B. and 107 moreRhie, A., McCarthy, S. A., Fedrigo, O., Damas, J., Formenti, G., Koren, S., Uliano-Silva, M., Chow, W., Fungtammasan, A., Kim, J., Lee, C., Ko, B. J., Chaisson, M., Gedman, G. L., Cantin, L. J., Thibaud-Nissen, F., Haggerty, L., Bista, I., Smith, M., Haase, B., Mountcastle, J., Winkler, S., Paez, S., Howard, J., Vernes, S. C., Lama, T. M., Grutzner, F., Warren, W. C., Balakrishnan, C. N., Burt, D., George, J. M., Biegler, M. T., Iorns, D., Digby, A., Eason, D., Robertson, B., Edwards, T., Wilkinson, M., Turner, G., Meyer, A., Kautt, A. F., Franchini, P., Detrich, H. W., Svardal, H., Wagner, M., Naylor, G. J. P., Pippel, M., Malinsky, M., Mooney, M., Simbirsky, M., Hannigan, B. T., Pesout, T., Houck, M., Misuraca, A., Kingan, S. B., Hall, R., Kronenberg, Z., Sović, I., Dunn, C., Ning, Z., Hastie, A., Lee, J., Selvaraj, S., Green, R. E., Putnam, N. H., Gut, I., Ghurye, J., Garrison, E., Sims, Y., Collins, J., Pelan, S., Torrance, J., Tracey, A., Wood, J., Dagnew, R. E., Guan, D., London, S. E., Clayton, D. F., Mello, C. V., Friedrich, S. R., Lovell, P. V., Osipova, E., Al-Ajli, F. O., Secomandi, S., Kim, H., Theofanopoulou, C., Hiller, M., Zhou, Y., Harris, R. S., Makova, K. D., Medvedev, P., Hoffman, J., Masterson, P., Clark, K., Martin, F., Howe, K., Flicek, P., Walenz, B. P., Kwak, W., Clawson, H., Diekhans, M., Nassar, L., Paten, B., Kraus, R. H. S., Crawford, A. J., Gilbert, M. T. P., Zhang, G., Venkatesh, B., Murphy, R. W., Koepfli, K.-P., Shapiro, B., Johnson, W. E., Di Palma, F., Marques-Bonet, T., Teeling, E. C., Warnow, T., Graves, J. M., Ryder, O. A., Haussler, D., O’Brien, S. J., Korlach, J., Lewin, H. A., Howe, K., Myers, E. W., Durbin, R., Phillippy, A. M., & Jarvis, E. D. (2021). Towards complete and error-free genome assemblies of all vertebrate species. Nature, 592, 737-746. doi:10.1038/s41586-021-03451-0.

    Abstract

    High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1,2,3,4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.
  • Rodd, J., Decuyper, C., Bosker, H. R., & Ten Bosch, L. (2021). A tool for efficient and accurate segmentation of speech data: Announcing POnSS. Behavior Research Methods, 53, 744-756. doi:10.3758/s13428-020-01449-6.

    Abstract

    Despite advances in automatic speech recognition (ASR), human input is still essential to produce research-grade segmentations of speech data. Con- ventional approaches to manual segmentation are very labour-intensive. We introduce POnSS, a browser-based system that is specialized for the task of segmenting the onsets and offsets of words, that combines aspects of ASR with limited human input. In developing POnSS, we identified several sub- tasks of segmentation, and implemented each of these as separate interfaces for the annotators to interact with, to streamline their task as much as possible. We evaluated segmentations made with POnSS against a base- line of segmentations of the same data made conventionally in Praat. We observed that POnSS achieved comparable reliability to segmentation us- ing Praat, but required 23% less annotator time investment. Because of its greater efficiency without sacrificing reliability, POnSS represents a distinct methodological advance for the segmentation of speech data.
  • Rösler, D., & Skiba, R. (1986). Ein vernetzter Lehrmaterial-Steinbruch für Deutsch als Zweitsprache (Projekt EKMAUS, FU Berlin). Deutsch Lernen: Zeitschrift für den Sprachunterricht mit ausländischen Arbeitnehmern, 2, 68-71. Retrieved from http://www.daz-didaktik.de/html/1986.html.
  • Rossi, G. (2021). Conversation analysis (CA). In J. Stanlaw (Ed.), The International Encyclopedia of Linguistic Anthropology. Wiley-Blackwell. doi:10.1002/9781118786093.iela0080.

    Abstract

    Conversation analysis (CA) is an approach to the study of language and social interaction that puts at center stage its sequential development. The chain of initiating and responding actions that characterizes any interaction is a source of internal evidence for the meaning of social behavior as it exposes the understandings that participants themselves give of what one another is doing. Such an analysis requires the close and repeated inspection of audio and video recordings of naturally occurring interaction, supported by transcripts and other forms of annotation. Distributional regularities are complemented by a demonstration of participants' orientation to deviant behavior. CA has long maintained a constructive dialogue and reciprocal influence with linguistic anthropology. This includes a recent convergence on the cross-linguistic and cross-cultural study of social interaction.
  • Rossi, G., & Stivers, T. (2021). Category-sensitive actions in interaction. Social Psychology Quarterly, 84(1), 49-74. doi:10.1177/0190272520944595.

    Abstract

    This article is concerned with how social categories (e.g., wife, mother, sister, tenant, guest) become visible through the actions that individuals perform in social interaction. Using audio and video recordings of social interaction as data and conversation analysis as a method, we examine how individuals display their rights or constraints to perform certain actions by virtue of occupying a certain social category. We refer to actions whose performance is sensitive to membership in a certain social category as category-sensitive actions. Most of the time, the social boundaries surrounding these actions remain invisible because participants in interaction typically act in ways that are consistent with their social status and roles. In this study, however, we specifically examine instances where category boundaries become visible as participants approach, expose, or transgress them. Our focus is on actions with relatively stringent category sensitivity such as requests, offers, invitations, or handling one’s possessions. Ultimately, we believe these are the tip of an iceberg that potentially includes most, if not all, actions.
  • Royo, J., Forkel, S. J., Pouget, P., & Thiebaut de Schotten, M. (2021). The squirrel monkey model in clinical neuroscience. Neuroscience and Biobehavioral Reviews, 128, 152-164. doi:10.1016/j.neubiorev.2021.06.006.

    Abstract

    Clinical neuroscience research relying on animal models brought valuable translational insights into the function and pathologies of the human brain. The anatomical, physiological, and behavioural similarities between humans and mammals have prompted researchers to study cerebral mechanisms at different levels to develop and test new treatments. The vast majority of biomedical research uses rodent models, which are easily manipulable and have a broadly resembling organisation to the human nervous system but cannot satisfactorily mimic some disorders. For these disorders, macaque monkeys have been used as they have a more comparable central nervous system. Still, this research has been hampered by limitations, including high costs and reduced samples. This review argues that a squirrel monkey model might bridge the gap by complementing translational research from rodents, macaque, and humans. With the advent of promising new methods such as ultrasound imaging, tool miniaturisation, and a shift towards open science, the squirrel monkey model represents a window of opportunity that will potentially fuel new translational discoveries in the diagnosis and treatment of brain pathologies.
  • Rubio-Fernández, P. (2021). Color discriminability makes over-specification efficient: Theoretical analysis and empirical evidence. Humanities and Social Sciences Communications, 8: 147. doi:10.1057/s41599-021-00818-6.

    Abstract

    A psychophysical analysis of referential communication establishes a causal link between a visual stimulus and a speaker’s perception of this stimulus, and between the speaker’s internal representation and their reference production. Here, I argue that, in addition to visual perception and language, social cognition plays an integral part in this complex process, as it enables successful speaker-listener coordination. This pragmatic analysis of referential communication tries to explain the redundant use of color adjectives. It is well documented that people use color words when it is not necessary to identify the referent; for instance, they may refer to “the blue star” in a display of shapes with a single star. This type of redundancy challenges influential work from cognitive science and philosophy of language, suggesting that human communication is fundamentally efficient. Here, I explain these seemingly contradictory findings by confirming the visual efficiency hypothesis: redundant color words can facilitate the listener’s visual search for a referent, despite making the description unnecessarily long. Participants’ eye movements revealed that they were faster to find “the blue star” than “the star” in a display of shapes with only one star. A language production experiment further revealed that speakers are highly sensitive to a target’s discriminability, systematically reducing their use of redundant color adjectives as the color of the target became more pervasive in a display. It is concluded that a referential expression’s efficiency should be based not only on its informational value, but also on its discriminatory value, which means that redundant color words can be more efficient than shorter descriptions.
  • Rubio-Fernández, P., Mollica, F., & Jara-Ettinger, J. (2021). Speakers and listeners exploit word order for communicative efficiency: A cross-linguistic investigation. Journal of Experimental Psychology: General, 150, 583-594. doi:10.1037/xge0000963.

