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Perceptual scales of color saturation obtained by direct estimation (DE) and maximum likelihood conjoint measurement (MLCM) were compared for red checkerboard patterns and uniform red squares. For the DE task, observers were asked to rate the saturation level as a percentage, indicating the chromatic sensation for each pattern and contrast. For the MLCM procedure, observers judged on each trial which of two stimuli that varied in chromatic contrast and/or spatial pattern evoked the most salient color. In separate experiments, patterns varying only in luminance contrast were also tested. The MLCM data confirmed previous results reported with DE indicating that the slope of the checkerboard scale with cone contrast levels is steeper than that for the uniform square. Similar results were obtained with patterns modulated only in luminance. DE methods were relatively more variable within an observer, reflecting observer uncertainty, while MLCM scales showed greater relative variability across observers, perhaps reflecting individual differences in the appearance of the stimuli. MLCM provides a reliable scaling method, based only on ordinal judgments between pairs of stimuli and that provides less opportunity for subject-specific biases and strategies to intervene in perceptual judgements.
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Hierarchy is a major organizational principle of the cortex and underscores modern computational theories of cortical function. The local microcircuit amplifies long-distance inter-areal input, which show distance-dependent changes in their laminar profiles. Statistical modeling of these changes in laminar profiles demonstrates that inputs from multiple hierarchical levels to their target areas show remarkable consistency, allowing the construction of a cortical hierarchy based on a principle of hierarchical distance. The statistical modeling that is applied to structure can also be applied to laminar differences in the oscillatory coherence between areas thereby determining a functional hierarchy of the cortex. Close examination of the anatomy of inter-areal connectivity reveals a dual counterstream architecture with well-defined distance-dependent feedback and feedforward pathways in both the supra- and infragranular layers, suggesting a multiplicity of feedback pathways with well-defined functional properties. These findings are consistent with feedback connections providing a generative network involved in a wide range of cognitive functions. A dynamical model constrained by connectivity data sheds insight into the experimentally observed signatures of frequency-dependent Granger causality for feedforward versus feedback signaling. Concerted experiments capitalizing on recent technical advances and combining tract-tracing, high-resolution fMRI, optogenetics and mathematical modeling hold the promise of a much improved understanding of lamina-constrained mechanisms of neural computation and cognition. However, because inter-areal interactions involve cortical layers that have been the target of important evolutionary changes in the primate lineage, these investigations will need to include human and non-human primate comparisons.
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Modelos Neurológicos , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiología , Animales , Corteza Cerebral/anatomía & histología , Corteza Cerebral/fisiología , Conectoma/métodos , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Multi-modal neuroimaging projects such as the Human Connectome Project (HCP) and UK Biobank are advancing our understanding of human brain architecture, function, connectivity, and their variability across individuals using high-quality non-invasive data from many subjects. Such efforts depend upon the accuracy of non-invasive brain imaging measures. However, 'ground truth' validation of connectivity using invasive tracers is not feasible in humans. Studies using nonhuman primates (NHPs) enable comparisons between invasive and non-invasive measures, including exploration of how "functional connectivity" from fMRI and "tractographic connectivity" from diffusion MRI compare with long-distance connections measured using tract tracing. Our NonHuman Primate Neuroimaging & Neuroanatomy Project (NHP_NNP) is an international effort (6 laboratories in 5 countries) to: (i) acquire and analyze high-quality multi-modal brain imaging data of macaque and marmoset monkeys using protocols and methods adapted from the HCP; (ii) acquire quantitative invasive tract-tracing data for cortical and subcortical projections to cortical areas; and (iii) map the distributions of different brain cell types with immunocytochemical stains to better define brain areal boundaries. We are acquiring high-resolution structural, functional, and diffusion MRI data together with behavioral measures from over 100 individual macaques and marmosets in order to generate non-invasive measures of brain architecture such as myelin and cortical thickness maps, as well as functional and diffusion tractography-based connectomes. We are using classical and next-generation anatomical tracers to generate quantitative connectivity maps based on brain-wide counting of labeled cortical and subcortical neurons, providing ground truth measures of connectivity. Advanced statistical modeling techniques address the consistency of both kinds of data across individuals, allowing comparison of tracer-based and non-invasive MRI-based connectivity measures. We aim to develop improved cortical and subcortical areal atlases by combining histological and imaging methods. Finally, we are collecting genetic and sociality-associated behavioral data in all animals in an effort to understand how genetic variation shapes the connectome and behavior.
