New evidence for involvement of the entorhinal region in schizophrenia: a combined MRI volumetric and DTI study

Postmortem examinations and magnetic resonance imaging (MRI) studies suggest involvement of the entorhinal cortex (EC) in schizophrenic psychoses. However, the extent and nature of the possible pathogenetical process underlying the observed alterations of this limbic key region for processing of multimodal sensory information remains unclear. Three-dimensional high-resolution MRI volumetry and evaluation of the regional diffusional anisotropy based on diffusion tensor imaging (DTI) were performed on the EC of 15 paranoid schizophrenic patients and 15 closely matched control subjects. In schizophrenic patients, EC volumes showed a slight, but not significant, decrease. However, the anisotropy values, expressed as inter-voxel coherences (COH), were found to be significantly decreased by 17.9% (right side) and 12.5% (left side), respectively, in schizophrenics. Reduction of entorhinal diffusional anisotropy can be hypothesized to be functionally related to disturbances in the perforant path, the principal efferent EC fiber tract supplying the limbic system with neuronal input from multimodal association centers. Combinations of different MRI modalities are a promising approach for the detection and characterization of subtle brain tissue alterations.

Expression of adenosine A2a receptor gene in rat dorsal root and autonomic ganglia

The adenosine A2a receptors (A2aR) play an important role in the purinergic mediated neuromodulation. The presence of A2aR in the brain is well established. In contrast, little is known about their expression in the periphery. The purpose of this study was to investigate the expression of A2aR gene in the autonomic (otic, sphenopalatine, ciliary, cervical superior ganglia and carotid body) and in the dorsal root ganglia of normal rat. Hybridization histochemistry with S35-labelled radioactive oligonucleotide probes was used. An expression of A2aR gene was found in the large neuronal cells of the rat dorsal root ganglia. The satellite cells showed no expression of A2aR gene. In the superior cervical ganglion, isolated ganglion cells expressed A2aR. In the carotid body clusters of cells with a strong A2aR gene expression were found. In contrast, the ciliary and otic ganglia did not expressed A2aR gene, and only few small sized A2aR expressing cells were demonstrated in the sphenopalatine ganglion. The discrete distribution of A2aR gene expression in the peripheral nervous system speaks for a role of this receptor in the purinergic modulation of sensory information as well as in the sympathetic nervous system.

Exploring Urban Environments Using Virtual and Augmented Reality

In this paper, we propose the use of specific system architecture, based on mobile device, for navigation in urban environments. The aim of this work is to assess how virtual and augmented reality interface paradigms can provide enhanced location based services using real-time techniques in the context of these two different technologies. The virtual reality interface is based on faithful graphical representation of the localities of interest, coupled with sensory information on the location and orientation of the user, while the augmented reality interface uses computer vision techniques to capture patterns from the real environment and overlay additional way-finding information, aligned with real imagery, in real-time. The knowledge obtained from the evaluation of the virtual reality navigational experience has been used to inform the design of the augmented reality interface. Initial results of the user testing of the experimental augmented reality system for navigation are presented.

Non-Hebbian Long-Term Potentiation of Inhibitory Synapses in the Thalamus

The thalamus integrates and transmits sensory information to the neocortex. The activity of thalamocortical relay (TC) cells is modulated by specific inhibitory circuits. Although this inhibition plays a crucial role in regulating thalamic activity, little is known about long-term changes in synaptic strength at these inhibitory synapses. Therefore, we studied long-term plasticity of inhibitory inputs to TC cells in the posterior medial nucleus of the thalamus by combining patch-clamp recordings with two-photon fluorescence microscopy in rat brain slices. We found that specific activity patterns in the postsynaptic TC cell induced inhibitory long-term potentiation (iLTP). This iLTP was non-Hebbian because it did not depend on the timing between presynaptic and postsynaptic activity, but it could be induced by postsynaptic burst activity alone. iLTP required postsynaptic dendritic Ca2+ influx evoked by low-threshold Ca2+ spikes. In contrast, tonic postsynaptic spiking from a depolarized membrane potential (−50 mV), which suppressed these low-threshold Ca2+ spikes, induced no plasticity. The postsynaptic dendritic Ca2+ increase triggered the synthesis of nitric oxide that retrogradely activated presynaptic guanylyl cyclase, resulting in the presynaptic expression of iLTP. The dependence of iLTP on the membrane potential and therefore on the postsynaptic discharge mode suggests that this form of iLTP might occur during sleep, when TC cells discharge in bursts. Therefore, iLTP might be involved in sleep state-dependent modulation of thalamic information processing and thalamic oscillations.

