Functional imaging of visuospatial processing in Alzheimer's disease

Alzheimer's disease (AD) is known to cause a variety of disturbances of higher visual functions that are closely related to the neuropathological changes. Visual association areas are more affected than primary visual cortex. Additionally, there is evidence from neuropsychological and imaging studies during rest or passive visual stimulation that the occipitotemporal pathway is less affected than the parietal pathway. Our goal was to investigate functional activation patterns during active visuospatial processing in AD patients and the impact of local cerebral atrophy on the strength of functional activation. Fourteen AD patients and fourteen age-matched controls were measured with functional magnetic resonance imaging (fMRI) while they performed an angle discrimination task. Both groups revealed overlapping networks engaged in angle discrimination including the superior parietal lobule (SPL), frontal and occipitotemporal (OTC) cortical regions, primary visual cortex, basal ganglia, and thalamus. The most pronounced differences between the two groups were found in the SPL (more activity in controls) and OTC (more activity in patients). The differences in functional activation between the AD patients and controls were partly explained by the differences in individual SPL atrophy. These results indicate that parietal dysfunction in mild to moderate AD is compensated by recruitment of the ventral visual pathway. We furthermore suggest that local cerebral atrophy should be considered as a covariate in functional imaging studies of neurodegenerative disorders.

Understanding Neural Maps with Topographica

The biological function of neurons can often be understood only in the context of large, highly interconnected networks. These networks typically form two-dimensional topographic maps, such as the retinotopic maps in mammalian visual cortex. Computational simulations of these areas have led to valuable insights about how cortical topography develops and functions, but further progress has been hindered due to the lack of appropriate simulation tools. This paper introduces the freely available Topographica maplevel simulator, originally developed at the University of Texas at Austin and now maintained at the University of Edinburgh, UK. Topographica is designed to make large-scale, detailed models practical. The goal is to allow neuroscientists and computational scientists to work together to understand how topographic maps and their connections organize and operate. This understanding will be crucial for integrating experimental observations into a comprehensive theory of brain function.

Chronic administration of methylphenidate produces neurophysiological and behavioral sensitization.

The electrophysiological properties of acute and chronic methylphenidate (MPD) on neurons of the prefrontal cortex (PFC) and caudate nucleus (CN) have not been studied in awake, freely behaving animals. The present study was designed to investigate the dose-response effects of MPD on sensory evoked potentials recorded from the PFC and CN in freely behaving rats previously implanted with permanent electrodes, as well as their behavioral (locomotor) activities. On experimental day 1, locomotor behavior of rats was recorded for 2 h post-saline injection, and sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10 mg/kg, i.p., MPD administration. Animals were injected for the next five days with daily 2.5 mg/kg MPD to elicit behavioral sensitization. Locomotor recording was resumed on experimental days 2 and 6 after the MPD maintenance dose followed by 3 days of washout. On experimental day 10, rats were connected again to the electrophysiological recording system and rechallenged with saline and the identical MPD doses as on experimental day 1. On experimental day 11, rat's locomotor recording was resumed before and after 2.5 mg/kg MPD administration. Behavioral results showed that repeated administration of MPD induced behavioral sensitization. Challenge doses (0.6, 2.5, and 10.0 mg/kg) of MPD on experimental day 1 elicited dose-response attenuation in the response amplitude of the average sensory evoked field potential components recorded from the PFC and CN. Chronic MPD administration resulted in attenuation of the PFC's baseline recorded on experimental day 10, while the same treatment did not modulate the baseline recorded from the CN. Treatment of MPD on experimental day 10 resulted in further decrease of the average sensory evoked response compared to that obtained on experimental day 1. This observation of further decrease in the electrophysiological responses after chronic administration of MPD suggests that the sensory evoked responses on experimental day 10 represent neurophysiological sensitization. Moreover, two different response patterns were obtained from PFC and CN following chronic methylphenidate administration. In PFC, the baseline and effect of methylphenidate expressed electrophysiological sensitization on experimental day 10, while recording from CN did not exhibit any electrophysiological sensitization.

Modulation of orientation-selective neurons by motion: when additive, when multiplicative?

