First Signs of Emerging Psychosis

The majority of first-episode psychoses are preceded by a prodromal phase that is several years on average, frequently leads to some decline in psychosocial functioning and offers the opportunity for early detection within the framework of an indicated prevention. To this, two approaches are currently mainly followed. The ultra-high-risk (UHR) criteria were explicitly developed to predict first-episode psychosis within 12 months, and indeed the majority of conversions in clinical UHR samples seem to occur within the first 12 months of initial assessment. Their main criterion, the attenuated psychotic symptoms criterion, captures symptoms that resemble positive symptoms of psychosis (i.e. delusions, hallucinations and formal thought disorders) with the exception that some level of insight is still maintained, and these frequently compromise functioning already. In contrast, the basic symptom criteria try to catch patients at increased risk of psychoses at the earliest possible time, i.e. ideally when only the first subtle disturbances in information processing have developed that are experienced with full insight and do not yet overload the person's coping abilities, and thus have not yet resulted in any functional decline. First results from prospective studies not only support this view, but indicate that the combination of both approaches might be a more favorable way to increase sensitivity and detect risk earlier, as well as to establish a change-sensitive risk stratification approach.

15 Years of Microstate Research in Schizophrenia - Where Are We? A Meta-Analysis

Schizophrenia patients show abnormalities in a broad range of task demands. Therefore, an explanation common to all these abnormalities has to be sought independently of any particular task, ideally in the brain dynamics before a task takes place or during resting state. For the neurobiological investigation of such baseline states, EEG microstate analysis is particularly well suited, because it identifies subsecond global states of stable connectivity patterns directly related to the recruitment of different types of information processing modes (e.g., integration of top-down and bottom-up information). Meanwhile, there is an accumulation of evidence that particular microstate networks are selectively affected in schizophrenia. To obtain an overall estimate of the effect size of these microstate abnormalities, we present a systematic meta-analysis over all studies available to date relating EEG microstates to schizophrenia. Results showed medium size effects for two classes of microstates, namely, a class labeled C that was found to be more frequent in schizophrenia and a class labeled D that was found to be shortened. These abnormalities may correspond to core symptoms of schizophrenia, e.g., insufficient reality testing and self-monitoring as during auditory verbal hallucinations. As interventional studies have shown that these microstate features may be systematically affected using antipsychotic drugs or neurofeedback interventions, these findings may help introducing novel diagnostic and treatment options.

Intelligence and the psychological refractory period: A lateralized readiness potential study

The psychological refractory period (PRP) refers to a delay of response times (RT) to the second of two stimuli when these stimuli are presented in rapid succession. If this limitation of rapidly processing the second stimulus contributes to the well-known differences in speed of information processing between individuals with higher and lower mental ability, individuals with lower mental ability should exhibit a more pronounced PRP effect than individuals with higher mental ability. Previous studies on this question, however, yielded inconsistent results. In the present study, we assessed mental ability-related differences in the PRP by measuring lateralized readiness potentials (LRPs) to separate premotor and motor aspects of speed of information processing in 95 individuals with higher and 95 individuals with lower mental ability. Although individuals with higher mental ability processed information faster than individuals with lower mental ability as indicated by shorter RTs and shorter premotor LRP latencies, the PRP effect was equally pronounced in both groups. These findings suggest that the processes underlying the PRP effect do not contribute to mental ability-related differences in speed of information processing. Rather, these differences seem to occur at an earlier stage of information processing such as stimulus encoding, stimulus analysis, or stimulus evaluation.

Elucidating underlying processes of psychometric intelligence: A comparison of behavioral response latency and P3 latency in a modified Hick reaction time paradigm

The mental speed approach explains individual differences in intelligence by faster information processing in individuals with higher compared to lower intelligence - especially in elementary cognitive tasks (ECTs). One of the most examined ECTs is the Hick paradigm. The present study aimed to contrast reaction time (RT) and P3 latency in a Hick task as predictors of intelligence. Although both, RT and P3 latency, are commonly used as indicators of mental speed, it is also known that they measure different aspects of information processing. Participants were 113 female students. RT and P3 latency were measured while participants completed the Hick task with four levels of complexity. Intelligence was assessed with Cattell's Culture Fair Test. A RT factor and a P3 factor were extracted by employing a PCA across complexity levels. There was no significant correlation between the factors. Commonality analysis was used to determine the proportions of unique and shared variance in intelligence explained by the RT and P3 latency factors. RT and P3 latency explained 5.5% and 5% of unique variance in intelligence. However, the two speed factors did not explain a significant portion of shared variance. This result suggests that RT and P3 latency in the Hick paradigm are measuring different aspects of information processing that explain different parts of variance in intelligence.