    Abstract

    Pragmatic theories and computational models of reference must account for people’s frequent use of redundant color adjectives (e.g., referring to a single triangle as “the blue triangle”). The standard pragmatic view holds that the informativity of a referential expression depends on pragmatic contrast: Color adjectives should be used to contrast competitors of the same kind to preempt an ambiguity (e.g., between several triangles of different colors), otherwise they are redundant. Here we propose an alternative to the standard view, the incremental efficiency hypothesis, according to which the efficiency of a referential expression must be calculated incrementally over the entire visual context. This is the first theoretical account of referential efficiency that is sensitive to the incrementality of language processing, making different cross-linguistic predictions depending on word order. Experiment 1 confirmed that English speakers produced more redundant color adjectives (e.g., “the blue triangle”) than Spanish speakers (e.g., “el triángulo azul”), but both language groups used more redundant color adjectives in denser displays where it would be more efficient. In Experiments 2A and 2B, we used eye tracking to show that pragmatic contrast is not a processing constraint. Instead, incrementality and efficiency determine that English listeners establish color contrast across categories (BLUE SHAPES > TRIANGULAR ONE), whereas Spanish listeners establish color contrast within a category (TRIANGLES > BLUE ONE). Spanish listeners, however, reversed their visual search strategy when tested in English immediately after. Our results show that speakers and listeners of different languages exploit word order to increase communicative efficiency.
  • Rubio-Fernández, P. (2021). Pragmatic markers: the missing link between language and Theory of Mind. Synthese, 199, 1125-1158. doi:10.1007/s11229-020-02768-z.

    Abstract

    Language and Theory of Mind come together in communication, but their relationship has been intensely contested. I hypothesize that pragmatic markers connect language and Theory of Mind and enable their co-development and co-evolution through a positive feedback loop, whereby the development of one skill boosts the development of the other. I propose to test this hypothesis by investigating two types of pragmatic markers: demonstratives (e.g., ‘this’ vs. ‘that’ in English) and articles (e.g., ‘a’ vs. ‘the’). Pragmatic markers are closed-class words that encode non-representational information that is unavailable to consciousness, but accessed automatically in processing. These markers have been associated with implicit Theory of Mind because they are used to establish joint attention (e.g., ‘I prefer that one’) and mark shared knowledge (e.g., ‘We bought the house’ vs. ‘We bought a house’). Here I develop a theoretical account of how joint attention (as driven by the use of demonstratives) is the basis for children’s later tracking of common ground (as marked by definite articles). The developmental path from joint attention to common ground parallels language change, with demonstrative forms giving rise to definite articles. This parallel opens the possibility of modelling the emergence of Theory of Mind in human development in tandem with its routinization across language communities and generations of speakers. I therefore propose that, in order to understand the relationship between language and Theory of Mind, we should study pragmatics at three parallel timescales: during language acquisition, language use, and language change.
  • Rubio-Fernández, P., Southgate, V., & Király, I. (2021). Pragmatics for infants: commentary on Wenzelet al. (2020). Royal Society Open Science, 8: 210247. doi:10.1098/rsos.210247.
  • De Rue, N., Snijders, T. M., & Fikkert, P. (2021). Contrast and conflict in Dutch vowels. Frontiers in Human Neuroscience, 15: 629648. doi:10.3389/fnhum.2021.629648.

    Abstract

    The nature of phonological representations has been extensively studied in phonology and psycholinguistics. While full specification is still the norm in psycholinguistic research, underspecified representations may better account for perceptual asymmetries. In this paper, we report on a mismatch negativity (MMN) study with Dutch listeners who took part in a passive oddball paradigm to investigate when the brain notices the difference between expected and observed vowels. In particular, we tested neural discrimination (indicating perceptual discrimination) of the tense mid vowel pairs /o/-/ø/ (place contrast), /e/-/ø/ (labiality or rounding contrast), and /e/-/o/ (place and labiality contrast). Our results show (a) a perceptual asymmetry for place in the /o/-/ø/ contrast, supporting underspecification of [CORONAL] and replicating earlier results for German, and (b) a perceptual asymmetry for labiality for the /e/-/ø/ contrast, which was not reported in the German study. A labial deviant [ø] (standard /e/) yielded a larger MMN than a deviant [e] (standard /ø/). No asymmetry was found for the two-feature contrast. This study partly replicates a similar MMN study on German vowels, and partly presents new findings indicating cross-linguistic differences. Although the vowel inventory of Dutch and German is to a large extent comparable, their (morpho)phonological systems are different, which is reflected in processing.

    Additional information

    supplementary material
  • Ruggeri, K., Većkalov, B., Bojanić, L., Andersen, T. L., Ashcroft-Jones, S., Ayacaxli, N., Barea-Arroyo, P., Berge, M. L., Bjørndal, L. D., Bursalıoğlu, A., Bühler, V., Čadek, M., Çetinçelik, M., Clay, G., Cortijos-Bernabeu, A., Damnjanović, K., Dugue, T. M., Esberg, M., Esteban-Serna, C., Felder, E. N. and 63 moreRuggeri, K., Većkalov, B., Bojanić, L., Andersen, T. L., Ashcroft-Jones, S., Ayacaxli, N., Barea-Arroyo, P., Berge, M. L., Bjørndal, L. D., Bursalıoğlu, A., Bühler, V., Čadek, M., Çetinçelik, M., Clay, G., Cortijos-Bernabeu, A., Damnjanović, K., Dugue, T. M., Esberg, M., Esteban-Serna, C., Felder, E. N., Friedemann, M., Frontera-Villanueva, D. I., Gale, P., Garcia-Garzon, E., Geiger, S. J., George, L., Girardello, A., Gracheva, A., Gracheva, A., Guillory, M., Hecht, M., Herte, K., Hubená, B., Ingalls, W., Jakob, L., Janssens, M., Jarke, H., Kácha, O., Kalinova, K. N., Karakasheva, R., Khorrami, P. R., Lep, Ž., Lins, S., Lofthus, I. S., Mamede, S., Mareva, S., Mascarenhas, M. F., McGill, L., Morales-Izquierdo, S., Moltrecht, B., Mueller, T. S., Musetti, M., Nelsson, J., Otto, T., Paul, A. F., Pavlović, I., Petrović, M. B., Popović, D., Prinz, G. M., Razum, J., Sakelariev, I., Samuels, V., Sanguino, I., Say, N., Schuck, J., Soysal, I., Todsen, A. L., Tünte, M. R., Vdovic, M., Vintr, J., Vovko, M., Vranka, M. A., Wagner, L., Wilkins, L., Willems, M., Wisdom, E., Yosifova, A., Zeng, S., Ahmed, M. A., Dwarkanath, T., Cikara, M., Lees, J., & Folke, T. (2021). The general fault in our fault lines. Nature Human Behaviour, 5, 1369-1380. doi:10.1038/s41562-021-01092-x.

    Abstract

    Pervading global narratives suggest that political polarization is increasing, yet the accuracy of such group meta-perceptions has been drawn into question. A recent US study suggests that these beliefs are inaccurate and drive polarized beliefs about out-groups. However, it also found that informing people of inaccuracies reduces those negative beliefs. In this work, we explore whether these results generalize to other countries. To achieve this, we replicate two of the original experiments with 10,207 participants across 26 countries. We focus on local group divisions, which we refer to as fault lines. We find broad generalizability for both inaccurate meta-perceptions and reduced negative motive attribution through a simple disclosure intervention. We conclude that inaccurate and negative group meta-perceptions are exhibited in myriad contexts and that informing individuals of their misperceptions can yield positive benefits for intergroup relations. Such generalizability highlights a robust phenomenon with implications for political discourse worldwide.

    Additional information

    supplementary information data via OSF
  • De Ruiter, L. E., Lemen, H., Lieven, E. V. M., Brandt, S., & Theakston, A. L. (2021). Structural and interactional aspects of adverbial sentences in English mother-child interactions: an analysis of two dense corpora. Journal of Child Language, 48(6), 1150-1184. doi:10.1017/S0305000920000641.

    Abstract

    We analysed both structural and functional aspects of sentences containing the four
    adverbials “after”, “before”, “because”, and “if” in two dense corpora of parent-child
    interactions from two British English-acquiring children (2;00–4;07). In comparing
    mothers’ and children’s usage we separate out the effects of frequency, cognitive
    complexity and pragmatics in explaining the course of acquisition of adverbial
    sentences. We also compare these usage patterns to stimuli used in a range of
    experimental studies and show how differences may account for some of the difficulties
    that children have shown in experiments. In addition, we report descriptive data on
    various aspects of adverbial sentences that have not yet been studied as a resource for
    future investigations.

    Additional information

    S0305000920000641sup001.docx
  • San Jose, A., Roelofs, A., & Meyer, A. S. (2021). Modeling the distributional dynamics of attention and semantic interference in word production. Cognition, 211: 104636. doi:10.1016/j.cognition.2021.104636.

    Abstract

    In recent years, it has become clear that attention plays an important role in spoken word production. Some of this evidence comes from distributional analyses of reaction time (RT) in regular picture naming and picture-word interference. Yet we lack a mechanistic account of how the properties of RT distributions come to reflect attentional processes and how these processes may in turn modulate the amount of conflict between lexical representations. Here, we present a computational account according to which attentional lapses allow for existing conflict to build up unsupervised on a subset of trials, thus modulating the shape of the resulting RT distribution. Our process model resolves discrepancies between outcomes of previous studies on semantic interference. Moreover, the model's predictions were confirmed in a new experiment where participants' motivation to remain attentive determined the size and distributional locus of semantic interference in picture naming. We conclude that process modeling of RT distributions importantly improves our understanding of the interplay between attention and conflict in word production. Our model thus provides a framework for interpreting distributional analyses of RT data in picture naming tasks.
  • Santin, M., Van Hout, A., & Flecken, M. (2021). Event endings in memory and language. Language, Cognition and Neuroscience, 36(5), 625-648. doi:10.1080/23273798.2020.1868542.

