Aging modulates fronto-temporal cortical interactions during lexical production. A dynamic causal modeling study.

In this dynamic causal modeling (DCM) study, we evaluated the effect of age on the effective connectivity of a cerebral network involved in lexical production. Younger and older adults performed an object naming task during fMRI. The DCM was used to explore the interactions between four regions of interest: the occipital cortex, OC; the lateral temporal cortex, LTC; the medial temporal cortex, MTC; and the inferior frontal cortex, IFC. We mainly focused on the modulation of the fronto-temporal interaction, according to the hypothesis that aging requires strategies that modulate the access to the semantic knowledge, either through a neural reserve mechanism (increased MTC-LTC connectivity) or through a neural compensation mechanism (supplementary IFC-MTC connectivity). For younger adults, our results indicated a bi-directional interaction between the left IFC and LTC suggesting a typical activation related to lexico-semantic representations. For older adults, our results reveal the existence of bi-directional interaction between the IFC and MTC, but not between the IFC and LTC - which in turn suggests that older adults adapt a new strategy, via supplemental access to conceptual access and semantic retrieval processes. This neural compensation strategy would be facilitated by a top-down mechanism from the IFC to the MTC. We discuss our results in the context of the possible additional strategies used by older compared to younger adults, to retrieve and produce words.

Neural correlates of the healthiness evaluation processes of food labels.

OBJECTIVES: This fMRI study evaluated the cognitive mechanisms and the cerebral substrates when evaluating the healthiness of food products from nutritional information displayed either with a traffic light (TL) system, a colored nutritional label, or with a guideline daily amount (GDA) system, a numeric label. We postulated that TL label would recruit emotional processes and activation of subjacent cerebral regions (e.g. insula and amygdala). On the contrary, the nutritional information presented in a GDA label, would recruit, due to its numeric format and higher complexity, supplementary cognitive processes and activation of related brain regions (e.g. middle and superior frontal as well as parietal cortices). METHODS: We examined 50 healthy participants during an evaluation task on the healthiness of real food products from nutritional information only. Per total, 60 food products nutritional labels have been presented, with either colored (TL) or numeric (GDA) nutritional information and three levels of complexity of nutritional information. RESULTS: In line with our predictions, evaluations based on GDA recruited prefrontal and parietal regions reported for analytic processes. Contrary to our predictions, the same network has been recruited when evaluations were based on TL. Finally, we found significant correlation between response time and the superior parietal lobule in the GDA condition. DISCUSSION: Our results suggested that TL did not have an effect on the used strategy compared to GDA, based on calculation and arithmetic processes. Correlations between response time and brain activations suggested a significant involvement of the arithmetic mechanisms in the evaluation of food healthiness.

Functional MRI evidence for the decline of word retrieval and generation during normal aging.

This fMRI study aimed to explore the effect of normal aging on word retrieval and generation. The question addressed is whether lexical production decline is determined by a direct mechanism, which concerns the language operations or is rather indirectly induced by a decline of executive functions. Indeed, the main hypothesis was that normal aging does not induce loss of lexical knowledge, but there is only a general slowdown in retrieval mechanisms involved in lexical processing, due to possible decline of the executive functions. We used three tasks (verbal fluency, object naming, and semantic categorization). Two groups of participants were tested (Young, Y and Aged, A), without cognitive and psychiatric impairment and showing similar levels of vocabulary. Neuropsychological testing revealed that older participants had lower executive function scores, longer processing speeds, and tended to have lower verbal fluency scores. Additionally, older participants showed higher scores for verbal automatisms and overlearned information. In terms of behavioral data, older participants performed as accurate as younger adults, but they were significantly slower for the semantic categorization and were less fluent for verbal fluency task. Functional MRI analyses suggested that older adults did not simply activate fewer brain regions involved in word production, but they actually showed an atypical pattern of activation. Significant correlations between the BOLD (Blood Oxygen Level Dependent) signal of aging-related (A > Y) regions and cognitive scores suggested that this atypical pattern of the activation may reveal several compensatory mechanisms (a) to overcome the slowdown in retrieval, due to the decline of executive functions and processing speed and (b) to inhibit verbal automatic processes. The BOLD signal measured in some other aging-dependent regions did not correlate with the behavioral and neuropsychological scores, and the overactivation of these uncorrelated regions would simply reveal dedifferentiation that occurs with aging. Altogether, our results suggest that normal aging is associated with a more difficult access to lexico-semantic operations and representations by a slowdown in executive functions, without any conceptual loss.

