Early auditory processing

ABSTRACT (English)An accurate processing of the order between sensory events at the millisecond time scale is crucial for both sensori-motor and cognitive functions. Temporal order judgment (TOJ) tasks, is the ability of discriminating the order of presentation of several stimuli presented in a rapid succession. The aim of the present thesis is to further investigate the spatio-temporal brain mechanisms supporting TOJ. In three studies we focus on the dependency of TOJ accuracy on the brain states preceding the presentation of TOJ stimuli, the neural correlates of accurate vs. inaccurate TOJ and whether and how TOJ performance can be improved with training.In "Pre-stimulus beta oscillations within left posterior sylvian regions impact auditory temporal order judgment accuracy" (Bernasconi et al., 2011), we investigated if the brain activity immediately preceding the presentation of the stimuli modulates TOJ performance. By contrasting the electrophysiological activity before the stimulus presentation as a function of TOJ accuracy we observed a stronger pre-stimulus beta (20Hz) oscillatory activity within the left posterior sylvian region (PSR) before accurate than inaccurate TOJ trials.In "Interhemispheric coupling between the posterior sylvian regions impacts successful auditory temporal order judgment" (Bernasconi et al., 2010a), and "Plastic brain mechanisms for attaining auditory temporal order judgment proficiency" (Bernasconi et al., 2010b), we investigated the spatio-temporal brain dynamics underlying auditory TOJ. In both studies we observed a topographic modulation as a function of TOJ performance at ~40ms after the onset of the first sound, indicating the engagement of distinct configurations of intracranial generators. Source estimations in the first study revealed a bilateral PSR activity for both accurate and inaccurate TOJ trials. Moreover, activity within left, but not right, PSR correlated with TOJ performance. Source estimations in the second study revealed a training-induced left lateralization of the initial bilateral (i.e. PSR) brain response. Moreover, the activity within the left PSR region correlated with TOJ performance.Based on these results, we suggest that a "temporal stamp" is established within left PSR on the first sound within the pair at early stages (i.e. ~40ms) of cortical processes, but is critically modulated by inputs from right PSR (Bernasconi et al., 2010a; b). The "temporal stamp" on the first sound may be established via a sensory gating or prior entry mechanism.Behavioral and brain responses to identical stimuli can vary due to attention modulation, vary with experimental and task parameters or "internal noise". In a fourth experiment (Bernasconi et al., 2011b) we investigated where and when "neural noise" manifest during the stimulus processing. Contrasting the AEPs of identical sound perceived as High vs. Low pitch, a topographic modulation occurred at ca. 100ms after the onset of the sound. Source estimation revealed activity within regions compatible with pitch discrimination. Thus, we provided neurophysiological evidence for the variation in perception induced by "neural noise".ABSTRACT (French)Un traitement précis de l'ordre des événements sensoriels sur une échelle de temps de milliseconde est crucial pour les fonctions sensori-motrices et cognitives. Les tâches de jugement d'ordre temporel (JOT), consistant à présenter plusieurs stimuli en succession rapide, sont traditionnellement employées pour étudier les mécanismes neuronaux soutenant le traitement d'informations sensorielles qui varient rapidement. Le but de cette thèse est d'étudier le mécanisme cérébral soutenant JOT. Dans les trois études présentées nous nous sommes concentrés sur les états du cerveau précédant la présentation des stimuli de JOT, les bases neurales pour un JOT correct vs. incorrect et sur la possibilité et les moyens d'améliorer l'exécution du JOT grâce à un entraînement.Dans "Pre-stimulus beta oscillations within left posterior sylvian regions impact auditory temporal order judgment accuracy" (Bernasconi et al., 2011),, nous nous sommes intéressé à savoir si l'activité oscillatoire du cerveau au pré-stimulus modulait la performance du JOT. Nous avons contrasté l'activité électrophysiologique en fonction de la performance TOJ, mesurant une activité oscillatoire beta au pré-stimulus plus fort dans la région sylvian postérieure gauche (PSR) liée à un JOT correct.Dans "Interhemispheric coupling between the posterior sylvian regions impacts successful auditory temporal order judgment" (Bernasconi et al., 2010a), et "Plastic brain mechanisms for attaining auditory temporal order judgment proficiency" (Bernasconi et al., 2010b), nous avons étudié la dynamique spatio-temporelle dans le cerveau impliqué dans le traitement du JOT auditif. Dans ses deux études, nous avons observé une modulation topographique à ~40ms après le début du premier son, en fonction de la performance JOT, indiquant l'engagement des configurations de générateurs intra- crâniens distincts. La localisation de source dans la première étude indique une activité bilatérale de PSR pour des JOT corrects vs. incorrects. Par ailleurs, l'activité dans PSR gauche, mais pas dans le droit, est corrélée avec la performance du JOT. La localisation de source dans la deuxième étude indiquait une latéralisation gauche induite par l'entraînement d'une réponse initialement bilatérale du cerveau. D'ailleurs, l'activité dans la région PSR gauche corrèlait avec la performance de TOJ.Basé sur ces résultats, nous proposons qu'un « timbre-temporel » soit établi très tôt (c.-à-d. à ~40ms) sur le premier son par le PSR gauche, mais module par l'activité du PSR droite (Bernasconi et al., 2010a ; b). « Le timbre- temporel » sur le premier son peut être établi par le mécanisme neuronal de type « sensory gating » ou « prior entry ».Les réponses comportementales et du cerveau aux stimuli identiques peut varier du à des modulations d'attention ou à des variations dans les paramètres des tâches ou au bruit interne du cerveau. Dans une quatrième expérience (Bernasconi et al. 2011B), nous avons étudié où et quand le »bruit neuronal« se manifeste pendant le traitement des stimuli. En contrastant les AEPs de sons identiques perçus comme aigus vs. grave, nous avons mesuré une modulation topographique à env. 100ms après l'apparition du son. L'estimation de source a révélé une activité dans les régions compatibles avec la discrimination de fréquences. Ainsi, nous avons fourni des preuves neurophysiologiques de la variation de la perception induite par le «bruit neuronal».