    Abstract

    Memory is fundamental for comprehending and segmenting the flow of activity around us into units called “events”. Here, we investigate the effect of the movement dynamics of actions (ceased, ongoing) and the inner structure of events (with or without object-state change) on people's event memory. Furthermore, we investigate how describing events, and the meaning and form of verb predicates used (denoting a culmination moment, or not, in single verbs or verb-satellite constructions), affects event memory. Before taking a surprise recognition task, Spanish and Mandarin speakers (who lexicalise culmination in different verb predicate forms) watched short videos of events, either in a non-verbal (probe-recognition) or a verbal experiment (event description). Results show that culminated events (i.e. ceased change-of-state events) were remembered best across experiments. Language use showed to enhance memory overall. Further, the form of the verb predicates used for denoting culmination had a moderate effect on memory.
  • Sauppe, S., & Flecken, M. (2021). Speaking for seeing: Sentence structure guides visual event apprehension. Cognition, 206: 104516. doi:10.1016/j.cognition.2020.104516.

    Abstract

    Human experience and communication are centred on events, and event apprehension is a rapid process that draws on the visual perception and immediate categorization of event roles (“who does what to whom”). We demonstrate a role for syntactic structure in visual information uptake for event apprehension. An event structure foregrounding either the agent or patient was activated during speaking, transiently modulating the apprehension of subsequently viewed unrelated events. Speakers of Dutch described pictures with actives and passives (agent and patient foregrounding, respectively). First fixations on pictures of unrelated events that were briefly presented (for 300 ms) next were influenced by the active or passive structure of the previously produced sentence. Going beyond the study of how single words cue object perception, we show that sentence structure guides the viewpoint taken during rapid event apprehension.

    Additional information

    supplementary material
  • Scala, M., Anijs, M., Battini, R., Madia, F., Capra, V., Scudieri, P., Verrotti, A., Zara, F., Minetti, C., Vernes, S. C., & Striano, P. (2021). Hyperkinetic stereotyped movements in a boy with biallelic CNTNAP2 variants. Italian Journal of Pediatrics, 47: 208. doi:10.1186/s13052-021-01162-w.

    Abstract

    Background

    Heterozygous variants in CNTNAP2 have been implicated in a wide range of neurological phenotypes, including intellectual disability (ID), epilepsy, autistic spectrum disorder (ASD), and impaired language. However, heterozygous variants can also be found in unaffected individuals. Biallelic CNTNAP2 variants are rarer and cause a well-defined genetic syndrome known as CASPR2 deficiency disorder, a condition characterised by ID, early-onset refractory epilepsy, language impairment, and autistic features.
    Case-report

    A 7-year-old boy presented with hyperkinetic stereotyped movements that started during early infancy and persisted over childhood. Abnormal movements consisted of rhythmic and repetitive shaking of the four limbs, with evident stereotypic features. Additional clinical features included ID, attention deficit-hyperactivity disorder (ADHD), ASD, and speech impairment, consistent with CASPR2 deficiency disorder. Whole-genome array comparative genomic hybridization detected a maternally inherited 0.402 Mb duplication, which involved intron 1, exon 2, and intron 2 of CNTNAP2 (c.97 +?_209-?dup). The affected region in intron 1 contains a binding site for the transcription factor FOXP2, potentially leading to abnormal CNTNAP2 expression regulation. Sanger sequencing of the coding region of CNTNAP2 also identified a paternally-inherited missense variant c.2752C > T, p.(Leu918Phe).
    Conclusion

    This case expands the molecular and phenotypic spectrum of CASPR2 deficiency disorder, suggesting that Hyperkinetic stereotyped movements may be a rare, yet significant, clinical feature of this complex neurological disorder. Furthermore, the identification of an in-frame, largely non-coding duplication in CNTNAP2 points to a sophisticated underlying molecular mechanism, likely involving impaired FOXP2 binding.

    Additional information

    additional files
  • Schilberg, L., Ten Oever, S., Schuhmann, T., & Sack, A. T. (2021). Phase and power modulations on the amplitude of TMS-induced motor evoked potentials. PLoS One, 16(9): e0255815. doi:10.1371/journal.pone.0255815.

    Abstract

    The evaluation of transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) promises valuable information about fundamental brain related mechanisms and may serve as a diagnostic tool for clinical monitoring of therapeutic progress or surgery procedures. However, reports about spontaneous fluctuations of MEP amplitudes causing high intra-individual variability have led to increased concerns about the reliability of this measure. One possible cause for high variability of MEPs could be neuronal oscillatory activity, which reflects fluctuations of membrane potentials that systematically increase and decrease the excitability of neuronal networks. Here, we investigate the dependence of MEP amplitude on oscillation power and phase by combining the application of single pulse TMS over the primary motor cortex with concurrent recordings of electromyography and electroencephalography. Our results show that MEP amplitude is correlated to alpha phase, alpha power as well as beta phase. These findings may help explain corticospinal excitability fluctuations by highlighting the modulatory effect of alpha and beta phase on MEPs. In the future, controlling for such a causal relationship may allow for the development of new protocols, improve this method as a (diagnostic) tool and increase the specificity and efficacy of general TMS applications.

    Additional information

    data and supporting information
  • Schoenmakers, G.-J., & Storment, J. D. (2021). Going city: Directional predicates and preposition incorporation in youth vernaculars of Dutch. Linguistics in the Netherlands, 38(1), 65-80. doi:10.1075/avt.00050.sch.

    Abstract

    In certain varieties of Dutch spoken among young people, the preposition and determiner in locative and directional PPs can sometimes be omitted. We argue on the basis of language data taken from Twitter and intuitions of young speakers of Dutch that nominal arguments in these constructions do not have a DP layer, the absence of which leads to a special interpretation. The option to omit the preposition is related to the structural and semantic complexity of the verb. The bare construction is possible only with simple verbs, and not with manner-of-motion verbs. We present an analysis that accounts for the non-pronunciation of prepositions in directional predicates by claiming that they can be licensed through incorporation into the verb. This type of incorporation is blocked if the verb is structurally complex.
  • Schubotz, L., Holler, J., Drijvers, L., & Ozyurek, A. (2021). Aging and working memory modulate the ability to benefit from visible speech and iconic gestures during speech-in-noise comprehension. Psychological Research, 85, 1997-2011. doi:10.1007/s00426-020-01363-8.

    Abstract

    When comprehending speech-in-noise (SiN), younger and older adults benefit from seeing the speaker’s mouth, i.e. visible speech. Younger adults additionally benefit from manual iconic co-speech gestures. Here, we investigate to what extent younger and older adults benefit from perceiving both visual articulators while comprehending SiN, and whether this is modulated by working memory and inhibitory control. Twenty-eight younger and 28 older adults performed a word recognition task in three visual contexts: mouth blurred (speech-only), visible speech, or visible speech + iconic gesture. The speech signal was either clear or embedded in multitalker babble. Additionally, there were two visual-only conditions (visible speech, visible speech + gesture). Accuracy levels for both age groups were higher when both visual articulators were present compared to either one or none. However, older adults received a significantly smaller benefit than younger adults, although they performed equally well in speech-only and visual-only word recognition. Individual differences in verbal working memory and inhibitory control partly accounted for age-related performance differences. To conclude, perceiving iconic gestures in addition to visible speech improves younger and older adults’ comprehension of SiN. Yet, the ability to benefit from this additional visual information is modulated by age and verbal working memory. Future research will have to show whether these findings extend beyond the single word level.

    Additional information

    supplementary material
  • Schubotz, L. (2021). Effects of aging and cognitive abilities on multimodal language production and comprehension in context. PhD Thesis, Radboud University Nijmegen, Nijmegen.
  • Seijdel, N., Loke, J., Van de Klundert, R., Van der Meer, M., Quispel, E., Van Gaal, S., De Haan, E. H., & Scholte, H. S. (2021). On the necessity of recurrent processing during object recognition: It depends on the need for scene segmentation. Journal of Neuroscience, 41(29), 6281-6289. doi:10.1523/JNEUROSCI.2851-20.2021.

