Évaluation électrophysiologique auditive et examen du langage et de l’attention chez l’enfant né prématurément et l’enfant né à terme

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.

Increased frequency of the autism broader phenotype in mothers transmitting etiological CNVs to sons affected by Autism Spectrum Disorder (ASD)

Introduction: Autism Spectrum Disorder (ASD) is a frequent and complex neurodevelopmental disorder, characterized by impairments in social communication and repetitive behaviors and with a high male to female ratio: ~4:1. Genetic factors, including rare Copy Number Variants (CNVs), have a substantial impact in ASD risk 1, and are associated with specific phenotypic manifestations 2. Recent studies reported that rare inherited CNVs are enriched in mothers of ASD children compared with mothers of controls and are preferentially transmitted from mothers to ASD children suggesting a sex bias in CNV transmission; further, the imbalanced transmission of small pathogenic CNVs from unaffected mothers to their sons with ASD has been described 3, 4. An increased prevalence of autism - like personality traits is found in unaffected relatives of ASD children, suggesting a genetic liability of a broader autism phenotype (BAP) 5. The BAP in parents of autistic children can be assessed by the Social Responsiveness Scale (SRS) 6 and Broad Autism Phenotype Questionnaire (BAPQ) 7 reports . The SRS is 65 - item questionnaire to identify sub - clinical social impairments and interpersonal behaviour in individuals . The BAPQ is a 36 - item questionnaire measures social aloofness, rigid personality, and pragmatic language deficits in both parents and children.

Évaluation électrophysiologique auditive et examen du langage et de l’attention chez l’enfant né prématurément et l’enfant né à terme

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.

Increased frequency of the autism broader phenotype in mothers transmitting etiological CNVs to sons affected by Autism Spectrum Disorder (ASD)

Autism Spectrum Disorder (ASD) is a frequent and complex neurodevelopmental disorder, characterized by impairments in social communication and repetitive behaviors and with a high male to female ratio: ~4:1. Genetic factors, including rare Copy Number Variants (CNVs), have a substantial impact in ASD risk1, and are associated with specific phenotypic manifestations2. Recent studies reported that rare inherited CNVs are enriched in mothers of ASD children compared with mothers of controls and are preferentially transmitted from mothers to ASD children suggesting a sex bias in CNV transmission; further, the imbalanced transmission of small pathogenic CNVs from unaffected mothers to their sons with ASD has been described3,4. An increased prevalence of autism-like personality traits is found in unaffected relatives of ASD children, suggesting a genetic liability of a broader autism phenotype (BAP)5. The BAP in parents of autistic children can be assessed by the Social Responsiveness Scale (SRS)6 and Broad Autism Phenotype Questionnaire (BAPQ)7 reports. The SRS is 65-item questionnaire to identify sub-clinical social impairments and interpersonal behaviour in individuals. The BAPQ is a 36-item questionnaire measures social aloofness, rigid personality, and pragmatic language deficits in both parents and children.

Language-universal Sensory Deficits in Developmental Dyslexia: English, Spanish, and Chinese

Studies in sensory neuroscience reveal the critical importance of accurate sensory perception for cognitive development. There is considerable debate concerning the possible sensory correlates of phonological processing, the primary cognitive risk factor for developmental dyslexia. Across languages, children with dyslexia have a specific difficulty with the neural representation of the phonological structure of speech. The identification of a robust sensory marker of phonological difficulties would enable early identification of risk for developmental dyslexia and early targeted intervention. Here, we explore whether phonological processing difficulties are associated with difficulties in processing acoustic cues to speech rhythm. Speech rhythm is used across languages by infants to segment the speech stream into words and syllables. Early difficulties in perceiving auditory sensory cues to speech rhythm and prosody could lead developmentally to impairments in phonology. We compared matched samples of children with and without dyslexia, learning three very different spoken and written languages, English, Spanish, and Chinese. The key sensory cue measured was rate of onset of the amplitude envelope (rise time), known to be critical for the rhythmic timing of speech. Despite phonological and orthographic differences, for each language, rise time sensitivity was a significant predictor of phonological awareness, and rise time was the only consistent predictor of reading acquisition. The data support a language-universal theory of the neural basis of developmental dyslexia on the basis of rhythmic perception and syllable segmentation. They also suggest that novel remediation strategies on the basis of rhythm and music may offer benefits for phonological and linguistic development.