Function of histaminergic retinopetal axons in rat and primate retinas

Mammalian retinas receive input from histaminergic neurons in the posterior hypothalamus. These neurons are most active during the waking state of the animal, but their role in retinal information processing is not known. To determine the function of these retinopetal axons, their targets in the rat and monkey retina were identified. Using antibodies to three histamine receptors, HR1, HR2, and HR3, the immunolabeling was analyzed by confocal and electron microscopy. These experiments showed that mammalian retinas possess histamine receptors. In macaques and baboons, diurnal species, HR3 receptors were found at the apex of ON-bipolar cell dendrites in cone pedicles and rod spherules, sclerad to the other neurotransmitter receptors that have been localized there. In addition, HR1 histamine receptors were localized to large puncta in the inner plexiform layer, a subset of ganglion cells and retinal blood vessels. In rats, a nocturnal species, the localization of histamine receptors in the retina was markedly different. Most HR1 receptors were localized to dopaminergic amacrine cells and on elements in the rod spherule. To determine how histaminergic retinopetal axons contribute to retinal information processing, responses of retinal ganglion cells to histamine were analyzed. The effects of histamine on the maintained and light-evoked activity of retinal ganglion cells were analyzed. In monkeys, histamine and the HR3 agonist, methylhistamine, increased or decreased the maintained activity of most ganglion cells, but a few did not respond. The responses of a subset of ganglion cells to light stimuli were decreased by histamine, a finding suggesting that histaminergic retinopetal axons contribute to light adaptation during the day. In rats, histamine nearly always increased the maintained activity and produced both increases and decreases in the light responses. The effects of histamine on maintained activity of ganglion cells in the rat can be partially attributed to HR1-mediated changes in the activity of dopaminergic amacrine cells, at night. Together, these experiments provide the first indication of the function of retinopetal axons in mammalian retinas. ^

Mechanisms of heterosynaptic modulation of transmission in Aplysia

Heterosynaptic plasticity has received considerable attention as a means to induce and maintain cell-wide, as opposed to synapse-specific, learning-related modifications. Modulatory neurotransmitters are thought to provide the attentional and motivational state for memory formation. However, the cellular and molecular mechanisms mediating the effects of most of these modulators on synaptic plasticity and learning remain unclear. A well established system for the study of heterosynaptic plasticity is the Aplysia sensorimotor synapse, which is subject regulation by at least two neuromodulators, serotonin (5-HT) and FMRFa. ^ 5-HT engages multiple second messenger cascades to induce short- and long-term facilitation (STF and LTF, respectively) of synaptic transmission. One mechanism proposed to be involved in STF is mobilization of synaptic vesicles from a storage pool to a releasable pool. To investigate this hypothesis, we examined the involvement of the protein synapsin, a central element in the regulation of the storage pool of vesicles in nerve terminals, in STF. 5-HT induced phosphorylation of synapsin and modified its subcellular distribution via PKA and p42/44 MAPK. Electrophysiological experiments and computer simulations suggested that synapsin can support heterosynaptic plasticity by regulating vesicle mobilization. ^ FMRFa induce short- and long-term synaptic depression in Aplysia . Long-term depression (LTD) correlates with morphological changes, the mechanisms of which remain elusive. LTD is also transcription- and translation-dependent, but little is known about the genes expressed and their regulation. We investigated the role of protein degradation via the ubiquitin-proteasome system and the regulation of one of its components, ubiquitin C-terminal hydrolase (ap-uch), in LTD. LTD was sensitive to inhibition of the proteasome and was associated with upregulation of ap-uch mRNA and protein. This upregulation appeared to be mediated by the transcription factor CREB2, which is generally regarded as a transcription repressor. These results suggest that proteasome-mediated protein degradation is engaged in LTD and that CREB2 may act as a transcription activator under certain conditions. ^ These and additional studies on the interaction of the 5-HT and FMRFa-activated pathways suggest that different neuromodulators, by activating several and sometimes overlapping signaling cascades, can exercise bidirectional control on synaptic gain and information processing.^