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Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Internacionalidad , Neuroanatomía/métodos , Neuroimagen/métodos , Animales , Callithrix , Conectoma/métodos , Conectoma/tendencias , Humanos , Procesamiento de Imagen Asistido por Computador/tendencias , Macaca mulatta , Neuroanatomía/tendencias , Neuroimagen/tendencias , Primates , Especificidad de la EspecieRESUMEN
Perturbation of the developmental refinement of the corticospinal (CS) pathway leads to motor disorders. While non-primate developmental refinement is well documented, in primates invasive investigations of the developing CS pathway have been confined to neonatal and postnatal stages when refinement is relatively modest. Here, we investigated the developmental changes in the distribution of CS projection neurons in cynomolgus monkey (Macaca fascicularis). Injections of retrograde tracer at cervical levels of the spinal cord at embryonic day (E) 95 and E105 show that: (i) areal distribution of back-labeled neurons is more extensive than in the neonate and dense labeling is found in prefrontal, limbic, temporal, and occipital cortex; (ii) distributions of contralateral and ipsilateral projecting CS neurons are comparable in terms of location and numbers of labeled neurons, in contrast to the adult where the contralateral projection is an order of magnitude higher than the ipsilateral projection. Findings from one largely restricted injection suggest a hitherto unsuspected early innervation of the gray matter. In the fetus there was in addition dense labeling in the central nucleus of the amygdala, the hypothalamus, the subthalamic nucleus, and the adjacent region of the zona incerta, subcortical structures with only minor projections in the adult control.
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Encéfalo/citología , Encéfalo/embriología , Neuronas/fisiología , Tractos Piramidales/citología , Tractos Piramidales/embriología , Animales , Axones/fisiología , Macaca fascicularis , Vías Nerviosas/citología , Vías Nerviosas/embriología , Técnicas de Trazados de Vías NeuroanatómicasRESUMEN
There is an extensive modification of the functional organization of the brain in the congenital blind human, although there is little understanding of the structural underpinnings of these changes. The visual system of macaque has been extensively characterized both anatomically and functionally. We have taken advantage of this to examine the influence of congenital blindness in a macaque model of developmental anophthalmia. Developmental anophthalmia in macaque effectively removes the normal influence of the thalamus on cortical development leading to an induced "hybrid cortex (HC)" combining features of primary visual and extrastriate cortex. Here we show that retrograde tracers injected in early visual areas, including HC, reveal a drastic reduction of cortical projections of the reduced lateral geniculate nucleus. In addition, there is an important expansion of projections from the pulvinar complex to the HC, compared to the controls. These findings show that the functional consequences of congenital blindness need to be considered in terms of both modifications of the interareal cortical network and the ascending visual pathways.
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Ceguera/congénito , Cuerpos Geniculados/fisiopatología , Corteza Visual/fisiopatología , Vías Visuales/fisiología , Animales , Ceguera/fisiopatología , Mapeo Encefálico/métodos , Femenino , Cuerpos Geniculados/fisiología , Macaca fascicularis , Masculino , Neuronas/fisiología , Tálamo/fisiología , Tálamo/fisiopatología , Corteza Visual/fisiología , Vías Visuales/fisiopatologíaRESUMEN
Maximum likelihood difference scaling was used to measure suprathreshold contrast response difference scales for low-frequency Gabor patterns, modulated along luminance and L-M color directions in normal, protanomalous, and deuteranomalous observers. Based on a signal-detection model, perceptual scale values, parameterized as $ d^\prime $d', were estimated by maximum likelihood. The difference scales were well fit by a Michaelis-Menten model, permitting estimates of response and contrast gain parameters for each subject. Anomalous observers showed no significant differences in response or contrast gain from normal observers for luminance contrast. For chromatic modulation, however, anomalous observers displayed higher contrast and lower response gain compared to normal observers. These effects cannot be explained by simple pigment shift models, and they support a compensation mechanism to optimize the mapping of the input contrast range to the neural response range. A linear relation between response and contrast gain suggests a neural trade-off between them.
