Efectos de tipicidad en la percepción visual de escenas naturales

La actuación de las estructuras de conocimiento en el proceso de identificación y codificación de estimulos visuales se ha operativizado frecuentemente mediante conceptos como contexto o tipicidad. Ambos efectos pueden considerarse complementarios y producidos por la actuación de un mecanisrno de tipo atencional. Dicho mecanisrno fue aplicado al procesamiento de escenas por Arnau, Carreras y Salvador (en prensa). A partir de los términos propuestos en dicho modelo se intenta comprobar si la tipicidad es una variable relevante para la identificación de 10s objetos que forman una escena. Los resultados obtenidos en el experimento 1 permiten afirmar que el grado de tipicidad de un objeto respecto a una escena determina el tiempo y exactitud de su identificación. Por otra parte, en el experimento 2 se demuestra que en procesos de memoria a corto plazo el efecto de tipicidad detectado en el experimento 1 se anula. Finalmente se discuten las implicaciones de estos resultados para el estudio de la percepción visual de escenas naturales.

Comparing 'visual' effect size indices for single-case designs

Effect size indices are indispensable for carrying out meta-analyses and can also be seen as an alternative for making decisions about the effectiveness of a treatment in an individual applied study. The desirable features of the procedures for quantifying the magnitude of intervention effect include educational/clinical meaningfulness, calculus easiness, insensitivity to autocorrelation, low false alarm and low miss rates. Three effect size indices related to visual analysis are compared according to the aforementioned criteria. The comparison is made by means of data sets with known parameters: degree of serial dependence, presence or absence of general trend, changes in level and/or in slope. The percent of nonoverlapping data showed the highest discrimination between data sets with and without intervention effect. In cases when autocorrelation or trend is present, the percentage of data points exceeding the median may be a better option to quantify the effectiveness of a psychological treatment.

Factors affecting visual analysis in single-case designs

Visual inspection remains the most frequently applied method for detecting treatment effects in single-case designs. The advantages and limitations of visual inference are here discussed in relation to other procedures for assessing intervention effectiveness. The first part of the paper reviews previous research on visual analysis, paying special attention to the validation of visual analysts" decisions, inter-judge agreement, and false alarm and omission rates. The most relevant factors affecting visual inspection (i.e., effect size, autocorrelation, data variability, and analysts" expertise) are highlighted and incorporated into an empirical simulation study with the aim of providing further evidence about the reliability of visual analysis. Our results concur with previous studies that have reported the relationship between serial dependence and increased Type I rates. Participants with greater experience appeared to be more conservative and used more consistent criteria when assessing graphed data. Nonetheless, the decisions made by both professionals and students did not match sufficiently the simulated data features, and we also found low intra-judge agreement, thus suggesting that visual inspection should be complemented by other methods when assessing treatment effectiveness.

Mental imagery for full and upper human bodies: common right hemisphere activations and distinct extrastriate activations.

The processing of human bodies is important in social life and for the recognition of another person's actions, moods, and intentions. Recent neuroimaging studies on mental imagery of human body parts suggest that the left hemisphere is dominant in body processing. However, studies on mental imagery of full human bodies reported stronger right hemisphere or bilateral activations. Here, we measured functional magnetic resonance imaging during mental imagery of bilateral partial (upper) and full bodies. Results show that, independently of whether a full or upper body is processed, the right hemisphere (temporo-parietal cortex, anterior parietal cortex, premotor cortex, bilateral superior parietal cortex) is mainly involved in mental imagery of full or partial human bodies. However, distinct activations were found in extrastriate cortex for partial bodies (right fusiform face area) and full bodies (left extrastriate body area). We propose that a common brain network, mainly on the right side, is involved in the mental imagery of human bodies, while two distinct brain areas in extrastriate cortex code for mental imagery of full and upper bodies.

Synapse formation in adult barrel cortex following naturalistic environmental enrichment.

