Deontological and altruistic guilt: evidence for distinct neurobiological substrates.

The feeling of guilt is a complex mental state underlying several human behaviors in both private and social life. From a psychological and evolutionary viewpoint, guilt is an emotional and cognitive function, characterized by prosocial sentiments, entailing specific moral believes, which can be predominantly driven by inner values (deontological guilt) or by more interpersonal situations (altruistic guilt). The aim of this study was to investigate whether there is a distinct neurobiological substrate for these two expressions of guilt in healthy individuals. We first run two behavioral studies, recruiting a sample of 72 healthy volunteers, to validate a set of stimuli selectively evoking deontological and altruistic guilt, or basic control emotions (i.e., anger and sadness). Similar stimuli were reproduced in a event-related functional magnetic resonance imaging (fMRI) paradigm, to investigate the neural correlates of the same emotions, in a new sample of 22 healthy volunteers. We show that guilty emotions, compared to anger and sadness, activate specific brain areas (i.e., cingulate gyrus and medial frontal cortex) and that different neuronal networks are involved in each specific kind of guilt, with the insula selectively responding to deontological guilt stimuli. This study provides evidence for the existence of distinct neural circuits involved in different guilty feelings. This complex emotion might account for normal individual attitudes and deviant social behaviors. Moreover, an abnormal processing of specific guilt feelings might account for some psychopathological manifestation, such as obsessive-compulsive disorder and depression.

Ultrastructural analysis of neuronal plasticity in the adult mouse

ABSTRACT Adult neuronal plasticity is a term that corresponds to a set of biological mechanisms allowing a neuronal circuit to respond and adapt to modifications of the received inputs. Mystacial whiskers of the mouse are the starting point of a major sensory pathway that provides the animal with information from its immediate environment. Through whisking, information is gathered that allows the animal to orientate itself and to recognize objects. This sensory system is crucial for nocturnal behaviour during which vision is not of much use. Sensory information of the whiskers are sent via brainstem and thalamus to the primary somatosensory area (S1) of the cerebral cortex in a strictly topological manner. Cell bodies in the layer N of S 1 are arranged in ring forming structures called barrels. As such, each barrel corresponds to the cortical representation in layer IV of a single whisker follicle. This histological feature allows to identify with uttermost precision the part of the cortex devoted to a given whisker and to study modifications induced by different experimental conditions. The condition used in the studies of my thesis is the passive stimulation of one whisker in the adult mouse for a period of 24 hours. It is performed by glueing a piece of metal on one whisker and placing the awake animal in a cage surrounded by an electromagnetic coil that generates magnetic field burst inducing whisker movement at a given frequency during 24 hours. I analysed the ultrastructure of the barrel corresponding the stimulated whisker using serial sections electron microscopy and computer-based three-dimensional reconstructions; analysis of neighbouring, unstimulated barrels as well as those from unstimulated mice served as control. The following elements were structurally analyzed: the spiny dendrites, the axons of excitatory as well as inhibitory cells, their connections via synapses and the astrocytic processes. The density of synapses and spines is upregulated in a barrel corresponding to a stimulated whisker. This upregulation is absent in the BDNF heterozygote mice, indicating that a certain level of activity-dependent released BDNF is required for synaptogenesis in the adult cerebral cortex. Synpaptogenesis is correlated with a modification of the astrocytes that place themselves in closer vicinity of the excitatory synapses on spines. Biochemical analysis revealed that the astrocytes upregulate the expression of transporters by which they internalise glutamate, the neurotransmitter responsible for the excitatory response of cortical neurons. In the final part of my thesis, I show that synaptogenesis in the stimulated barrel is due to the increase in the size of excitatory axonal boutons that become more frequently multisynaptic, whereas the inhibitory axons do not change their morphology but form more synapses with spines apposed to them. Taken together, my thesis demonstrates that all the cellular elements present in the neuronal tissue of the adult brain contribute to activity-dependent cortical plasticity and form part of a mechanism by which the animal responds to a modified sensory experience. Throughout life, the neuronal circuit keeps the faculty to adapt its function. These adaptations are partially transitory but some aspects remain and could be the structural basis of a memory trace in the cortical circuit. RESUME La plasticité neuronale chez l'adulte désigne un ensemble de mécanismes biologiques qui permettent aux circuits neuronaux de répondre et de s'adapter aux modifications des stimulations reçues. Les vibrisses des souris sont un système crucial fournissant des informations sensorielles au sujet de l'environnement de l'animal. L'information sensorielle collectée par les vibrisses est envoyée via le tronc cérébral et le thalamus à l'aire sensorielle primaire (S 1) du cortex cérébral en respectant strictement la somatotopie. Les corps cellulaires dans la couche IV de S 1 sont organisés en anneaux délimitant des structures nommées tonneaux. Chaque tonneau reçoit l'information d'une seule vibrisse et l'arrangement des tonneaux dans le cortex correspond à l'arrangement des vibrisses sur le museau de la souris. Cette particularité histologique permet de sélectionner avec certitude la partie du cortex dévolue à une vibrisse et de l'étudier dans diverses conditions. Le paradigme expérimental utilisé dans cette thèse est la stimulation passive d'une seule vibrisse durant 24 heures. Pour ce faire, un petit morceau de métal est collé sur une vibrisse et la souris est placée dans une cage entourée d'une bobine électromagnétique générant un champ qui fait vibrer le morceau de métal durant 24 heures. Nous analysons l'ultrastructure du cortex cérébral à l'aide de la microscopie électronique et des coupes sériées permettant la reconstruction tridimensionnelle à l'aide de logiciels informatiques. Nous observons les modifications des structures présentes : les dendrites épineuses, les axones des cellules excitatrices et inhibitrices, leurs connections par des synapses et les astrocytes. Le nombre de synapses et d'épines est augmenté dans un tonneau correspondant à une vibrisse stimulée 24 heures. Basé sur cela, nous montrons dans ces travaux que cette réponse n'est pas observée dans des souris hétérozygotes BDNF+/-. Cette neurotrophine sécrétée en fonction de l'activité neuronale est donc nécessaire pour la synaptogenèse. La synaptogenèse est accompagnée d'une modification des astrocytes qui se rapprochent des synapses excitatrices au niveau des épines dendritiques. Ils expriment également plus de transporteurs chargés d'internaliser le glutamate, le neurotransmetteur responsable de la réponse excitatrice des neurones. Nous montrons aussi que les axones excitateurs deviennent plus larges et forment plus de boutons multi-synaptiques à la suite de la stimulation tandis que les axones inhibiteurs ne changent pas de morphologie mais forment plus de synapses avec des épines apposées à leur membrane. Tous les éléments analysés dans le cerveau adulte ont maintenu la capacité de réagir aux modifications de l'activité neuronale et répondent aux modifications de l'activité permettant une constante adaptation à de nouveaux environnements durant la vie. Les circuits neuronaux gardent la capacité de créer de nouvelles synapses. Ces adaptations peuvent être des réponses transitoires aux stimuli mais peuvent aussi laisser une trace mnésique dans les circuits.

