| Publications of year 2000 |
| Book chapters |
| Articles in journals |
| Abstract: | Neuronal responses are conspicuously variable. We focus on one particular aspect of that variability: the precision of action potential timing. We show that for common models of noisy spike generation, elementary considerations imply that such variability is a function of the input, and can be made arbitrarily large or small by a suitable choice of inputs. Our considerations are expected to extend to virtually any mechanism of spike generation, and we illustrate them with data from the visual pathway. Thus, a simplification usually made in the application of information theory to neural processing is violated: noise is not independent of the message. However, we also show the existence of error-correcting topologies, which can achieve better timing reliability than their components |
| Abstract: | Neuronal network models have been proposed for the organization of evaluation and decision processes in prefrontal circuitry and their putative neuronal and molecular bases. The models all include an implementation and simulation of an elementary reward mechanism. Their central hypothesis is that tentative rules of behavior, which are coded by clusters of active neurons in prefrontal cortex, are selected or rejected based on an evaluation by this reward signal, which may be conveyed, for instance, by the mesencephalic dopaminergic neurons with which the prefrontal cortex is densely interconnected. At the molecular level, the reward signal is postulated to be a neurotransmitter such as dopamine, which exerts a global modulatory action on prefrontal synaptic efficacies, either via volume transmission or via targeted synaptic triads. Negative reinforcement has the effect of destabilizing the currently active rule-coding clusters; subsequently, spontaneous activity varies again from one cluster to another, giving the organism the chance to discover and learn a new rule. Thus, reward signals function as effective selection signals that either maintain or suppress currently active prefrontal representations as a function of their current adequacy. Simulations of this variation-selection have successfully accounted for the main features of several major tasks that depend on prefrontal cortex integrity, such as the delayed-response test, the Wisconsin card sorting test, the Tower of London test and the Stroop test. For the more complex tasks, we have found it necessary to supplement the external reward input with a second mechanism that supplies an internal reward; it consists of an auto-evaluation loop which short-circuits the reward input from the exterior. This allows for an internal evaluation of covert motor intentions without actualizing them as behaviors, by simply testing them covertly by comparison with memorized former experiences. This element of architecture gives access to enhanced rates of learning via an elementary process of internal or covert mental simulation. We have recently applied these ideas to a new model, developed with M. Kerszberg, which hypothesizes that prefrontal cortex and its reward-related connections contribute crucially to conscious effortful tasks. This model distinguishes two main computational spaces within the human brain: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative and attentional processors. We postulate that workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice; they selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously co-activated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. This model makes predictions concerning the spatio-temporal activation patterns during brain imaging of cognitive tasks, particularly concerning the conditions of activation of dorsolateral prefrontal cortex and anterior cingulate, their relation to reward mechanisms, and their specific reaction during error processing |
| Abstract: | This study was designed to test the Fundamental Difference Hypoth- esis (Bley-Vroman, 1988), which states that, whereas children are known to learn language almost completely through (implicit) do- main-specific mechanisms, adults have largely lost the ability to learn a language without reflecting on its structure and have to use alternative mechanisms, drawing especially on their problem-solving capacities, to learn a second language. The hypothesis implies that only adults with a high level of verbal analytical ability will reach near-native competence in their second language, but that this ability will not be a significant predictor of success for childhood second language acquisition. A study with 57 adult Hungarian-speaking immigrants confirmed the hypothesis in the sense that very few adult immigrants scored within the range of child arrivals on a grammaticality judgment test, and that the few who did had high levels of verbal analytical ability; this ability was not a significant predictor for childhood arrivals. This study replicates the findings of Johnson and Newport (1989) and provides an explanation for the apparent exceptions in their study. These findings lead to a reconceptualization of the Critical Period Hypothesis: If the scope of this hypothesis is limited to implicit learning mechanisms, then it appears that there may be no exceptions to the age effects that the hypothesis seeks to explain |
| Abstract: | We studied the transition of stimuli from novel to familiar in visual search and in the guidance of attention to a particular object. Ability to identify an object improved dramatically over several days of training. The learning was specific for the object's position in the visual field, orientation and configuration. Improvement was initially localized to one or two positions near the fixation spot and then expanded radially to include the full area of the stimulus array. Characteristics of this learning process may reflect a shift in the cortical representation of complex features toward earlier stages in the visual pathway |
| Abstract: | Progression of inflammatory processes correlates with the release of cell-derived mediators from the local site of inflammation. These mediators, including cytokines of the IL-1 and IL-6 families, act on host cells and exert their action by activating their signal transduction pathways leading to specific target gene activation. Parthenolide, a sesquiterpene lactone found in many medical plants, is an inhibitor of IL-1-type cytokine signaling that blocks the activation of NF-kappaB. Here we show that parthenolide is also an effective inhibitor of IL-6-type cytokines. It inhibits IL-6-type cytokine-induced gene expression by blocking STAT3 phosphorylation on Tyr705. This prevents STAT3 dimerization necessary for its nuclear translocation and consequently STAT3-dependent gene expression. This is a new molecular mechanism of parthenolide action that additionally explains its anti-inflammatory activities. |
| Conference proceedings |
| Miscellaneous |
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