Environmental enrichment paradigms in adult laboratory animals, consisting of physical, perceptual, and social stimulation, have been shown to affect synapse and cell morphology in sensory cortex and enhance learning ability, whereas enrichment, which is in harmony with the animal's natural habitat may have even greater implications for plasticity. Previous studies in our laboratory have shown that whisker stimulation induced the formation of synapses and spines in the corresponding barrel. In the present study adult C57/Bl6J female laboratory mice at 6 weeks of age were placed during 2 months in a protected enrichment enclosure in a forest clearing at the Chisti Les Biological Station, Tvier, Russia. We analyzed neuropil ultrastructure in the C2 barrel using serial-section electron microscopy on a total of eight mice (n=4 enriched, n=4 standard cagemate controls). Quantitative analyses of volumes of neuropil showed a significant increase in excitatory and inhibitory synapses on spines and excitatory synapses on dendritic shafts in the C2 barrel in the enriched group compared with standard cagemate controls. These results demonstrate that naturalistic experience alters the synaptic circuitry in layer IV of the somatosensory cortex, the first cortical relay of sensory information, leaving a lasting trace that may guide subsequent behavior.

Tuning In to Sound: Frequency-Selective Attentional Filter in Human Primary Auditory Cortex.

Cocktail parties, busy streets, and other noisy environments pose a difficult challenge to the auditory system: how to focus attention on selected sounds while ignoring others? Neurons of primary auditory cortex, many of which are sharply tuned to sound frequency, could help solve this problem by filtering selected sound information based on frequency-content. To investigate whether this occurs, we used high-resolution fMRI at 7 tesla to map the fine-scale frequency-tuning (1.5 mm isotropic resolution) of primary auditory areas A1 and R in six human participants. Then, in a selective attention experiment, participants heard low (250 Hz)- and high (4000 Hz)-frequency streams of tones presented at the same time (dual-stream) and were instructed to focus attention onto one stream versus the other, switching back and forth every 30 s. Attention to low-frequency tones enhanced neural responses within low-frequency-tuned voxels relative to high, and when attention switched the pattern quickly reversed. Thus, like a radio, human primary auditory cortex is able to tune into attended frequency channels and can switch channels on demand.

Auditory cues support place navigation in rats when associated with a visual cue.

Rats, like other crepuscular animals, have excellent auditory capacities and they discriminate well between different sounds [Heffner HE, Heffner RS, Hearing in two cricetid rodents: wood rats (Neotoma floridana) and grasshopper mouse (Onychomys leucogaster). J Comp Psychol 1985;99(3):275-88]. However, most experimental literature concerning spatial orientation almost exclusively emphasizes the use of visual landmarks [Cressant A, Muller RU, Poucet B. Failure of centrally placed objects to control the firing fields of hippocampal place cells. J Neurosci 1997;17(7):2531-42; and Goodridge JP, Taube JS. Preferential use of the landmark navigational system by head direction cells in rats. Behav Neurosci 1995;109(1):49-61]. To address the important issue of whether rats are able to achieve a place navigation task relative to auditory beacons, we designed a place learning task in the water maze. We controlled cue availability by conducting the experiment in total darkness. Three auditory cues did not allow place navigation whereas three visual cues in the same positions did support place navigation. One auditory beacon directly associated with the goal location did not support taxon navigation (a beacon strategy allowing the animal to find the goal just by swimming toward the cue). Replacing the auditory beacons by one single visual beacon did support taxon navigation. A multimodal configuration of two auditory cues and one visual cue allowed correct place navigation. The deletion of the two auditory or of the one visual cue did disrupt the spatial performance. Thus rats can combine information from different sensory modalities to achieve a place navigation task. In particular, auditory cues support place navigation when associated with a visual one.

Chronic low-frequency rTMS of primary motor cortex diminishes exercise training-induced gains in maximal voluntary force in humans.