The recurrent interaction among orientation-selective neurons in the primary visual cortex (V1) is suited to enhance contours in a noisy visual scene. Motion is known to have a strong pop-up effect in perceiving contours, but how motion-sensitive neurons in V1 support contour detection remains vastly elusive. Here we suggest how the various types of motion-sensitive neurons observed in V1 should be wired together in a micro-circuitry to optimally extract contours in the visual scene. Motion-sensitive neurons can be selective about the direction of motion occurring at some spot or respond equally to all directions (pandirectional). We show that, in the light of figure-ground segregation, direction-selective motion neurons should additively modulate the corresponding orientation-selective neurons with preferred orientation orthogonal to the motion direction. In turn, to maximally enhance contours, pandirectional motion neurons should multiplicatively modulate all orientation-selective neurons with co-localized receptive fields. This multiplicative modulation amplifies the local V1-circuitry among co-aligned orientation-selective neurons for detecting elongated contours. We suggest that the additive modulation by direction-specific motion neurons is achieved through synaptic projections to the somatic region, and the multiplicative modulation by pandirectional motion neurons through projections to the apical region of orientation-specific pyramidal neurons. For the purpose of contour detection, the V1-intrinsic integration of motion information is advantageous over a downstream integration as it exploits the recurrent V1-circuitry designed for that task.

Simulating Cortical Development as a Self Constructing Process: A Novel Multi-Scale Approach Combining Molecular and Physical Aspects

Current models of embryological development focus on intracellular processes such as gene expression and protein networks, rather than on the complex relationship between subcellular processes and the collective cellular organization these processes support. We have explored this collective behavior in the context of neocortical development, by modeling the expansion of a small number of progenitor cells into a laminated cortex with layer and cell type specific projections. The developmental process is steered by a formal language analogous to genomic instructions, and takes place in a physically realistic three-dimensional environment. A common genome inserted into individual cells control their individual behaviors, and thereby gives rise to collective developmental sequences in a biologically plausible manner. The simulation begins with a single progenitor cell containing the artificial genome. This progenitor then gives rise through a lineage of offspring to distinct populations of neuronal precursors that migrate to form the cortical laminae. The precursors differentiate by extending dendrites and axons, which reproduce the experimentally determined branching patterns of a number of different neuronal cell types observed in the cat visual cortex. This result is the first comprehensive demonstration of the principles of self-construction whereby the cortical architecture develops. In addition, our model makes several testable predictions concerning cell migration and branching mechanisms.

Contrast Formation in Kelvin Probe Force Microscopy of Single π-Conjugated Molecules

We report the contrast formation in the local contact potential difference (LCPD) measured by Kelvin probe force microscopy (KPFM) on single charge-transfer complexes (CTCs) on a NaCl bilayer on Cu(111). At different tip heights, we found quantitatively different LCPD contrasts that characterize different properties of the molecule. In the small distance regime, the tip penetrates the electron density of the molecule, and the contrast is related to the size and topography of the electron shell of the molecule. For larger distances, the LCPD contrast corresponds to the electrostatic field above the molecule. However, in the medium-distance regime, that is, for tip heights similar to the size of the molecule, the nonspherical distribution of π- and σ-electrons often conceals the effect of the partial charges within the molecule. Only for large distances does the LCPD map converge toward the simple field of a dipole for a polar molecule.

Organization of the inferotemporal cortex in the macaque monkey: Connections of areas PITv and CITvp

Visual cortex of macaque monkeys consists of a large number of cortical areas that span the occipital, parietal, temporal, and frontal lobes and occupy more than half of cortical surface. Although considerable progress has been made in understanding the contributions of many occipital areas to visual perceptual processing, much less is known concerning the specific functional contributions of higher areas in the temporal and frontal lobes. Previous behavioral and electrophysiological investigations have demonstrated that the inferotemporal cortex (IT) is essential to the animal's ability to recognize and remember visual objects. While it is generally recognized that IT consists of a number of anatomically and functionally distinct visual-processing areas, there remains considerable controversy concerning the precise number, size, and location of these areas. Therefore, the precise delineation of the cortical subdivisions of inferotemporal cortex is critical for any significant progress in the understanding of the specific contributions of inferotemporal areas to visual processing. In this study, anterograde and/or retrograde neuroanatomical tracers were injected into two visual areas in the ventral posterior and central portions of IT (areas PITv and CITvp) to elucidate the corticocortical connections of these areas with well known areas of occipital cortex and with less well understood regions of inferotemporal cortex. The locations of injection sites and the delineation of the borders of many occipital areas were aided by the pattern of interhemispheric connections, revealed following callosal transection and subsequent labeling with HRP. The resultant patterns of connections were represented on two-dimensional computational (CARET) and manual cortical maps and the laminar characteristics and density of the projection fields were quantified. The laminar and density features of these corticocortical connections demonstrate thirteen anatomically distinct subdivisions or areas distributed within the superior temporal sulcus and across the inferotemporal gyrus. These results serve to refine previous descriptions of inferotemporal areas, validate recently identified areas, and provide a new description of the hierarchical relationships among occipitotemporal cortical areas in macaques. ^