Synchronization of symmetric chaotic systems

This paper contains a study of the synchronization by homogeneous nonlinear driving of systems that are symmetric in phase space. The main consequence of this symmetry is the ability of the response to synchronize in more than just one way to the driving systems. These different forms of synchronization are to be understood as generalized synchronization states in which the motions of drive and response are in complete correlation, but the phase space distance between them does not converge to zero. In this case the synchronization phenomenon becomes enriched because there is multistability. As a consequence, there appear multiple basins of attraction and special responses to external noise. It is shown, by means of a computer simulation of various nonlinear systems, that: (i) the decay to the generalized synchronization states is exponential, (ii) the basins of attraction are symmetric, usually complicated, frequently fractal, and robust under the changes in the parameters, and (iii) the effect of external noise is to weaken the synchronization, and in some cases to produce jumps between the various synchronization states available

Chaotic systems with a null conditional Lyapunov exponent under nonlinear driving.

Control of a chaotic system by homogeneous nonlinear driving, when a conditional Lyapunov exponent is zero, may give rise to special and interesting synchronizationlike behaviors in which the response evolves in perfect correlation with the drive. Among them, there are the amplification of the drive attractor and the shift of it to a different region of phase space. In this paper, these synchronizationlike behaviors are discussed, and demonstrated by computer simulation of the Lorentz model [E. N. Lorenz, J. Atmos. Sci. 20 130 (1963)] and the double scroll [T. Matsumoto, L. O. Chua, and M. Komuro, IEEE Trans. CAS CAS-32, 798 (1985)].

Gambling against neglect: unconscious spatial biases induced by reward reinforcement in healthy people and brain-damaged patients.