Comorbid motor deficits in a clinical sample of children with specific language impairment

The aim of the present study was to compare the motor function of a clinical sample of children with specific language impairment (SLI) to a language-matched comparison group that had not been referred for SLI assessment. A typical language comparison group with similar nonverbal IQ was also included. There were approximately 35 children in each group, aged 9- to 10-years-old, and the children completed a range of standardised language, motor and literacy measures. The results showed that the SLI group scored significantly lower than the language-matched and typical language comparison groups on all of the motor and literacy measures. We conclude that language factors alone are insufficient to explain the extensive comorbid motor and literacy deficits shown by the children with SLI in this study. We suggest that the clinical diagnosis of SLI may be influenced by the presence of additional developmental difficulties, which should be made explicit in assessment procedures, and that intervention strategies which address the broad range of difficulties experienced by children with a clinical diagnosis of SLI, should be prioritised.

Procedural learning deficits in specific language impairment (SLI): a meta-analysis of serial reaction time task performance

Meta-analysis and meta-regression were used to evaluate whether evidence to date demonstrates deficits in procedural memory in individuals with specific language impairment (SLI), and to examine reasons for inconsistencies of findings across studies. The Procedural Deficit Hypothesis (PDH) proposes that SLI is largely explained by abnormal functioning of the frontal-basal ganglia circuits that support procedural memory. It has also been suggested that declarative memory can compensate for at least some of the problems observed in individuals with SLI. A number of studies have used Serial Reaction Time (SRT) tasks to investigate procedural learning in SLI. In this report, results from eight studies that collectively examined 186 participants with SLI and 203 typically-developing peers were submitted to a meta-analysis. The average mean effect size was .328 (CI95: .071, .584) and was significant. This suggests SLI is associated with impairments of procedural learning as measured by the SRT task. Differences among individual study effect sizes, examined with meta-regression, indicated that smaller effect sizes were found in studies with older participants, and in studies that had a larger number of trials on the SRT task. The contributions of age and SRT task characteristics to learning are discussed with respect to impaired and compensatory neural mechanisms in SLI.

Verbal declarative memory impairments in specific language impairment are related to working memory deficits

This study examined verbal declarative memory functioning in SLI and its relationship to working memory. Encoding, recall, and recognition of verbal information was examined in children with SLI who had below average working memory (SLILow WM), children with SLI who had average working memory (SLIAvg. WM) and, a group of non-language impaired children with average working memory (TDAvg. WM). The SLILow WM group was significantly worse than both the SLIAvg. WM and TDAvg. WM groups at encoding verbal information and at retrieving verbal information following a delay. In contrast, the SLIAvg. WM group showed no verbal declarative memory deficits. The study demonstrates that verbal declarative memory deficits in SLI only occur when verbal working memory is impaired. Thus SLI declarative memory is largely intact and deficits are likely to be related to working memory impairments.

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

Cerebellar dysfunction has been proposed to lead to “cognitive dysmetria” in schizophrenia via the cortico-cerebellar-thalamic-cortical circuit, contributing to a range of cognitive and clinical symptoms of the disorder. Here we investigated total cerebellar grey and white matter volumes and cerebellar regional grey matter abnormalities in 13 remitted first-episode schizophrenia patients with less than 2 years’ duration of illness. Patient data were compared to 13 pair-wise age, gender, and handedness-matched healthy volunteers using cortical pattern averaging on high-resolution magnetic resonance images. Total cerebellar volume and total grey matter volumes in first-episode schizophrenia patients did not differ from healthy control subjects, but total cerebellar white matter was increased and total grey to white matter ratios were reduced in patients. Four clusters of cerebellar grey matter reduction were identified: (i) in superior vermis; (ii) in the left lobuli VI; (iii) in right-inferior lobule IX, extending into left lobule IX; and (iv) bilaterally in the areas of lobuli III, peduncle and left flocculus. Grey matter deficits were particularly prominent in right lobuli III and IX, left flocculus and bilateral pedunculi. These cerebellar areas have been implicated in attention control, emotional regulation, social functioning, initiation of smooth pursuit eye movements, eye-blink conditioning, language processing, verbal memory, executive function and the processing of spatial and emotional information. Consistent with common clinical, cognitive, and pathophysiological signs of established illness, our findings demonstrate cerebellar pathology as early as in first-episode schizophrenia.