A new method to analyse the perception of size

In living bodies, the correct perceptual representation of size constancy requires that an object's size appear the same when it changes its location with respect to the observer. At the same time, it is necessary that objects at different locations appear to be the same size if they are. In order to do that, the perceptual system must recover from the stimuli impinging on the individual, from the light falling on the retina, a representation of the relative sizes of objects in the environment. Moreover, at the same time, image perception is related to another type of phenomena. It corresponds to the well known perceptual illusions. To analyze this facts, we propose a system based on a particular arrays of receptive points composed by optical fibers and dummy fibers. The structure is based on the first layers of the mammalians primary visual cortex. At that part of the brain, the neurons located at certain columns, respond to particular directions. This orientation changes in a systematic way as one moves across the cortical surface. In our case, the signals from the above-mentioned array are analyzed and information concerning orientation and size of a particular line is obtained. With this system, the Muelle-Lyer illusion has been studied and some rules to interpret why equal length objects give rise to different interpretations are presented.

Desarrollo de capacidades para el liderazgo en proyectos de desarrollo rural. Aplicación a comunidades Aymaras

Los proyectos de desarrollo en el medio rural han cambiado en las últimas décadas, desde un enfoque tecnocrático y descendente, que resultó insuficiente, a otro que otorga un papel principal a las personas locales. En este contexto, los nuevos modelos de planificación y gestión de los proyectos de desarrollo a menudo incluyen entre sus objetivos el desarrollo de las capacidades locales y el liderazgo, dedicándose a ellos anualmente billones de dólares. Ambos conceptos son considerados elementos indispensables para aumentar la sostenibilidad de las acciones desde un enfoque endógeno, lo que genera un gran interés tanto desde el ámbito científico como en los debates y objetivos de los organismos internacionales. Sin embargo no existe un consenso sobre el marco conceptual del desarrollo de capacidades ni sobre las metodologías adecuadas para evaluarlo. Por otra parte, en el caso del desarrollo de liderazgo, la mayoría de los estudios e investigaciones se han centrado en entornos empresariales, siendo escasos los trabajos centrados en el ámbito rural. En dicho contexto, la complejidad se incrementa debido a que a menudo la autoridad y poder de los líderes no están dados por puestos formales, sino por relaciones sociales y vínculos de confianza. Esta investigación presenta una primera fase conceptual, que aborda el marco teórico, analizando y clarificando los conceptos de desarrollo de capacidades, competencias y liderazgo en el contexto de los proyectos de desarrollo rural. Así mismo, en esta fase se clasifican los principales instrumentos para evaluar el desarrollo de capacidades, para así definir las variables que conforman el constructo de capacidades. Además se determina la multidimensionalidad del concepto de capacidades y por ello la conveniencia de abordarlo a nivel individual y colectivo. También se analizan los distintos estilos de liderazgo para llegar a una definición propia de desarrollo de capacidades y de liderazgo adaptadas al medio rural. El marco teórico anterior permite sentar, en una segunda fase de la investigación, las bases científicas del modelo que se propone: el modelo DCL de Desarrollo de Capacidades para el Liderazgo en los proyectos de desarrollo rural. Este modelo incorpora elementos del marco conceptual Working With People (Cazorla et al., 2013), fruto de 25 años de experiencia en el ámbito de la planificación de proyectos de desarrollo rural desde el grupo de investigación GESPLAN de la Universidad Politécnica de Madrid. El modelo DCL integra metodologías cuantitativas y cualitativas y una doble escala de análisis para promover y evaluar el desarrollo de capacidades en la población local desde tres componentes: técnico-empresarial, relacional y contextual. Además el modelo DCL incorpora un proceso metodológico para poder integrar el seguimiento y la evaluación de las capacidades a lo largo del ciclo del