Το ακουστικό σύστημα έχει να μας διδάξει πολλά σχετικά με τις κεντρικές ακουστικές διαδικασίες, όμως ο τρόπος με τον οποίο συμπεριφέρεται και λειτουργεί σε διάφορα νοσήματα (αυτισμός, σ.Αsperger, σχιζοφρένεια), όσο και σε καταστάσεις τόσο προβληματικές (δυσλεξία, αλκοολισμός, κώμα) όσο και φυσιολογικές (εκμάθηση ξένων γλωσσών), είναι ακόμη άγνωστος. Ο λεπτός κρίκος που παρεμβάλλεται μεταξύ όλων αυτών των καταστάσεων και της λειτουργίας του ακουστικού συστήματος είναι ένα (ακουστικό) προκλητό δυναμικό, το αρνητικό δυναμικό ασυμφωνίας (ΑΔΑ). Το δυναμικό αυτό εκλύεται από τον εγκέφαλο οποτεδήποτε ένας διαφορετικός ήχος επιδράσει σε μια ακολουθία σταθερών ήχων. Πρόκειται για ένα αυτόματο φαινόμενο το οποίο υπάρχει στη φύση, είναι όμως δυνατό να εκλυθεί και να μελετηθεί και πειραματικά. Στην παρούσα εργασία αναλύεται το δυναμικό ΑΔΑ, περιγράφονται κάποιες κλινικές χρησιμότητες και μερικά πλεονεκτήματά του και αναλυτικά η μεθοδολογία και η πειραματική διάταξη που ακολουθήθηκε για την ανάδειξη του σημαντικού αυτού δυναμικού. Η πειραματική διάταξη που χρησιμοποιήθηκε στην παρούσα εργασία, επέτρεψε την ανίχνευση ισχυρών και διακριτών δυναμικών ΑΔΑ. Η διάταξη είναι εύκολα αναπαραγώγιμη και θα μπορούσε να τύχει πολλών κλινικών εφαρμογών. / By studying the function of the auditory system, it is possible to also elucidate the function of several central auditory procedures. It is however largely unknown how these are related to diseases such as autism, Asperger's syndrome, schizophrenia, but also to other situations such as dyslexia, coma, alcoholism, or the learning of foreign languages. The tiny bond that connects all these functions with central auditory processes is an auditory evoked potential called mismatch negativity (MMN). The MMN is elicited whenever a deviant sound interferes in a sequence of standard tones. Elicitation of MMN potentials is an automatic procedure that happens in nature all the time. It can however also be produced and detected in the laboratory. The present work starts with a detailed description of the MMN potential. Some of its advantages, as well as its clinical uses are also presented. This work also includes a very detailed description of the methhodology used to detect and study MMN potentials in experimental conditions. The experimental setup used in this work allowed us to detect substantial and discernible MMNs. This setup, and hence the study of MMNs is easily replicable, could therefore be also used in clinical praxis.

The human central auditory system can automatically extract abstract regularities from a variant auditory input. To this end, temporarily separated events need to be related. This study tested whether the timing between events, falling either within or outside the temporal window of integration (~350 ms), impacts the extraction of abstract feature relations. We utilized tone pairs for which tones within but not across pairs revealed a constant pitch relation (e.g., pitch of second tone of a pair higher than pitch of first tone, while absolute pitch values varied across pairs). We measured the mismatch negativity (MMN; the brain’s error signal to auditory regularity violations) to second tones that rarely violated the pitch relation (e.g., pitch of second tone lower). A Short condition in which tone duration (90 ms) and stimulus onset asynchrony between the tones of a pair were short (110 ms) was compared to two conditions, where this onset asynchrony was long (510 ms). In the Long Gap condition, the tone durations were identical to Short (90 ms), but the silent interval was prolonged by 400 ms. In Long Tone, the duration of the first tone was prolonged by 400 ms, while the silent interval was comparable to Short (20 ms). Results show a frontocentral MMN of comparable amplitude in all conditions. Thus, abstract pitch relations can be extracted even when the within-pair timing exceeds the integration period. Source analyses indicate MMN generators in the supratemporal cortex. Interestingly, they were located more anterior in Long Gap than in Short and Long Tone. Moreover, frontal generator activity was found for Long Gap and Long Tone. Thus, the way in which the system automatically registers irregular abstract pitch relations depends on the timing of the events to be linked. Pending that the current MMN data mirror established abstract rule representations coding the regular pitch relation, neural processes building these templates vary with timing.:Introduction; Materials and methods; Results; Discussion; Conclusion