Brain surface non-rigid registration in auditory processing

Résumé: Le développement rapide de nouvelles technologies comme l'imagerie médicale a permis l'expansion des études sur les fonctions cérébrales. Le rôle principal des études fonctionnelles cérébrales est de comparer l'activation neuronale entre différents individus. Dans ce contexte, la variabilité anatomique de la taille et de la forme du cerveau pose un problème majeur. Les méthodes actuelles permettent les comparaisons interindividuelles par la normalisation des cerveaux en utilisant un cerveau standard. Les cerveaux standards les plus utilisés actuellement sont le cerveau de Talairach et le cerveau de l'Institut Neurologique de Montréal (MNI) (SPM99). Les méthodes de recalage qui utilisent le cerveau de Talairach, ou celui de MNI, ne sont pas suffisamment précises pour superposer les parties plus variables d'un cortex cérébral (p.ex., le néocortex ou la zone perisylvienne), ainsi que les régions qui ont une asymétrie très importante entre les deux hémisphères. Le but de ce projet est d'évaluer une nouvelle technique de traitement d'images basée sur le recalage non-rigide et utilisant les repères anatomiques. Tout d'abord, nous devons identifier et extraire les structures anatomiques (les repères anatomiques) dans le cerveau à déformer et celui de référence. La correspondance entre ces deux jeux de repères nous permet de déterminer en 3D la déformation appropriée. Pour les repères anatomiques, nous utilisons six points de contrôle qui sont situés : un sur le gyrus de Heschl, un sur la zone motrice de la main et le dernier sur la fissure sylvienne, bilatéralement. Evaluation de notre programme de recalage est accomplie sur les images d'IRM et d'IRMf de neuf sujets parmi dix-huit qui ont participés dans une étude précédente de Maeder et al. Le résultat sur les images anatomiques, IRM, montre le déplacement des repères anatomiques du cerveau à déformer à la position des repères anatomiques de cerveau de référence. La distance du cerveau à déformer par rapport au cerveau de référence diminue après le recalage. Le recalage des images fonctionnelles, IRMf, ne montre pas de variation significative. Le petit nombre de repères, six points de contrôle, n'est pas suffisant pour produire les modifications des cartes statistiques. Cette thèse ouvre la voie à une nouvelle technique de recalage du cortex cérébral dont la direction principale est le recalage de plusieurs points représentant un sillon cérébral. Abstract : The fast development of new technologies such as digital medical imaging brought to the expansion of brain functional studies. One of the methodolgical key issue in brain functional studies is to compare neuronal activation between individuals. In this context, the great variability of brain size and shape is a major problem. Current methods allow inter-individual comparisions by means of normalisation of subjects' brains in relation to a standard brain. A largerly used standard brains are the proportional grid of Talairach and Tournoux and the Montreal Neurological Insititute standard brain (SPM99). However, there is a lack of more precise methods for the superposition of more variable portions of the cerebral cortex (e.g, neocrotex and perisyvlian zone) and in brain regions highly asymmetric between the two cerebral hemipsheres (e.g. planum termporale). The aim of this thesis is to evaluate a new image processing technique based on non-linear model-based registration. Contrary to the intensity-based, model-based registration uses spatial and not intensitiy information to fit one image to another. We extract identifiable anatomical features (point landmarks) in both deforming and target images and by their correspondence we determine the appropriate deformation in 3D. As landmarks, we use six control points that are situated: one on the Heschl'y Gyrus, one on the motor hand area, and one on the sylvian fissure, bilaterally. The evaluation of this model-based approach is performed on MRI and fMRI images of nine of eighteen subjects participating in the Maeder et al. study. Results on anatomical, i.e. MRI, images, show the mouvement of the deforming brain control points to the location of the reference brain control points. The distance of the deforming brain to the reference brain is smallest after the registration compared to the distance before the registration. Registration of functional images, i.e fMRI, doesn't show a significant variation. The small number of registration landmarks, i.e. six, is obvious not sufficient to produce significant modification on the fMRI statistical maps. This thesis opens the way to a new computation technique for cortex registration in which the main directions will be improvement of the registation algorithm, using not only one point as landmark, but many points, representing one particular sulcus.

