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JRLnAS(RAJh0 Pediatr (Rio J). 2016;92(3 Suppl 1) ARTICLEanguage and reading development in the brain today:euromarkers and the case for predictionugusto Buchweitzchool of Letters, Instituto do Crebro do Rio Grande do Sul (Inscer), Pontifcia Universidade Catlica do Rio Grande do SulPUCRS), Porto Alegre, RS, Brazileceived 4 January 2016; accepted 15 February 2016vailable online 16 March 2016KEYWORDSLanguagedevelopment;Brain imaging;PredictionAbstractObjectives: The goal of this article is to provide an account of language development in thebrain using the new information about brain function gleaned from cognitive neuroscience. Thisaccount goes beyond describing the association between language and specific brain areas toadvocate the possibility of predicting language outcomes using brain-imaging data. The goalis to address the current evidence about language development in the brain and prediction oflanguage outcomes.Sources: Recent studies will be discussed in the light of the evidence generated for predictinglanguage outcomes and using new methods of analysis of brain data.Summary of the data: The present account of brain behavior will address: (1) the developmentof a hardwired brain circuit for spoken language; (2) the neural adaptation that follows readinginstruction and fosters the grafting of visual processing areas of the brain onto the hardwiredcircuit of spoken language; and (3) the prediction of language development and the possibilityof translational neuroscience.Conclusions: Brain imaging has allowed for the identification of neural indices (neuromarkers)that reflect typical and atypical language development; the possibility of predicting risk forlanguage disorders has emerged. A mandate to develop a bridge between neuroscience andhealth and cognition-related outcomes may pave the way for translational neuroscience. 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved. Please cite this article as: Buchweitz A. Language and reading development in the brain today: neuromarkers and the case for prediction. Pediatr (Rio J). 2016;92(3 Suppl 1):S8---13.E-mail: augusto.buchweitz@pucrs.brttp:// 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights development today S9PALAVRAS-CHAVEDesenvolvimentoda linguagem;Imagem cerebral;PredicoDesenvolvimento da linguagem e da leitura no crebro atualmente: neuromarcadorese o caso de predicoResumoObjetivos: O objetivo deste trabalho apresentar um relato sobre o desenvolvimento dalinguagem no crebro utilizando as novas informaces sobre funco cerebral obtidas na neu-rocincia cognitiva. o relato vai alm da descrico da associaco entre linguagem e reasespecficas do crebro e defende a possibilidade de predizer os resultados de linguagem pormeio de dados de imagens cerebrais. O objetivo tratar das evidncias atuais sobre desen-volvimento da linguagem no crebro e abordar a possibilidade de predico de resultados delinguagem.Fontes: Estudos recentes sero discutidos em face das evidncias geradas pela predico deresultados de linguagem e pelo uso de novos mtodos de anlise de dados cerebrais.Resumo dos dados: Este relato de comportamento cerebral abordar: (1) o desenvolvimentode um circuito cerebral de linguagem falada; (2) a adaptaco neural que segue a instruco daleitura e incentiva a inserco de reas de processamento visual do crebro no circuito delinguagem falada; e (3) a predico do desenvolvimento da linguagem e a possibilidade de umaneurocincia translacional.Concluses: As imagens cerebrais permitiram a identificaco de ndices neurais (neuromar-cadores) que refletem o desenvolvimento da linguagem tpico e atpico; surge a possibilidadede prever o risco de disfunces de linguagem. A responsabilidade de desenvolver uma ligacoentre neurocincia e resultados relacionados a sade e cognico pode abrir o caminho para aneurocincia translacional. 2016 Sociedade Brasileira de Pediatria. Publicado por Elsevier Editora Ltda. Todos os direitosreservados.pcieriirigocasstNTgcTs(rdischarges from neurons and the BOLD signal.16,17 Other MRIIntroductionOne of the key challenges for the neurosciences is to becomefaster and more effective at producing evidence thattransforms health and education-related practice. Neuro-scientific studies of neuronal markers hold promise for moresuccessful health and education policies. The obstacles tomaking predictions from brain data involve producing moregeneralizable, robust results; establishing communicationchannels with education and healthcare decision-makersand professionals; and addressing ethical issues that arisefrom making such predictions. The present article focuses ona specific type of evidence: functional brain data obtainedfrom noninvasive brain imaging to predict developmentaland clinical outcomes. Recent studies will be discussed inthe light of the evidence generated for predicting languageoutcomes and of using new methods of analysis of brain data.With the advent of magnetic resonance imaging (MRI)and its varied functional and structural procedures, stud-ies of the brain mechanisms that underpin cognition andpsychiatric disorders have flourished.1 Studies using func-tional MRI (fMRI) have unveiled specific neural circuitry andmechanisms for language acquisition, language disorders,and language-related processes.2---4 Language developmenthas been shown to be amenable to investigation by MRI pro-cedures.Research on the brains structural and functional indicesthat predict language outcome5---11 