Motor deficits in children with autism spectrum disorder: A cross-syndrome study

Recent research suggests that children with autism spectrum disorder (ASD) experience some level of motor difficulty, and that this may be associated with social communication skills. However, other studies show that children with language impairments, but without the social communication problems, are at risk of motor difficulties as well. The aim of the present study was to determine if children with ASD have syndrome specific motor deficits in comparison to children with specific language impairment (SLI). We used an independent groups design with three groups of children (8-10 years old) matched on age and nonverbal IQ; an ASD group, an SLI group, and a typically developing (TD) group. All of the children completed an individually administered, standardized motor assessment battery. We found that the TD group demonstrated significantly better motor skills than either the ASD or SLI groups. Detailed analyses of the motor subtests revealed that the ASD and SLI groups had very similar motor profiles across a range of fine and gross motor skills, with one exception. We conclude that children with ASD, and SLI, are at risk of clinically significant motor deficits. However, future behavioural and neurological studies of motor skills in children with ASD should include an SLI comparison group in order to identify possible autism specific deficits.

Electrophysiological and behavioural correlates of facial identity and expression perception deficits following a closed head injury /

A large variety of social signals, such as facial expression and body language, are conveyed in everyday interactions and an accurate perception and interpretation of these social cues is necessary in order for reciprocal social interactions to take place successfully and efficiently. The present study was conducted to determine whether impairments in social functioning that are commonly observed following a closed head injury, could at least be partially attributable to disruption in the ability to appreciate social cues. More specifically, an attempt was made to determine whether face processing deficits following a closed head injury (CHI) coincide with changes in electrophysiological responsivity to the presentation of facial stimuli. A number of event-related potentials (ERPs) that have been linked specifically to various aspects of visual processing were examined. These included the N170, an index of structural encoding ability, the N400, an index of the ability to detect differences in serially presented stimuli, and the Late Positivity (LP), an index of the sensitivity to affective content in visually-presented stimuli. Electrophysiological responses were recorded while participants with and without a closed head injury were presented with pairs of faces delivered in a rapid sequence and asked to compare them on the basis of whether they matched with respect to identity or emotion. Other behavioural measures of identity and emotion recognition were also employed, along with a small battery of standard neuropsychological tests used to determine general levels of cognitive impairment. Participants in the CHI group were impaired in a number of cognitive domains that are commonly affected following a brain injury. These impairments included reduced efficiency in various aspects of encoding verbal information into memory, general slower rate of information processing, decreased sensitivity to smell, and greater difficulty in the regulation of emotion and a limited awareness of this impairment. Impairments in face and emotion processing were clearly evident in the CHI group. However, despite these impairments in face processing, there were no significant differences between groups in the electrophysiological components examined. The only exception was a trend indicating delayed N170 peak latencies in the CHI group (p = .09), which may reflect inefficient structural encoding processes. In addition, group differences were noted in the region of the N100, thought to reflect very early selective attention. It is possible, then, that facial expression and identity processing deficits following CHI are secondary to (or exacerbated by) an underlying disruption of very early attentional processes. Alternately the difficulty may arise in the later cognitive stages involved in the interpretation of the relevant visual information. However, the present data do not allow these alternatives to be distinguished. Nonetheless, it was clearly evident that individuals with CHI are more likely than controls to make face processing errors, particularly for the more difficult to discriminate negative emotions. Those working with individuals who have sustained a head injury should be alerted to this potential source of social monitoring difficulties which is often observed as part of the sequelae following a CHI.

Cognitive deficits in alcoholism

Contexte : Les répercussions de l’alcool au niveau des fonctions cognitives sont bien documentées. Certaines hypothèses suggèrent que l’alcool affecte des fonctions cognitives spécifiques alors que d’autres avancent l’hypothèse de déficits diffus. Cependant, une ambigüité persiste concernant quelles fonctions cognitives sont le plus touchées par l’alcool, et à quel point la durée d’abstinence affecte la récupération cognitive. Nous avons procédé à une des premières méta-analyses qui s’intéresse aux différentes fonctions cognitives touchées par la consommation problématique d’alcool et à la durée d’abstinence requise pour une récupération au niveau des cognitions. Méthodes : Une recherche de la littérature a permis d’identifier 62 études évaluant les cognitions chez les personnes présentant des troubles liés à l’utilisation d’alcool. Les estimations de la taille d’effet ont été calculées avec la Comprehensive Meta Analysis –V2 pour les 12 domaines cognitifs suivants : quotient intellectuel, fluidité verbale/langage, vitesse de traitement de l’information, mémoire de travail, attention, résolution de problème/fonctions exécutives, inhibition/impulsivité, apprentissage verbal, mémoire verbale, apprentissage visuel, mémoire visuelle, habiletés visuo-spatiales. Parmi ces 12 domaines cognitifs, 3 estimations de la taille d’effet ont été calculées selon les durées d’abstinences suivantes : court- (<1 mois), moyen- (2 à 12 mois) et long- (>1 an) termes. Résultats : Les résultats ont révélé la présence de dysfonctions modérées dans 11 domaines cognitifs durant l’abstinence à court terme, et dans 10 domaines cognitifs pour le moyen-terme. Des dysfonctions cognitives minimales furent notées durant l’abstinence à long-terme. Conclusions : Ces résultats révèlent des déficits cognitifs significatifs et diffus durant la première année d’abstinence. Déficits qui se normalisent après un an. Ces résultats soutiennent l’hypothèse de déficits cognitifs diffus reliés à l’alcoolisme et suggèrent que la cognition devrait faire partie intégrante du traitement d’alcoolisme.

