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».

A high-resolution anatomical atlas of the transcriptome in the mouse embryo.

Ascertaining when and where genes are expressed is of crucial importance to understanding or predicting the physiological role of genes and proteins and how they interact to form the complex networks that underlie organ development and function. It is, therefore, crucial to determine on a genome-wide level, the spatio-temporal gene expression profiles at cellular resolution. This information is provided by colorimetric RNA in situ hybridization that can elucidate expression of genes in their native context and does so at cellular resolution. We generated what is to our knowledge the first genome-wide transcriptome atlas by RNA in situ hybridization of an entire mammalian organism, the developing mouse at embryonic day 14.5. This digital transcriptome atlas, the Eurexpress atlas (http://www.eurexpress.org), consists of a searchable database of annotated images that can be interactively viewed. We generated anatomy-based expression profiles for over 18,000 coding genes and over 400 microRNAs. We identified 1,002 tissue-specific genes that are a source of novel tissue-specific markers for 37 different anatomical structures. The quality and the resolution of the data revealed novel molecular domains for several developing structures, such as the telencephalon, a novel organization for the hypothalamus, and insight on the Wnt network involved in renal epithelial differentiation during kidney development. The digital transcriptome atlas is a powerful resource to determine co-expression of genes, to identify cell populations and lineages, and to identify functional associations between genes relevant to development and disease.

Neural plasticity associated with recently versus often heard objects.

In natural settings the same sound source is often heard repeatedly, with variations in spectro-temporal and spatial characteristics. We investigated how such repetitions influence sound representations and in particular how auditory cortices keep track of recently vs. often heard objects. A set of 40 environmental sounds was presented twice, i.e. as prime and as repeat, while subjects categorized the corresponding sound sources as living vs. non-living. Electrical neuroimaging analyses were applied to auditory evoked potentials (AEPs) comparing primes vs. repeats (effect of presentation) and the four experimental sections. Dynamic analysis of distributed source estimations revealed i) a significant main effect of presentation within the left temporal convexity at 164-215ms post-stimulus onset; and ii) a significant main effect of section in the right temporo-parietal junction at 166-213ms. A 3-way repeated measures ANOVA (hemisphere×presentation×section) applied to neural activity of the above clusters during the common time window confirmed the specificity of the left hemisphere for the effect of presentation, but not that of the right hemisphere for the effect of section. In conclusion, spatio-temporal dynamics of neural activity encode the temporal history of exposure to sound objects. Rapidly occurring plastic changes within the semantic representations of the left hemisphere keep track of objects heard a few seconds before, independent of the more general sound exposure history. Progressively occurring and more long-lasting plastic changes occurring predominantly within right hemispheric networks, which are known to code for perceptual, semantic and spatial aspects of sound objects, keep track of multiple exposures.

Space-time front-ends for RAKE receivers in the FDD mode of UTRA

A unified and general vision of different space-time processors is presented. Many popular receivers can beaccomodated, like V-RAKE receivers, weighted V-RAKE, or spatial narrowband beamforming. By makingappropriate assumptions on the space/time characteristic of the interference it is possible to enhance theperformance of the receiver through spatial/temporal pre-processors. These receivers will be tested in the FDDmode of UTRA.

Working memory load improves early stages of independent visual processing.

Increasing evidence suggests that working memory and perceptual processes are dynamically interrelated due to modulating activity in overlapping brain networks. However, the direct influence of working memory on the spatio-temporal brain dynamics of behaviorally relevant intervening information remains unclear. To investigate this issue, subjects performed a visual proximity grid perception task under three different visual-spatial working memory (VSWM) load conditions. VSWM load was manipulated by asking subjects to memorize the spatial locations of 6 or 3 disks. The grid was always presented between the encoding and recognition of the disk pattern. As a baseline condition, grid stimuli were presented without a VSWM context. VSWM load altered both perceptual performance and neural networks active during intervening grid encoding. Participants performed faster and more accurately on a challenging perceptual task under high VSWM load as compared to the low load and the baseline condition. Visual evoked potential (VEP) analyses identified changes in the configuration of the underlying sources in one particular period occurring 160-190 ms post-stimulus onset. Source analyses further showed an occipito-parietal down-regulation concurrent to the increased involvement of temporal and frontal resources in the high VSWM context. Together, these data suggest that cognitive control mechanisms supporting working memory may selectively enhance concurrent visual processing related to an independent goal. More broadly, our findings are in line with theoretical models implicating the engagement of frontal regions in synchronizing and optimizing mnemonic and perceptual resources towards multiple goals.