An fMRI study of the social competition in healthy subjects.

Social interaction requires the ability to infer another person's mental state (Theory of Mind, ToM) and also executive functions. This fMRI study aimed to identify the cerebral correlates activated by ToM during a specific social interaction, the human-human competition. In this framework, we tested a conflict resolution task (Stroop) adapted to a virtual situation of competition. The participants were instructed to play in order to win either against a human-like competitor (human-human competition) or against a non-human competitor (human-machine competition). Only the human-human competition requires ToM as this type of competition is performed under social interaction. We identified first the classical network of executive regions activated by Stroop. Secondly, we identified the social (human-human) competition regions, represented by the bilateral superior and inferior frontal gyri, the anterior cingulate, the insula, the superior and anterior temporal, the hippocampus, the fusiform gyrus, the cuneus and the precuneus. Finally, we identified the executive regions that were modulated by the human-human competition, i.e., the executive control regions additionally activated when mentalizing in the context of social competition. They constituted a network predominant to the right and composed of the superior and middle frontal, anterior cingulate, insula and fusiform gyrus. We suggest that our experimental paradigm may be useful in exploration of the cerebral correlates of social adjustments in several situations such as psychiatric disorders presenting executive and social dysfunctions.

Catching falling objects: the role of the cerebellum in processing sensory-motor errors that may influence updating of feedforward commands. An fMRI study.

The human motor system continuously adapts to changes in the environment by comparing differences between the brain's predicted outcome of a certain behavior and the observed outcome. This discrepancy signal triggers a sensory-motor error and it is assumed that the cerebellum is a key structure in updating this error and associated feedforward commands. Using fMRI, the aim of the present study was to determine the main cerebellar structures that are involved in the processing of sensory-motor errors and in updating feedforward commands when simply catching a falling ball without displacement of the hand. Subjects only grasped the ball with their fingers when receiving it in their hand. By contrasting functional imaging signal obtained in conditions in which it was possible and impossible to predict the weight of the ball, we aimed to highlight sensory-motor error processing which we expected to be more marked in the conditions without prediction (less accurate feedforward process or more important feedback corrections) with respect to conditions with prediction (more accurate feedforward process or less important feedback corrections). When catching a falling ball and the possibility of prediction about the ball weight was manipulated, our results showed that both the right and left cerebellum is engaged in processing sensory-motor errors. It may also be involved in updating feedforward motor commands, perhaps on a trial by trial basis. In addition, when subjects were blindfolded, we observed a similar network but centered in a more anterior portion of the right cerebellum and we noted the presence of a cerebellar-thalamo-prefrontral network that may be involved in cognitive prediction (rather than sensory prediction) about ball weight.

Simple relationship between acid dissociation constant and minimal pH for microbial growth in laboratory medium.

A simple relationship was observed in growth medium, between the dissociation constant (via the pKa) of the acid used to control pH and the minimum pH at which Salmonellae and Escherichia coli initiate growth. From this new relationship, a simple method was proposed to predict the minimum growth pH for a given strain and different acid types. This method, illustrated on Listeria monocytogenes, would merely require the knowledge of two minimum pH values, one for a strong acid (e.g. hydrochloric acid) and one for a weak acid (e.g. acetic or propionic acid). From these two values, it seems possible to estimate for a given growth medium, the minimum pH value for any other acid within the defined pKa range.