Orienting attention in space recruits fronto-parietal networks whose damage results in unilateral spatial neglect. However, attention orienting may also be governed by emotional and motivational factors; but it remains unknown whether these factors act through a modulation of the fronto-parietal attentional systems or distinct neural pathways. Here we asked whether attentional orienting is affected by learning about the reward value of targets in a visual search task, in a spatially specific manner, and whether these effects are preserved in right-brain damaged patients with left spatial neglect. We found that associating rewards with left-sided (but not right-sided) targets during search led to progressive exploration biases towards left space, in both healthy people and neglect patients. Such spatially specific biases occurred even without any conscious awareness of the asymmetric reward contingencies. These results show that reward-induced modulations of space representation are preserved despite a dysfunction of fronto-parietal networks associated with neglect, and therefore suggest that they may arise through spared subcortical networks directly acting on sensory processing and/or oculomotor circuits. These effects could be usefully exploited for potentiating rehabilitation strategies in neglect patients.

Closed loop electrical muscle stimulation in spinal cord injured rehabilitation

The effect of motor training using closed loop controlled Functional Electrical Stimulation (FES) on motor performance was studied in 5 spinal cord injured (SCI) volunteers. The subjects trained 2 to 3 times a week during 2 months on a newly developed rehabilitation robot (MotionMaker?). The FES induced muscle force could be adequately adjusted throughout the programmed exercises by the way of a closed loop control of the stimulation currents. The software of the MotionMaker? allowed spasms to be detected accurately and managed in a way to prevent any harm to the SCI persons. Subjects with incomplete SCI reported an increased proprioceptive awareness for motion and were able to achieve a better voluntary activation of their leg muscles during controlled FES. At the end of the training, the voluntary force of the 4 incomplete SCI patients was found increased by 388% on their most affected leg and by 193% on the other leg. Active mobilisation with controlled FES seems to be effective in improving motor function in SCI persons by increasing the sensory input to neuronal circuits involved in motor control as well as by increasing muscle strength.

Electrophysiological markers of rapid cognitive decline in mild cognitive impairment

Electroencephalography (EEG) is an easily accessible and low-cost modality that might prove to be a particularly powerful tool for the identification of subtle functional changes preceding structural or metabolic deficits in progressive mild cognitive impairment (PMCI). Most previous contributions in this field assessed quantitative EEG differences between healthy controls, MCI and Alzheimer's disease(AD) cases leading to contradictory data. In terms of MCI conversion to AD, certain longitudinal studies proposed various quantitative EEG parameters for an a priori distinction between PMCI and stable MCI. However, cross-sectional comparisons revealed a substantial overlap in these parameters between MCI patients and elderly controls. Methodological differences including variable clinical definition of MCI cases and substantial interindividual differences within the MCI group could partly explain these discrepancies. Most importantly, EEG measurements without cognitive demand in both cross-sectional and longitudinal designs have demonstrated limited sensitivity and generally do not produce significant group differences in spectral EEG parameters. Since the evolution of AD is characterized by the progressive loss of functional connectivity within neocortical association areas, event-modulated EEG dynamic analysis which makes it possible to investigate the functional activation of neocortical circuits may represent a more sensitive method to identify early alterations of neuronal networks predictive of AD development among MCI cases. The present review summarizes clinically significant results of EEG activation studies in this field and discusses future perspectives of research aiming to reach an early and individual prediction of cognitive decline in healthy elderly controls.

On the thermal noise introduced by a resistor in a circuit

Comentari sobre l'article publicat anteriorment pels mateixos autors: Vargas, M; Pallás, R; The seemingly paradoxical noise behaviour some active circuits. IEEE Transactions on Instrumentation and Measurement. 1994, vol. 43, núm. 5, p. 764-767

A two-dimensional doppler-radiometer for earth observation

Compared to synthetic aperture radars (SARs), the angular resolution of microwave radiometers is quite poor. Traditionally, it has been limited by the physical size of the antenna. However, the angular resolution can be improved by means of aperture synthesis interferometric techniques. A narrow beam is synthesized during the image formation processing of the cross-correlations measured at zero-lag between pairs of signals collected by an array of antennas. The angular resolution is then determined by the maximum antenna spacing normalized to the wavelength (baseline). The next step in improving the angular resolution is the Doppler-Radiometer, somehow related to the super-synthesis radiometers and the Radiometer-SAR. This paper presents the concept of a three-antenna Doppler-Radiometer for 2D imaging. The performance of this instrument is evaluated in terms of angular/spatial resolution and radiometric sensitivity, and an L-band illustrative example is presented.