may be an effectivemeans to translate new evidence into applications.4---12However, the influence of the research outside the scien-tific community appears to fall short of its promise.1 Thepturoduction of generalizable models of clinical and edu-ational outcomes based on these indices (neuromarkers)s an exciting possibility for changing the way health andducation-related decisions benefit from brain imaging. Aecent review13 advocated the application of brain measuresn the prediction of outcomes in several fields, includ-ng education and learning; health-related behaviors andesponses to treatments; and relapse for alcohol, smok-ng, and drug addiction. Prediction was defined as producingeneralizable models that effectively identify outcomes inut-of-sample individuals; in the interest of the present arti-le, this would mean establishing neuromarkers that can bepplied to more diverse populations outside the smaller-ample brain imaging studies.13 Prediction, in this broadense, is the ultimate test of a neuromarker after passing theest of reliable within-subject and in-sample predictions.oninvasive brain imaging measures: fMRIhe present article focuses on evidence from fMRI investi-ations of language development. This technique identifieshanges in metabolism and oxygen levels in the brain.14,15hough the increase in metabolism is not a direct mea-ure of neuronal activity, the blood-oxygen level dependentBOLD) signal acquired during fMRI procedures reflects neu-al responses: there is a correlation between electricalrocedures, such as diffusion-tensor imaging, used for inves-igations of white matter pathways, are increasingly beingsed in multimodal studies of language processes, disorders,Saro3abpiaSiEaafttpobsskrommbce(abwacpmcswctrdtlTmwiisttfi2gactlaoaediuaiaiHglfloipaag(nisfwvpobFig. 1 demonstrates the overlap in centers involved forspeech and print processing for Portuguese (adapted fromBuchweitz et al.).29 Similar centers were identified in thestudy of four different languages.10 nd development.13,18---21 Other methods, such as event-elated potentials, have also effectively predicted languageutcomes: neonatal event-related potentials (as early as6 h after birth) were predictive of language outcomest 8 years of age.22 Multimodal investigations that com-ine procedures eliminate the shortcomings of the differentrocedures.23 A more in-depth discussion of multimodalnvestigation and methods is beyond the scope of the presentrticle.poken language development: a resilient process,ts milestones, and hardwired brain circuitryarly language development and emerging communicationbilities are fundamental for the development of cognitivend social skills.24 Language development is one of the keyactors associated with the development of mental capital;his means ensuring that each person is given the chanceo achieve their full cognitive potential, and is allowed torosper and flourish within modern society.25The United States Committee on Integrating the Sciencef Early Childhood Development produced an evidence-ased report on early brain development, language,ocialization, and self-regulation. In the words of the report:poken language is resilient, literacy is fragile.24 These twoey aspects of oral and written language development,esilience and fragility, have been investigated in the lightf brain imaging. There are language milestones (behavioralarkers) associated with neural signatures of language. Theilestones provide evidence that helps establish predictiverain---behavior relationships for language.Spoken language develops without instruction. The pro-ess of development occurs in almost all children despiteconomic and social hardships, as well as lack of instructionbut such hardships influence qualitative and quantitativespects of language and cognitive development).24,26---28 Therain circuits that develop for spoken language are hard-ired in the brain. The components of the language circuitryre associated with levels of auditory comprehension pro-esses; the key centers and processes include: (1) therimary auditory cortex, which processes raw auditory infor-ation; (2) the posterior temporal and inferior parietalortices, which process the systematic organization of wordounds; (3) the middle temporal cortex, which is associatedith accessing word meaning; (4) and the inferior frontalortex, which processes the structure of language. Overhe past 25 years, noninvasive brain imaging has providedobust and replicable evidence about the brain circuits thatevelop for spoken language. It is worth mentioning thathe brain areas involved depend on the granularity of theanguage process being investigated.2,3,9,29,30At times there are delays in oral language development.he age at which a child begins to speak is a behavioralarker of such delay. Children usually produce their firstords between 10 and 15 months of age. A delay in speakingndicates atypical language development, and is one of thendicators of risk for reading disorder.31---33 Language mile-tones such as age at speaking can be evaluated in terms ofhe typical neural circuits that develop in the child.A recent study of early and late talkers identified cor-ical and subcortical markers of children who spoke theirFiBuchweitz Arst words at 1.2 years (early) versus those who spoke at.5 years (late).34 In addition to better performance in lan-uage tests at 8 years of age, early talkers (also at 8 years ofge) showed more activation in subcortical structures asso-iated with