Social interaction deficits and conversational inadequacy in Williams syndrome

Research on social communication skills in individuals with Williams syndrome has been inconclusive, with some arguing that these skills are a relative strength and others that they are a weakness. The aim of the present study was to investigate social interaction abilities in a group of children with WS, and to compare them to a group of children with specific language impairment and a group of typically developing children. Semi-structured conversations were conducted and 100-150 utterances were selected for analysis in terms of exchange structure, turn taking, information transfer and conversational inadequacy. The statistical analyses showed that the children with WS had difficulties with exchange structure and responding appropriately to the interlocutor's requests for information and clarification. They also had significant difficulties with interpreting meaning and providing enough information for the conversational partner. Despite similar language abilities with a group of children with specific language impairment, the children with WS had different social interaction skills, which suggests that they follow an atypical trajectory of development and their neurolinguistic profile does not directly support innate modularity. (c) 2005 Elsevier Ltd. All rights reserved.

Right hemisphere language functions and schizophrenia: the forgotten hemisphere?

This review highlights the importance of right hemisphere language functions for successful social communication and advances the hypothesis that the core deficit in psychosis is a failure of segregation of right from left hemisphere functions. Lesion studies of stroke patients and dichotic listening and functional imaging studies of healthy people have shown that some language functions are mediated by the right hemisphere rather than the left. These functions include discourse planning/comprehension, understanding humour, sarcasm, metaphors and indirect requests, and the generation/comprehension of emotional prosody. Behavioural evidence indicates that patients with typical schizophrenic illnesses perform poorly on tests of these functions, and aspects of these functions are disturbed in schizo-affective and affective psychoses. The higher order language functions mediated by the right hemisphere are essential to an accurate understanding of someone's communicative intent, and the deficits displayed by patients with schizophrenia may make a significant contribution to their social interaction deficits. We outline a bi-hemispheric theory of the neural basis of language that emphasizes the role of the sapiens-specific cerebral torque in determining the four-chambered nature of the human brain in relation to the origins of language and the symptoms of schizophrenia. Future studies of abnormal lateralization of left hemisphere language functions need to take account of the consequences of a failure of lateralization of language functions to the right as well as the left hemisphere.

Autistic symptomatology and language ability in autism spectrum disorder and specific language impairment

Background: Autism spectrum disorders (ASD) and specific language impairment (SLI) are common developmental disorders characterised by deficits in language and communication. The nature of the relationship between them continues to be a matter of debate. This study investigates whether the co-occurrence of ASD and language impairment is associated with differences in severity or pattern of autistic symptomatology or language profile. Methods: Participants (N = 97) were drawn from a total population cohort of 56,946 screened as part of study to ascertain the prevalence of ASD, aged 9 to 14 years. All children received an ICD-10 clinical diagnosis of ASD or No ASD. Children with nonverbal IQ 80 were divided into those with a language impairment (language score of 77 or less) and those without, creating three groups: children with ASD and a language impairment (ALI; N = 41), those with ASD and but no language impairment (ANL; N = 31) and those with language impairment but no ASD (SLI; N = 25). Results: Children with ALI did not show more current autistic symptoms than those with ANL. Children with SLI were well below the threshold for ASD. Their social adaptation was higher than the ASD groups, but still nearly 2 SD below average. In ALI the combination of ASD and language impairment was associated with weaker functional communication and more severe receptive language difficulties than those found in SLI. Receptive and expressive language were equally impaired in ALI, whereas in SLI receptive language was stronger than expressive. Conclusions: Co-occurrence of ASD and language impairment is not associated with increased current autistic symptomatology but appears to be associated with greater impairment in receptive language and functional communication.