[Interpretative reading and quality control of an antibiotic sensitivity test using an expert system. Application to the API ATB system and Enterobacteriaceae]. / Lecture interprétative et contrôle de qualité de l'antibiogramme à l'aide d'un système expert. Application à l'automate API ATB et aux entérobactéries.

An expert system (cadi-yac), written in Turbo-Prolog and working on IBM PC and Bacanal + (a management software of microbiology laboratory) was used to recognize and correct the phenotype of antibiotic sensibility. The results were there of API ATB system. The knowledge was adapted from two references works. A routine use of the expert system give a correct recognition of enzymatic profile in more than 80% cases for the beta-lactams and more than 98% cases for the aminosides. The mistakes detected by cadi-yac, were often interpreted as deficiency of API system by humans experts. The expert system mistakes (1.5%) were due composites phenotypes.

[Bacteriostatic and bactericidal antibiotics: differences in subinhibitory concentration effects on the growth of Escherichia coli]. / Antibiotiques bactériostatiques et bactéricides: différences des effets des concentrations subinhibitrices sur la croissance de Escherichia coli.

The growth of Escherichia coli in synthetic medium was mathematically analysed at subinhibitory levels of bactericidal and bacteriostatic antibiotics. Over a threshold of concentration, bactericidal antibiotics induce an unexpected change of growth pattern. Bacteriostatic antibiotics induce a progressive effect linked to a continuously altered growth pattern that still remains close to the controls. This fundamental differential of antibiotic effects is reflecting well-known bacteriostatic or bactericidal phenomena. In vitro this analysis of the growth enables to measure the level of the antibiotic sensitivity. In vivo, these results must be taken into account when subinhibitory concentrations of antimicrobial agent are reached at the infection site.

Mathematical modelling of growth of Escherichia coli at subinhibitory levels of chloramphenicol or tetracyclines.

A mathematical model is suggested to describe the subinhibitory effects of chloramphenicol upon growth of Escherichia coli. It represents a generalization of Monod's equation. Our model was constructed entirely on the basis of biochemical factors, such as the reversibility of the interaction between the drug and its ribosomal target or intracellular uptake. The subinhibitory effects of chloramphenicol were satisfactorily described by this law within the range of 0.4-2.4 micrograms/ml. After simplifying the equation, this model was extrapolated to provide an accurate description of the mode of action of other bacteriostatic antibiotics which also inhibit the 50-S ribosomal subunit (tetracycline and doxycycline). The expanded model seems to accurately typify the effect of these antibiotics, whereas bactericidal aminoglycosides follow a completely different growth law.

Mathematical modelling of bacterial growth at subinhibitory levels of aminoglycosides.

The subinhibitory effect of antibiotics has often been studied without any clear theoretical framework; we have chosen to use mathematical bacterial growth modelling as a useful tool to analyse these biological states in a more rigorous manner. Since their mode of action and molecular target are relatively well known, aminoglycosides were well suited for this more sophisticated study of subinhibitory action. We have shown that two models (the Monod and the logistic models) regularly used in bacteriology, were adequate to describe these effects in a glucose-limited medium. A change of model, according to antibiotic concentration, revealed the existence of two separate actions. At lower concentrations, inhibition affected mainly glucose use, the substrate remained limiting and growth mode did not change. As soon as the concentration exceeded a threshold, growth was totally disturbed, probably through a physiological "catastrophe". This threshold can be used to estimate bacterial susceptibility to these antibiotics.

[Demonstration of an inoculum effect on the estimation of the minimal inhibitory concentration of LY 146032]. / Mise en évidence d'un effet inoculum sur l'estimation de la concentration minimale inhibitrice du LY 146032.

This work has been performed to study the inoculum effect on the in vitro activity of LY 146032, a new lipopeptide antibiotic. A statistical analysis (X2 and t test) of the data concerning the MIC of different bacterial groups has been carried out to appreciate the phenomenon. The activity of vancomycin has been compared. A major inoculum effect has been detected for LY 146032. It must be taken into account to evaluate the activity of this new antibiotic.