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Dopamine is thought to directly influence the neurophysiological mechanisms of both performance monitoring and cognitive control-two processes that are critically linked in the production of adapted behaviour. Changing dopamine levels are also thought to induce cognitive changes in several neurological and psychiatric conditions. But the working model of this system as a whole remains untested. Specifically, although many researchers assume that changing dopamine levels modify neurophysiological mechanisms and their markers in frontal cortex, and that this in turn leads to cognitive changes, this causal chain needs to be verified. Using longitudinal recordings of frontal neurophysiological markers over many months during progressive dopaminergic lesion in non-human primates, we provide data that fail to support a simple interaction between dopamine, frontal function, and cognition. Feedback potentials, which are performance-monitoring signals sometimes thought to drive successful control, ceased to differentiate feedback valence at the end of the lesion, just before clinical motor threshold. In contrast, cognitive control performance and beta oscillatory markers of cognitive control were unimpaired by the lesion. The differing dynamics of these measures throughout a dopamine lesion suggests they are not all driven by dopamine in the same way. These dynamics also demonstrate that a complex non-linear set of mechanisms is engaged in the brain in response to a progressive dopamine lesion. These results question the direct causal chain from dopamine to frontal physiology and on to cognition. They imply that biomarkers of cognitive functions are not directly predictive of dopamine loss.
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Cognición , Dopamina/fisiología , Corteza Prefrontal/fisiopatología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Biomarcadores , Electroencefalografía , Potenciales Evocados , Femenino , Macaca mulatta , Masculino , Motivación , Corteza Prefrontal/efectos de los fármacos , Análisis y Desempeño de TareasRESUMEN
Mammals show a wide range of brain sizes, reflecting adaptation to diverse habitats. Comparing interareal cortical networks across brains of different sizes and mammalian orders provides robust information on evolutionarily preserved features and species-specific processing modalities. However, these networks are spatially embedded, directed, and weighted, making comparisons challenging. Using tract tracing data from macaque and mouse, we show the existence of a general organizational principle based on an exponential distance rule (EDR) and cortical geometry, enabling network comparisons within the same model framework. These comparisons reveal the existence of network invariants between mouse and macaque, exemplified in graph motif profiles and connection similarity indices, but also significant differences, such as fractionally smaller and much weaker long-distance connections in the macaque than in mouse. The latter lends credence to the prediction that long-distance cortico-cortical connections could be very weak in the much-expanded human cortex, implying an increased susceptibility to disconnection syndromes such as Alzheimer disease and schizophrenia. Finally, our data from tracer experiments involving only gray matter connections in the primary visual areas of both species show that an EDR holds at local scales as well (within 1.5 mm), supporting the hypothesis that it is a universally valid property across all scales and, possibly, across the mammalian class.