The regular behavior of sound sources helps us to make sense of the auditory environment. Regular patterns may, for instance, convey information on the identity of a sound source (such as the acoustic signature of a train moving on the rails). Yet typically, this signature overlaps in time with signals emitted from other sound sources. It is generally assumed that auditory regularity extraction cannot operate upon this mixture of signals because it only finds regularities between adjacent sounds. In this view, the auditory environment would be grouped into separate entities by means of readily available acoustic cues such as separation in frequency and location. Regularity extraction processes would then operate upon the resulting groups. Our new experimental evidence challenges this view. We presented two interleaved sound sequences which overlapped in frequency range and shared all acoustic parameters. The sequences only differed in their underlying regular patterns. We inserted deviants into one of the sequences to probe whether the regularity was extracted. In the first experiment, we found that these deviants elicited the mismatch negativity (MMN) component. Thus the auditory system was able to find the regularity between the non-adjacent sounds. Regularity extraction was not influenced by sequence cohesiveness as manipulated by the relative duration of tones and silent inter-tone-intervals. In the second experiment, we showed that a regularity connecting non-adjacent sounds was discovered only when the intervening sequence also contained a regular pattern, but not when the intervening sounds were randomly varying. This suggests that separate regular patterns are available to the auditory system as a cue for identifying signals coming from distinct sound sources. Thus auditory regularity extraction is not necessarily confined to a processing stage after initial sound grouping, but may precede grouping when other acoustic cues are unavailable.

L’objectif de cette thèse est l’étude du développement de l’attention auditive et des capacités de discrimination langagière chez l’enfant né prématurément ou à terme. Les derniers mois de grossesse sont particulièrement importants pour le développement cérébral de l’enfant et les conséquences d’une naissance prématurée sur le développement peuvent être considérables. Les enfants nés prématurément sont plus à risque de développer une variété de troubles neurodéveloppementaux que les enfants nés à terme. Même en l’absence de dommages cérébraux visibles, de nombreux enfants nés avant terme sont à risque de présenter des troubles tels que des retards langagiers ou des difficultés attentionnelles. Dans cette thèse, nous proposons donc une méthode d’investigation des processus préattentionnels auditifs et de discrimination langagière, à l’aide de l’électrophysiologie à haute densité et des potentiels évoqués auditifs (PEAs). Deux études ont été réalisées. La première visait à mettre sur pied un protocole d’évaluation de l’attention auditive et de la discrimination langagière chez l’enfant en santé, couvrant différents stades de développement (3 à 7 ans, 8 à 13 ans, adultes ; N = 40). Pour ce faire, nous avons analysé la composante de Mismatch Negativity (MMN) évoquée par la présentation de sons verbaux (syllabes /Ba/ et /Da/) et non verbaux (tons synthétisés, Ba : 1578 Hz/2800 Hz ; Da : 1788 Hz/2932 Hz). Les résultats ont révélé des patrons d’activation distincts en fonction de l’âge et du type de stimulus présenté. Chez tous les groupes d’âge, la présentation des stimuli non verbaux a évoqué une MMN de plus grande amplitude et de latence plus rapide que la présentation des stimuli verbaux. De plus, en réponse aux stimuli verbaux, les deux groupes d’enfants (3 à 7 ans, 8 à 13 ans) ont démontré une MMN de latence plus tardive que celle mesurée dans le groupe d’adultes. En revanche, en réponse aux stimuli non verbaux, seulement le groupe d’enfants de 3 à 7 ans a démontré une MMN de latence plus tardive que le groupe d’adulte. Les processus de discrimination verbaux semblent donc se développer plus tardivement dans l’enfance que les processus de discrimination non verbaux. Dans la deuxième étude, nous visions à d’identifier les marqueurs prédictifs de déficits attentionnels et langagiers pouvant découler d’une naissance prématurée à l’aide des PEAs et de la MMN. Nous avons utilisé le même protocole auprès de 74 enfants âgés de 3, 12 et 36 mois, nés prématurément (avant 34 semaines de gestation) ou nés à terme (au moins 37 semaines de gestation). Les résultats ont révélé que les enfants nés prématurément de tous les âges démontraient un délai significatif