Forebrain-cerebellum interactions revealed by trace eyelid conditioning

While it is commonly assumed that brain systems receive and process information from other brain systems, there are few examples of tractable behaviors that allow such interactions to be studied. With the experiments presented in this dissertation we provide evidence that trace eyelid conditioning, a simple form of associative learning, is mediated by cerebellar learning in response to the output of persistent neural activity in the prefrontal cortex (PFC) and thus may be useful in analyses of PFC-cerebellar interactions. In a series of stimulation and reversible inactivation experiments we provide evidence that trace eyelid conditioning is mediated by cerebellar learning in response to a learned forebrain-driven input. Specifically, we provide evidence that this input is driven by the medial PFC and persists through the stimulus free trace interval of trace eyelid conditioning. In the next set of experiments we show that directly presenting the cerebellum with a pattern of input that mimics the classic persistent activity of PFC neurons reconstitutes trace eyelid conditioning, as assessed by a number of stringent tests. Finally, in set of reversible inactivation experiments, we provide evidence that bidirectional learning during trace eyelid conditioning involves the omission of the persistent, PFC-driven input that the cerebellum learns and responds to during trace eyelid conditioning. Given that persistent activity in PFC is often associated with working memory, these experiments suggest that trace eyelid conditioning may be useful in analyses of working memory mechanisms, cerebellar information processing and their interaction. To facilitate future analyses, we conclude with a working hypothesis of forebrain-cerebellum interactions during trace eyelid conditioning that addresses how persistent activity in PFC is induced and how the cerebellum decodes and uses PFC-driven input. ^

STUDIES ON CHOLINERGIC FUNCTION AND MEMORY IN MICE (CHOLINOTOXINS, WORKING, REFERENCE MEMORY, RADIAL ARM MAZE)

Considerable evidence suggests that central cholinergic neurons participate in either acquisition, storage or retrieval of information. Experiments were designed to evaluate information processing in mice following either reversible or irreversible impairment in central cholinergic activity. The cholinergic receptor antagonists, atropine and methylatropine were used to reversibly inhibit cholinergic transmission. Irreversible impairment in central cholinergic function was achieved by central administration of the cholinergic-specific neurotoxins, N-ethyl-choline aziridinium (ECA) and N-ethyl-acetylcholine aziridinium (EACA).^ ECA and EACA appear to act by irreversible inhibition of high affinity choline uptake (proposed rate-limiting step in acetylcholine synthesis). Intraventricular administration of ECA or EACA produced persistent reduction in hippocampal choline acetyltransferase activity. Other neuronal systems and brain regions showed no evidence of toxicity.^ Mice treated with either ECA or EACA showed behavioral deficits associated with cholinergic dysfunction. Passive avoidance behavior was significantly impaired by cholinotoxin treatment. Radial arm maze performance was also significantly impaired in cholinotoxin-treated animals. Deficits in radial arm maze performance were transient, however, such that rapid and apparent complete behavioral recovery was seen during retention testing. The centrally active cholinergic receptor antagonist atropine also caused significant impairment in radial arm maze behavior, while equivalent doses of methylatropine were without effect.^ The relative effects of cholinotoxin and receptor antagonist treatment on short-term (working) memory and long-term (reference) memory in radial arm maze behavior were examined. Maze rotation studies indicated that there were at least two different response strategies which could result in accurate maze performance. One strategy involved the use of response algorithms and was considered to be a function of reference memory. Another strategy appeared to be primarily dependent on spatial working memory. However, all behavioral paradigms with multiple trails have reference memory requirements (i.e. information useful over all trials). Performance was similarly affected following either cholinotoxin or anticholinergic treatment, regardless of the response strategy utilized. In addition, rates of behavioral recovery following cholinotoxin treatment were similar between response groups. It was concluded that both cholinotoxin and anticholinergic treatment primarily resulted in impaired reference memory processes. ^