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Corteza Cerebral/fisiología , Conectoma/métodos , Modelos Neurológicos , Red Nerviosa/fisiología , Vías Nerviosas/fisiología , Algoritmos , Animales , Corteza Cerebral/anatomía & histología , Simulación por Computador , Femenino , Humanos , Macaca , Masculino , Ratones , Modelos Anatómicos , Red Nerviosa/anatomía & histología , Vías Nerviosas/anatomía & histología , Especificidad de la EspecieRESUMEN
There is little understanding of the structural underpinnings of the functional reorganization of the cortex in the congenitally blind human. Taking advantage of the extensive characterization of the macaque visual system, we examine in macaque the influence of congenital blindness resulting from the removal of the retina during in utero development. This effectively removes the normal influence of the thalamus on cortical development leading to an induced hybrid cortex (HC) combining features of primary visual and extrastriate cortex. Retrograde tracers injected in HC reveal a local, intrinsic connectivity characteristic of higher order areas and show that the HC receives a uniquely strong, purely feedforward projection from striate cortex but no ectopic inputs, except from subiculum, and entorhinal cortex. Statistical modeling of quantitative connectivity data shows that HC is relatively high in the cortical hierarchy and receives a reinforced input from ventral stream areas while the overall organization of the functional streams are conserved. The directed and weighted anophthalmic cortical graph from the present study can be used to construct dynamic and structural models. These findings show how the sensory periphery governs cortical phenotype and reveal the importance of developmental arealization for understanding the functional reorganization in congenital blindness.
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Mapeo Encefálico , Amaurosis Congénita de Leber/patología , Neuronas/fisiología , Corteza Visual/patología , Corteza Visual/fisiopatología , Vías Visuales/fisiopatología , Animales , Modelos Animales de Enfermedad , Macaca fascicularis , Red Nerviosa/patología , Pentobarbital/metabolismoRESUMEN
Surface color appearance depends on both local surface chromaticity and global context. How are these inter-dependencies supported by cortical networks? Combining functional imaging and psychophysics, we examined if color from long-range filling-in engages distinct pathways from responses caused by a field of uniform chromaticity. We find that color from filling-in is best classified and best correlated with appearance by two dorsal areas, V3A and V3B/KO. In contrast, a field of uniform chromaticity is best classified by ventral areas hV4 and LO. Dynamic causal modeling revealed feedback modulation from area V3A to areas V1 and LO for filling-in, contrasting with feedback from LO modulating areas V1 and V3A for a matched uniform chromaticity. These results indicate a dorsal stream role in color filling-in via feedback modulation of area V1 coupled with a cross-stream modulation of ventral areas suggesting that local and contextual influences on color appearance engage distinct neural networks.
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Mapeo Encefálico/métodos , Percepción de Color/fisiología , Sensibilidad de Contraste/fisiología , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Corteza Visual/fisiología , Adulto , Femenino , Humanos , Masculino , Reconocimiento de Normas Patrones Automatizadas/métodos , Máquina de Vectores de Soporte , Corteza Visual/diagnóstico por imagen , Adulto JovenRESUMEN
UNLABELLED: Tractography based on diffusion MRI offers the promise of characterizing many aspects of long-distance connectivity in the brain, but requires quantitative validation to assess its strengths and limitations. Here, we evaluate tractography's ability to estimate the presence and strength of connections between areas of macaque neocortex by comparing its results with published data from retrograde tracer injections. Probabilistic tractography was performed on high-quality postmortem diffusion imaging scans from two Old World monkey brains. Tractography connection weights were estimated using a fractional scaling method based on normalized streamline density. We found a correlation between log-transformed tractography and tracer connection weights of r = 0.59, twice that reported in a recent study on the macaque. Using a novel method to estimate interareal connection lengths from tractography streamlines, we regressed out the distance dependence of connection strength and found that the correlation between tractography and tracers remains positive, albeit substantially reduced. Altogether, these observations provide a valuable, data-driven perspective on both the strengths and limitations of tractography for analyzing interareal corticocortical connectivity in nonhuman primates and a framework for assessing future tractography methodological refinements objectively. SIGNIFICANCE STATEMENT: Tractography based on diffusion MRI has great potential for a variety of applications, including estimation of comprehensive maps of neural connections in the brain ("connectomes"). Here, we describe methods to assess quantitatively tractography's performance in detecting interareal cortical connections and estimating connection strength by comparing it against published results using neuroanatomical tracers. We found the correlation of tractography's estimated connection strengths versus tracer to be twice that of a previous study. Using a novel method for calculating interareal cortical distances, we show that tractography-based estimates of connection strength have useful predictive power beyond just interareal separation. By freely sharing these methods and datasets, we provide a valuable resource for future studies in cortical connectomics.