Detection of clusters using space-time scan statistics

This paper aims at detecting spatio-temporal clustering in fire sequences using space?time scan statistics, a powerful statistical framework for the analysis of point processes. The methodology is applied to active fire detection in the state of Florida (US) identified by MODIS (Moderate Resolution Imaging Spectroradiometer) during the period 2003?06. Results of the present study show that statistically significant clusters can be detected and localized in specific areas and periods of the year. Three out of the five most likely clusters detected for the entire frame period are localized in the north of the state, and they cover forest areas; the other two clusters cover a large zone in the south, corresponding to agricultural land and the prairies in the Everglades. In order to analyze if the wildfires recur each year during the same period, the analyses have been performed separately for the 4 years: it emerges that clusters of forest fires are more frequent in hot seasons (spring and summer), while in the southern areas, they are widely present during the whole year. The recognition of overdensities of events and the ability to locate them in space and in time can help in supporting fire management and focussing on prevention measures.

Coscheduling techniques and monitoring tools for non-dedicated cluster computing

Our efforts are directed towards the understanding of the coscheduling mechanism in a NOW system when a parallel job is executed jointly with local workloads, balancing parallel performance against the local interactive response. Explicit and implicit coscheduling techniques in a PVM-Linux NOW (or cluster) have been implemented. Furthermore, dynamic coscheduling remains an open question when parallel jobs are executed in a non-dedicated Cluster. A basis model for dynamic coscheduling in Cluster systems is presented in this paper. Also, one dynamic coscheduling algorithm for this model is proposed. The applicability of this algorithm has been proved and its performance analyzed by simulation. Finally, a new tool (named Monito) for monitoring the different queues of messages in such an environments is presented. The main aim of implementing this facility is to provide a mean of capturing the bottlenecks and overheads of the communication system in a PVM-Linux cluster.

Genome-wide transcriptional responses to shade: Linking shade avoidance and auxin

Plants have the ability to use the composition of incident light as a cue to adapt development and growth to their environment. Arabidopsis thaliana as well as many crops are best adapted to sunny habitats. When subjected to shade, these plants exhibit a variety of physiological responses collectively called shade avoidance syndrome (SAS). It includes increased growth of hypocotyl and petioles, decreased growth rate of cotyledons and reduced branching and crop yield. These responses are mainly mediated by phytochrome photoreceptors, which exist either in an active, far-red light (FR) absorbing or an inactive, red light (R) absorbing isoform. In direct sunlight, the R to FR light (R/FR) ratio is high and converts the phytochromes into their physiologically active state. The phytochromes interact with downstream transcription factors such as PHYTOCHROME INTERACTING FACTOR (PIF), which are subsequently degraded. Light filtered through a canopy is strongly depleted in R, which result in a low R/FR ratio and renders the phytochromes inactive. Protein levels of downstream transcription factors are stabilized, which initiates the expression of shade-induced genes such as HFR1, PIL1 or ATHB-2. In my thesis, I investigated transcriptional responses mediated by the SAS in whole Arabidopsis seedlings. Using microarray and chromatin immunoprecipitation data, we identified genome-wide PIF4 and PIF5 dependent shade regulated gene as well as putative direct target genes of PIF5. This revealed evidence for a direct regulatory link between phytochrome signaling and the growth promoting phytohormone auxin (IAA) at the level of biosynthesis, transport and signaling. Subsequently, it was shown, that free-IAA levels are upregulated in response to shade. It is assumed that shade-induced auxin production takes predominantly place in cotyledons of seedlings. This implies, that IAA is subsequently transported basipetally to the hypocotyl and enhances elongation growth. The importance of auxin transport for growth responses has been established by chemical and genetic approaches. To gain a better understanding of spatio-temporal transcriptional regulation of shade-induce auxin, I generated in a second project, an organ specific high throughput data focusing on cotyledon and hypocotyl of young Arabidopsis seedlings. Interestingly, both organs show an opposite growth regulation by shade. I first investigated the spatio-transcriptional regulation of auxin re- sponsive gene, in order to determine how broad gene expression pattern can be explained by the hypothesized movement of auxin from cotyledons to hypocotyls in shade. The analysis suggests, that several genes are indeed regulated according to our prediction and others are regulated in a more complex manner. In addition, analysis of gene families of auxin biosynthetic and transport components, lead to the identification of essential family members for shade-induced growth re- sponses, which were subsequently experimentally confirmed. Finally, the analysis of expression pattern identified several candidate genes, which possibly explain aspects of the opposite growth response of the different organs.