Although there is consensus that the central nervous system mediates the increases in maximal voluntary force (maximal voluntary contraction, MVC) produced by resistance exercise, the involvement of the primary motor cortex (M1) in these processes remains controversial. We hypothesized that 1-Hz repetitive transcranial magnetic stimulation (rTMS) of M1 during resistance training would diminish strength gains. Forty subjects were divided equally into five groups. Subjects voluntarily (Vol) abducted the first dorsal interosseus (FDI) (5 bouts x 10 repetitions, 10 sessions, 4 wk) at 70-80% MVC. Another group also exercised but in the 1-min-long interbout rest intervals they received rTMS [Vol+rTMS, 1 Hz, FDI motor area, 300 pulses/session, 120% of the resting motor threshold (rMT)]. The third group also exercised and received sham rTMS (Vol+Sham). The fourth group received only rTMS (rTMS_only). The 37.5% and 33.3% gains in MVC in Vol and Vol+Sham groups, respectively, were greater (P = 0.001) than the 18.9% gain in Vol+rTMS, 1.9% in rTMS_only, and 2.6% in unexercised control subjects who received no stimulation. Acutely, within sessions 5 and 10, single-pulse TMS revealed that motor-evoked potential size and recruitment curve slopes were reduced in Vol+rTMS and rTMS_only groups and accumulated to chronic reductions by session 10. There were no changes in rMT, maximum compound action potential amplitude (M(max)), and peripherally evoked twitch forces in the trained FDI and the untrained abductor digiti minimi. Although contributions from spinal sources cannot be excluded, the data suggest that M1 may play a role in mediating neural adaptations to strength training.

Subretinal neovascular membranes complicating uveitis : frequency, treatments and visual outcome

RESUME Les membranes néovasculaires (MNV) compliquent diverses pathologies ophtalmiques. Elles sont à l'origine d'une importante baisse de l'acuité visuelle lorsque elles se situent à proximité de la fovéa. A l'heure actuelle, peu de données relatives à leur association aux pathologies inflammatoires de l'oeil (uvéites) existent. Dans ce travail, la fréquence de MNV a été évaluée parmi 643 patients avec uvéite. Leur impact sur l'acuité visuelle ainsi que le pronostic en fonction des différents traitements effectués ont été étudiés. Les dossiers des 643 patients souffrant d'uvéite ont été étudiés. Les patients présentant une MNV ont été classés en trois groupes en fonction de l'importance de l'inflammation intraoculaire: élevée (2+ cellules dans le vitré), moyenne (1/2+ à 1+ cellules dans le vitré) ou absente (0 cellules dans le vitré). L'évolution de l'acuité visuelle fut considérée comme favorable (+VA: maintient de l'acuité visuelle ou gain d'une ou plusieurs lignes de Snellen) ou défavorable (-VA: perte d'une ou plusieurs lignes Snellen). Chez 9 patients, le traitement instauré a consisté, initialement, en l'administration orale de corticostéroïdes (CST) à haute dose qui, dans le cas d'évolution favorable (-FVA ou régression angiographique de la MNV), était arrêtée en doses dégressives. Dans les évolutions défavorables (-VA ou progression angiographique de la MNV), les CST étaient maintenus à dose moyenne en complémentation d'un traitement par thérapie laser (photothérapie dynamique (PDT), thermothérapie transpupillaire (TTT) ou laser Argon). Ce protocole thérapeutique ne fut appliqué chez trois patients en raison de la non disponibilité de PDT ou d'un diagnostic manqué d'uvéite. Douze patients sur 643 avec uvéite ont présenté une MNV. L'impact visuel moyen était de 4.5 lignes de Snellen et le temps moyen de suivi était de 19.5 mois. Deux patients avec inflammation intraoculaire élevée ont évolué favorablement sous CST seuls. Huit patients avec inflammation intraoculaire moyenne ont évolué favorablement sous CST seuls chez trois patients, alors que quatre patients ont nécessité une thérapie laser additionnelle. Le dernier patient ne fut traité que par thérapie laser sans CST (diagnostic manqué d'uvéite). Deux patients sans inflammation intraoculaire ont eu un pronostic défavorable sous CST seuls (pas d'autre alternative thérapeutique). Notre étude a démontré que les MNV sont une complication rare de l'uvéite qui, après traitement adéquat, ont un pronostic visuel relativement favorable. Bien que les CST semblent être la première modalité thérapeutique, les traitements laser devraient être adoptés tôt dans les situations d'inflammation intraoculaire moyenne ou absente.