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Corteza Cerebral/diagnóstico por imagen , Imagen de Difusión Tensora , Fibras Nerviosas/fisiología , Red Nerviosa/diagnóstico por imagen , Animales , Mapeo Encefálico , Cercopithecidae , Conectoma , Lateralidad Funcional , Procesamiento de Imagen Asistido por Computador , Modelos Neurológicos , Red Nerviosa/fisiologíaRESUMEN
Frontal beta oscillations are associated with top-down control mechanisms but also change over time during a task. It is unclear whether change over time represents another control function or a neural instantiation of vigilance decrements over time, the time-on-task effect. We investigated how frontal beta oscillations are modulated by cognitive control and time. We used frontal chronic electrocorticography in monkeys performing a trial-and-error task, comprising search and repetition phases. Specific beta oscillations in the delay period of each trial were modulated by task phase and adaptation to feedback. Beta oscillations in this same period showed a significant within-session change. These separate modulations of beta oscillations did not interact. Crucially, and in contrast to previous investigations, we examined modulations of beta around spontaneous pauses in work. After pauses, the beta power modulation was reset and the cognitive control effect was maintained. Cognitive performance was also maintained whereas behavioral signs of fatigue continued to increase. We propose that these beta oscillations reflect multiple factors contributing to the regulation of cognitive control. Due to the effect of pauses, the time-sensitive factor cannot be a neural correlate of time-on-task but may reflect attentional effort.
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Ritmo beta , Cognición/fisiología , Función Ejecutiva/fisiología , Lóbulo Frontal/fisiología , Animales , Atención/fisiología , Electrocorticografía , Femenino , Macaca mulatta , Masculino , Solución de Problemas/fisiología , Factores de TiempoRESUMEN
Luminance contrast is a fundamental visual cue. Using a dedicated neuroimaging framework, we sought to characterize typical Blood Oxygen Level Dependent (BOLD) responses in two subcortical regions, the superior colliculus (SC) and the lateral geniculate nucleus (LGN), and V1, the primary visual cortex area, and how they change over the lifespan. For imaging subcortical activity related to luminance contrast modulation, specific measurements were introduced to rule out possible signal contamination by cardiovascular activity and vascular alterations with age that could hamper the BOLD signal interpretation. Clearly, BOLD responses increased in these three regions with luminance contrast, with a statistically significant diminution in LGN and V1 for older compared to younger participants, while basal perfusion remained unchanged. Additionally, perceptual responses, as assessed with psychophysical experiments, were highly correlated to BOLD measures in the three studied regions. Taken together, fMRI and psychophysics results indicate an alteration of luminance contrast processing with normal aging. Based on this knowledge we can better recognize when age-related brain changes vary from these expectations especially during neurodegenerative diseases progression where the functioning of subcortical structures is altered. The proposed fMRI-physchophysics methodology allows performing such investigation.
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Envejecimiento , Encéfalo/fisiología , Sensibilidad de Contraste/fisiología , Adulto , Anciano , Mapeo Encefálico , Femenino , Cuerpos Geniculados/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Psicofísica , Colículos Superiores/fisiología , Corteza Visual/fisiologíaRESUMEN
Color varies along dimensions of lightness, hue, and chroma. We used maximum likelihood conjoint measurement to investigate how lightness and chroma influence color judgments. Observers judged lightness and chroma of stimuli that varied in both dimensions in a paired-comparison task. We modeled how changes in one dimension influenced judgment of the other. An additive model best fit the data in all conditions except for judgment of red chroma where there was a small but significant interaction. Lightness negatively contributed to perception of chroma for red, blue, and green hues but not for yellow. The method permits quantification of lightness and chroma contributions to color appearance.