    Abstract

    Although feedforward activity may suffice for recognizing objects in isolation, additional visual operations that aid object recognition might be needed for real-world scenes. One such additional operation is figure-ground segmentation, extracting the relevant features and locations of the target object while ignoring irrelevant features. In this study of 60 human participants (female and male), we show objects on backgrounds of increasing complexity to investigate whether recurrent computations are increasingly important for segmenting objects from more complex backgrounds. Three lines of evidence show that recurrent processing is critical for recognition of objects embedded in complex scenes. First, behavioral results indicated a greater reduction in performance after masking objects presented on more complex backgrounds, with the degree of impairment increasing with increasing background complexity. Second, electroencephalography (EEG) measurements showed clear differences in the evoked response potentials between conditions around time points beyond feedforward activity, and exploratory object decoding analyses based on the EEG signal indicated later decoding onsets for objects embedded in more complex backgrounds. Third, deep convolutional neural network performance confirmed this interpretation. Feedforward and less deep networks showed a higher degree of impairment in recognition for objects in complex backgrounds compared with recurrent and deeper networks. Together, these results support the notion that recurrent computations drive figure-ground segmentation of objects in complex scenes.SIGNIFICANCE STATEMENT The incredible speed of object recognition suggests that it relies purely on a fast feedforward buildup of perceptual activity. However, this view is contradicted by studies showing that disruption of recurrent processing leads to decreased object recognition performance. Here, we resolve this issue by showing that how object recognition is resolved and whether recurrent processing is crucial depends on the context in which it is presented. For objects presented in isolation or in simple environments, feedforward activity could be sufficient for successful object recognition. However, when the environment is more complex, additional processing seems necessary to select the elements that belong to the object and by that segregate them from the background.
  • Seijdel, N., Scholte, H. S., & de Haan, E. H. (2021). Visual features drive the category-specific impairments on categorization tasks in a patient with object agnosia. Neuropsychologia, 161: 108017. doi:10.1016/j.neuropsychologia.2021.108017.

    Abstract

    Object and scene recognition both require mapping of incoming sensory information to existing conceptual knowledge about the world. A notable finding in brain-damaged patients is that they may show differentially impaired performance for specific categories, such as for “living exemplars”. While numerous patients with category-specific impairments have been reported, the explanations for these deficits remain controversial. In the current study, we investigate the ability of a brain injured patient with a well-established category-specific impairment of semantic memory to perform two categorization experiments: ‘natural’ vs. ‘manmade’ scenes (experiment 1) and objects (experiment 2). Our findings show that the pattern of categorical impairment does not respect the natural versus manmade distinction. This suggests that the impairments may be better explained by differences in visual features, rather than by category membership. Using Deep Convolutional Neural Networks (DCNNs) as ‘artificial animal models’ we further explored this idea. Results indicated that DCNNs with ‘lesions’ in higher order layers showed similar response patterns, with decreased relative performance for manmade scenes (experiment 1) and natural objects (experiment 2), even though they have no semantic category knowledge, apart from a mapping between pictures and labels. Collectively, these results suggest that the direction of category-effects to a large extent depends, at least in MS′ case, on the degree of perceptual differentiation called for, and not semantic knowledge.

    Additional information

    data and code
  • Senft, G. (2021). A very special letter. In T. Szczerbowski (Ed.), Language "as round as an orange".. In memory of Professor Krystyna Pisarkowa on the 90th anniversary of her birth (pp. 367). Krakow: Uniwersytetu Pedagogicznj.
  • Senft, G., & Wilkins, D. (1995). A man, a tree, and forget about the pigs: Space games, spatial reference and cross-linguistic comparison. Plenary paper presented by at the 19th international LAUD symposium "Language and space" Duisburg. Mimeo: Nijmegen.
  • Senft, G. (1995). Crime and custom auf den Trobriand-Inseln: Der Fall Tokurasi. Anthropos, 90, 17-25.
  • Senft, G. (1995). Elicitation. In J. Blommaert, J.-O. Östman, & J. Verschueren (Eds.), Handbook of Pragmatics: Manual (pp. 577-581). Amsterdam: John Benjamins.
  • Senft, G. (1995). 'Noble savages' and 'the islands of love': Trobriand Islanders in 'popular publications'. In C. Baak, M. Bakker, & D. Van der Meij (Eds.), Tales from a concave world: Liber amicorum Bert Voorhoeve (pp. 480-510). Leiden: Projects division, department of languages and cultures of South East Asia and Oceania, Leiden University.
  • Senft, G. (1986). [Review of the book Under the Tumtum tree: From nonsense to sense in nonautomatic comprehension by Marlene Dolitsky]. Journal of Pragmatics, 10, 273-278. doi:10.1016/0378-2166(86)90094-9.
  • Senft, G. (1995). Fieldwork. In J. Blommaert, J.-O. Östman, & J. Verschueren (Eds.), Handbook of Pragmatics: Manual (pp. 595-601). Amsterdam: John Benjamins.
  • Senft, G. (1995). Mit Tinkertoy in die Tiefe(n) des Raumes: Zum räumlichen Verweisen im Kilivila - Eine Fallstudie. In R. Fiehler, & D. Metzing (Eds.), Untersuchungen zur Kommunikationstruktur (Bielefelder Schriften zu Linguistik und Literaturwissenschaft, pp. 139-162). Bielefeld: Aisthesis Verlag.
  • Senft, G. (1986). Kilivila: The language of the Trobriand Islanders. Berlin: Mouton de Gruyter.
  • Senft, B., & Senft, G. (1986). Ninikula - Fadenspiele auf den Trobriand Inseln: Untersuchungen zum Spiele-Repertoire unter besonderer Berürcksichtigung der Spiel-begeleitenden Texte. Baessler Archiv: Beiträge zur Völkerkunde, N.F. 34, 92-235.
  • Senft, G., & Senft, B. (1986). Ninikula Fadenspiele auf den Trobriand-Inseln, Papua-Neuguinea: Untersuchungen zum Spiele-Repertoire unter besonderer Berücksichtigung der Spiel-begleitendenden Texte. Baessler-Archiv: Beiträge zur Völkerkunde, 34(1), 93-235.
  • Senft, G. (1995). Notes from the field: Ain't misbehavin'? Trobriand pragmatics and the field researcher's opportunity to put his (or her) foot in it. Oceanic Linguistics, 34, 211-226.
  • Senft, G. (1995). Sprache, Kognition und Konzepte des Raums in verschiedenen Kulturen. Kognitionswissenschaft, 4, 166-170.
  • Senft, G. (2021). [Review of the book Approaches to Language and Culture ed. by Svenja Völkel and Nico Nassenstein]. Anthropological Linguistics, 63(3), 318-321.
  • Seuren, P. A. M. (2021). Saving the square of opposition. History and Philosophy of Logic, 42(1), 72-96. doi:10.1080/01445340.2020.1865782.

    Abstract

    Contrary to received opinion, the Aristotelian Square of Opposition (square) is logically sound, differing from standard modern predicate logic (SMPL) only in that it restricts the universe U of cognitively constructible situations by banning null predicates, making it less unnatural than SMPL. U-restriction strengthens the logic without making it unsound. It also invites a cognitive approach to logic. Humans are endowed with a cognitive predicate logic (CPL), which checks the process of cognitive modelling (world construal) for consistency. The square is considered a first approximation to CPL, with a cognitive set-theoretic semantics. Not being cognitively real, the null set Ø is eliminated from the semantics of CPL. Still rudimentary in Aristotle’s On Interpretation (Int), the square was implicitly completed in his Prior Analytics (PrAn), thereby introducing U-restriction. Abelard’s reconstruction of the logic of Int is logically and historically correct; the loca (Leaking O-Corner Analysis) interpretation of the square, defended by some modern logicians, is logically faulty and historically untenable. Generally, U-restriction, not redefining the universal quantifier, as in Abelard and loca, is the correct path to a reconstruction of CPL. Valuation Space modelling is used to compute the effects of U-restriction.
  • Seuren, P. A. M. (1986). Adjectives as adjectives in Sranan. Journal of Pidgin and Creole Languages, 1(1), 123-134.
  • Seuren, P. A. M. (2021). Essentials of semantic syntax: An appetiser. Cadernos de Linguística, 2(1). doi:10.25189/2675-4916.2021.v2.n1.id290.

