AbstractTo understand language, humans must encode information from rapid, sequential streams of syllables – tracking their order and organizing them into words, phrases, and sentences. We used Near‐Infrared Spectroscopy (NIRS) to determine whether human neonates are born with the capacity to track the positions of syllables in multisyllabic sequences. After familiarization with a six‐syllable sequence, the neonate brain responded to the change (as shown by an increase in oxy‐hemoglobin) when the two edge syllables switched positions but not when two middle syllables switched positions (Experiment 1), indicating that they encoded the syllables at the edges of sequences better than those in the middle. Moreover, when a 25 ms pause was inserted between the middle syllables as a segmentation cue, neonates' brains were sensitive to the change (Experiment 2), indicating that subtle cues in speech can signal a boundary, with enhanced encoding of the syllables located at the edges of that boundary. These findings suggest that neonates' brains can encode information from multisyllabic sequences and that this encoding is constrained. Moreover, subtle segmentation cues in a sequence of syllables provide a mechanism with which to accurately encode positional information from longer sequences. Tracking the order of syllables is necessary to understand language and our results suggest that the foundations for this encoding are present at birth.
Consortia for the ALBINO Study Group: Axel R. Franz, Mario Rüdiger, Christian F. Poets, Manon Benders, Frank van Bel, Karel Allegaert, Gunnar Naulaers, Dirk Bassler, Katrin Klebermaß-Schrehof, Maximo Vento, Hercilia Guimarães, Tom Stiris, Luigi Cattarossi, Marjo Metsäranta, Sampsa Vanhatalo, Jan Mazela, Tuuli Metsvaht, Cees van Veldhuizen, Corinna Engel, Christian A. Maiwald, Gabriele von Oldershausen, Iris Bergmann, Monika Weiss, Caroline J. B. R. Wichera, Andreas Eichhorn, Michael Raubuch, Birgit Schuler, Cees K. W. van Veldhuizen, Bas Laméris, Yannique Jacobs, Roselinda van der Vlught-Meijer, Elke Griesmaier, Johannes Brandner, Marie Tackoen, Ruth Reibel, Chantal Lecart, Luc Cornette, Genevieve Malfilatre, Renaud Viellevoye, Tuuli Metsvaht, Mari-Liis Ilmoja, Pille Saik, Ruth Käär, Pille Andresson, Marjo Metsaranta, Axel R. Franz, Rolf Schloesser, Torsten Ott, Stefan Winkler, Thomas Hoehn, Norbert Teig, Michael Schroth, Ulrich H. Thome, Harald Ehrhardt, Luigi Cattarossi, Isabella Mauro, Eugenio Baraldi, Virgilio Carnielli, Giuseppe Paterlini, Marcello Napolitano, Paola Francesca Faldini, Gianluca Lista, Gianluca Visintin, Mario Barbarini, Laura Pagani, Emmanuele Mastretta, Giovanni Vento, Monica Fumagalli, Marco Binotti, Mirjam M. van Weissenbruch, Henrica L. M. van Straaten, Manon J. N. L. Benders, Kim V. Annink, Frank van Bel, Jeroen Dudink, Jan B. Derks, Inge P. de Boer, Clemens B. Meijssen, Timo R. de Haan, Linda G. van Rooij, Jacqueline L. van Hillegersberg, Minouche van Dongen, Jos Bruinenberg, Koen P. Dijkman, Marlies A. van Houten, Sophie R. D. van der Schoor, Tom Stiris, Bodil Salvesen, Moritz Schneider, Eirik Nestaas, Britt Nakstad, Jan Mazela, Lukas Karpinski, Ewa Gulczynska, Barbara Królak-Olejnik, Renata Bokiniec, Ana I. Vilan, Liliana Flores de Pinho, Claudia Ferraz, Almerinda Pereira, Rosalina Barroso, André Mendes da Graça, Teresa Tomé, Filomena Pinto, Maximo Vento, Juan Martínez Rodilla, Simón Lubián, Marta Campubri Camprubí, José Antonio Hurtado Suazo, Eva Valverde, José Ramón Fernández Lorenzo, José Martinez Orgado, Héctor Boix, Francisco Jimenez Parrilla, Maria Teresa Moral-Pumarega, Julia Maletzki, Claudia Knoepfli, Cornelia Hagmann, Sven Schulzke, Martin Stocker, André Birkenmaier, Thomas Riedel, Hans-Jörg Ehni, Annie Janvier & Georg Marckmann. ; [Background]: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. ; [Methods]: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. ; [Discussion]: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. ; [Trial registration]: NCT03162653, www.ClinicalTrials.gov, May 22, 2017. ; This study is funded under the Horizon 2020 Framework Program of the European Union, call H2020-PHC-2015-two-stage, grant 667224. Publication of this manuscript was supported by Deutsche Forschungsgemeinschaft and the Open Access Publishing Fund of the University of Tuebingen. ; Peer reviewed
