Modularity of auditory spatial representations

Abstract : Auditory spatial functions are of crucial importance in everyday life. Determining the origin of sound sources in space plays a key role in a variety of tasks including orientation of attention, disentangling of complex acoustic patterns reaching our ears in noisy environments. Following brain damage, auditory spatial processing can be disrupted, resulting in severe handicaps. Complaints of patients with sound localization deficits include the inability to locate their crying child or being over-loaded by sounds in crowded public places. Yet, the brain bears a large capacity for reorganization following damage and/or learning. This phenomenon is referred as plasticity and is believed to underlie post-lesional functional recovery as well as learning-induced improvement. The aim of this thesis was to investigate the organization and plasticity of different aspects of auditory spatial functions. Overall, we report the outcomes of three studies: In the study entitled "Learning-induced plasticity in auditory spatial representations" (Spierer et al., 2007b), we focused on the neurophysiological and behavioral changes induced by auditory spatial training in healthy subjects. We found that relatively brief auditory spatial discrimination training improves performance and modifies the cortical representation of the trained sound locations, suggesting that cortical auditory representations of space are dynamic and subject to rapid reorganization. In the same study, we tested the generalization and persistence of training effects over time, as these are two determining factors in the development of neurorehabilitative intervention. In "The path to success in auditory spatial discrimination" (Spierer et al., 2007c), we investigated the neurophysiological correlates of successful spatial discrimination and contribute to the modeling of the anatomo-functional organization of auditory spatial processing in healthy subjects. We showed that discrimination accuracy depends on superior temporal plane (STP) activity in response to the first sound of a pair of stimuli. Our data support a model wherein refinement of spatial representations occurs within the STP and that interactions with parietal structures allow for transformations into coordinate frames that are required for higher-order computations including absolute localization of sound sources. In "Extinction of auditory stimuli in hemineglect: space versus ear" (Spierer et al., 2007a), we investigated auditory attentional deficits in brain-damaged patients. This work provides insight into the auditory neglect syndrome and its relation with neglect symptoms within the visual modality. Apart from contributing to a basic understanding of the cortical mechanisms underlying auditory spatial functions, the outcomes of the studies also contribute to develop neurorehabilitation strategies, which are currently being tested in clinical populations.

Codage de l’information visuelle par la plasticité et la synchronisation des réponses neuronales dans le cortex visuel primaire du chat

Les systèmes sensoriels encodent l’information sur notre environnement sous la forme d’impulsions électriques qui se propagent dans des réseaux de neurones. Élucider le code neuronal – les principes par lesquels l’information est représentée dans l’activité des neurones – est une question fondamentale des neurosciences. Cette thèse constituée de 3 études (E) s’intéresse à deux types de codes, la synchronisation et l’adaptation, dans les neurones du cortex visuel primaire (V1) du chat. Au niveau de V1, les neurones sont sélectifs pour des propriétés comme l’orientation des contours, la direction et la vitesse du mouvement. Chaque neurone ayant une combinaison de propriétés pour laquelle sa réponse est maximale, l’information se retrouve distribuée dans différents neurones situés dans diverses colonnes et aires corticales. Un mécanisme potentiel pour relier l’activité de neurones répondant à des items eux-mêmes reliés (e.g. deux contours appartenant au même objet) est la synchronisation de leur activité. Cependant, le type de relations potentiellement encodées par la synchronisation n’est pas entièrement clair (E1). Une autre stratégie de codage consiste en des changements transitoires des propriétés de réponse des neurones en fonction de l’environnement (adaptation). Cette plasticité est présente chez le chat adulte, les neurones de V1 changeant d’orientation préférée après exposition à une orientation non préférée. Cependant, on ignore si des neurones spatialement proches exhibent une plasticité comparable (E2). Finalement, nous avons étudié la dynamique de la relation entre synchronisation et plasticité des propriétés de réponse (E3). Résultats principaux — (E1) Nous avons montré que deux stimuli en mouvement soit convergent soit divergent élicitent plus de synchronisation entre les neurones de V1 que deux stimuli avec la même direction. La fréquence de décharge n’était en revanche pas différente en fonction du type de stimulus. Dans ce cas, la synchronisation semble coder pour la relation de cocircularité dont le mouvement convergent (centripète) et divergent (centrifuge) sont deux cas particuliers, et ainsi pourrait jouer un rôle dans l’intégration des contours. Cela indique que la synchronisation code pour une information qui n’est pas présente dans la fréquence de décharge des neurones. (E2) Après exposition à une orientation non préférée, les neurones changent d’orientation préférée dans la même direction que leurs voisins dans 75% des cas. Plusieurs propriétés de réponse des neurones de V1 dépendent de leur localisation dans la carte fonctionnelle corticale pour l’orientation. Les comportements plus diversifiés des 25% de neurones restants sont le fait de différences fonctionnelles que nous avons observé et qui suggèrent une localisation corticale particulière, les singularités, tandis que la majorité des neurones semblent situés dans les domaines d’iso-orientation. (E3) Après adaptation, les paires de neurones dont les propriétés de réponse deviennent plus similaires montrent une synchronisation accrue. Après récupération, la synchronisation retourne à son niveau initial. Par conséquent, la synchronisation semble refléter de façon dynamique la similarité des propriétés de réponse des neurones. Conclusions — Cette thèse contribue à notre connaissance des capacités d’adaptation de notre système visuel à un environnement changeant. Nous proposons également des données originales liées au rôle potentiel de la synchronisation. En particulier, la synchronisation semble capable de coder des relations entre objets similaires ou dissimilaires, suggérant l’existence d’assemblées neuronales superposées.