POPULATION CODING IN LAMINAR CORTICAL CIRCUITS

One of the fundamental questions in neuroscience is to understand how encoding of sensory inputs is distributed across neuronal networks in cerebral cortex to influence sensory processing and behavioral performance. The fact that the structure of neuronal networks is organized according to cortical layers raises the possibility that sensory information could be processed differently in distinct layers. The goal of my thesis research is to understand how laminar circuits encode information in their population activity, how the properties of the population code adapt to changes in visual input, and how population coding influences behavioral performance. To this end, we performed a series of novel experiments to investigate how sensory information in the primary visual cortex (V1) emerges across laminar cortical circuits. First, it is commonly known that the amount of information encoded by cortical circuits depends critically on whether or not nearby neurons exhibit correlations. We examined correlated variability in V1 circuits from a laminar-specific perspective and observed that cells in the input layer, which have only local projections, encode incoming stimuli optimally by exhibiting low correlated variability. In contrast, output layers, which send projections to other cortical and subcortical areas, encode information suboptimally by exhibiting large correlations. These results argue that neuronal populations in different cortical layers play different roles in network computations. Secondly, a fundamental feature of cortical neurons is their ability to adapt to changes in incoming stimuli. Understanding how adaptation emerges across cortical layers to influence information processing is vital for understanding efficient sensory coding. We examined the effects of adaptation, on the time-scale of a visual fixation, on network synchronization across laminar circuits. Specific to the superficial layers, we observed an increase in gamma-band (30-80 Hz) synchronization after adaptation that was correlated with an improvement in neuronal orientation discrimination performance. Thus, synchronization enhances sensory coding to optimize network processing across laminar circuits. Finally, we tested the hypothesis that individual neurons and local populations synchronize their activity in real-time to communicate information about incoming stimuli, and that the degree of synchronization influences behavioral performance. These analyses assessed for the first time the relationship between changes in laminar cortical networks involved in stimulus processing and behavioral performance.

Food quality awareness : cases from shrimp producers in Thailand and vegetable producers in Vietnam

The high number of import rejections of food commodities suggests that producers in exporting countries are not complying with established standards. To understand why this is the case, we explore the behavior of producers and consumers in developing countries. First, we examine the successful transformation of production practices adopted by shrimp producers in Thailand. In support of the dramatic change in practices, we observe an important role played by the public sector in providing a means to visualize chemical residues and to control processes upstream of the supply chain via a registration system and a traceability system called Movement Document. Furthermore, very active information sharing by the private sector contributes to the dissemination of useful technical and market information among producers. We also examine the knowledge and perceptions of consumers with respect to food safety in Vietnam. We find that consumers in Hanoi and Ho Chi Minh City behave differently toward the third-party certification VietGAP, probably owing to differences in the history of market mechanisms between the two cities.

Communication-efficient and crash-quiescent Omega with unknown membership

The failure detector class Omega (Ω) provides an eventual leader election functionality, i.e., eventually all correct processes permanently trust the same correct process. An algorithm is communication-efficient if the number of links that carry messages forever is bounded by n, being n the number of processes in the system. It has been defined that an algorithm is crash-quiescent if it eventually stops sending messages to crashed processes. In this regard, it has been recently shown the impossibility of implementing Ω crash quiescently without a majority of correct processes. We say that the membership is unknown if each process pi only knows its own identity and the number of processes in the system (that is, i and n), but pi does not know the identity of the rest of processes of the system. There is a type of link (denoted by ADD link) in which a bounded (but unknown) number of consecutive messages can be delayed or lost. In this work we present the first implementation (to our knowledge) of Ω in partially synchronous systems with ADD links and with unknown membership. Furthermore, it is the first implementation of Ω that combines two very interesting properties: communication-efficiency and crash-quiescence when the majority of processes are correct. Finally, we also obtain with the same algorithm a failure detector () such that every correct process eventually and permanently outputs the set of all correct processes.