Decoding auditory EEG responses in healthy and clinical populations: A comparative study.

BACKGROUND: Analyses of brain responses to external stimuli are typically based on the means computed across conditions. However in many cognitive and clinical applications, taking into account their variability across trials has turned out to be statistically more sensitive than comparing their means. NEW METHOD: In this study we present a novel implementation of a single-trial topographic analysis (STTA) for discriminating auditory evoked potentials at predefined time-windows. This analysis has been previously introduced for extracting spatio-temporal features at the level of the whole neural response. Adapting the STTA on specific time windows is an essential step for comparing its performance to other time-window based algorithms. RESULTS: We analyzed responses to standard vs. deviant sounds and showed that the new implementation of the STTA gives above-chance decoding results in all subjects (in comparison to 7 out of 11 with the original method). In comatose patients, the improvement of the decoding performance was even more pronounced than in healthy controls and doubled the number of significant results. COMPARISON WITH EXISTING METHOD(S): We compared the results obtained with the new STTA to those based on a logistic regression in healthy controls and patients. We showed that the first of these two comparisons provided a better performance of the logistic regression; however only the new STTA provided significant results in comatose patients at group level. CONCLUSIONS: Our results provide quantitative evidence that a systematic investigation of the accuracy of established methods in normal and clinical population is an essential step for optimizing decoding performance.

Brain dynamics of meal size selection in humans.

Although neuroimaging research has evidenced specific responses to visual food stimuli based on their nutritional quality (e.g., energy density, fat content), brain processes underlying portion size selection remain largely unexplored. We identified spatio-temporal brain dynamics in response to meal images varying in portion size during a task of ideal portion selection for prospective lunch intake and expected satiety. Brain responses to meal portions judged by the participants as 'too small', 'ideal' and 'too big' were measured by means of electro-encephalographic (EEG) recordings in 21 normal-weight women. During an early stage of meal viewing (105-145ms), data showed an incremental increase of the head-surface global electric field strength (quantified via global field power; GFP) as portion judgments ranged from 'too small' to 'too big'. Estimations of neural source activity revealed that brain regions underlying this effect were located in the insula, middle frontal gyrus and middle temporal gyrus, and are similar to those reported in previous studies investigating responses to changes in food nutritional content. In contrast, during a later stage (230-270ms), GFP was maximal for the 'ideal' relative to the 'non-ideal' portion sizes. Greater neural source activity to 'ideal' vs. 'non-ideal' portion sizes was observed in the inferior parietal lobule, superior temporal gyrus and mid-posterior cingulate gyrus. Collectively, our results provide evidence that several brain regions involved in attention and adaptive behavior track 'ideal' meal portion sizes as early as 230ms during visual encounter. That is, responses do not show an increase paralleling the amount of food viewed (and, in extension, the amount of reward), but are shaped by regulatory mechanisms.

Multi-scale effects of nestling diet on breeding performance in a terrestrial top predator inferred from stable isotope analysis

Inter-individual diet variation within populations is likely to have important ecological and evolutionary implications. The diet-fitness relationships at the individual level and the emerging population processes are, however, poorly understood for most avian predators inhabiting complex terrestrial ecosystems. In this study, we use an isotopic approach to assess the trophic ecology of nestlings in a long-lived raptor, the Bonelli"s eagle Aquila fasciata, and investigate whether nestling dietary breath and main prey consumption can affect the species" reproductive performance at two spatial scales: territories within populations and populations over a large geographic area. At the territory level, those breeding pairs whose nestlings consumed similar diets to the overall population (i.e. moderate consumption of preferred prey, but complemented by alternative prey categories) or those disproportionally consuming preferred prey were more likely to fledge two chicks. An increase in the diet diversity, however, related negatively with productivity. The age and replacements of breeding pair members had also an influence on productivity, with more fledglings associated to adult pairs with few replacements, as expected in long-lived species. At the population level, mean productivity was higher in those population-years with lower dietary breadth and higher diet similarity among territories, which was related to an overall higher consumption of preferred prey. Thus, we revealed a correspondence in diet-fitness relationships at two spatial scales: territories and populations. We suggest that stable isotope analyses may be a powerful tool to monitor the diet of terrestrial avian predators on large spatio-temporal scales, which could serve to detect potential changes in the availability of those prey on which predators depend for breeding. We encourage ecologists and evolutionary and conservation biologists concerned with the multi-scale fitness consequences of inter-individual variation in resource use to employ similar stable isotope-based approaches, which can be successfully applied to complex ecosystems such as the Mediterranean.