Terapias no farmacológicas en el manejo del dolor en neonatos pretérmino. revisión sistemática de la literatura

Antecedentes El dolor en neonatos ha sido un problema poco explorado. Se ha propuesto el uso de las terapias no farmacológicas para su tratamiento, sin embargo existen pocas aproximaciones sistemáticas para la evaluación de su eficacia. Objetivos Determinar la eficacia de las terapias no farmacológicas en el manejo del dolor en neonatos pretérmino a través de una revisión sistemática. Metodología Se realizó una revisión sistemática de la literatura para evaluar la eficacia de las terapias no farmacológicas en el manejo del dolor en el recién nacido petérmino. La búsqueda se realizó a través de las bases de datos Embase, Cochrane, Bireme y Embase. Se identificaron estudios publicados inglés y español. Se realizó un análisis cualitativo y cuantitativo. Resultados Se incluyeron 10 ensayos clínicos. La solución de sacarosa administrada por vía oral mostró reducir la intensidad del dolor en el recién nacido. La intubación y toma de muestras facilitada por el cuidador mostró también reducir la intensidad del dolor. Conclusión Se recomienda la administración solución de sacarosa y acompañamiento del cuidador durante los procedimientos como medidas para reducir el dolor en el recién nacido pretérmino.

The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.

NEONATAL HANDLING AND THE MATERNAL ODOR PREFERENCE IN RAT PUPS: INVOLVEMENT OF MONOAMINES AND CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN PATHWAY IN THE OLFACTORY BULB

Early-life environmental events, such as the handling procedure, can induce long-lasting alterations upon several behavioral and neuroendocrine systems. However, the changes within the pups that could be causally related to the effects in adulthood are still poorly understood. In the present study, we analyzed the effects of neonatal handling on behavioral (maternal odor preference) and biochemical (cyclic AMP response element-binding protein (CREB) phosphorylation, noradrenaline (NA), and serotonin (5-HT) levels in the olfactory bulb (OB)) parameters in 7-day-old male and female rat pups. Repeated handling (RH) abolished preference for the maternal odor in female pups compared with nonhandled (NH) and the single-handled (SH) ones, while in RH males the preference was not different than NH and SH groups. In both male and female pups, RH decreased NA activity in the OB, but 5-HT activity increased only in males. Since preference for the maternal odor involves the synergic action of NA and 5-HT in the OB, the maintenance of the behavior in RH males could be related to the increased 5-HT activity, in spite of reduction in the NA activity in the OB. RH did not alter CREB phosphorylation in the OB of both male and females compared with NH pups. The repeated handling procedure can affect the behavior of rat pups in response to the maternal odor and biochemical parameters related to the olfactory learning mechanism. Sex differences were already detected in 7-day-old pups. Although the responsiveness of the hypothalamic-pituitary-adrenal axis to stressors is reduced in the neonatal period, environmental interventions may impact behavioral and biochemical mechanisms relevant to the animal at that early age. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Statistical analysis of finite element modeling in sheet metal forming and springback analysis

This work focuses on development of a method to statistically study forming and springback problems of TRansformation Induced Plasticity (TRIP) through an industrial case study. A Design of Experiments (DOE) approach was used to study the sensitivity of predictions to four user input parameters in implicit and explicit sheet metal forming codes. Numerical results were compared to experimental measurements of parts stamped in an industrial production line. The accuracy of forming strain predictions for TRIP steel were comparable with conventional steel, but the springback predictions of TRIP steel were far less accurate. The statistical importance of selected parameters for forming and springback prediction is also discussed. Changes of up to ±10% in Young's modulus and coefficient of friction were found to be insignificant in improving or deteriorating the statistical correlation of springback accuracies.