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Percepción de Color/efectos de la radiación , Luz , Modelos Biológicos , Adulto , Sensibilidad de Contraste/efectos de la radiación , Femenino , Humanos , Funciones de Verosimilitud , Masculino , Estimulación Luminosa , Psicofísica , Adulto JovenRESUMEN
The canonical application of multidimensional scaling (MDS) methods has been to color dissimilarities, visualizing these as distances in a low-dimensional space. Some questions remain: How well can the locations of stimuli in color space be recovered when data are sparse, and how well can systematic individual variations in perceptual scaling be distinguished from stochastic noise? We collected triadic comparisons for saturated and desaturated sets of Natural Color System samples, each set forming an approximate hue circle. Maximum likelihood MDS was used to reconstruct the configuration of stimuli more accurately than the standard "vote-count" approach. Individual departures from the consensus response pattern were minor, but repeated across stimulus sets, and identifiable as variations in the salience of color-space axes. No gender differences could be discerned, contrary to earlier results.
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Pruebas de Percepción de Colores/métodos , Percepción Espacial/fisiología , Algoritmos , Humanos , Funciones de Verosimilitud , Estimulación Luminosa , Análisis de Componente Principal , Adulto JovenRESUMEN
We investigated the influence of interareal distance on connectivity patterns in a database obtained from the injection of retrograde tracers in 29 areas distributed over six regions (occipital, temporal, parietal, frontal, prefrontal, and limbic). One-third of the 1,615 pathways projecting to the 29 target areas were reported only recently and deemed new-found projections (NFPs). NFPs are predominantly long-range, low-weight connections. A minimum dominating set analysis (a graph theoretic measure) shows that NFPs play a major role in globalizing input to small groups of areas. Randomization tests show that (i) NFPs make important contributions to the specificity of the connectivity profile of individual cortical areas, and (ii) NFPs share key properties with known connections at the same distance. We developed a similarity index, which shows that intraregion similarity is high, whereas the interregion similarity declines with distance. For area pairs, there is a steep decline with distance in the similarity and probability of being connected. Nevertheless, the present findings reveal an unexpected binary specificity despite the high density (66%) of the cortical graph. This specificity is made possible because connections are largely concentrated over short distances. These findings emphasize the importance of long-distance connections in the connectivity profile of an area. We demonstrate that long-distance connections are particularly prevalent for prefrontal areas, where they may play a prominent role in large-scale communication and information integration.
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Mapeo Encefálico , Corteza Cerebral , Bases de Datos Factuales , Red Nerviosa , Animales , Corteza Cerebral/anatomía & histología , Corteza Cerebral/fisiología , Macaca , Red Nerviosa/anatomía & histología , Red Nerviosa/fisiologíaRESUMEN
Information processing in the medial frontal cortex is often said to be modulated in pathological conditions or by individual traits. This has been observed in neuroimaging and event-related potential studies centered in particular on midcingulate cortex (MCC) functions. This region of the brain is characterized by considerable intersubject morphological variability. Whereas in a subset of hemispheres only a single cingulate sulcus (cgs) is present, a majority of hemispheres exhibit an additional sulcus referred to as the paracingulate sulcus (pcgs). The present functional magnetic resonance imaging study defined the relationship between the local morphology of the cingulate/paracingulate sulcal complex and feedback-related activity. Human subjects performed a trial-and-error learning task in which they had to discover which one of a set of abstract stimuli was the best option. Feedback was provided by means of fruit juice, as in studies with monkeys. A subject-by-subject analysis revealed that the feedback-related activity during exploration was systematically located in the cgs when no pcgs was observed, but in the pcgs when the latter sulcus was present. The activations had the same functional signature when located in either the cgs or in the pcgs, confirming that both regions were homologues. Together, the results show that the location of feedback-related MCC activity can be predicted from morphological features of the cingulate/paracingulate complex.