the learning of rule-based systems (putamen andhalamus); these subcortical structures are at the basis ofearning new linguistic skills.35,36 Early milestones as simples uttering two to three word sentences are strong indicatorsf language outcome, and the effects of age at speaking aressociated with markers of brain development. Identifyingarly behaviors and understanding the consequences brainevelopment provide a path for cognitive neuroscience tonform early intervention. Brain---behavior relationships helpnderstand the typical interaction between psychologicalnd biological processes, and the missing biological piecesn atypical development.The development of spoken language is resilient andlso remarkably similar across languages. Recently, a brainmaging study of four different languages (Spanish, English,ebrew, and Chinese) showed the universality of the lan-uage network in the brain.9 In all languages, the traditionaleft frontal---temporal network of the brain was activatedor listening comprehension, and it was remarkably over-apping. Such findings provide the basis for future modelsf prediction of language outcome across cultures. Theres invariance in structures that develop for speech com-rehension despite the different characteristics of soundnd structure of spoken languages. The study also showed common brain signature for reading in the four lan-uages. Despite the significant differences in writing systemsalphabetic and ideographic, for example), the brain sig-ature for reading is largely similar in the four languages;t is also largely constrained by the speech processingystem.9 Earlier studies showed how the centers that adaptor processing print are constrained by the centers hard-ired for spoken language (of course, with the exception ofisual centers). Once children learn to read, the centers forrocessing print are grafted onto a left-lateralized networkf language areas hardwired for spoken language. This haseen shown for English and for Portuguese, for example.29,30igure 1 The left frontoparietal network of regions for listen-ng and reading (red: listening; green: reading; white: overlap).S11Table 1 Brain regions associated with readingdevelopment.Region (left hemisphere) Brain---behaviorrelationshipReferenceOccipitotemporala Recognition ofletters; adaptationof the visualcircuit to reading.6,9,40,43,45Temporoparietal Development ofthe phonologicalroute(letter-sound33,44,47,48ldlawpcdvwvrtipilfbwtddiscussed above, the occipitotemporal and the temporopari-etal regions.In sum, cognitive neuroscience and brain imaging haveproduced evidence of brain and behavior relationships thatLanguage development today Based on the notion that there is a hardwired languagecircuitry, and that instruction-dependent reading develop-ment is constrained by this circuitry, it is possible to reframethis information in the light of prediction of language out-come. By knowing what underlying biological centers haveto develop and the adaptations that follow from learning,it is possible to establish a neural account of spoken lan-guage and reading development within the framework ofprediction. Some of the neural adaptations to reading arediscussed below.Reading development: a fragile process and itsassociated adaptations in the brainLearning to read is instruction-dependent, and it system-atically changes the human visual circuitry and the waylanguage sounds are processed. Studies show lasting effectson the processing of auditory word-form. Illiterate adults areincapable of deleting or adding sounds from pseudowords(words that do not exist, but are made up of regular conso-nant and vowel structures).37 The systematic changes inbrain function that take place are likely candidates for neu-romarkers of typical and poor reading development. Onesuch change has been identified in illiterate adults: theydo not process made-up words using the same brain cen-ters literate adults do38 and they have difficulty repeatingback made-up words and making word associations basedon sound.39 These difficulties follow from not having learnedthe visual boundaries of words and the corresponding bound-aries in sound.One of the consequences of learning to read is that thehuman ability to recognize mirror images slows down (con-trary to natural human mirror-imaging abilities, learningto read means unlearning to mirror b and d, forexample).40 When one learns to read, a specific center in theoccipitotemporal region reprograms itself; it adapts from itsoriginal function of processing faces and objects to special-izing in the identification of the visual form of words.41---43The activation of the occipitotemporal region in associationwith the presentation of letters and words is a marker ofreading development. The more a child learns to read, themore the occipitotemporal region activates in response tovisual processing of words. The specific region that adaptsto the recognition of letters and words has been coined thevisual word form area (VWFA).43---45 In illiterate adults, theVWFA does not light up when words are presented visually. Itdoes not activate for visual linguistic stimuli differently thanit activates for nonlinguistic visual stimuli. Also, the activa-tion of the region is modulated by how late one learns toread. The VWFA activates significantly more in people whohave learned to read as children than in those who learnedto read only as adults. The different levels of activation ofthe VWFA correlate with reading fluency.44 The activation ofthe