proyecto. Finalmente, en una fase de aplicación, se acomete la validación del modelo DCL a través del caso de estudio de un proyecto de desarrollo con una organización de mujeres artesanas de comunidades aymaras de Puno (Perú). Este proyecto, que incorpora el marco conceptual WWP, integra 5 años de experiencia con comunidades aymaras desde el grupo de investigación GESPLAN. La aplicación muestra cómo el modelo DCL permite evaluar el desarrollo de capacidades para el liderazgo. Así mismo, la incorporación de los aprendizajes tras las evaluaciones de desarrollo de capacidades permite reorientar las acciones del proyecto para mejorar su planificación y gestión y producir un verdadero empoderamiento y liderazgo de la organización local. Lo anterior se traduce en un aumento de la sostenibilidad del proyecto y de la resiliencia social de la organización. ABSTRACT Development projects in rural areas have changed in recent decades, from a technocratic and top-down approach, which proved insufficient, to another that gives a major role to local people. In this context, the new models of planning and management of development projects often include among their objectives the development of local capacities and leadership and engage billions of dollars annually. Both concepts are considered essential for enhancing the sustainability of the actions from an endogenous approach, generating great interest both from the scientific field and in the debates and objectives of international organizations. However there is no consensus on the conceptual framework of capacity development and on appropriate methodologies to evaluate it. Moreover, in the case of leadership development, most of the studies and research have focused on business environments, with few studies focusing on rural areas. In this context, the complexity is increased because often the authority and power of the leaders are not given for formal positions, but by social relationships and bonds of trust. This research presents an initial conceptual phase, which addresses the theoretical framework, analyzing and clarifying the concepts of capacity development, competencies and leadership in the context of rural development projects. Also, at this stage the main instruments to assess capacity development are classified so as to define the variables that shape the capacity construct. Besides the multidimensionality of the concept of capacity is determined and therefore the convenience of addressing it at an individual and colective level. Different leadership styles are also analyzed to propose a definition of capacity development and leadership adapted to the rural environment. The above theoretical framework allows to set, in a second research phase, the scientific basis of the proposed model: the model DCL of Capacity Development for Leadership in rural development projects. This model incorporates elements of the conceptual framework Working With People (Cazorla et al., 2013), the result of 25 years of experience in the field of project planning for rural development from the research group GESPLAN of the Technical University of Madrid. The DCL model integrates quantitative and qualitative methodologies and a double scale of analysis to promote and evaluate capacity development in the local population from three components: technical-entrepreneurial, relational and contextual. Besides the DCL model incorporates a methodological process to integrate monitoring and evaluation of capacities throughout the project cycle. Finally, in an application phase, DCL model validation is undertaken through the case study of a development project with an organization of women artisans of Aymara communities in Puno (Peru). This project, that incorporates the WWP conceptual framework, integrates 5 years of experience with Aymara communities from GESPLAN research group. The application shows how the DCL model allows to assess the development of capacities for leadership. Also, the incorporation of lessons learned after monitoring and evaluation of capacity development allows to redirect actions to improve project planning and management and produce a true empowerment and leadership of the local organization. This translates into increased project sustainability and social resilience of the organization.

Nanoinformatics approaches for information extraction and text mining in nanomedical research texts