Effect of grain size on deformation twinning behaviour of high MN steel

The effect of grain size on the mechanical properties and deformation twinning behaviour in high manganese steel was investigated. In order to generate different grain sizes, the samples were subjected to hot rolling, cold rolling and annealing. Room temperature tensile testing of the steel with different grain sizes (5-50 µm) indicated the occurrence of twinning induced plasticity (TWIP) in all the samples. Also, changes in work-hardening behaviour accompanied changes in the grain size. The results are discussed in terms of the enhanced sensitivity of twinning to the grain size.

A study of the strengthening mechanism in the thermomechanically processed TRIP/TWIP steel

The strengthening mechanism responsible for the unique combination of ultimate tensile strength and elongation in a multiphase Fe-0.2C-1.5Mn-1.2Si-0.3Mo-0.6Al-0.02Nb (wt%) steel was studied. The microstructures with different volume fraction of polygonal fenite, bainite and retained austenite were simulated by controlled thermomechanical processing. The interupted tensile test was used to study the bainitic ferrite, retained austenite and polygonal ferrite behavior as a function of plastic strain. X-ray analysis was used to characterize the volume fraction and carbon content of retained austenite. TEM and heat-tinting were utilized to analyze the effect of bainitic fenite morphology on the strain induced transformation of retained austenite and retained austenite twinning as a function of strain in the bulk material. The study has shown that the austenite twinning mechanism is more preferable than the transformation induced plasticity mechanism during the early stages of deformation for a microstructure containing I5% polygonal ferrite, while the transformation induced plasticity effect is the main mechanism in when there is 50% of polygonal ferrite in the microstructure. The baillitic fenite morphology affects the deformation mode of retained austenite during straining. The polygonal fenite behavior during straining depends on dislocation substructure tonned due to the deformation and the additional mobile dislocations caused by the TRIP effect. TRIP and TWIP effects depend not only on the chemical and mechanical stability of retained austenite, but also on the interaction of the phases during straining.

Microstructure and mechanical properties of thermomechanically processed TRIP steel

The strengthening mechanism responsible for the unique combination of ultimate tensile strength and elongation in a multiphase Fe-0.2C-1.5Mn-1.2Si-0.3Mo-0.6Al-0.02Nb (wt%) steel was studied. The microstructures with different volume fractions of polygonal ferrite, bainite and retained austenite were simulated by controlled thermomechanical processing. The interrupted tensile test was used to study the bainitic ferrite, retained austenite and polygonal ferrite behaviour as a function of plastic strain. X-ray analysis was used to characterise the volume fraction and carbon content of retained austenite. Transmission electron microscopy was utilised to analyse the effect of bainitic ferrite morphology on the strain induced transformation of retained austenite and retained austenite twinning as a function of strain in the bulk material. The study has shown that the austenite twinning mechanism is more preferable than the transformation induced plasticity (TRIP) mechanism during the early stages of deformation for a microstructure containing 15% polygonal ferrite, while the transformation induced plasticity effect is the main mechanism when there is 50% of polygonal ferrite in the microstructure. The bainitic ferrite morphology affects the deformation mode of retained austenite during straining. The polygonal ferrite behaviour during straining depends on dislocation substructure formed due to the deformation and the additional mobile dislocations caused by the TRIP effect. Operation of TRIP or twinning mechanisms depends not only on the chemical and mechanical stability of retained austenite, but also on the interaction of the phases during straining.

Prenatal environmental effects match offspring begging to parental provisioning

The solicitation behaviours performed by dependent young are under selection from the environment created by their parents, as well as wider ecological conditions. Here we show how mechanisms acting before hatching enable canary offspring to adapt their begging behaviour to a variable post-hatching world. Cross-fostering experiments revealed that canary nestling begging intensity is positively correlated with the provisioning level of their own parents (to foster chicks). When we experimentally increased food quality before and during egg laying, mothers showed higher faecal androgen levels and so did their nestlings, even when they were cross-fostered before hatching to be reared by foster mothers that had been exposed to a standard regime of food quality. Higher parental androgen levels were correlated with greater levels of post-hatching parental provisioning and (we have previously shown) increased faecal androgens in chicks were associated with greater begging intensity. We conclude that androgens mediate environmentally induced plasticity in the expression of both parental and offspring traits, which remain correlated as a result of prenatal effects, probably acting within the egg. Offspring can thus adapt their begging intensity to variable family and ecological environments.