VWFA in early years is predictive of reading outcomesand is a marker of fluent reading.6,42,45Pathways from the human visual circuitry to othercenters in the brain develop with reading. Two pathways,or routes, develop in parallel: the dorsal, or phonologicalroute and the ventral, or lexical route. The left tem-poroparietal region is part of the dorsal route of the brainthat develops with reading. The dorsal pathway includesFtdassociations)a Also known as the visual word form area.eft temporoparietal and left inferior frontal regions. Theevelopment of the dorsal pathway is associated withearning print and sound associations.43 Brain imaging haslso revealed that activation of the dorsal pathway developsith age46; and that the temporoparietal component of theathway is hypoactive in dyslexic children.33,47 It is a brainircuitry that develops with learning to read and fails toevelop when there are obstacles to reading fluently. Theentral pathway, in turn, develops with reader fluency andith the learning of irregularities of language (such as oneowel having more than one possible sound).Brain imaging has produced evidence about markers ofeading development, and the importance of early instruc-ion for reading. The question is no longer whether brainmaging has the potential to inform practices and generateredictions. The scientific question, it seems, lies in produc-ng more generalizable evidence and replicating studies witharger populations; the political and ethical issues shouldollow. One promise for prediction lies in the interactionetween brain imaging and machine learning algorithms,hich is briefly addressed below. Table 1 shows studieshat identified neural markers in association with readingevelopment. Fig. 2 shows a rendering of the two centersigure 2 The visual word form area (red circle) and theemporoparietal region (blue circle): brain markers of readingevelopment.SimrpbieAhTpiirtampafeeidtpTmrcelbaaattCTR111111111122222212 nform the basis of typical and atypical language develop-ent. The challenge is how to make the evidence moreeliable to the point of informing educational and healtholicies. The application of machine learning algorithms torain imaging data in combination with large-scale brainmaging studies is an exciting possibility to produce morevidence-based educational policies. mandate for the neurosciences: prediction ofealth and education-related outcomeshe application of machine learning algorithms to identifyatterns in human activity is changing the way human behav-or can be investigated and predicted. These algorithmsdentify patterns in instant messaging, traffic, and health-elated Internet queries (i.e., for the word influenza)hat may raise red flags for possible epidemics.48 The recentdvances in the use of machine learning algorithms haveade it possible to reliably identify cognitive states andsychiatric disorders using brain imaging data.49---53Machine learning algorithms can unveil patterns of brainctivity that can be tested on new sets of brain imaging dataor their generalizability; patterns associated with humanmotions or with clinical populations have been tested onntirely new brain imaging data sets.50,54 Machine learn-ng has been applied to identify autism from the brainata alone,50 to identify cognitive states,51,54,49 to iden-ify brain patterns for emotions,52 and to identify brainatterns that identify when new concepts are learned.55he issue that emerges is how to support more use ofachine learning algorithms and knowledge in the neu-osciences. Identification of early markers of health andognition-related outcomes holds promise for a positiveffect in quality of life and in return-on-investment of pub-ic funding for science and healthcare. These algorithms cane used to test whether the neural markers of languagend reading development extrapolate to larger populations,nd predict language outcomes. Brain imaging evidence isccumulating and artificial intelligence algorithms continueo improve. Education and healthcare should benefit fromhese advances.onflicts of interesthe author declares no conflicts of interest.eferences1. Rosen BR, Savoy RL. fMRI at 20: has it changed the world? Neu-roimage. 2012;62:1316---24.2. Price CJ. The anatomy of language: a review of 100 fMRI studiespublished in 2009. Ann NY Acad Sci. 2010;1191:62---88.3. Cabeza R, Nyberg L. Imaging cognition II: an empirical reviewof 275 PET and fMRI studies. J Cogn Neurosci. 2000;12:1---47.4. Gabrieli JD. 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Chang KM, Mitchell T, Just MA. Quantitative modeling ofthe neural representation of objects: how semantic featurenorms can account for fMRI activation. Neuroimage. 2011;56:716---27.4. Mitchell TM, Shinkareva SV, Carlson A, Chang KM, MalaveVL, Mason RA, et al. Predicting human brain activity asso-ciated with the meanings of nouns. Science. 2008;320:1191---5.5. Bauer AJ, Just MA. Monitoring the growth of the neuralrepresentations of new animal concepts. Hum Brain Mapp.2015;36:3213---26. and reading development in the brain today: neuromarkers and the case for predictionIntroductionNoninvasive brain imaging measures: fMRISpoken language development: a resilient process, its milestones, and hardwired brain circuitryReading development: a fragile process and its associated adaptations in the brainA mandate for the neurosciences: prediction of health and education-related outcomesConflicts of interestReferences


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