Diffusion Tensor Imaging in Alzheimer's disease

Attentional control and Information processing speed are central concepts in cognitive psychology and neuropsychology. Functional neuroimaging and neuropsychological assessment have depicted theoretical models considering attention as a complex and non-unitary process. One of its component processes, Attentional set-shifting ability, is commonly assessed using the Trail Making Test (TMT). Performance in the TMT decreases with increasing age in adults, Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD). Besides, speed of information processing (SIP) seems to modulate attentional performance. While neural correlates of attentional control have been widely studied, there are few evidences about the neural substrates of SIP in these groups of patients. Different authors have suggested that it could be a property of cerebral white matter, thus, deterioration of the white matter tracts that connect brain regions related to set-shifting may underlie the age-related, MCI and AD decrease in performance. The aim of this study was to study the anatomical dissociation of attentional and speed mechanisms. Diffusion tensor imaging (DTI) provides a unique insight into the cellular integrity of the brain, offering an in vivo view into the microarchitecture of cerebral white matter. At the same time, the study of ageing, characterized by white matter decline, provides the opportunity to study the anatomical substrates speeded or slowed information processing. We hypothesized that FA values would be inversely correlated with time to completion on Parts A and B of the TMT, but not the derived scores B/A and B-A.

The role of computational logic as a hinge paradigm among deduction, problem solving, programming, and parallelism

This paper presents some brief considerations on the role of Computational Logic in the construction of Artificial Intelligence systems and in programming in general. It does not address how the many problems in AI can be solved but, rather more modestly, tries to point out some advantages of Computational Logic as a tool for the AI scientist in his quest. It addresses the interaction between declarative and procedural views of programs (deduction and action), the impact of the intrinsic limitations of logic, the relationship with other apparently competing computational paradigms, and finally discusses implementation-related issues, such as the efficiency of current implementations and their capability for efficiently exploiting existing and future sequential and parallel hardware. The purpose of the discussion is in no way to present Computational Logic as the unique overall vehicle for the development of intelligent systems (in the firm belief that such a panacea is yet to be found) but rather to stress its strengths in providing reasonable solutions to several aspects of the task.