Listening to your heart and feeling yourself: effects of exposure to interoceptive signals during the ultimatum game

The ultimatum game (UG) is commonly used to study the tension between financial self-interest and social equity motives. Here, we investigated whether experimental exposure to interoceptive signals influences participants' behavior in the UG. Participants were presented with various bodily sounds--i.e., their own heart, another person's heart, or the sound of footsteps--while acting both in the role of responder and proposer. We found that listening to one's own heart sound, compared to the other bodily sounds: (1) increased subjective feelings of unfairness, but not rejection behavior, in response to unfair offers and (2) increased the unfair offers while playing in the proposer role. These findings suggest that heightened feedback of one's own visceral processes may increase a self-centered perspective and drive socioeconomic exchanges accordingly. In addition, this study introduces a valuable procedure to manipulate online the access to interoceptive signals and for exploring the interplay between viscero-sensory information and cognition.

Meditators and non-meditators: EEG source imaging during resting

Many meditation exercises aim at increased awareness of ongoing experiences through sustained attention and at detachment, i.e., non-engaging observation of these ongoing experiences by the intent not to analyze, judge or expect anything. Long-term meditation practice is believed to generalize the ability of increased awareness and greater detachment into everyday life. We hypothesized that neuroplasticity effects of meditation (correlates of increased awareness and detachment) would be detectable in a no-task resting state. EEG recorded during resting was compared between Qigong meditators and controls. Using LORETA (low resolution electromagnetic tomography) to compute the intracerebral source locations, differences in brain activations between groups were found in the inhibitory delta EEG frequency band. In the meditators, appraisal systems were inhibited, while brain areas involved in the detection and integration of internal and external sensory information showed increased activation. This suggests that neuroplasticity effects of long-term meditation practice, subjectively described as increased awareness and greater detachment, are carried over into non-meditating states.

CHOLINERGIC MODULATION OF THALAMIC INPUT INTO THE CINGULATE CORTEX

This research demonstrates cholinergic modulation of thalamic input into the limbic cortex. A projection from the mediodorsal thalamus (MD) to the anterior cingulate cortex was defined anatomically and physiologically. Injections of horse-radish peroxidase into the anterior cingulate cortex labels neurons in the lateral, parvocellular, region of MD. Electrical Stimulation of this area produces a complex field potential in the anterior cingulate cortex which was further characterized by current density analysis and single cell recordings.^ The monsynaptic component of the response was identified as a large negative field which is maximal in layer IV of the anterior cingulate cortex. This response shows remarkable tetanic potentiation of frequencies near 7 Hz. During a train of 50 or more stimuli, the response would grow quickly and remain at a fairly stable potentiated level throughout the train.^ Cholinergic modulation of this thalamic response was demonstrated by iontophoretic application of the cholinergic agonist carbachol decreased the effectiveness of the thalamic imput by rapidly attenuation the response during a train of stimuli. The effect was apparently mediated by muscarinic receptors since the effect of carbachol was blocked by atropine but not by hexamethonium.^ To determine the source of the cingulate cortex cholinergic innervation, lesions were made in the anterior and medial thalamus and in the nucleus of the diagonal band of Broca. The effects of these lesions on choline acetyltranferase activity in the cingulate cortex were determined by a micro-radio-enzymatical assay. Only the lesions of the nucleus of the diagonal band significantly decreased the choline acetyltransferase activity in the cingulate cortex regions. Therefore, the diagonal band appears to be a major source of sensory cholinergic innervation and may be involved in gating of sensory information from the thalamus into the limbic cortex. Attempts to modulate the cingulate response to MD stimulation with electrical stimulation of the diagonal band, however were not successful.^

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.

Arquitectura cognitiva basada en el gradiente sensorial y su aplicación a la robótica móvil