    Abstract

    Semantic Syntax (SeSyn), originally called Generative Semantics, is an offshoot of Chomskyan generative grammar (ChoGG), rejected by Chomsky and his school in the late 1960s. SeSyn is the theory of algorithmical grammars producing the well-formed sentences of a language L from the corresponding semantic input, the Semantic Analysis (SA), represented as a traditional tree structure diagram in a specific formal language of incremental predicate logic with quantifying and qualifying operators (including the truth functions), and with all lexical items filled in. A SeSyn-type grammar is thus by definition transformational, but not generative. The SA originates in cognition in a manner that is still largely mysterious, but its actual form can be distilled from the Surface Structure (SS) of the sentences of L following the principles set out in SeSyn. In this presentation we provide a more or less technical résumé of the SeSyn theory. A comparison is made with ChoGG-type grammars, which are rejected on account of their intrinsic unsuitability as a cognitive-realist grammar model. The ChoGG model follows the pattern of a 1930s neopositivist Carnap-type grammar for formal logical languages. Such grammars are random sentence generators, whereas, obviously, (nonpathological) humans are not. A ChoGG-type grammar is fundamentally irreconcilable with a mentalist-realist theory of grammar. The body of the paper consists in a demonstration of the production of an English and a French sentence, the latter containing a classic instance of the cyclic rule of Predicate Raising (PR), essential in the general theory of clausal complementation yet steadfastly repudiated in ChoGG for reasons that have never been clarified. The processes and categories defined in SeSyn are effortlessly recognised in languages all over the world, whether indigenous or languages of a dominant culture—taking into account language-specific values for the general theoretical parameters involved. This property makes SeSyn particularly relevant for linguistic typology, which now ranks as the most promising branch of linguistics but has so far conspicuously lacked an adequate theoretical basis.
  • Seuren, P. A. M. (1986). Anaphora resolution. In T. Myers, K. Brown, & B. McGonigle (Eds.), Reasoning and discourse processes (pp. 187-207). London: Academic Press.
  • Seuren, P. A. M. (1973). [Review of the book A comprehensive etymological dictionary of the English language by Ernst Klein]. Neophilologus, 57(4), 423-426. doi:10.1007/BF01515518.
  • Seuren, P. A. M. (1973). [Review of the book Philosophy of language by Robert J. Clack and Bertrand Russell]. Foundations of Language, 9(3), 440-441.
  • Seuren, P. A. M. (1973). [Review of the book Semantics. An interdisciplinary reader in philosophy, linguistics and psychology ed. by Danny D. Steinberg and Leon A. Jakobovits]. Neophilologus, 57(2), 198-213. doi:10.1007/BF01514332.
  • Seuren, P. A. M. (1986). Formal theory and the ecology of language. Theoretical Linguistics, 13(1), 1-18. doi:10.1515/thli.1986.13.1-2.1.
  • Seuren, P. A. M. (1973). Generative Semantik: Semantische syntax. Düsseldorf: Schwann Verlag.
  • Seuren, P. A. M. (1963). Naar aanleiding van Dr. F. Balk-Smit Duyzentkunst "De Grammatische Functie". Levende Talen, 219, 179-186.
  • Seuren, P. A. M. (1986). La transparence sémantique et la genèse des langues créoles: Le cas du Créole mauricien. Études Créoles, 9, 169-183.
  • Seuren, P. A. M. (1986). Helpen en helpen is twee. Glot, 9(1/2), 110-117.
  • Seuren, P. A. M. (1995). Notes on the history and the syntax of Mauritian Creole. Linguistics, 33, 531-577. doi:10.1515/ling.1995.33.3.531.
  • Seuren, P. A. M. (1995). Reflections on negation. In H. C. M. De Swart, & L. J. M. Bergmans (Eds.), Perspectives on Negation. Essays in honour of Johan J. de Iongh on his 80th birthday (pp. 153-176). Tilburg: Tilburg University Press.
  • Seuren, P. A. M. (1973). The comparative. In F. Kiefer, & N. Ruwet (Eds.), Generative grammar in Europe (pp. 528-564). Reidel: Dordrecht.

    Abstract

    No idea is older in the history of linguistics than the thought that there is, somehow hidden underneath the surface of sentences, a form or a structure which provides a semantic analysis and lays bare their logical structure. In Plato’s Cratylus the theory was proposed, deriving from Heraclitus’ theory of explanatory underlying structure in physical nature, that words contain within themselves bits of syntactic structure giving their meanings. The Stoics held the same view and maintained moreover that every sentence has an underlying logical structure, which for them was the Aristotelian subject- predicate form. They even proposed transformational processes to derive the surface from the deep structure. The idea of a semantically analytic logical form underlying the sentences of every language kept reappearing in various guises at various times. Quite recently it re-emerged under the name of generative semantics.
  • Seuren, P. A. M., & Wekker, H. (1986). Semantic transparency as a factor in Creole genesis. In P. Muysken, & N. Smith (Eds.), Substrata versus universals in Creole genesis: Papers from the Amsterdam Creole Workshop, April 1985 (pp. 57-70). Amsterdam: Benjamins.
  • Seuren, P. A. M. (1973). Predicate raising and dative in French and Sundry languages. Trier: L.A.U.T. (Linguistic Agency University of Trier).
  • Seuren, P. A. M. (1973). The new approach to the study of language. In B. Douglas (Ed.), Linguistics and the mind (pp. 11-20). Sydney: Sydney University Extension Board.
  • Seuren, P. A. M. (1986). The self-styling of relevance theory [Review of the book Relevance, Communication and Cognition by Dan Sperber and Deirdre Wilson]. Journal of Semantics, 5(2), 123-143. doi:10.1093/jos/5.2.123.
  • Seuren, P. A. M. (1973). Zero-output rules. Foundations of Language, 10(2), 317-328.
  • Severijnen, G. G. A., Bosker, H. R., Piai, V., & McQueen, J. M. (2021). Listeners track talker-specific prosody to deal with talker-variability. Brain Research, 1769: 147605. doi:10.1016/j.brainres.2021.147605.

    Abstract

    One of the challenges in speech perception is that listeners must deal with considerable
    segmental and suprasegmental variability in the acoustic signal due to differences between talkers. Most previous studies have focused on how listeners deal with segmental variability.
    In this EEG experiment, we investigated whether listeners track talker-specific usage of suprasegmental cues to lexical stress to recognize spoken words correctly. In a three-day training phase, Dutch participants learned to map non-word minimal stress pairs onto different object referents (e.g., USklot meant “lamp”; usKLOT meant “train”). These non-words were
    produced by two male talkers. Critically, each talker used only one suprasegmental cue to signal stress (e.g., Talker A used only F0 and Talker B only intensity). We expected participants to learn which talker used which cue to signal stress. In the test phase, participants indicated whether spoken sentences including these non-words were correct (“The word for lamp is…”).
    We found that participants were slower to indicate that a stimulus was correct if the non-word was produced with the unexpected cue (e.g., Talker A using intensity). That is, if in training Talker A used F0 to signal stress, participants experienced a mismatch between predicted and perceived phonological word-forms if, at test, Talker A unexpectedly used intensity to cue
    stress. In contrast, the N200 amplitude, an event-related potential related to phonological
    prediction, was not modulated by the cue mismatch. Theoretical implications of these
    contrasting results are discussed. The behavioral findings illustrate talker-specific prediction of prosodic cues, picked up through perceptual learning during training.
  • Sha, Z., Schijven, D., & Francks, C. (2021). Patterns of brain asymmetry associated with polygenic risks for autism and schizophrenia implicate language and executive functions but not brain masculinization. Molecular Psychiatry, 26(12), 7652-7660. doi:10.1038/s41380-021-01204-z.

    Abstract

    Autism spectrum disorder (ASD) and schizophrenia have been conceived as partly opposing disorders in terms of systemizing versus empathizing cognitive styles, with resemblances to male versus female average sex differences. Left-right asymmetry of the brain is an important aspect of its organization that shows average differences between the sexes, and can be altered in both ASD and schizophrenia. Here we mapped multivariate associations of polygenic risk scores for ASD and schizophrenia with asymmetries of regional cerebral cortical surface area, thickness and subcortical volume measures in 32,256 participants from the UK Biobank. Polygenic risks for the two disorders were positively correlated (r=0.08, p=7.13×10-50), and both were higher in females compared to males, consistent with biased participation against higher-risk males. Each polygenic risk score was associated with multivariate brain asymmetry after adjusting for sex, ASD r=0.03, p=2.17×10-9, schizophrenia r=0.04, p=2.61×10-11, but the multivariate patterns were mostly distinct for the two polygenic risks, and neither resembled average sex differences. Annotation based on meta-analyzed functional imaging data showed that both polygenic risks were associated with asymmetries of regions important for language and executive functions, consistent with behavioural associations that arose in phenome-wide association analysis. Overall, the results indicate that distinct patterns of subtly altered brain asymmetry may be functionally relevant manifestations of polygenic risks for ASD and schizophrenia, but do not support brain masculinization or feminization in their etiologies.
  • Sha, Z., Pepe, A., Schijven, D., Carrion Castillo, A., Roe, J. M., Westerhausen, R., Joliot, M., Fisher, S. E., Crivello, F., & Francks, C. (2021). Handedness and its genetic influences are associated with structural asymmetries of the cerebral cortex in 31,864 individuals. Proceedings of the National Academy of Sciences of the United States of America, 118(47): e2113095118. doi:10.1073/pnas.2113095118.

    Abstract

    Roughly 10% of the human population is left-handed, and this rate is increased in some brain-related disorders. The neuroanatomical correlates of hand preference have remained equivocal. We resampled structural brain image data from 28,802 right-handers and 3,062 left-handers (UK Biobank population dataset) to a symmetrical surface template, and mapped asymmetries for each of 8,681 vertices across the cerebral cortex in each individual. Left-handers compared to right-handers showed average differences of surface area asymmetry within the fusiform cortex, the anterior insula, the anterior middle cingulate cortex, and the precentral cortex. Meta-analyzed functional imaging data implicated these regions in executive functions and language. Polygenic disposition to left-handedness was associated with two of these regional asymmetries, and 18 loci previously linked with left-handedness by genome-wide screening showed associations with one or more of these asymmetries. Implicated genes included six encoding microtubule-related proteins: TUBB, TUBA1B, TUBB3, TUBB4A, MAP2, and NME7—mutations in the latter can cause left to right reversal of the visceral organs. There were also two cortical regions where average thickness asymmetry was altered in left-handedness: on the postcentral gyrus and the inferior occipital cortex, functionally annotated with hand sensorimotor and visual roles. These cortical thickness asymmetries were not heritable. Heritable surface area asymmetries of language-related regions may link the etiologies of hand preference and language, whereas nonheritable asymmetries of sensorimotor cortex may manifest as consequences of hand preference.
  • Sha, Z., Schijven, D., Carrion Castillo, A., Joliot, M., Mazoyer, B., Fisher, S. E., Crivello, F., & Francks, C. (2021). The genetic architecture of structural left–right asymmetry of the human brain. Nature Human Behaviour, 5, 1226-1236. doi:10.1038/s41562-021-01069-w.