La nanotecnología es un área de investigación de reciente creación que trata con la manipulación y el control de la materia con dimensiones comprendidas entre 1 y 100 nanómetros. A escala nanométrica, los materiales exhiben fenómenos físicos, químicos y biológicos singulares, muy distintos a los que manifiestan a escala convencional. En medicina, los compuestos miniaturizados a nanoescala y los materiales nanoestructurados ofrecen una mayor eficacia con respecto a las formulaciones químicas tradicionales, así como una mejora en la focalización del medicamento hacia la diana terapéutica, revelando así nuevas propiedades diagnósticas y terapéuticas. A su vez, la complejidad de la información a nivel nano es mucho mayor que en los niveles biológicos convencionales (desde el nivel de población hasta el nivel de célula) y, por tanto, cualquier flujo de trabajo en nanomedicina requiere, de forma inherente, estrategias de gestión de información avanzadas. Desafortunadamente, la informática biomédica todavía no ha proporcionado el marco de trabajo que permita lidiar con estos retos de la información a nivel nano, ni ha adaptado sus métodos y herramientas a este nuevo campo de investigación. En este contexto, la nueva área de la nanoinformática pretende detectar y establecer los vínculos existentes entre la medicina, la nanotecnología y la informática, fomentando así la aplicación de métodos computacionales para resolver las cuestiones y problemas que surgen con la información en la amplia intersección entre la biomedicina y la nanotecnología. Las observaciones expuestas previamente determinan el contexto de esta tesis doctoral, la cual se centra en analizar el dominio de la nanomedicina en profundidad, así como en el desarrollo de estrategias y herramientas para establecer correspondencias entre las distintas disciplinas, fuentes de datos, recursos computacionales y técnicas orientadas a la extracción de información y la minería de textos, con el objetivo final de hacer uso de los datos nanomédicos disponibles. El autor analiza, a través de casos reales, alguna de las tareas de investigación en nanomedicina que requieren o que pueden beneficiarse del uso de métodos y herramientas nanoinformáticas, ilustrando de esta forma los inconvenientes y limitaciones actuales de los enfoques de informática biomédica a la hora de tratar con datos pertenecientes al dominio nanomédico. Se discuten tres escenarios diferentes como ejemplos de actividades que los investigadores realizan mientras llevan a cabo su investigación, comparando los contextos biomédico y nanomédico: i) búsqueda en la Web de fuentes de datos y recursos computacionales que den soporte a su investigación; ii) búsqueda en la literatura científica de resultados experimentales y publicaciones relacionadas con su investigación; iii) búsqueda en registros de ensayos clínicos de resultados clínicos relacionados con su investigación. El desarrollo de estas actividades requiere el uso de herramientas y servicios informáticos, como exploradores Web, bases de datos de referencias bibliográficas indexando la literatura biomédica y registros online de ensayos clínicos, respectivamente. Para cada escenario, este documento proporciona un análisis detallado de los posibles obstáculos que pueden dificultar el desarrollo y el resultado de las diferentes tareas de investigación en cada uno de los dos campos citados (biomedicina y nanomedicina), poniendo especial énfasis en los retos existentes en la investigación nanomédica, campo en el que se han detectado las mayores dificultades. El autor ilustra cómo la aplicación de metodologías provenientes de la informática biomédica a estos escenarios resulta efectiva en el dominio biomédico, mientras que dichas metodologías presentan serias limitaciones cuando son aplicadas al contexto nanomédico. Para abordar dichas limitaciones, el autor propone un enfoque nanoinformático, original, diseñado específicamente para tratar con las características especiales que la información presenta a nivel nano. El enfoque consiste en un análisis en profundidad de la literatura científica y de los registros de ensayos clínicos disponibles para extraer información relevante sobre experimentos y resultados en nanomedicina —patrones textuales, vocabulario en común, descriptores de experimentos, parámetros de caracterización, etc.