Evaluating the efficacy of monaural vs. binaural FM fittings in children with auditory processing disorders

The purpose of this project was to determine whether a monaural FM or binaural FM fitting strategy is more appropriate for children with Auditory Processing Disorders.

Desempenho de escolares com distúrbio de aprendizagem e dislexia em testes de processamento auditivo

OBJETIVO: caracterizar e comparar, por meio de testes comportamentais, o processamento auditivo de escolares com diagnóstico interdisciplinar de (I) distúrbio da aprendizagem, (II) dislexia e (III) escolares com bom desempenho acadêmico. MÉTODOS: participaram deste estudo 30 escolares na faixa etária de 8 a 16 anos de idade, de ambos os gêneros, de 2ª a 4ª séries do ensino fundamental, divididos em três grupos: GI composto por 10 escolares com diagnóstico interdisciplinar de distúrbio de aprendizagem, GII: composto por 10 escolares com diagnóstico interdisciplinar de dislexia e GIII composto por 10 escolares sem dificuldades de aprendizagem, pareados segundo gênero e faixa etária com os grupos GI e GII. Foram realizadas avaliação audiológica e de processamento auditivo. RESULTADOS: os escolares de GIII apresentaram desempenho superior nos testes de processamento auditivo em relação aos escolares de GI e GII. GI apresentou desempenho inferior nas habilidades auditivas avaliadas para testes dicóticos de dígitos e dissílabos alternados, logoaudiometria pediátrica, localização sonora, memória verbal e não-verbal, ao passo que GII apresentou as mesmas alterações de GI, com exceção do teste de logoaudiometria pediátrica. CONCLUSÃO: os escolares com transtornos de aprendizagem apresentaram desempenho inferior nos testes de processamento auditivo, sendo que os escolares com distúrbio de aprendizagem apresentaram maior número de habilidades auditivas alteradas, em comparação com os escolares com dislexia, por terem apresentado atenção sustentada reduzida. O grupo de escolares com dislexia apresentou alterações decorrentes da dificuldade relacionada à codificação e decodificação de estímulos sonoros.