    Abstract

    Left–right hemispheric asymmetry is an important aspect of healthy brain organization for many functions including language, and it can be altered in cognitive and psychiatric disorders. No mechanism has yet been identified for establishing the human brain’s left–right axis. We performed multivariate genome-wide association scanning of cortical regional surface area and thickness asymmetries, and subcortical volume asymmetries, using data from 32,256 participants from the UK Biobank. There were 21 significant loci associated with different aspects of brain asymmetry, with functional enrichment involving microtubule-related genes and embryonic brain expression. These findings are consistent with a known role of the cytoskeleton in left–right axis determination in other organs of invertebrates and frogs. Genetic variants associated with brain asymmetry overlapped with those associated with autism, educational attainment and schizophrenia. Comparably large datasets will likely be required in future studies, to replicate and further clarify the associations of microtubule-related genes with variation in brain asymmetry, behavioural and psychiatric traits.
  • Shapland, C. Y., Verhoef, E., Smith, G. D., Fisher, S. E., Verhulst, B., Dale, P. S., & St Pourcain, B. (2021). Multivariate genome-wide covariance analyses of literacy, language and working memory skills reveal distinct etiologies. npj Science of Learning, 6: 23. doi:10.1038/s41539-021-00101-y.

    Abstract

    Several abilities outside literacy proper are associated with reading and spelling, both phenotypically and genetically, though our knowledge of multivariate genomic covariance structures is incomplete. Here, we introduce structural models describing genetic and residual influences between traits to study multivariate links across measures of literacy, phonological awareness, oral language, and phonological working memory (PWM) in unrelated UK youth (8-13 years, N=6,453). We find that all phenotypes share a large proportion of underlying genetic variation, although especially oral language and PWM reveal substantial differences in their genetic variance composition with substantial trait-specific genetic influences. Multivariate genetic and residual trait covariance showed concordant patterns, except for marked differences between oral language and literacy/phonological awareness, where strong genetic links contrasted near-zero residual overlap. These findings suggest differences in etiological mechanisms, acting beyond a pleiotropic set of genetic variants, and implicate variation in trait modifiability even among phenotypes that have high genetic correlations.

    Additional information

    supplementary information
  • Li, Y., Wu, S., Shi, S., Tong, S., Zhang, Y., & Guo, X. (2021). Enhanced inter-brain connectivity between children and adults during cooperation: a dual EEG study. In 43RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE & BIOLOGY SOCIETY (EMBC) (pp. 6289-6292). doi:10.1109/EMBC46164.2021.9630330.

    Abstract

    Previous fNIRS studies have suggested that adult-child cooperation is accompanied by increased inter-brain synchrony. However, its reflection in the electrophysiological synchrony remains unclear. In this study, we designed a naturalistic and well-controlled adult-child interaction paradigm using a tangram solving video game, and recorded dual-EEG from child and adult dyads during cooperative and individual conditions. By calculating the directed inter-brain connectivity in the theta and alpha bands, we found that the inter-brain frontal network was more densely connected and stronger in strength during the cooperative than the individual condition when the adult was watching the child playing. Moreover, the inter-brain network across different dyads shared more common information flows from the player to the observer during cooperation, but was more individually different in solo play. The results suggest an enhancement in inter-brain EEG interactions during adult-child cooperation. However, the enhancement was evident in all cooperative cases but partly depended on the role of participants.
  • Shipley, J. M., Birdsall, S., Clark, J., Crew, J., Gill, S., Linehan, M., Gnarra, J., Fisher, S. E., Craig, I. W., & Cooper, C. S. (1995). Mapping the X chromosome breakpoint in two papillary renal cell carcinoma cell lines with a t(X;1)(p11.2;q21.2) and the first report of a female case. Cytogenetic and genome research, 71(3), 280-284. doi:DOI: 10.1159/000134127.

    Abstract

    A t(X;1)(p11.2;q21.2) has been reported in cases of papillary renal cell tumors arising in males. In this study two cell lines derived from this tumor type have been used to indicate the breakpoint region on the X chromosome. Both cell lines have the translocation in addition to other rearrangements and one is derived from the first female case to be reported with the t(X;1)(p11.2;q21.2). Fluorescence in situ hybridization (FISH) has been used to position YACs belonging to contigs in the Xp11.2 region relative to the breakpoint. When considered together with detailed mapping information from the Xp11.2 region the position of the breakpoint in both cell lines was suggested as follows: Xpter-->Xp11.23-OATL1-GATA1-WAS-TFE3-SY P-t(X;1)-DXS255-CLCN5-DXS146-OATL2- Xp11.22-->Xcen. The breakpoint was determined to lie in an uncloned region between SYP and a YAC called FTDM/1 which extends 1 Mb distal to DXS255. These results are contrary to the conclusion from previous FISH studies that the breakpoint was near the OATL2 locus, but are consistent with, and considerably refine, the position that had been established by molecular analysis.
  • Shkaravska, O., & Van Eekelen, M. (2021). Polynomial solutions of algebraic difference equations and homogeneous symmetric polynomials. Journal of Symbolic Computation, 103, 22-45. doi:10.1016/j.jsc.2019.10.022.

    Abstract

    This article addresses the problem of computing an upper bound of
    the degree d of a polynomial solution P(x) of an algebraic differ-
    ence equation of the form Gx)(P(x −τ1), . . . , P(x −τs) + G0(x) =

    0 when such P(x) with the coefficients in a field K of character-
    istic zero exists and where G is a non-linear s-variable polynomial
    with coefficients in K[x] and G0 is a polynomial with coefficients
    in K.
    It will be shown that if G is a quadratic polynomial with constant
    coefficients then one can construct a countable family of polynomi-
    als fl(u0) such that if there exists a (minimal) index l0 with fl0(u0)
    being a non-zero polynomial, then the degree d is one of its roots
    or d ≤ l0, or d < deg(G0). Moreover, the existence of such l0 will
    be proven for K being the field of real numbers. These results are
    based on the properties of the modules generated by special fami-
    lies of homogeneous symmetric polynomials.
    A sufficient condition for the existence of a similar bound of the
    degree of a polynomial solution for an algebraic difference equation
    with G of arbitrary total degree and with variable coefficients will
    be proven as well.
  • Skiba, R., & Steinmüller, U. (1995). Pragmatics of compositional word formation in technical languages. In H. Pishwa, & K. Maroldt (Eds.), The development of morphological systematicity: A cross-linguistic perspective (pp. 305-321). Tübingen: Narr.
  • Slim, M. S., Lauwers, P., & Hartsuiker, R. J. (2021). Monolingual and bilingual logical representations of quantificational scope: Evidence from priming in language comprehension. Journal of Memory and Language, 116: 104184. doi:10.1016/j.jml.2020.104184.

    Abstract

    A doubly quantified sentence, such as All hikers climbed a hill, allows two interpretations: Did all hikers climb different hills, or did they climb the same hill? Previous work has shown that comprehenders construct disambiguated logical representations of these interpretations (Raffray & Pickering, 2010). We extended this line of research by investigating whether bilingual logical representations are shared between languages or separate per language. We conducted four sentence-picture matching experiments in which we primed interpretations of doubly quantified sentences in Dutch and French monolingual and bilingual language comprehension. These experiments showed that bilinguals have fully shared logical representations and that logical representations constructed in the L1 and the L2 are comparable. Moreover, a control experiment ruled out that the priming effects were driven by visual overlap between prime and target pictures. We discuss these findings in terms of a language-dependent account of logical representations, although these findings can also be reconciled with the idea that logical representations involve conceptual mental models of sentence meaning.
  • Slivac, K., Hervais-Adelman, A., Hagoort, P., & Flecken, M. (2021). Linguistic labels cue biological motion perception and misperception. Scientific Reports, 11: 17239. doi:10.1038/s41598-021-96649-1.

    Abstract

    Linguistic labels exert a particularly strong top-down influence on perception. The potency of this influence has been ascribed to their ability to evoke category-diagnostic features of concepts. In doing this, they facilitate the formation of a perceptual template concordant with those features, effectively biasing perceptual activation towards the labelled category. In this study, we employ a cueing paradigm with moving, point-light stimuli across three experiments, in order to examine how the number of biological motion features (form and kinematics) encoded in lexical cues modulates the efficacy of lexical top-down influence on perception. We find that the magnitude of lexical influence on biological motion perception rises as a function of the number of biological motion-relevant features carried by both cue and target. When lexical cues encode multiple biological motion features, this influence is robust enough to mislead participants into reporting erroneous percepts, even when a masking level yielding high performance is used.
  • Slonimska, A., Ozyurek, A., & Capirci, O. (2021). Using depiction for efficient communication in LIS (Italian Sign Language). Language and Cognition, 13(3), 367 -396. doi:10.1017/langcog.2021.7.