Exploring the rate-limiting steps in visual phototransduction recovery by bottom-up kinetic modeling

Phototransduction in vertebrate photoreceptor cells represents a paradigm of signaling pathways mediated by G-protein-coupled receptors (GPCRs), which share common modules linking the initiation of the cascade to the final response of the cell. In this work, we focused on the recovery phase of the visual photoresponse, which is comprised of several interacting mechanisms. We employed current biochemical knowledge to investigate the response mechanisms of a comprehensive model of the visual phototransduction pathway. In particular, we have improved the model by implementing a more detailed representation of the recoverin (Rec)-mediated calcium feedback on rhodopsin kinase and including a dynamic arrestin (Arr) oligomerization mechanism. The model was successfully employed to investigate the rate limiting steps in the recovery of the rod photoreceptor cell after illumination. Simulation of experimental conditions in which the expression levels of rhodospin kinase (RK), of the regulator of the G-protein signaling (RGS), of Arr and of Rec were altered individually or in combination revealed severe kinetic constraints to the dynamics of the overall network. Our simulations confirm that RGS-mediated effector shutdown is the rate-limiting step in the recovery of the photoreceptor and show that the dynamic formation and dissociation of Arr homodimers and homotetramers at different light intensities significantly affect the timing of rhodopsin shutdown. The transition of Arr from its oligomeric storage forms to its monomeric form serves to temper its availability in the functional state. Our results may explain the puzzling evidence that overexpressing RK does not influence the saturation time of rod cells at bright light stimuli. The approach presented here could be extended to the study of other GPCR signaling pathways.