—, seguido del desarrollo de mecanismos para estructurar y analizar dicha información automáticamente. Este análisis concluye con la generación de un modelo de datos de referencia (gold standard) —un conjunto de datos de entrenamiento y de test anotados manualmente—, el cual ha sido aplicado a la clasificación de registros de ensayos clínicos, permitiendo distinguir automáticamente los estudios centrados en nanodrogas y nanodispositivos de aquellos enfocados a testear productos farmacéuticos tradicionales. El presente trabajo pretende proporcionar los métodos necesarios para organizar, depurar, filtrar y validar parte de los datos nanomédicos existentes en la actualidad a una escala adecuada para la toma de decisiones. Análisis similares para otras tareas de investigación en nanomedicina ayudarían a detectar qué recursos nanoinformáticos se requieren para cumplir los objetivos actuales en el área, así como a generar conjunto de datos de referencia, estructurados y densos en información, a partir de literatura y otros fuentes no estructuradas para poder aplicar nuevos algoritmos e inferir nueva información de valor para la investigación en nanomedicina. ABSTRACT Nanotechnology is a research area of recent development that deals with the manipulation and control of matter with dimensions ranging from 1 to 100 nanometers. At the nanoscale, materials exhibit singular physical, chemical and biological phenomena, very different from those manifested at the conventional scale. In medicine, nanosized compounds and nanostructured materials offer improved drug targeting and efficacy with respect to traditional formulations, and reveal novel diagnostic and therapeutic properties. Nevertheless, the complexity of information at the nano level is much higher than the complexity at the conventional biological levels (from populations to the cell). Thus, any nanomedical research workflow inherently demands advanced information management. Unfortunately, Biomedical Informatics (BMI) has not yet provided the necessary framework to deal with such information challenges, nor adapted its methods and tools to the new research field. In this context, the novel area of nanoinformatics aims to build new bridges between medicine, nanotechnology and informatics, allowing the application of computational methods to solve informational issues at the wide intersection between biomedicine and nanotechnology. The above observations determine the context of this doctoral dissertation, which is focused on analyzing the nanomedical domain in-depth, and developing nanoinformatics strategies and tools to map across disciplines, data sources, computational resources, and information extraction and text mining techniques, for leveraging available nanomedical data. The author analyzes, through real-life case studies, some research tasks in nanomedicine that would require or could benefit from the use of nanoinformatics methods and tools, illustrating present drawbacks and limitations of BMI approaches to deal with data belonging to the nanomedical domain. Three different scenarios, comparing both the biomedical and nanomedical contexts, are discussed as examples of activities that researchers would perform while conducting their research: i) searching over the Web for data sources and computational resources supporting their research; ii) searching the literature for experimental results and publications related to their research, and iii) searching clinical trial registries for clinical results related to their research. The development of these activities will depend on the use of informatics tools and services, such as web browsers, databases of citations and abstracts indexing the biomedical literature, and web-based clinical trial registries, respectively. For each scenario, this document provides a detailed analysis of the potential information barriers that could hamper the successful development of the different research tasks in both fields (biomedicine and nanomedicine), emphasizing the existing challenges for nanomedical research —where the major barriers have been found. The author illustrates how the application of BMI methodologies to these scenarios can be proven successful in the biomedical domain, whilst these methodologies present severe limitations when applied to the nanomedical context. To address such limitations, the author proposes an original nanoinformatics approach specifically designed to deal with the special characteristics of information at the nano level. This approach consists of an in-depth analysis of the scientific literature and available clinical trial registries to extract relevant information about experiments and results in nanomedicine —textual patterns, common vocabulary, experiment descriptors, characterization parameters, etc.—, followed by the development of mechanisms to automatically structure and analyze this information. This analysis resulted in the generation of a gold standard —a manually annotated training or reference set—, which was applied to the automatic classification of clinical trial summaries, distinguishing studies focused on nanodrugs and nanodevices from those aimed at testing traditional pharmaceuticals. The present work aims to provide the necessary methods for organizing, curating and validating existing nanomedical data on a scale suitable for decision-making. Similar analysis for different nanomedical research tasks would help to detect which nanoinformatics resources are required to meet current goals in the field, as well as to generate densely populated and machine-interpretable reference datasets from the literature and other unstructured sources for further testing novel algorithms and inferring new valuable information for nanomedicine.