Effect of bake-hardening treatment on the mechanical properties of high strength bainitic steel produced by thermomechanical processing

The influence of pre-straining and bake-hardening on the mechanical properties of thermomechanically processed 0.2C-1.5Si-1.5Mn-0.2Mo-0.004Nb (wt%) steel was analysed using tensile test, transmission electron microscopy (TEM) and atom probe tomography (APT). This steel after processing had high strength (~1200MPa) and good ductility (~20%) due to the formation of fully bainitic microstructure with nano-layers of bainitic ferrite and retained austenite. The bake hardening (BH) of pre-strained (PS) samples increased the yield strength of steel up to 690MPa and showed the bake-hardening response of 220MPa due to the operation of several strengthening mechanisms such as transformation induced plasticity during pre-straining and pinning the dislocations by carbon during bake-hardening treatment. The carbon content of the bainitic ferrite and retained austenite before and after bake-hardening treatment, the solute distribution between these phases and the local composition of fine Fe-C clusters and particles formed during bake-hardening treatment was calculated using APT. The bainitic ferrite and retained austenite microstructural characteristics such as thickness of the layers and their dislocation density before and after bake-hardening treatment were studied using TEM.

Effect of thermomechanical processing on the microstructure and retained austenite stability during in situ tensile testing using synchrotron X-Ray diffraction of NbMoAl TRIP steel

In this work we compare and contrast the stability of retained austenite during tensile testing of Nb-Mo-Al transformation-induced plasticity steel subjected to different thermomechanical processing schedules. The obtained microstructures were characterised using optical metallography, transmission electron microscopy and X-ray diffraction. The transformation of retained austenite to martensite under tensile loading was observed by in-situ high energy X-ray diffraction at 1ID / APS. It has been shown that the variations in the microstructure of the steel, such as volume fractions of present phases, their morphology and dimensions, play a critical role in the strain-induced transition of retained austenite to martensite.

On the low temperature strain aging of bainite in the TRIP steel

The aging behavior of a thermomechanically processed Mo-Al-Nb transformation-induced plasticity steel with ultrafine microstructure was investigated using transmission electron microscopy and atom probe tomography (APT). Strain aging at 73 K (200 °C) for 1800 seconds led to a significant bake-hardening response (up to 222 MPa). Moreover, aging for 1800 seconds at room temperature after 4 pct pre-strain also revealed a bake-hardening response (~60 MPa). The experimental results showed the formation of carbon Cottrell atmospheres around dislocations and the formation of carbon clusters/fine carbides in the bainitic ferrite during aging. It is proposed that this is associated with the high dislocation density of bainitic ferrite with formation of a complex dislocation substructure after pre-straining and its high average carbon content (~0.35 at. pct). The segregation of carbon and substitutional elements such as Mn and Mo to the retained austenite/bainitic ferrite interface during aging was observed by APT. This segregation is likely to be the preliminary stage for Mo-C particles’ formation. The aging after pre-straining also induced the decomposition of retained austenite with formation of ferrite and carbides.

The effect of deformation twinning on stress localization in a three dimensional TWIP steel microstructure

We present an investigation of the effect of deformation twinning on the visco-plastic response and stress localization in a low stacking fault energy twinning-induced plasticity (TWIP) steel under uniaxial tension loading. The three-dimensional full field response was simulated using the fast Fourier transform method. The initial microstructure was obtained from a three dimensional serial sectionusing electron backscatter diffraction. Twin volume fraction evolution upon strain was measured so the hardening parameters of the simple Voce model could be identified to fit both the stress-strain behavior and twinning activity. General trends of texture evolution were acceptably predicted including the typical sharpening and balance between the 1 1 1 fiber and the 1 0 0 fiber. Twinning was found to nucleate preferentially at grain boundaries although the predominant twin reorientation scheme did not allow spatial propagation to be captured. Hot spots in stress correlated with the boundaries of twinned voxel domains, which either impeded or enhanced twinning based on which deformation modes were active locally.

Temperature and grain orientation dependence of mechanical twinning in a high manganese TWIP steel

 This thesis contains fundamental studies of the deformation mechanisms of the third generation steel at different deformation temperatures. To analyse the microstructure of the steel a unique characterisation technique was implemented for the first time. These analyses provided with vital parameters for modelling the stress-strain behaviour of the steel at different deformation temperatures.