Auditory processing in children and adolescents in situations of risk and vulnerability

CONTEXTO E OBJETIVO: Crianças e adolescentes que vivem em situação de vulnerabilidade social apresentam uma série de problemas de saúde. Apesar disso, ainda é controversa a afirmação sobre a existência de alterações cognitivas e/ou sensoriais. O objetivo deste estudo foi investigar aspectos relacionados ao processamento auditivo, através da aplicação de testes de potencial evocado auditivo de tronco encefálico (PEATE) e avaliação comportamental do processamento auditivo em crianças em situação de rua, comparando a um grupo controle. TIPO DE ESTUDO E LOCAL: Estudo transversal no Laboratório de Processamento Auditivo, Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Os testes de processamento auditivo foram aplicados em um grupo de 27 indivíduos, subdivididos em grupos de 11 crianças (7 a 10 anos) e 16 adolescentes (11 a 16 anos) de ambos os sexos, em situação de vulnerabilidade social, e comparado a um grupo controle, formado por 21 crianças, subdivididas em grupos de 10 crianças e 11 adolescentes, pareados por idade, sem queixas. Também se aplicou os PEATE para investigação da integridade da via auditiva. RESULTADOS: Para ambas as faixas etárias, foram encontradas diferenças significantes entre grupos estudo e controle para a maioria dos testes aplicados, sendo que o grupo estudo apresentou desempenho estatisticamente pior do que o controle para todos os testes, exceto para o teste pediatric speech intelligibility. Apenas uma criança apresentou resultado alterado para os PEATE. CONCLUSÕES: Os resultados demonstraram pior desempenho do grupo estudo (crianças e adolescentes) para os testes comportamentais de processamento auditivo, apesar de estes apresentarem integridade da via auditiva em nível de tronco encefálico, demonstrada pela normalidade nos resultados do PEATE.

Long latency auditory evoked potential in Asperger Syndrome: two case studies

Introduction: Auditory Late Responses (ALR) assess central auditory processing by neuro electric activity of the auditory pathway and analyse the activities involved in cortical abilities of discrimination, attention and integration of the brain. Individuals withAsperger Syndrome experience changes in these skills, so it is important to research these potential this population. The objective of this paper was to describe the auditory late responses of two patients with Asperger Syndrome. Methods: The study included two male patients with Asperger Syndrome, of 7 and 12 years of age, treated in a study centre. The patients did not present any auditory complaint detected by an amnesis. The external auditory canal was inspected and audiological and auditory late responses assessed. After evaluation the components P2, N2 and P3 were analysed. Results: In both patients, the latency of the components P2, N2 and P3 were elongated in both ears. Regarding the amplitude of the P2 component, reduced values were found for the left ear of patient 1 and the right ear of patient 2. The N2 amplitude was reduced for both ears of patient 1 and only the right ear of patient 2. The two patients showed a decrease in the amplitude of the P3 only in the right ear. Conclusion:This study concludes that there were changes in the ALR results in both patients with Asperger Syndrome, suggesting alteration of the auditory function at the cortex level.

Early influence of auditory stimuli on upper-limb movements in young human infants: an overview

Given that the auditory system is rather well developed at the end of the third trimester of pregnancy, it is likely that couplings between acoustics and motor activity can be integrated as early as at the beginning of postnatal life. The aim of the present mini-review was to summarize and discuss studies on early auditory-motor integration, focusing particularly on upper-limb movements (one of the most crucial means to interact with the environment) in association with auditory stimuli, to develop further understanding of their significance with regard to early infant development. Many studies have investigated the relationship between various infant behaviors (e.g., sucking, visual fixation, head turning) and auditory stimuli, and established that human infants can be observed displaying couplings between action and environmental sensory stimulation already from just after birth, clearly indicating a propensity for intentional behavior. Surprisingly few studies, however, have investigated the associations between upper-limb movements and different auditory stimuli in newborns and young infants, infants born at risk for developmental disorders/delays in particular. Findings from studies of early auditory-motor interaction support that the developing integration of sensory and motor systems is a fundamental part of the process guiding the development of goal-directed action in infancy, of great importance for continued motor, perceptual, and cognitive development. At-risk infants (e.g., those born preterm) may display increasing central auditory processing disorders, negatively affecting early sensorymotor integration, and resulting in long-term consequences on gesturing, language development, and social communication. Consequently, there is a need for more studies on such implications.