Intelligent context-aware services based on internet of things architectures

La Internet de las Cosas (IoT), como parte de la Futura Internet, se ha convertido en la actualidad en uno de los principales temas de investigación; en parte gracias a la atención que la sociedad está poniendo en el desarrollo de determinado tipo de servicios (telemetría, generación inteligente de energía, telesanidad, etc.) y por las recientes previsiones económicas que sitúan a algunos actores, como los operadores de telecomunicaciones (que se encuentran desesperadamente buscando nuevas oportunidades), al frente empujando algunas tecnologías interrelacionadas como las comunicaciones Máquina a Máquina (M2M). En este contexto, un importante número de actividades de investigación a nivel mundial se están realizando en distintas facetas: comunicaciones de redes de sensores, procesado de información, almacenamiento de grandes cantidades de datos (big--‐data), semántica, arquitecturas de servicio, etc. Todas ellas, de forma independiente, están llegando a un nivel de madurez que permiten vislumbrar la realización de la Internet de las Cosas más que como un sueño, como una realidad tangible. Sin embargo, los servicios anteriormente mencionados no pueden esperar a desarrollarse hasta que las actividades de investigación obtengan soluciones holísticas completas. Es importante proporcionar resultados intermedios que eviten soluciones verticales realizadas para desarrollos particulares. En este trabajo, nos hemos focalizado en la creación de una plataforma de servicios que pretende facilitar, por una parte la integración de redes de sensores y actuadores heterogéneas y geográficamente distribuidas, y por otra lado el desarrollo de servicios horizontales utilizando dichas redes y la información que proporcionan. Este habilitador se utilizará para el desarrollo de servicios y para la experimentación en la Internet de las Cosas. Previo a la definición de la plataforma, se ha realizado un importante estudio focalizando no sólo trabajos y proyectos de investigación, sino también actividades de estandarización. Los resultados se pueden resumir en las siguientes aseveraciones: a) Los modelos de datos definidos por el grupo “Sensor Web Enablement” (SWE™) del “Open Geospatial Consortium (OGC®)” representan hoy en día la solución más completa para describir las redes de sensores y actuadores así como las observaciones. b) Las interfaces OGC, a pesar de las limitaciones que requieren cambios y extensiones, podrían ser utilizadas como las bases para acceder a sensores y datos. c) Las redes de nueva generación (NGN) ofrecen un buen sustrato que facilita la integración de redes de sensores y el desarrollo de servicios. En consecuencia, una nueva plataforma de Servicios, llamada Ubiquitous Sensor Networks (USN), se ha definido en esta Tesis tratando de contribuir a rellenar los huecos previamente mencionados. Los puntos más destacados de la plataforma USN son: a) Desde un punto de vista arquitectónico, sigue una aproximación de dos niveles (Habilitador y Gateway) similar a otros habilitadores que utilizan las NGN (como el OMA Presence). b) Los modelos de datos están basado en los estándares del OGC SWE. iv c) Está integrado en las NGN pero puede ser utilizado sin ellas utilizando infraestructuras IP abiertas. d) Las principales funciones son: Descubrimiento de sensores, Almacenamiento de observaciones, Publicacion--‐subscripcion--‐notificación, ejecución remota homogénea, seguridad, gestión de diccionarios de datos, facilidades de monitorización, utilidades de conversión de protocolos, interacciones síncronas y asíncronas, soporte para el “streaming” y arbitrado básico de recursos. Para demostrar las funcionalidades que la Plataforma USN propuesta pueden ofrecer a los futuros escenarios de la Internet de las Cosas, se presentan resultados experimentales de tres pruebas de concepto (telemetría, “Smart Places” y monitorización medioambiental) reales a pequeña escala y un estudio sobre semántica (sistema de información vehicular). Además, se está utilizando actualmente como Habilitador para desarrollar tanto experimentación como servicios reales en el proyecto Europeo SmartSantander (que aspira a integrar alrededor de 20.000 dispositivos IoT). v Abstract Internet of Things, as part of the Future Internet, has become one of the main research topics nowadays; in part thanks to the pressure the society is putting on the development of a particular kind of services (Smart metering, Smart Grids, eHealth, etc.), and by the recent business forecasts that situate some players, like Telecom Operators (which are desperately seeking for new opportunities), at the forefront pushing for some interrelated technologies like Machine--‐to--‐Machine (M2M) communications. Under this context, an important number of research activities are currently taking place worldwide at different levels: sensor network communications, information processing, big--‐ data storage, semantics, service level architectures, etc. All of them, isolated, are arriving to a level of maturity that envision the achievement of Internet of Things (IoT) more than a dream, a tangible goal. However, the aforementioned services cannot wait to be developed until the holistic research actions bring complete solutions. It is important to come out with intermediate results that avoid vertical solutions tailored for particular deployments. In the present work, we focus on the creation of a Service--‐level platform intended to facilitate, from one side the integration of heterogeneous and geographically disperse Sensors and Actuator Networks (SANs), and from the other the development of horizontal services using them and the information they provide. This enabler will be used for horizontal service development and for IoT experimentation. Prior to the definition of the platform, we have realized an important study targeting not just research works and projects, but also standardization topics. The results can be summarized in the following assertions: a) Open Geospatial Consortium (OGC®) Sensor Web Enablement (SWE™) data models today represent the most complete solution to describe SANs and observations. b) OGC interfaces, despite the limitations that require changes and extensions, could be used as the bases for accessing sensors and data. c) Next Generation Networks (NGN) offer a good substrate that facilitates the integration of SANs and the development of services. Consequently a new Service Layer platform, called Ubiquitous Sensor Networks (USN), has been defined in this Thesis trying to contribute to fill in the previous gaps. The main highlights of the proposed USN Platform are: a) From an architectural point of view, it follows a two--‐layer approach (Enabler and Gateway) similar to other enablers that run on top of NGN (like the OMA Presence). b) Data models and interfaces are based on the OGC SWE standards. c) It is integrated in NGN but it can be used without it over open IP infrastructures. d) Main functions are: Sensor Discovery, Observation Storage, Publish--‐Subscribe--‐Notify, homogeneous remote execution, security, data dictionaries handling, monitoring facilities, authorization support, protocol conversion utilities, synchronous and asynchronous interactions, streaming support and basic resource arbitration. vi In order to demonstrate the functionalities that the proposed USN Platform can offer to future IoT scenarios, some experimental results have been addressed in three real--‐life small--‐scale proofs--‐of concepts (Smart Metering, Smart Places and Environmental monitoring) and a study for semantics (in--‐vehicle information system). Furthermore we also present the current use of the proposed USN Platform as an Enabler to develop experimentation and real services in the SmartSantander EU project (that aims at integrating around 20.000 IoT devices).