dans la latence de la réponse MMN et de la P150 par rapport aux enfants nés à terme lors de la présentation des sons verbaux. De plus, les latences plus tardives de la MMN et de la P150 étaient également corrélées à des performances langagières plus faibles lors d’une évaluation neurodéveloppementale. Toutefois, aucune différence n’a été observée entre les enfants nés à terme ou prématurément lors de la discrimination des stimuli non verbaux, suggérant des capacités préattentionnelles auditives préservées chez les enfants prématurés. Dans l’ensemble, les résultats de cette thèse indiquent que les processus préattentionnels auditifs se développent plus tôt dans l'enfance que ceux associés à la discrimination langagière. Les réseaux neuronaux impliqués dans la discrimination verbale sont encore immatures à la fin de l'enfance. De plus, ceux-ci semblent être particulièrement vulnérables aux impacts physiologiques liés à la prématurité. L’utilisation des PEAs et de la MMN en réponse aux stimuli verbaux en bas âge peut fournir des marqueurs prédictifs des difficultés langagières fréquemment observées chez l’enfant prématuré. / The aim of this thesis is to investigate early auditory attention and language development in full-term and preterm children. The last months of pregnancy are particularly important for the child’s cerebral development, and the impacts of a premature birth on his/her neurodevelopment can be substantial. Prematurely born children are at higher risk of developing a variety of neurodevelopmental disorders compared to full-terms. Even without visible brain injury, many premature children are at risk of presenting disorders such as language delays and attentional difficulties. In this thesis, we suggest an approach to investigate pre-attentional processes and early language discrimination abilities in infants using high-density electrophysiology and auditory event-related potentials (AERPs). We conducted two studies. The first one aimed at establishing a paradigm to evaluate auditory attention and language discrimination development in healthy full-term children, over different developmental stages (3 to 7 years, 8 to 13 years, adults; N = 40). To do so, we analyzed the Mismatch Negativity (MMN) component in response to speech (spoken syllables /Ba/ and /Da/) and non-speech stimuli (frequency-synthesized tones, Ba: 1578 Hz/2800 Hz; Da: 1788 Hz/2932 Hz). Distinct patterns of activation were revealed according to stimulus type and age. In all groups, non-speech stimuli elicited an MMN of larger amplitude and earlier latency than did the presentation of speech stimuli. Moreover, in response to speech stimuli, both children groups (3 to 7 years, 8 to 13 years) showed a significantly delayed MMN response compared to the adults group. In contrast, in response to non-speech stimuli, only the youngest group (3 to 7 years) showed a significantly delayed MMN compared to the adults. Age-related differences for tone discrimination therefore appear to occur earlier in children’s development than do the discriminative processes for speech sounds. In the second study, we aimed at identifying the electrophysiological markers of auditory attention and language deficits often incurred by a premature birth. We thus presented this paradigm to 74 infants born preterm (before 34 gestational weeks) or full-term (at least 37 gestational weeks), aged 3, 12 and 36 months old. Our results indicated that preterm children of all age groups showed a significantly delayed MMN and P150 responses to speech stimuli compared to full-terms. Moreover, significant correlations were found between the delayed MMN and P150 responses to speech sounds and lower language scores on a neurodevelopmental assessment. However, no significant differences were found between full-term and preterm children for the MMN in response to non-speech stimuli, suggesting preserved pre-attentional auditory discrimination abilities in these children. Altogether, the findings from this thesis indicate that the neurodevelopmental processes associated with auditory pre-attentional skills occur earlier in childhood compared to language discrimination processes. Cerebral networks involved in speech discrimination are still immature in late childhood. Furthermore, neural networks involved in speech discrimination and language development also appear to be particularly vulnerable to the impacts of prematurity. The use of AERPs and the MMN response to speech stimuli in infancy can thus provide predictive markers of language difficulties commonly seen in premature infants.