Desarrollo de un proceso de razonamiento visual para la valoración del patrimonio

El tema de la presente tesis es la valoración del patrimonio y en ella se considera que el patrimonio es un proceso cultural interesado en negociar, crear y recrear recuerdos, valores y significados culturales. Actualmente el patrimonio como proceso se está consolidando en la literatura científica, aunque la idea de que es una ‘cosa’ es dominante en el debate internacional y está respaldada tanto por políticas como prácticas de la UNESCO. El considerar el patrimonio como un proceso permite una mirada crítica, que subraya la significación. Es decir, supone el correlato que conlleva definir algo como ‘patrimonio’, o hacer que lo vaya siendo. Esta visión del concepto permite la posibilidad de comprender no sólo lo que se ha valorado, sino también lo que se ha olvidado y el porqué. El principal objetivo de esta investigación es explorar las características de un proceso de razonamiento visual para aplicarlo en el de valoración del patrimonio. Éste que se presenta, implica la creación de representaciones visuales y sus relaciones, además su meta no está centrada en producir un ambiente que sea indiferenciado de la realidad física. Con él se pretende ofrecer la posibilidad de comunicar la dimensión ‘poliédrica’ del patrimonio. Para que este nuevo proceso que propongo sea viable y sostenible, existe la necesidad de tener en cuenta el fin que se quiere lograr: la valoración. Es importante considerar que es un proceso en el cual las dinámicas de aprendizaje, comportamientos y exploración del patrimonio están directamente relacionadas con su valoración. Por lo tanto, hay que saber cómo se genera la valoración del patrimonio, con el fin de ser capaces de desarrollar el proceso adaptado a estas dinámicas. La hipótesis de esta tesis defiende que un proceso de razonamiento visual para la valoración del patrimonio permite que las personas involucradas en el proceso inicien un proceso de interacción con un elemento patrimonial y su imagen mental para llegar a ciertas conclusiones con respecto a su valor y significado. El trabajo describe la metodología que da lugar al proceso de razonamiento visual para el patrimonio, que ha sido concebido sobre un modelado descriptivo de procesos, donde se han caracterizado tres niveles: meta-nivel, de análisis y operacional. En el modelado del proceso los agentes, junto con el patrimonio, son los protagonistas. El enfoque propuesto no es sólo sobre el patrimonio, sino sobre la compleja relación entre las personas y el patrimonio. Los agentes humanos dan valor a los testimonios de la vida pasada y les imbuyen de significado. Por lo tanto, este enfoque de un proceso de razonamiento visual sirve para detectar los cambios en el valor del patrimonio, además de su dimensión poliédrica en términos espaciales y temporales. Además se ha propuesto una nueva tipología de patrimonio necesaria para sustentar un proceso de razonamiento visual para su valoración. Esta tipología está apoyada en la usabilidad del patrimonio y dentro de ella se encuentran los siguientes tipos de patrimonio: accesible, cautivo, contextualizado, descontextualizado, original y vicarial. El desarrollo de un proceso de razonamiento visual para el patrimonio es una propuesta innovadora porque integra el proceso para su valoración, contemplando la dimensión poliédrica del patrimonio y explotando la potencialidad del razonamiento visual. Además, los posibles usuarios del proceso propuesto van a tener interacción de manera directa con el patrimonio e indirecta con la información relativa a él, como por ejemplo, con los metadatos. Por tanto, el proceso propuesto posibilita que los posibles usuarios se impliquen activamente en la propia valoración del patrimonio. ABSTRACT The subject of this thesis is heritage valuation and it argues that heritage is a cultural process that is inherited, transmitted, and transformed by individuals who are interested in negotiating, creating and recreating memories and cultural meanings. Recently heritage as a process has seen a consolidation in the research, although the idea that heritage is a ‘thing’ is dominant in the international debate and is supported by policies and practice of UNESCO. Seeing heritage as a process enables a critical view, underscoring the significance. That is, it is the correlate involved in defining something as ‘heritage’, or converting it into heritage. This view of the concept allows the possibility to understand not only what has been valued, but also what has been forgotten and why. The main objective of this research is to explore the characteristics of a visual reasoning process in order to apply it to a heritage valuation. The goal of the process is not centered on producing an environment that is undifferentiated from physical reality. Thus, the objective of the process is to provide the ability to communicate the ‘polyhedral’ dimension of heritage. For this new process to be viable and sustainable, it is necessary to consider what is to be achieved: heritage valuation. It is important to note that it is a process in which the dynamics of learning, behavior and exploration heritage are directly related to its valuation. Therefore, we need to know how this valuation takes place in order to be able to develop a process that is adapted to these dynamic. The hypothesis of this thesis argues that a visual reasoning process for heritage valuation allows people involved in the process to initiate an interaction with a heritage and to build its mental image to reach certain conclusions regarding its value and meaning. The thesis describes the methodology that results in a visual reasoning process for heritage valuation, which has been based on a descriptive modeling process and have characterized three levels: meta, analysis and operational -level. The agents are the protagonists in the process, along with heritage. The proposed approach is not only about heritage but the complex relationship between people and heritage. Human operators give value to the testimonies of past life and imbue them with meaning. Therefore, this approach of a visual reasoning process is used to detect changes in the value of heritage and its multifaceted dimension in spatial and temporal terms. A new type of heritage required to support a visual reasoning process for heritage valuation has also been proposed. This type is supported by its usability and it covers the following types of heritage: available, captive, contextualized, decontextualized, original and vicarious. The development of a visual reasoning process for heritage valuation is innovative because it integrates the process for valuation of heritage, considering the multifaceted dimension of heritage and exploiting the potential of visual reasoning. In addition, potential users of the proposed process will have direct interaction with heritage and indirectly with the information about it, such as the metadata. Therefore, the proposed process enables potential users to be actively involved in their own heritage valuation.