Time and space: genetic structure of the common sea urchin paracentrotus lividus in the south-eastern iberian coast

Spatio-temporal variability in settlement and recruitment, high mortality during the first life-history stages, and selection may determine the genetic structure of cohorts of long-lived marine invertebrates at small scales. We conducted a spatial and temporal analysis of the common Mediterranean Sea urchin Paracentrotus lividus to determine the genetic structure of cohorts at different scales. In Tossa de Mar (NW Mediterranean), recruitment was followed over 5 consecutive springs (2006-2010). In spring 2008, recruits and two-year-old individuals were collected at 6 locations along East and South Iberian coasts separated from 200 to over 1,100 km. All cohorts presented a high genetic diversity based on a fragment of mtCOI. Our results showed a marked genetic homogeneity in the temporal monitoring and a low degree of spatial structure in 2006. In 2008, coupled with an abnormality in the usual circulation patterns in the area, the genetic structure of the southern populations studied changed markedly, with arrival of many private haplotypes. This fact highlights the importance of point events in renewing the genetic makeup of populations, which can only be detected through analysis of the cohort structure coupling temporal and spatial perspectives.

Historical first descriptions of Cajal-Retzius cells: from pioneer studies to current knowledge

Santiago Ramón y Cajal developed a great body of scientific research during the last decade of 19th century, mainly between 1888 and 1892, when he published more than 30 manuscripts. The neuronal theory, the structure of dendrites and spines, and fine microscopic descriptions of numerous neural circuits are among these studies. In addition, numerous cell types (neuronal and glial) were described by Ramón y Cajal during this time using this 'reazione nera' or Golgi method. Among these neurons were the special cells of the molecular layer of the neocortex. These cells were also termed Cajal cells or Retzius cells by other colleagues. Today these cells are known as Cajal-Retzius cells. From the earliest description, several biological aspects of these fascinating cells have been analyzed (e.g., cell morphology, physiological properties, origin and cellular fate, putative function during cortical development, etc). In this review we will summarize in a temporal basis the emerging knowledge concerning this cell population with specific attention the pioneer studies of Santiago Ramón y Cajal.

Dpp spreading is required for medial but not for lateral wing disc growth.

Drosophila Decapentaplegic (Dpp) has served as a paradigm to study morphogen-dependent growth control. However, the role of a Dpp gradient in tissue growth remains highly controversial. Two fundamentally different models have been proposed: the 'temporal rule' model suggests that all cells of the wing imaginal disc divide upon a 50% increase in Dpp signalling, whereas the 'growth equalization model' suggests that Dpp is only essential for proliferation control of the central cells. Here, to discriminate between these two models, we generated and used morphotrap, a membrane-tethered anti-green fluorescent protein (GFP) nanobody, which enables immobilization of enhanced (e)GFP::Dpp on the cell surface, thereby abolishing Dpp gradient formation. We find that in the absence of Dpp spreading, wing disc patterning is lost; however, lateral cells still divide at normal rates. These data are consistent with the growth equalization model, but do not fit a global temporal rule model in the wing imaginal disc.

The impact of bioavailability limitations on microbial stable isotope fractionation in a multiphase system

Stable isotope fractionation analysis of contaminants is a promising method for assessing biodegradation of contaminants in natural systems. However, standard procedures to determine stable isotope fractionation factors, so far, neglect the influence of pollutant bioavailability on stable isotope fractionation. On a microscale, bioavailability may vary due to the spatio-temporal variability of local contaminant concentrations, limited effective diffusivities of the contaminants and cell densities, and thus, the pollutant supply might not meet the intrinsic degradation capacity of the microorganisms. The aim of this study was to demonstrate the effect of bioavailability on the apparent stable isotope fractionation, using a multiphase laboratory setup. The data gained show that the apparent isotope fractionation factors observed during biodegradation processes depend on the amount of biomass and/or the rate of toluene mass transfer from a second to the aqueous phase. They indicate that physico-chemical processes need to be taken into account when stable isotope fractionation analysis is used for the quantification of environmental contaminant degradation.