Power supply noise and logic error probability

Voltage fluctuations caused by parasitic impedances in the power supply rails of modern ICs are a major concern in nowadays ICs. The voltage fluctuations are spread out to the diverse nodes of the internal sections causing two effects: a degradation of performances mainly impacting gate delays anda noisy contamination of the quiescent levels of the logic that drives the node. Both effects are presented together, in thispaper, showing than both are a cause of errors in modern and future digital circuits. The paper groups both error mechanismsand shows how the global error rate is related with the voltage deviation and the period of the clock of the digital system.

Via-configurable transistor array: a regular design technique to improve ICs yield

Process variations are a major bottleneck for digital CMOS integrated circuits manufacturability and yield. That iswhy regular techniques with different degrees of regularity are emerging as possible solutions. Our proposal is a new regular layout design technique called Via-Configurable Transistors Array (VCTA) that pushes to the limit circuit layout regularity for devices and interconnects in order to maximize regularity benefits. VCTA is predicted to perform worse than the Standard Cell approach designs for a certain technology node but it will allow the use of a future technology on an earlier time. Ourobjective is to optimize VCTA for it to be comparable to the Standard Cell design in an older technology. Simulations for the first unoptimized version of our VCTA of delay and energy consumption for a Full Adder circuit in the 90 nm technology node are presented and also the extrapolation for Carry-RippleAdders from 4 bits to 64 bits.

Voltage fluctuations in IC power supply distribution

The supply voltage decrease and powerconsumption increase of modern ICs made the requirements for low voltage fluctuation caused by packaging and on-chip parasitic impedances more difficult to achieve. Most of the research works on the area assume that all the nodes of the chip are fed at thesame voltage, in such a way that the main cause of disturbance or fluctuation is the parasitic impedance of packaging. In the paper an approach to analyze the effect of high and fast current demands on the on-chip power supply network. First an approach to model the entire network by considering a homogeneous conductive foil is presented. The modification of the timing parameters of flipflops caused by spatial voltage drops through the IC surface are also investigated.

Disseny d’un circuit analògic reconfigurable

En l’actualitat, l’electrònica digital s’està apoderant de la majoria de camps de desenvolupament, ja que ofereix un gran ventall de possibilitats que permeten fer front a gran quantitat de problemàtiques. Poc a Poc s’ha anat prescindint el màxim possible de l’electrònica analògica i en el seu lloc s’han utilitzat sistemes microprocessats, PLDs o qualsevol altre dispositiu digital, que proporciona beneficis enlluernadors davant la fatigosa tasca d’implementar una solució analògica.Tot i aquesta tendència, és inevitable la utilització de l’electrònica analògica, ja que el mon que ens envolta és l’entorn en el que han de proporcionar servei els diferents dissenys que es realitzen, i aquest entorn no és discret sinó continu. Partint d’aquest punt ben conegut hem de ser conscients que com a mínim els filtres d’entrada i sortida de senyal juntament amb els convertidors D/A A/D mai desapareixeran.Així doncs, aquests circuits analògics, de la mateixa forma que els digitals, han de sercomprovats un cop dissenyats, és en aquest apartat on el nostre projecte desenvoluparà un paper protagonista, ja que serà la eina que ha de permetre obtenir les diferents senyals característiques d’un determinat circuit, per posteriorment realitzar els tests que determinaran si es compleix el rang de correcte funcionament, i en cas de no complir, poder concretar quin paràmetre és el causant del defecte

Re-usable ASIC integrationverification software architecture

Mikropiirien valmistus- ja suunnittelutekniikoiden kehittyminen mahdollistaa yhä monimutkaisempien mikropiirien valmistamisen. Piirien verifioinnista onkin tullut prosessin aikaa vievin osa,sillä kompleksisuuden kasvaessa kasvaa verifioinnin tarve eksponentiaalisesti. Vaikka erinäisiä strategioita piirien integroinnin verifiointiin on esitetty, mm. verifioinnin jakaminen koko suunnitteluprosessin ajalle, jopa yli puolet koko piirin suunnitteluun ja valmistukseen käytetystä työmäärästä kuluu verifiointiin. Uudelleenkäytettävät komponentit ovat pääosassa piirin suunnittelussa, mutta verifioinnissa uudelleenkäytettävyyttä ei ole otettu kunnolla käyttöön ainakaan verifiointiohjelmistojen osalta. Tämä diplomityö esittelee uudelleenkäytettävän mikropiirien verifiointiohjelmistoarkkitehtuurin, jolla saadaan verifiointitaakkaa vähennettyä poistamalla verifioinnissa käytettävien ohjelmistojen uudelleensuunnittelun ja toteuttamisen tarvetta.