El objetivo de esta tesis es el desarrollo de un sistema completo de navegación, aprendizaje y planificación para un robot móvil. Dentro de los innumerables problemas que este gran objetivo plantea, hemos dedicado especial atención al problema del conocimiento autónomo del mundo. Nuestra mayor preocupación ha sido la de establecer mecanismos que permitan, a partir de información sensorial cruda, el desarrollo incremental de un modelo topológico del entorno en el que se mueve el robot. Estos mecanismos se apoyan invariablemente en un nuevo concepto propuesto en esta tesis: el gradiente sensorial. El gradiente sensorial es un dispositivo matemático que funciona como un detector de sucesos interesantes para el sistema. Una vez detectado uno de estos sucesos, el robot puede identificar su situación en un mapa topológico y actuar en consecuencia. Hemos denominado a estas situaciones especiales lugares sensorialmente relevantes, ya que (a) captan la atención del sistema y (b) pueden ser identificadas utilizando la información sensorial. Para explotar convenientemente los modelos construidos, hemos desarrollado un algoritmo capaz de elaborar planes internalizados, estableciendo una red de sugerencias en los lugares sensorialmente relevantes, de modo que el robot encuentra en estos puntos una dirección recomendada de navegación. Finalmente, hemos implementado un sistema de navegación robusto con habilidades para interpretar y adecuar los planes internalizados a las circunstancias concretas del momento. Nuestro sistema de navegación está basado en la teoría de campos de potencial artificial, a la que hemos incorporado la posibilidad de añadir cargas ficticias como ayuda a la evitación de mínimos locales. Como aportación adicional de esta tesis al campo genérico de la ciencia cognitiva, todos estos elementos se integran en una arquitectura centrada en la memoria, lo que pretende resaltar la importancia de ésta en los procesos cognitivos de los seres vivos y aporta un giro conceptual al punto de vista tradicional, centrado en los procesos. The general objective of this thesis is the development of a global navigation system endowed with planning and learning features for a mobile robot. Within this general objective we have devoted a special effort to the autonomous learning problem. Our main concern has been to establish the necessary mechanisms for the incremental development of a topological model of the robot’s environment using the sensory information. These mechanisms are based on a new concept proposed in the thesis: the sensory gradient. The sensory gradient is a mathematical device which works like a detector of “interesting” environment’s events. Once a particular event has been detected the robot can identify its situation in the topological map and to react accordingly. We have called these special situations relevant sensory places because (a) they capture the system’s attention and (b) they can be identified using the sensory information. To conveniently exploit the built-in models we have developed an algorithm able to make internalized plans, establishing a suggestion network in the sensory relevant places in such way that the robot can find at those places a recommended navigation direction. It has been also developed a robust navigation system able to navigate by means of interpreting and adapting the internalized plans to the concrete circumstances at each instant, i.e. a reactive navigation system. This reactive system is based on the artificial potential field approach with the additional feature introduced in the thesis of what we call fictitious charges as an aid to avoid local minima. As a general contribution of the thesis to the cognitive science field all the above described elements are integrated in a memory-based architecture, emphasizing the important role played by the memory in the cognitive processes of living beings and giving a conceptual turn in the usual process-based approach.

A new feature extraction method for signal classification applied to cat spinal cord signals

In the spinal cord of the anesthetized cat, spontaneous cord dorsum potentials (CDPs) appear synchronously along the lumbo-sacral segments. These CDPs have different shapes and magnitudes. Previous work has indicated that some CDPs appear to be specially associated with the activation of spinal pathways that lead to primary afferent depolarization and presynaptic inhibition. Visual detection and classification of these CDPs provides relevant information on the functional organization of the neural networks involved in the control of sensory information and allows the characterization of the changes produced by acute nerve and spinal lesions. We now present a novel feature extraction approach for signal classification, applied to CDP detection. The method is based on an intuitive procedure. We first remove by convolution the noise from the CDPs recorded in each given spinal segment. Then, we assign a coefficient for each main local maximum of the signal using its amplitude and distance to the most important maximum of the signal. These coefficients will be the input for the subsequent classification algorithm. In particular, we employ gradient boosting classification trees. This combination of approaches allows a faster and more accurate discrimination of CDPs than is obtained by other methods.

Use of Biological Motion based Cues and Ecological Sounds in the Neurorehabilitation of Apraxia

Technological progress in the area of informatics and human interface platforms create a window of opportunities for the neurorehablitation of patients with motor impairments. The CogWatch project (www.cogwatch.eu) aims to create an intelligent assistance system to improve motor planning and execution in patients with apraxia during their daily activities. Due to the brain damage caused by cardiovascular incident these patients suffer from impairments in the ability to use tools, and to sequence actions during daily tasks (such as making breakfast). Based on the common coding theory (Hommel et al., 2001) and mirror neuron primate research (Rizzolatti et al., 2001) we aim to explore use of cues, which incorporate aspects of biological motion from healthy adults performing everyday tasks requiring tool use and ecological sounds linked to the action goal. We hypothesize that patients with apraxia will benefit from supplementary sensory information relevant to the task, which will reinforce the selection of the appropriate motor plan. Findings from this study determine the type of sensory guidance in the CogWatch interface. Rationale for the experimental design is presented and the relevant literature is discussed.

