A mismatch negativity response (MMN) and a new differential waveform were derived in an effort to evaluate a neural refractory or recovery effect in adult listeners. The MMN was elicited using oddball test runs in which the standard and deviant stimuli differed in frequency. To derive the differential waveform, the same standard and deviant stimuli were presented alone. MMN responses were obtained by subtracting the averaged responses to standards from the deviants. The differential waveforms were obtained by subtracting the averaged responses to standards presented alone from deviants presented alone. Scalp topography for the MMN and differential waveforms were similar. A significant (p Se obtuvo una respuesta de negatividad desigual (MMN) y una nueva onda ?diferencial? en un esfuerzo por evaluar un efecto neural refractario o de recuperación en sujetos adultos. La MMN fue generada utilizando cursos peculiares de prueba en los que el estimulo estándar y el alterado tenían frecuencias diferentes. Para derivar la onda diferencial, se presentaron el mismo estímulo estándar y el alterado en forma aislada. Las respuestas MMN se obtuvieron restando las respuestas promediadas estándar de las alteradas. Las formas de onda diferenciales se obtuvieron restando las respuestas promediadas a estímulos estándar presentados aisladamente, de los estímulos alterados presentados también en forma aislada. La topografía craneana de los MMN y las onda diferenciales fueron similares. Se encontraron correlaciones positivas y negativas significativas (p

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Research Doctorate - Doctor of Philosophy (PhD) / This thesis investigates mechanisms of brain maturation by utilising the special advantages offered by the protracted maturation of neural circuits in chicken forebrain. Biochemical, behavioural and electrophysiological techniques are used in behaving animals to investigate the functional consequences of maturation changes at the molecular, behavioural and physiological levels. Two issues are addressed: (1) do immature (2 week) and mature (8 week) chickens employ different molecular mechanisms to produce changes in neuronal function after learning a behavioural task; and (2) can quantitative non-invasive measures of neuronal function be used to monitor maturation changes in chicken forebrain? Biochemical investigation of subcellular fractions using antibodies and western blots of chicken forebrain and intermediate medial mesopallium (IMM) revealed regional differences in expression levels of a number of components of the glutamatergic neurotransmitter system. The discriminative taste aversion learning (DTAL) task was used to assess whether an animal learns the same task at different ages using different intracellular signalling pathways. The patterns of biochemical change seen in the IMM after DTAL training was very different at 2 weeks and 8 weeks. Two major differences were observed. Firstly, the same type of training induced changes occurred at both ages in GluR1 and CaMKII but they occurred faster at 8 weeks. Secondly the difference in ERK and CREB responses is consistent with a change in the relative contribution made by the ERK signalling pathway and CREB requirement to learning at these two ages. These results imply that the molecular changes induced by learning a behavioural task are faster in mature than immature brain and may involve a different balance of intracellular signalling pathways. In order to be able to investigate biological mechanisms controlling maturation and to use the chicken as an animal model in which pharmacological and/or environmental agents can be screened for potentially harmful effects on brain maturation two non-invasive measures of neuronal function were investigated. One was behavioural (prepulse inhibition: PPI) and the other was electrophysiological (auditory evoked related potentials: AERP). PPI in the chicken was examined electromyographically and via whole body movement with a stabilimeter apparatus. In two strains of chicken (a meat breed and a laying breed) PPI was identified but shown to be small and variable compared to that in the rat. The results indicate that the phenomenon of PPI in the chicken is too small and variable to be used as a quantitative measure of neural circuit maturation. Quantitative analysis of the chicken AERP revealed a significant decrease in amplitude of the positive AERP component and a decrease in latency of the negative AERP component with maturation. These maturation changes were comparable to developmental changes seen in human and other mammal AERPs. Such changes may reflect changes in the intracortical synaptic organisation of the auditory cortex. This technique allowed for repeated measures to be undertaken on the same animal over a number of weeks and enabled developmental changes to be monitored. This technique was extended to investigate perturbed maturation via the induction of chemically induced hypothyroidism. Results from this study showed that the induction of late onset hypothyroidism produces measurable effects on the chicken AERP consistent with perturbation in maturation of neuronal circuits and synapses. This suggests that AERPs may be useful non-invasive functional measures of brain maturation that can be used to study the effects of endogenous or exogenous factors on brain maturation in the chicken. Since human brain also exhibits a protracted maturation period the availability of a well characterised animal model for protracted brain maturation provides an opportunity to identify molecules, genes and environmental factors that are important in the regulation of maturation. Such a model may provide the basis for developing rational therapies or prevention strategies for some neurodevelopmental disorders. The protracted maturation of neuronal circuits observed in chicken forebrain offers such a model.

L’hypothèse de ce travail est que les sujets schizophrènes souffrant d’hallucinations auditives verbales perçoivent leur propre voix comme une voix étrangère. L'objectif de notre travail est donc d'étudier les réponses électrophysiologiques évoquées par la voix des participants et celle d’une personne inconnue. Nos résultats chez les sujets sains montrent que nous allouons moins de ressources attentionnelles automatiques à notre propre voix que par rapport à une voix inconnue. Cet effet d’atténuation de l’orientation automatique de l’attention pour sa propre voix n’est pas observé chez les patients schizophrènes. De plus, conformément à notre hypothèse initiale, cet effet est d’autant plus faible que la sévérité des hallucinations est forte. / The hypothesis of this study was that schizophrenic patients with auditory verbal hallucinations perceive their own voices as alien voices. The aim of the study was to investigate the electrophysiological responses evoked by participants’own voices and those of unknown individuals. Our results in healthy subjects showed that they allocated fever automatic attentional resources to their own voices than to unfamiliar voices. This attenuation effect of the automatic orientation of attention to own voice was not observed in schizophrenic patients. In addition, in agreement with our initial hypothesis, the attenuation decreased even further as the hallucinations became more severe.