Optical imaging of functional domains in the cortex of the awake and behaving monkey

As demonstrated by anatomical and physiological studies, the cerebral cortex consists of groups of cortical modules, each comprising populations of neurons with similar functional properties. This functional modularity exists in both sensory and association neocortices. However, the role of such cortical modules in perceptual and cognitive behavior is unknown. To aid in the examination of this issue we have applied the high spatial resolution optical imaging methodology to the study of awake, behaving animals. In this paper, we report the optical imaging of orientation domains and blob structures, approximately 100–200 μm in size, in visual cortex of the awake and behaving monkey. By overcoming the spatial limitations of other existing imaging methods, optical imaging will permit the study of a wide variety of cortical functions at the columnar level, including motor and cognitive functions traditionally studied with positron-emission tomography or functional MRI techniques.

A perceptual memory for low-contrast visual signals

Detection of a visual signal can be facilitated by simultaneous presentation of a similar subthreshold signal. Here we show that the facilitatory effect of a subthreshold signal can persist for more than 16 s. Presenting a near-threshold Gabor signal (prime) produced a phase-independent increase in contrast sensitivity (40%) to similar successive signals (target) for a period of up to 16 s. This effect was obtained only when both prime and target were presented to the same eye. We further show that the memory trace is inactivated by presenting high-contrast signals before the target. These results suggest that activated neurons in the primary visual cortex retain a near-threshold memory trace that persists until reactivated.

Pattern of neuronal activity associated with conscious and unconscious processing of visual signals

Following striate cortex damage in monkeys and humans there can be residual function mediated by parallel visual pathways. In humans this can sometimes be associated with a “feeling” that something has happened, especially with rapid movement or abrupt onset. For less transient events, discriminative performance may still be well above chance even when the subject reports no conscious awareness of the stimulus. In a previous study we examined parameters that yield good residual visual performance in the “blind” hemifield of a subject with unilateral damage to the primary visual cortex. With appropriate parameters we demonstrated good discriminative performance, both with and without conscious awareness of a visual event. These observations raise the possibility of imaging the brain activity generated in the “aware” and the “unaware” modes, with matched levels of discrimination performance, and hence of revealing patterns of brain activation associated with visual awareness. The intact hemifield also allows a comparison with normal vision. Here we report the results of a functional magnetic resonance imaging study on the same subject carried out under aware and unaware stimulus conditions. The results point to a shift in the pattern of activity from neocortex in the aware mode, to subcortical structures in the unaware mode. In the aware mode prestriate and dorsolateral prefrontal cortices (area 46) are active. In the unaware mode the superior colliculus is active, together with medial and orbital prefrontal cortical sites.

A model of ocular dominance column development by competition for trophic factor

Recent experimental evidence has shown that application of certain neurotrophic factors (NTs) to the developing primary visual cortex prevents the development of ocular dominance (OD) columns. One interpretation of this result is that afferents from the lateral geniculate nucleus compete for postsynaptic trophic factor in an activity-dependent manner. Application of excess trophic factor eliminates this competition, thereby preventing OD column formation. We present a model of OD column development, incorporating Hebbian synaptic modification and activity-driven competition for NT, which accounts for both normal OD column development as well as the prevention of that development when competition is removed. In the “control” situation, when available NT is below a critical amount, OD columns form normally. These columns form without weight normalization procedures and in the presence of positive inter-eye correlations. In the “experimental” case, OD column development is prevented in a local neighborhood in which excess NT has been added. Our model proposes a biologically plausible mechanism for competition between neural populations that is motivated by several pieces of experimental data, thereby accounting for both normal and experimentally perturbed conditions.