Transforming neural computations and representing time

Motifs of neural circuitry seem surprisingly conserved over different areas of neocortex or of paleocortex, while performing quite different sensory processing tasks. This apparent paradox may be resolved by the fact that seemingly different problems in sensory information processing are related by transformations (changes of variables) that convert one problem into another. The same basic algorithm that is appropriate to the recognition of a known odor quality, independent of the strength of the odor, can be used to recognize a vocalization (e.g., a spoken syllable), independent of whether it is spoken quickly or slowly. To convert one problem into the other, a new representation of time sequences is needed. The time that has elapsed since a recent event must be represented in neural activity. The electrophysiological hallmarks of cells that are involved in generating such a representation of time are discussed. The anatomical relationships between olfactory and auditory pathways suggest relevant experiments. The neurophysiological mechanism for the psychophysical logarithmic encoding of time duration would be of direct use for interconverting olfactory and auditory processing problems. Such reuse of old algorithms in new settings and representations is related to the way that evolution develops new biochemistry.

ROP-1, an RNA quality-control pathway component, affects Caenorhabditis elegans dauer formation

Caenorhabditis elegans dauer formation is an alternative larval developmental pathway that the worm can take when environmental conditions become detrimental. Animals can survive several months in this stress-resistant stage and can resume normal development when growth conditions improve. Although the worms integrate a variety of sensory information to commit to dauer formation, it is currently unknown whether they also monitor internal cellular damage. The Ro ribonucleoprotein complex, which was initially described as a human autoantigen, is composed of one major 60-kDa protein, Ro60, that binds to one of four small RNA molecules, designated Y RNAs. Ro60 has been shown to bind mutant 5S rRNA molecules in Xenopus oocytes, suggesting a role for Ro60 in 5S rRNA biogenesis. Analysis of ribosomes from a C. elegans rop-1(−) strain, which is null for the expression of Ro60, demonstrated that they contain a high percentage of mutant 5S rRNA molecules, thereby strengthening the notion of a link between the rop-1 gene product and 5S rRNA quality control. The Ro particle was recently shown to be involved in the resistance of Deinococcus radiodurans to UV irradiation, suggesting a role for the Ro complex in stress resistance. We have studied the role of rop-1 in dauer formation. We present genetic and biochemical evidence that rop-1 interacts with dauer-formation genes and is involved in the regulation of the worms' entry into the dauer stage. Furthermore, we find that the rop-1 gene product undergoes a proteolytic processing step that is regulated by the dauer formation pathway via an aspartic proteinase. These results suggest that the Ro particle may function in an RNA quality-control checkpoint for dauer formation.

Phytochrome B binds with greater apparent affinity than phytochrome A to the basic helix–loop–helix factor PIF3 in a reaction requiring the PAS domain of PIF3

The signaling pathways by which the phytochrome (phy) family of photoreceptors transmits sensory information to light-regulated genes remain to be fully defined. Evidence for a relatively direct pathway has been provided by the binding of one member of the family, phyB, to a promoter-element-bound, basic helix–loop–helix protein, PIF3, specifically upon light-induced conversion of the photoreceptor molecule to its biologically active conformer (Pfr). Here, we show that phyA also binds selectively and reversibly to PIF3 upon photoconversion to Pfr, but that the apparent affinity of PIF3 for phyA is 10-fold lower than for phyB. This result is consistent with previous in vivo data from PIF3-deficient Arabidopsis, indicating that PIF3 has a major role in phyB signaling, but a more minor role in phyA signaling. We also show that phyB binds stoichiometrically to PIF3 at an equimolar ratio, suggesting that the resultant complex is the unit active in transcriptional regulation at target promoters. Deletion mapping suggests that a 37-aa segment present at the N terminus of phyB, but absent from phyA, contributes strongly to the high binding affinity of phyB for PIF3. Conversely, deletion mapping and point mutation analysis of PIF3 for determinants involved in recognition of phyB indicates that the PAS domain of PIF3 is a major contributor to this interaction, but that a second determinant in the C-terminal domain is also necessary.

Single neuron control over a complex motor program.

While there are many instances of single neurons that can drive rhythmic stimulus-elicited motor programs, such neurons have seldom been found to be necessary for motor program function. In the isolated central nervous system of the marine mollusc Tritonia diomedea, brief stimulation (1 sec) of a peripheral nerve activates an interneuronal central pattern generator that produces the long-lasting (approximately 30-60 sec) motor program underlying the animal's rhythmic escape swim. Here, we identify a single interneuron, DRI (for dorsal ramp interneuron), that (i) conveys the sensory information from this stimulus to the swim central pattern generator, (ii) elicits the swim motor program when driven with intracellular stimulation, and (iii) blocks the depolarizing "ramp" input to the central pattern generator, and consequently the motor program itself, when hyperpolarized during the nerve stimulus. Because most of the sensory information appears to be funneled through this one neuron as it enters the pattern generator, DRI presents a striking example of single neuron control over a complex motor circuit.