    Abstract

    Meanings communicated with depictions constitute an integral part of how speakers and signers actually use language (Clark, 2016). Recent studies have argued that, in sign languages, depicting strategy like constructed action (CA), in which a signer enacts the referent, is used for referential purposes in narratives. Here, we tested the referential function of CA in a more controlled experimental setting and outside narrative context. Given the iconic properties of CA we hypothesized that this strategy could be used for efficient information transmission. Thus, we asked if use of CA increased with the increase in the information required to be communicated. Twenty-three deaf signers of LIS described unconnected images, which varied in the amount of information represented, to another player in a director–matcher game. Results revealed that participants used CA to communicate core information about the images and also increased the use of CA as images became informatively denser. The findings show that iconic features of CA can be used for referential function in addition to its depictive function outside narrative context and to achieve communicative efficiency.
  • Smeets, C. J. L. M., Ma, K. Y., Fisher, S. E., & Verbeek, D. S. (2021). Cerebellar developmental deficits underlie neurodegenerative disorder spinocerebellar ataxia type 23. Brain Pathology, 31(2), 239-252. doi:10.1111/bpa.12905.

    Abstract

    Spinocerebellar ataxia type 23 (SCA23) is a late‐onset neurodegenerative disorder characterized by slowly progressive gait and limb ataxia, for which there is no therapy available. It is caused by pathogenic variants in PDYN, which encodes prodynorphin (PDYN). PDYN is processed into the opioid peptides α‐neoendorphin and dynorphins (Dyn) A and B; inhibitory neurotransmitters that function in pain signaling, stress‐induced responses and addiction. Variants causing SCA23 mostly affect Dyn A, leading to loss of secondary structure and increased peptide stability. PDYNR212W mice express human PDYN containing the SCA23 variant p.R212W. These mice show progressive motor deficits from 3 months of age, climbing fiber (CF) deficits from 3 months of age, and Purkinje cell (PC) loss from 12 months of age. A mouse model for SCA1 showed similar CF deficits, and a recent study found additional developmental abnormalities, namely increased GABAergic interneuron connectivity and non‐cell autonomous disruption of PC function. As SCA23 mice show a similar pathology to SCA1 mice in adulthood, we hypothesized that SCA23 may also follow SCA1 pathology during development. Examining PDYNR212W cerebella during development, we uncovered developmental deficits from 2 weeks of age, namely a reduced number of GABAergic synapses on PC soma, possibly leading to the observed delay in early phase CF elimination between 2 and 3 weeks of age. Furthermore, CFs did not reach terminal height, leaving proximal PC dendrites open to be occupied by parallel fibers (PFs). The observed increase in vGlut1 protein—a marker for PF‐PC synapses—indicates that PFs indeed take over CF territory and have increased connectivity with PCs. Additionally, we detected altered expression of several critical Ca2+ channel subunits, potentially contributing to altered Ca2+ transients in PDYNR212W cerebella. These findings indicate that developmental abnormalities contribute to the SCA23 pathology and uncover a developmental role for PDYN in the cerebellum.
  • Smith, A. C., Monaghan, P., & Huettig, F. (2021). The effect of orthographic systems on the developing reading system: Typological and computational analyses. Psychological Review, 128(1), 125-159. doi:10.1037/rev0000257.

    Abstract

    Orthographic systems vary dramatically in the extent to which they encode a language’s phonological and lexico-semantic structure. Studies of the effects of orthographic transparency suggest that such variation is likely to have major implications for how the reading system operates. However, such studies have been unable to examine in isolation the contributory effect of transparency on reading due to co-varying linguistic or socio-cultural factors. We first investigated the phonological properties of languages using the range of the world’s orthographic systems (alphabetic; alphasyllabic; consonantal; syllabic; logographic), and found that, once geographical proximity is taken into account, phonological properties do not relate to orthographic system. We then explored the processing implications of orthographic variation by training a connectionist implementation of the triangle model of reading on the range of orthographic systems whilst controlling for phonological and semantic structure. We show that the triangle model is effective as a universal model of reading, able to replicate key behavioural and neuroscientific results. Importantly, the model also generates new predictions deriving from an explicit description of the effects of orthographic transparency on how reading is realised and defines the consequences of orthographic systems on reading processes.
  • Snijders Blok, L., Goosen, Y. M., Haaften, L., Hulst, K., Fisher, S. E., Brunner, H. G., Egger, J. I. M., & Kleefstra, T. (2021). Speech‐language profiles in the context of cognitive and adaptive functioning inSATB2‐associated syndrome. Genes, Brain and Behavior, 20(7): e12761. doi:10.1111/gbb.12761.

    Abstract

    SATB2-associated syndrome (SAS) is a neurodevelopmental disorder caused by heterozygous pathogenic variants in the SATB2 gene, and is typically characterized by intellectual disability and severely impaired communication skills. The goal of this study was to contribute to the understanding of speech and language impairments in SAS, in the context of general developmental skills and cognitive and adaptive functioning. We performed detailed oral motor, speech and language profiling in combination with neuropsychological assessments in 23 individuals with a molecularly confirmed SAS diagnosis: 11 primarily verbal individuals and 12 primarily nonverbal individuals, independent of their ages. All individuals had severe receptive language delays. For all verbal individuals, we were able to define underlying speech conditions. While childhood apraxia of speech was most prevalent, oral motor problems appeared frequent as well and were more present in the nonverbal group than in the verbal group. For seven individuals, age-appropriate Wechsler indices could be derived, showing that the level of intellectual functioning of these individuals varied from moderate–mild ID to mild ID-borderline intellectual functioning. Assessments of adaptive functioning with the Vineland Screener showed relatively high scores on the domain “daily functioning” and relatively low scores on the domain “communication” in most individuals. Altogether, this study provides a detailed delineation of oral motor, speech and language skills and neuropsychological functioning in individuals with SAS, and can provide families and caregivers with information to guide diagnosis, management and treatment approaches.

    Additional information

    supporting information
  • Snijders Blok, L. (2021). Let the genes speak! De novo variants in developmental disorders with speech and language impairment. PhD Thesis, Radboud University Nijmegen, Nijmegen.
  • Snijders Blok, L., Vino, A., Den Hoed, J., Underhill, H. R., Monteil, D., Li, H., Reynoso Santos, F. J., Chung, W. K., Amaral, M. D., Schnur, R. E., Santiago-Sim, T., Si, Y., Brunner, H. G., Kleefstra, T., & Fisher, S. E. (2021). Heterozygous variants that disturb the transcriptional repressor activity of FOXP4 cause a developmental disorder with speech/language delays and multiple congenital abnormalities. Genetics in Medicine, 23, 534-542. doi:10.1038/s41436-020-01016-6.

    Abstract

    Heterozygous pathogenic variants in various FOXP genes cause specific developmental disorders. The phenotype associated with heterozygous variants in FOXP4 has not been previously described.
    We assembled a cohort of eight individuals with heterozygous and mostly de novo variants in FOXP4: seven individuals with six different missense variants and one individual with a frameshift variant. We collected clinical data to delineate the phenotypic spectrum, and used in silico analyses and functional cell-based assays to assess pathogenicity of the variants.
    We collected clinical data for six individuals: five individuals with a missense variant in the forkhead box DNA-binding domain of FOXP4, and one individual with a truncating variant. Overlapping features included speech and language delays, growth abnormalities, congenital diaphragmatic hernia, cervical spine abnormalities, and ptosis. Luciferase assays showed loss-of-function effects for all these variants, and aberrant subcellular localization patterns were seen in a subset. The remaining two missense variants were located outside the functional domains of FOXP4, and showed transcriptional repressor capacities and localization patterns similar to the wild-type protein.
    Collectively, our findings show that heterozygous loss-of-function variants in FOXP4 are associated with an autosomal dominant neurodevelopmental disorder with speech/language delays, growth defects, and variable congenital abnormalities.
  • Soares, S. M. P., & Rothman, J. (2021). Cognitive states in third language acquisition and beyond: theoretical and methodological paths forward. Linguistic Approaches to Bilingualism, 11(1), 89-95. doi:10.1075/lab.20080.per.
  • Sønderby, I. E., Van der Meer, D., Moreau, C., Kaufmann, T., Walters, G. B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N. J., Bernard, M., Blackburn, N. B., Blangero, J., Boomsma, D. I., Brodaty, H., Brouwer, R. M., Bülow, R., Bøen, R., Cahn, W. and 125 moreSønderby, I. E., Van der Meer, D., Moreau, C., Kaufmann, T., Walters, G. B., Ellegaard, M., Abdellaoui, A., Ames, D., Amunts, K., Andersson, M., Armstrong, N. J., Bernard, M., Blackburn, N. B., Blangero, J., Boomsma, D. I., Brodaty, H., Brouwer, R. M., Bülow, R., Bøen, R., Cahn, W., Calhoun, V. D., Caspers, S., Ching, C. R. K., Cichon, S., Ciufolini, S., Crespo-Facorro, B., Curran, J. E., Dale, A. M., Dalvie, S., Dazzan, P., De Geus, E. J. C., De Zubicaray, G. I., De Zwarte, S. M. C., Desrivieres, S., Doherty, J. L., Donohoe, G., Draganski, B., Ehrlich, S., Eising, E., Espeseth, T., Fejgin, K., Fisher, S. E., Fladby, T., Frei, O., Frouin, V., Fukunaga, M., Gareau, T., Ge, T., Glahn, D. C., Grabe, H. J., Groenewold, N. A., Gústafsson, Ó., Haavik, J., Haberg, A. K., Hall, J., Hashimoto, R., Hehir-Kwa, J. Y., Hibar, D. P., Hillegers, M. H. J., Hoffmann, P., Holleran, L., Holmes, A. J., Homuth, G., Hottenga, J.-J., Hulshoff Pol, H. E., Ikeda, M., Jahanshad, N., Jockwitz, C., Johansson, S., Jönsson, E. G., Jørgensen, N. R., Kikuchi, M., Knowles, E. E. M., Kumar, K., Le Hellard, S., Leu, C., Linden, D. E., Liu, J., Lundervold, A., Lundervold, A. J., Maillard, A. M., Martin, N. G., Martin-Brevet, S., Mather, K. A., Mathias, S. R., McMahon, K. L., McRae, A. F., Medland, S. E., Meyer-Lindenberg, A., Moberget, T., Modenato, C., Monereo Sánchez, J., Morris, D. W., Mühleisen, T. W., Murray, R. M., Nielsen, J., Nordvik, J. E., Nyberg, L., Olde Loohuis, L. M., Ophoff, R. A., Owen, M. J., Paus, T., Pausova, Z., Peralta, J. M., Pike, B., Prieto, C., Quinlan, E. B., Reinbold, C. S., Reis Marques, T., Rucker, J. J. H., Sachdev, P. S., Sando, S. B., Schofield, P. R., Schork, A. J., Schumann, G., Shin, J., Shumskaya, E., Silva, A. I., Sisodiya, S. M., Steen, V. M., Stein, D. J., Strike, L. T., Suzuki, I. K., Tamnes, C. K., Teumer, A., Thalamuthu, A., Tordesillas-Gutiérrez, D., Uhlmann, A., Úlfarsson, M. Ö., Van 't Ent, D., Van den Bree, M. B. M., Vanderhaeghen, P., Vassos, E., Wen, W., Wittfeld, K., Wright, M. J., Agartz, I., Djurovic, S., Westlye, L. T., Stefánsson, H., Stefánsson, K., Jacquemont, S., Thompson, P. M., Andreassen, O. A., & the ENIGMA-CNV working group (2021). 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans. Translational Psychiatry, 11: 182. doi:10.1038/s41398-021-01213-0.