Experience-dependent plasticity in the mouse barrel cortex

Abstract : Host-Cell Factor 1 (HCF-1) was first discovered in the study of the herpes simplex virus (HSV) infection. HCF-1 is one of the two cellular proteins that compose the VP16-induced complex, a key activator of HSV lytic infection. lncleed, when HSV infects human cells, it is able to enter two modes of infection: lytic or latent. The V`P16-induced complex promotes the lytic mode and in so doing the virus targets important cellular regulatory proteins, such as HCF-1, to manipulate the status of the infected cell. Indeed, HCF-1 regulates human cell proliferation and the cell cycle at different steps. In human, HCF-1 is unusual in that it undergoes a process of proteolytic maturation that results from cleavages at six centrally located 26 amino acid repeats called HCF-1pro repeats. This generates a heterodimeric complex of stably associated amino- (HCF-1n) and carboxy- (HCF-1c) terminal subunits. The absence of the HCF-1 N or HCF-1; subunit leads predominantly to either G1 or M phase defects, respectively. We have hypothesized that HCF-1 forms a heterodimeric complex to permit communication between the two subunits of HCF-1 involved in regulating different phases of the cell cycle. Indeed, there is evidence for such inter-subunit communication because a point mutation called P134S in the HCF-1N subunit in the temperature-sensitive hamster cell line tsBN67 causes, addition to G1- phase defects associated with the HCF-1n subunit, M-phase defects similar to the defects seen upon loss of HCF-1 function. Furthermore, inhibition of the proteolytic maturation of HCF-1 by deletion of the six HCF-1pro repeats (HCF-1Aimo) also leads to M-phase defects, specifically cytokinesis defects leading to binucleation, indicating that there is loss of HCF-15 function in the absence of HCF-1 maturation. I demonstrate that individual point mutations in each of the six HCF-1pro repeats that prevent HCF-1 proteolytic maturation also lead to binucleation; however, this defect can be latgely rescued by the presence of just one HCF-1pRO sequence in I-ICF»1. These results argue that processing itself is important for the HCF-1g function. In fact, until now, the hypothesis was that the proteolytic processing per se is more important for HCF-1C function than the proteolytic processing region. But I show that processing per se is not sufticient to rescue multinucleation, but that the HCF-lpm sequence itself is crucial. This discovery leads to the conclusion that the I-ICF-1pRO repeats have an additional function important for HCF-le function. From the studies of others, one potential function of the HCF-lrxo tepeats is as a binding site for O-link NAcetyl glycosamine tansferase (OGT) to glycosylate an HCF-1n-sunbunit region called the Basic region. This new function suggests the Basic region of HCF-1n is also implicated in the communication between the two subunits. This inter-subunit communication was analyzed in more detail with the studies of the Pl34S mutation and the residues 382-450 region of HCF-l that when removed prevents HCF-l subunit association. I demonstrate that the point mutation also leads to a binucleation defect in Hela cells as well as in the tsBN67 cells. In addition, the effect of this mutation on the regulation of HCF-1c activity seems to interfere with that of the HCF-lpgg repeats because the sum of the deletion of the proteolytic processing region and the point mutation surprisingly leads to re-establishment of correct cytokinesis. The study of the 382-450 HCF-lN region also yielded surprising results. This region important for the association of the two subunits is also important for both HCF-1c function in M phase and G1 phase progression. Thus, I have discovered two main functions of this region: its role in the regulation of HCF-lc function in M phase and its involvement in the regulation of G1/S phase ?- an HCF-1n function. These results support the importance of inter-subunit communication in HCF-1 functions. My research illuminates the understanding of the interaction of the two subunits by showing that the whole HCF-1n subunit is involved in the inter-subunit communication in order to regulate HCF-1c function. For this work, I was concentrated on the study of cytokinesis; the first phenotype showing the role of HCF-1c in the M phase. Then, I extended the study of the M phase with analysis of steps earlier to cytokinesis. Because some defects in the chromosome segregation was already described in the absence of HCF-1, I decided to continue the study of M phase by checking effects on the chromosome segregation. I showed that the HCF-1n subunit and HCF-1pro repeats are both important for this key step of M phase. I show that the binucleation phenotype resulting from deletion or mutation in HCF-1pro repeats, Pl34S point mutation or the lack of the region 382-450 are correlated with micronuclei, and chromosome segregation and alignment defects. This suggests that HCF«lç already regulates M phase during an early step and could be involved in the complex regulation of chromosome segregation. Because one of the major roles of HCF-1 is to be a transcription regulator, I also checked the capacity of HCF-1 to bind to the chromatin in my different cell lines. All my recombinant proteins can bind the chromatin, except for, as previously described, the HCF-1 with the P134S point mutation, This suggests that the binding of HCF-1 to the chromatin is not dependant to the Basic and proteolytic regions but more to the Kelch domain. Thus, if the function of HCF-ig in M phase is dependant to its chromatin association, the intercommunication and the proteolytic region are not involved in the ability to bind to the chromatin but more to bind to the right place of the chromatin or to be associated with the co-factors. Résumé : L'étude de l'infection par le virus Herpes Simplex (HSV) a permis la découverte de la protéine HCF-1 (Host-Cell Factor). HCF-1 est une des protéines cellulaires qui font partie du