Habilidade auditiva em criança desnutrida

PurposeTo characterize and compare the performance of malnourished children and normal children in auditory processing. MethodThe sample comprised 30 children from five to ten years old, both genders, being 15 malnourished children (G1) and 15 children with adequate nutritional status, as a control group (G2). The groups were paired according to gender, age and grade level. Both groups underwent peripheral and central auditory assessment, noting that malnourished children had higher changes in the skill of sequencing score for verbal and nonverbal when compared to normal children, and the same occurred in closing skills and background figure. ResultRegarding the degree of auditory processing disorder, it was more severe in malnourished children. ConclusionChildren with malnutrition have higher frequency alterations in auditory abilities when compared to normal children, being the temporal ordering skills, auditory memory, selective attention, figure-ground and closing the most affected skills.

Processamento auditivo (central) em escolares das séries iniciais de alfabetização

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Processamento auditivo (central) em escolares das séries iniciais de alfabetização

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Auditory processing in children and adolescents in situations of risk and vulnerability

CONTEXT AND OBJECTIVE: Children and adolescents who live in situations of social vulnerability present a series of health problems. Nonetheless, affirmations that sensory and cognitive abnormalities are present are a matter of controversy. The aim of this study was to investigate aspects to auditory processing, through applying the brainstem auditory evoked potential (BAEP) and behavioral auditory processing tests to children living on the streets, and comparison with a control group. DESIGN AND SETTING: Cross-sectional study in the Laboratory of Auditory Processing, School of Medicine, Universidade de São Paulo. METHODS: The auditory processing tests were applied to a group of 27 individuals, subdivided into 11 children (7 to 10 years old) and 16 adolescents (11 to 16 years old), of both sexes, in situations of social vulnerability, compared with an age-matched control group of 10 children and 11 adolescents without complaints. The BAEP test was also applied to investigate the integrity of the auditory pathway. RESULTS: For both children and adolescents, there were significant differences between the study and control groups in most of the tests applied, with significantly worse performance in the study group, except in the pediatric speech intelligibility test. Only one child had an abnormal result in the BAEP test. CONCLUSIONS: The results showed that the study group (children and adolescents) presented poor performance in the behavioral auditory processing tests, despite their unaltered auditory brainstem pathways, as shown by their normal results in the BAEP test.

Diagnosis of altered central pain processing

Nonsystematic review.

Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain

Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

Linking altered central pain processing and genetic polymorphism to drug efficacy in chronic low back pain.

BACKGROUND Inability to predict the therapeutic effect of a drug in individual pain patients prolongs the process of drug and dose finding until satisfactory pharmacotherapy can be achieved. Many chronic pain conditions are associated with hypersensitivity of the nervous system or impaired endogenous pain modulation. Pharmacotherapy often aims at influencing these disturbed nociceptive processes. Its effect might therefore depend on the extent to which they are altered. Quantitative sensory testing (QST) can evaluate various aspects of pain processing and might therefore be able to predict the analgesic efficacy of a given drug. In the present study three drugs commonly used in the pharmacological management of chronic low back pain are investigated. The primary objective is to examine the ability of QST to predict pain reduction. As a secondary objective, the analgesic effects of these drugs and their effect on QST are evaluated. METHODS/DESIGN In this randomized, double blinded, placebo controlled cross-over study, patients with chronic low back pain are randomly assigned to imipramine, oxycodone or clobazam versus active placebo. QST is assessed at baseline, 1 and 2 h after drug administration. Pain intensity, side effects and patients' global impression of change are assessed in intervals of 30 min up to two hours after drug intake. Baseline QST is used as explanatory variable to predict drug effect. The change in QST over time is analyzed to describe the pharmacodynamic effects of each drug on experimental pain modalities. Genetic polymorphisms are analyzed as co-variables. DISCUSSION Pharmacotherapy is a mainstay in chronic pain treatment. Antidepressants, anticonvulsants and opioids are frequently prescribed in a "trial and error" fashion, without knowledge however, which drug suits best which patient. The present study addresses the important need to translate recent advances in pain research to clinical practice. Assessing the predictive value of central hypersensitivity and endogenous pain modulation could allow for the implementation of a mechanism-based treatment strategy in individual patients. TRIAL REGISTRATION Clinicaltrials.gov, NCT01179828.