    Abstract

    Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

    Additional information

    figures and notes tables
  • Speed, L., Chen, J., Huettig, F., & Majid, A. (2021). Classifier categories reflect, but do not affect conceptual organization. Journal of Experimental Psychology: Learning, Memory, and Cognition, 47(4), 625-640. doi:10.1037/xlm0000967.

    Abstract

    Do we structure object-related conceptual information according to real-world sensorimotor experience, or can it also be shaped by linguistic information? This study investigates whether a feature of language coded in grammar—numeral classifiers—affects the conceptual representation of objects. We compared speakers of Mandarin (a classifier language) with speakers of Dutch (a language without classifiers) on how they judged object similarity in four studies. In the first three studies, participants had to rate how similar a target object was to four comparison objects, one of which shared a classifier with the target. Objects were presented as either words or pictures. Overall, the target object was always rated as most similar to the object with the shared classifier, but this was the case regardless of the language of the participant. In a final study employing a successive pile-sorting task, we also found that the underlying object concepts were similar for speakers of Mandarin and Dutch. Speakers of a non-classifier language are therefore sensitive to the same conceptual similarities that underlie classifier systems in a classifier language. Classifier systems may therefore reflect conceptual structure, rather than shape it.
  • Spychalska, M., Reimer, L., Schumacher, P. B., & Werning, M. (2021). The cost of the epistemic step: Investigating scalar implicatures in full and partial information contexts. Frontiers in Psychology, 12: 679491. doi:10.3389/fpsyg.2021.679491.

    Abstract

    We present the first ERP experiments that test the online processing of the scalar implicature some ⇝ not all in contexts where the speaker competence assumption is violated. Participants observe game scenarios with four open cards on the table and two closed cards outside of the table, while listening to statements made by a virtual player. In the full access context, the player makes a fully informed statement by referring only to the open cards, as cards on the table; in the partial access context, she makes a partially informed statement by referring to the whole set of cards, as cards in the game. If all of the open cards contain a given object X (Fullset condition), then some cards on the table contain Xs is inconsistent with the not all reading, whereas it is unknown whether some cards in the game contain X is consistent with this reading. If only a subset of the open cards contains X (Subset condition), then both utterances are known to be consistent with the not all implicature. Differential effects are observed depending on the quantifier reading adopted by the participant: For those participants who adopt the not all reading in the full access context, but not in the partial access context (weak pragmatic reading), a late posterior negativity effect is observed in the partial access context for the Fullset relative to the Subset condition. This effect is argued to reflect inference-driven context retrieval and monitoring processes related to epistemic reasoning involved in evaluating the competence assumption. By contrast, for participants who adopt the logical interpretation of some (some and possibly all), an N400 effect is observed in the partial access context, when comparing the Subset against the Fullset condition, which is argued to result from the competition between the two quantifying expressions some cards on the table and some cards in the game functioning in the experiment as scalar alternatives.

    Additional information

    supplementary material
  • Stark, B. C., Clough, S., & Duff, M. (2021). Suggestions for improving the investigation of gesture in aphasia. Journal of Speech, Language, and Hearing Research, 64(10), 4004-4013. doi:10.1044/2021_JSLHR-21-00125.

    Abstract

    Purpose: When we speak, we gesture, and indeed, persons with aphasia gesture more frequently. The reason(s) for this is still being investigated, spurring an increase in the number of studies of gesture in persons with aphasia. As the number of studies increases, so too does the need for a shared set of best practices for gesture research in aphasia. After briefly reviewing the importance and use of gesture in persons with aphasia, this viewpoint puts forth methodological and design considerations when evaluating gesture in persons with aphasia.
    Method & Results: We explore several different design and methodological considerations for gesture research specific to persons with aphasia, such as video angle specifications, data collection techniques, and analysis considerations. The goal of these suggestions is to develop transparent and reproducible methods for evaluating gesture in aphasia to build a solid foundation for continued work in this area.
    Conclusions: We have proposed that it is critical to evaluate multimodal communication in a methodologically robust way to facilitate increased knowledge about the relationship of gesture to spoken language, cognition, and to other aspects of living with aphasia and recovery from aphasia. We conclude by postulating future directions for gesture research in aphasia.
  • Stevelink, R., Luykx, J. J., Lin, B. D., Leu, C., Lal, D., Smith, A. W., Schijven, D., Carpay, J. A., Rademaker, K., Baldez, R., A., R., Devinsky, O., Braun, K. P. J., Jansen, F. E., Smit, D. J. A., Koeleman, B. P. C., International League Against Epilepsy Consortium on Complex Epilepsies, & Epi25 Collaborative (2021). Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations. Epilepsia, 62(7), 1518-1527. doi:10.1111/epi.16922.

    Abstract

    Abstract Objective Paroxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations. Methods Confounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses. Results Our analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations. Significance Our results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

    Additional information

    supporting information
  • Sutcliffe, D. J., Dinasarapu, A. R., Visser, J. E., Den Hoed, J., Seifar, F., Joshi, P., Ceballos-Picot, I., Sardar, T., Hess, E. J., Sun, Y. V., Wen, Z., Zwick, M. E., & Jinnah, H. A. (2021). Induced pluripotent stem cells from subjects with Lesch-Nyhan disease. Scientific Reports, 11: 8523. doi:10.1038/s41598-021-87955-9.

    Abstract

    Lesch-Nyhan disease (LND) is an inherited disorder caused by pathogenic variants in the HPRT1 gene, which encodes the purine recycling enzyme hypoxanthine–guanine phosphoribosyltransferase (HGprt). We generated 6 induced pluripotent stem cell (iPSC) lines from 3 individuals with LND, along with 6 control lines from 3 normal individuals. All 12 lines had the characteristics of pluripotent stem cells, as assessed by immunostaining for pluripotency markers, expression of pluripotency genes, and differentiation into the 3 primary germ cell layers. Gene expression profiling with RNAseq demonstrated significant heterogeneity among the lines. Despite this heterogeneity, several anticipated abnormalities were readily detectable across all LND lines, including reduced HPRT1 mRNA. Several unexpected abnormalities were also consistently detectable across the LND lines, including decreases in FAR2P1 and increases in RNF39. Shotgun proteomics also demonstrated several expected abnormalities in the LND lines, such as absence of HGprt protein. The proteomics study also revealed several unexpected abnormalities across the LND lines, including increases in GNAO1 decreases in NSE4A. There was a good but partial correlation between abnormalities revealed by the RNAseq and proteomics methods. Finally, functional studies demonstrated LND lines had no HGprt enzyme activity and resistance to the toxic pro-drug 6-thioguanine. Intracellular purines in the LND lines were normal, but they did not recycle hypoxanthine. These cells provide a novel resource to reveal insights into the relevance of heterogeneity among iPSC lines and applications for modeling LND.

    Additional information

    supplementary material

Share this page