Abstract To be able to acquire, produce, and comprehend language, precise central auditory processing (CAP), neural processes utilized for managing auditory input, is essential. However, the auditory environments are not always optimal for CAP because noise levels in children’s daily environments can be surprisingly high. In young children, CAP and its developmental trajectory as well as the influence of noise on it have scarcely been investigated. Event-related potentials (ERPs) offer promising means to study different stages of CAP in small children. Sound processing, preattentive auditory discrimination, and attention shifting processes can be addressed with obligatory responses, mismatch negativity (MMN), and novelty P3 of ERPs, respectively. In this thesis the developmental trajectory of CAP from 2 to 4 years of age as well as noise-induced changes on it, were investigated. In addition, the feasibility of the multi-feature paradigm with syllable stimuli and novel sounds in children was evaluated. To this end, obligatory responses (P1, N2, and N4) and MMNs for consonant, frequency, intensity, vowel, and vowel duration changes, as well as novelty P3 responses, were recorded in a silent condition and with babble noise using the multi-feature paradigm. The participants were voluntary, typically developing children. Significant P1, N2, N4, and MMN responses were elicited at both ages. Also a significant novelty P3, studied at the age of 2 years, was found. From 2 to 4 years, the P1 and N2 latencies shortened. The amplitudes of N2, N4, and MMNs increased and the increment was the largest at frontal electrode locations. During noise, P1 decreased, N2 increased, and the latency of N4 diminished as well as MMNs degraded. The noise-induced changes were largely similar at both ages. In conclusion, the multi-feature paradigm with five syllable deviant types and novel sounds was found to be an appropriate measure of CAP in toddlers. The changes in ERP morphology from 2 to 4 years of age suggest maturational changes in CAP. Noise degraded sound encoding, representation forming, and auditory discrimination. The children were similarly vulnerable to hampering effects of noise at both ages. Thus, noise might potentially harmfully influence language processing and thereby its acquisition in childhood. / Tiivistelmä Kielen omaksumiselle, tuottamiselle sekä ymmärtämiselle on tärkeää tarkka keskushermostollinen kuulotiedon käsittely eli ne hermostolliset prosessit, joita käytetään kuullun aineksen käsittelyyn. Kuunteluympäristöt eivät kuitenkaan aina ole optimaalisia kuulotiedon käsittelylle, sillä melutasot lasten elinympäristöissä voivat olla hyvinkin korkeita. Pienten lasten kuulotiedon käsittelyä, sen kehittymistä ja melun vaikutusta siihen on tutkittu vähän. Kuuloherätevasteet ovat toimiva tapa tarkastella pienten lasten kuulotiedon käsittelyä eri näkökulmista. Äänen käsittelyä, esitietoista kuuloerottelua ja tarkkaavuuden siirtymistä voidaan tarkastella obligatoristen vasteiden, poikkeavuusnegatiivisuuden ja novelty P3 -vasteiden avulla. Tässä väitöskirjassa tarkastellaan kuulotiedon käsittelyn kehittymistä kahden vuoden iästä neljän vuoden ikään sekä melun vaikutusta siihen. Lisäksi arvioidaan tavuärsykkeitä ja poikkeavia ääniä sisältävän monipiirreparadigman soveltuvuutta lapsitutkimuksiin. Tutkimuksissa rekisteröitiin monipiirreparadigman avulla obligatorisia vasteita (P1, N2 ja N4); konsonantin, taajuuden, intensiteetin, vokaalin ja vokaalin keston muutokselle syntyneitä MMN-vasteita sekä novelty P3 -vasteita hiljaisuudessa ja taustamelussa. Tutkimuksen osallistujat olivat vapaaehtoisia tyypillisesti kehittyviä lapsia. Molemmilla tutkimuskerroilla P1, N2, N4 ja MMN poikkesivat merkitsevästi nollatasosta samoin kuin kaksivuotiailta tutkittu novelty P3. Kahden vuoden iästä neljään vuoteen P1- ja N2-vasteiden latenssi lyheni sekä N2, N4 ja MMN vahvistuivat, muutoksen ollessa suurinta frontaalisilla elektrodeilla. Melun aikana P1 heikkeni, N2 vahvistui ja N4-vasteen latenssi lyhentyi. Lisäksi MMN-vaste heikkeni. Melun aiheuttamat muutokset olivat samankaltaisia sekä kahden että neljän vuoden iässä. Johtopäätöksenä voidaan todeta viittä eri tavuärsyketyyppiä ja yllättäviä ääniä sisältävän monipiirreparadigman olevan toimiva menetelmä taaperoiden kuulotiedon käsittelyn tutkimiseen. Kahden ja neljän ikävuoden välillä tapahtuvat muutokset vasteissa kuvastavat kehityksellisiä muutoksia kuulotiedon käsittelyssä. Melu heikentää äänitiedon peruskäsittelyä, edustumien muodostumista ja esitietoista kuuloerottelua. Lapset olivat lähes yhtä alttiita melun vaikutuksille sekä kahden että neljän vuoden iässä. Melu voi siis haitata kielen prosessointia ja sen omaksumista.