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Retroalimentación Fisiológica/fisiología , Giro del Cíngulo/anatomía & histología , Aprendizaje/fisiología , Solución de Problemas/fisiología , Adulto , Mapeo Encefálico , Femenino , Giro del Cíngulo/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , MasculinoRESUMEN
The spatial selectivity of the watercolor effect (WCE) was assessed by measuring its strength as a function of the luminance contrast of its inducing contours for different spatial configurations, using a maximum likelihood scaling procedure. The approach has previously been demonstrated to provide an efficient method for investigating the WCE as well as other perceptual dimensions. We show that the strength is narrowly tuned to the width of the contour, that it is optimal when its pair of inducing contours are of equal width, and that the strength can be increased by varying the overall size of the stimulus when the width of the inducing contour is not optimal. The results support a neural substrate that has characteristics not unlike double-opponent, color-luminance cells observed in cortical area V1.
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Percepción de Color/fisiología , Ilusiones Ópticas/fisiología , Adulto , Percepción de Forma/fisiología , Humanos , Funciones de Verosimilitud , Estimulación Luminosa , PsicofísicaRESUMEN
The retinal circadian clock is crucial for optimal regulation of retinal physiology and function, yet its cellular location in mammals is still controversial. We used laser microdissection to investigate the circadian profiles and phase relations of clock gene expression and Period gene induction by light in the isolated outer (rods/cones) and inner (inner nuclear and ganglion cell layers) regions in wild-type and melanopsin-knockout (Opn 4 (-/-) ) mouse retinas. In the wild-type mouse, all clock genes are rhythmically expressed in the photoreceptor layer but not in the inner retina. For clock genes that are rhythmic in both retinal compartments, the circadian profiles are out of phase. These results are consistent with the view that photoreceptors are a potential site of circadian rhythm generation. In mice lacking melanopsin, we found an unexpected loss of clock gene rhythms and of the photic induction of Per1-Per2 mRNAs only in the outer retina. Since melanopsin ganglion cells are known to provide a feed-back signalling pathway for photic information to dopaminergic cells, we further examined dopamine (DA) synthesis in Opn 4 (-/-) mice. The lack of melanopsin prevented the light-dependent increase of tyrosine hydroxylase (TH) mRNA and of DA and, in constant darkness, led to comparatively high levels of both components. These results suggest that melanopsin is required for molecular clock function and DA regulation in the retina, and that Period gene induction by light is mediated by a melanopsin-dependent, DA-driven signal acting on retinal photoreceptors.
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Relojes Circadianos , Dopamina/metabolismo , Regulación de la Expresión Génica , Luz , Células Fotorreceptoras de Vertebrados/metabolismo , Retina/metabolismo , Opsinas de Bastones/fisiología , Animales , Ritmo Circadiano , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Circadianas Period/genética , Opsinas de Bastones/genética , Transducción de Señal , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
The watercolor effect is a long-range, assimilative, filling-in phenomenon induced by a pair of distant, wavy contours of different chromaticities. Here, we measured joint influences of the contour frequency and amplitude and the luminance of the interior contour on the strength of the effect. Contour pairs, each enclosing a circular region, were presented with two of the dimensions varying independently across trials (luminance/frequency, luminance/amplitude, frequency/amplitude) in a conjoint measurement paradigm (Luce & Tukey, 1964). In each trial, observers judged which of the stimuli evoked the strongest fill-in color. Control stimuli were identical except that the contours were intertwined and generated little filling-in. Perceptual scales were estimated by a maximum likelihood method (Ho, Landy, & Maloney, 2008). An additive model accounted for the joint contributions of any pair of dimensions. As shown previously using difference scaling (Devinck & Knoblauch, 2012), the strength increases with luminance of the interior contour. The strength of the phenomenon was nearly independent of the amplitude of modulation of the contour but increased with its frequency up to an asymptotic level. On average, the strength of the effect was similar along a given dimension regardless of the other dimension with which it was paired, demonstrating consistency of the underlying estimated perceptual scales.