complexe induit par VP16 ; ce complexe est la clef pour l'activation de la phase lytique de HSV. Afin de manipuler les cellules infectées, le complexe induit pas le VPIG devrait donc cibler les protéines importantes pour la régulation cellulaire, telles que la protéine HCF-1. Cette dernière s'avère donc être un senseur pour la cellule et devrait également jouer un rôle de régulation lors des différentes phases du cycle cellulaire. Chez l'humain, HCF-1 a la particularité de devoir passer par une phase de maturation pour devenir active. Lors de cette maturation, la protéine subit une coupure protéolytique au niveau de six répétitions composées de 26 acides aminés, appelé HCF-1pro repeats. Cette coupure engendre la formation d'un complexe formé de deux sous-unités, HCF-1n et HCF-1c, associées l'une à l'autre de façon stable. Enlever la sous-unité HCF-IN ou C entraîne respectivement des défauts dans la phase G1 et M. Nous pensons donc que HCF-1 forme un complexe hétérodimérique afin de permettre la communication entre les molécules impliquées dans la régulation des différentes phases du cycle cellulaire. Cette hypothèse est déduite suite à deux études: l'une réalisée sur la lignée cellulaire tsBN67 et l'autre portant sur l'inhibition de la maturation protéolytique. La lignée cellulaire tsBN67, sensible à la température, porte la mutation Pl 345 dans la sous-unité HCF-1n. Cette mutation, en plus d'occasionner des défauts dans la phase G1 (défauts liés à la sous-unité HCF-1N), a aussi pour conséquence d'entrainer des défauts dans la phase M, défauts similaires à ceux dus a la perte de la sous-unité HCF-1c. Quant à la maturation protéolytique, l'absence de la région de la protéolyse provoque la binucléation, défaut lié à la cytokinèse, indiquant la perte de la fonction de la sous-unité HCF-1c. Au cours de ma thèse, j'ai démontré que des mutations dans les HCF-1=no repeats, qui bloquent la protéolyse, engendrent la binucléation ; cependant ce défaut peut être corrigé pas l'ajout d'un HCF-1pro repeat dans un HCF-1 ne contenant pas la région protéolytique. Ces résultats soutiennent l'idée que la région protéolytique est importante pour le bon fonctionnement de HCF-1c. En réalité jusqu'a maintenant on supposait que le mécanisme de coupure était plus important que la région impliquée pour la régulation de la fonction de HCF-1;. Mais mon étude montre que la protéolyse n'est pas suffisante pour éviter la binucléation ; en effet, les HCF-1pro repeats semblent jouer le rôle essentiel dans le cycle cellulaire. Cette découverte conduit à la conclusion que les HCF-1pro repeats ont sûrement une fonction autre qui serait cruciale pour la foncton de HCF-1c. Une des fonctions possibles est d'être le site de liaison de l'O-linked N-acetylglucosamine transférase (OGT) qui glycosylerait la région Basique de HCF-1n. Cette nouvelle fonction suggère que la région Basique est aussi impliquée dans la communication entre les deux sous- unités. L'intercommunication entre les deux sous-unités ai été d'ailleurs analysée plus en détail dans mon travail à travers l'étude de la mutation Pl34S et de la région 382-450, essentielle pour l'association des deux sous»unités. J'ai ainsi démontré que la mutation P134S entraînait aussi des défauts dans la cytokinése dans la lignée cellulaire Hela, de plus, son influence sur HCF-1c semble interférer avec celle de la région protéolytique. En effet, la superposition de ces deux modifications dans HCF-1 conduit au rétablissement d'une cytokinése correcte. Concernant la région 382 à 450, les résultats ont été assez surprenants, la perte de cette région provoque l'arrêt du cycle en G1 et la binucléation, ce qui tend à prouver son importance pour le bon fonctionnement de HCF-1n et de HCF-1c. Cette découverte appuie par conséquent l'hypotl1èse d'une intercommunicatzion entre les deux sous-unités mettant en jeu les différentes régions de HCF-1n. Grâce à mes recherches, j'ai pu améliorer la compréhension de l'interaction des deux sous-unités de HCF-1 en montrant que toutes les régions de HCF-1n sont engagées dans un processus d'intercommunication, dont le but est de réguler l'action de HCF-1c. J'ai également mis en évidence une nouvelle étape de la maturation de HCF-1 qui représente une phase importante pour l'activation de la fonction de HCF-1c. Afin de mettre à jour cette découverte, je me suis concentrée sur l'étude de l'impact de ces régions au niveau de la cytokinése qui fut le premier phénotype démontrant le rôle de HCF-1c dans la phase M. A ce jour, nous savons que HCF-1c joue un rôle dans la cytokinèse, nous ne connaissons pas encore sa fonction précise. Dans le but de cerner plus précisément cette fonction, j'ai investigué des étapes ultérieures ai la cytokinèse. Des défauts dans la ségrégation des chromosomes avaient déjà été observés, ai donc continué l'étude en prouvant que HCF-1n et les HCF-1pro repeats sont aussi importants pour le bon fonctionnement de cette étape clef également régulée par HCF-1c. J' ai aussi montré que la région 382-450 et la mutation P134S sont associées à un taux élevé de micronoyaux, de défauts dans la ségrégation des chromosomes. L'une des fonctions principales de HCF-1 étant la régulation de la transcription, j'ai aussi contrôlé la capacité de HCF-1 à se lier à la chromatine après insertion de mutations ou délétions dans HCF-1n et dans la région protéolytique. Or, à l'exception des HCF-1 contenant la mutation P134S, la sous-unité HCF-1c des HCF-1 tronquées se lie correctement à la chromatine. Cette constatation suggère que la liaison entre HCF-1c et chromatine n'est pas dépendante de la région Basique ou Protéolytique mais peut-être vraisemblablement de la région Kelch. Donc si le rôle de HCF-1c est dépendant de sa capacité â activer la transcription, l'intercommunication entre les deux sous-unités et la région protéolytique joueraient un rôle important non pas dans son habileté à se lier à la chromatine, mais dans la capacité de HCF-1 à s'associer aux co-facteurs ou à se placer sur les bonnes régions du génome.