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Numbers are thought to be spatially organized along a left-to-right horizontal axis with small/large numbers on its left/right respectively. Behavioral evidence for this mental number line (MNL) comes from studies showing that the reallocation of spatial attention by active left/right head rotation facilitated the generation of small/large numbers respectively. While spatial biases in random number generation (RNG) during active movement are well established in adults, comparable evidence in children is lacking and it remains unclear whether and how children's access to the MNL is affected by active head rotation. To get a better understanding of the development of embodied number processing, we investigated the effect of active head rotation on the mean of generated numbers as well as the mean difference between each number and its immediately preceding response (the first order difference; FOD) not only in adults ( n = 24), but also in 7- to 11-year-old elementary school children ( n = 70). Since the sign and absolute value of FODs carry distinct information regarding spatial attention shifts along the MNL, namely their direction (left/right) and size (narrow/wide) respectively, we additionally assessed the influence of rotation on the total of negative and positive FODs regardless of their numerical values as well as on their absolute values. In line with previous studies, adults produced on average smaller numbers and generated smaller mean FODs during left than right rotation. More concretely, they produced more negative/positive FODs during left/right rotation respectively and the size of negative FODs was larger (in terms of absolute value) during left than right rotation. Importantly, as opposed to adults, no significant differences in RNG between left and right head rotations were observed in children. Potential explanations for such age-related changes in the effect of active head rotation on RNG are discussed. Altogether, the present study confirms that numerical processing is spatially grounded in adults and suggests that its embodied aspect undergoes significant developmental changes.

Prior research has provided strong evidence for spatial-numerical associations. Single digits can for instance act as attentional cues, orienting visuo-spatial attention to the left or right hemifield depending on the digit's magnitude, thus facilitating target detection in the cued hemifield (left/right hemifield after small/large digits, respectively). Studies using other types of behaviourally or biologically relevant central cues known to elicit automated symbolic attention orienting effects such as arrows or gaze have shown that the initial facilitation of cued target detection can turn into inhibition at longer stimulus onset asynchronies (SOAs). However, no studies so far investigated whether inhibition of return (IOR) is also observed using digits as uninformative central cues. To address this issue we designed an attentional cueing paradigm using SOAs ranging from 500 ms to 1650 ms. As expected, the results showed a facilitation effect at the relatively short 650 ms SOA, replicating previous findings. At the long 1650 ms SOA, however, participants were faster to detect targets in the uncued hemifield compared to the cued hemifield, showing an IOR effect. A control experiment with letters showed no such congruency effects at any SOA. These findings provide the first evidence that digits not only produce facilitation effects at shorter intervals, but also induce inhibitory effects at longer intervals, confirming that Arabic digits engage automated symbolic orienting of attention., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Recent behavioural and brain imaging studies have provided evidence for rightward and leftward attention shifts while solving addition and subtraction problems respectively, suggesting that mental arithmetic makes use of mechanisms akin to those underlying spatial attention. However, this hypothesis mainly relies on correlative data and the causal relevance of spatial attention for mental arithmetic remains unclear. In order to test whether the mechanisms underlying spatial attention are necessary to perform arithmetic operations, we compared the performance of right brain-lesioned patients, with and without left unilateral neglect, and healthy controls in addition and subtraction of two-digit numbers. We predicted that patients with left unilateral neglect would be selectively impaired in the subtraction task while being unimpaired in the addition task. The results showed that neglect patients made more errors than the two other groups to subtract large numbers, whereas they were still able to solve large addition problems matched for difficulty and magnitude of the answer. This finding demonstrates a causal relationship between the ability to attend the left side of space and the solving of large subtraction problems. A plausible account is that attention shifts help localizing the position of the answer on a spatial continuum while subtracting large numbers., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Investigate the protective effect of multilingualism on cognition in seniors., Methods: As part of the MemoVie study conducted on 232 non-demented volunteers aged 65 and more, neurogeriatric and neuropsychological evaluations were performed. Participants were classified as presenting either cognitive impairment without dementia (CIND) or being free of any cognitive impairment (CIND-free). Language practices, socio-demographic data and lifestyle habits were recorded. In this retrospective nested case-control design, we used as proxies of multilingualism: number of languages practiced, age of acquisition and duration of practice, emphasizing the temporal pattern of acquisition, and the resulting practice of several languages sequentially or concomitantly during various periods of life. This special angle on the matter offered to our work a dimension particularly original and innovative., Results: 44 subjects (19%) had CIND, the others were cognitively normal. All practiced from 2 to 7 languages. When compared with bilinguals, participants who practiced more than 2 languages presented a lower risk of CIND, after adjustment for education and age (odds ratio (OR) = 0.30, 95% confidence limits (95%CL) = [0.10-0.92]). Progressing from 2 to 3 languages, instead of staying bilingual, was associated with a 7-fold protection against CIND (OR = 0.14, 95%CL = [0.04-0.45], p = 0.0010). A one year delay to reach multilingualism (3 languages practiced being the threshold) multiplied the risk of CIND by 1.022 (OR = 1.022, 95%CL = [1.01-1.04], p = 0.0044). Also noteworthy, just as for multilingualism, an impact of cognitively stimulating activities on the occurrence of CIND was found as well (OR = 0.979, 95%CL = [0.961-0.998], p = 0.033)., Conclusion: The study did not show independence of multilingualism and CIND. Rather it seems to show a strong association toward a protection against CIND. Practicing multilingualism from early life on, and/or learning it at a fast pace is even more efficient. This protection might be related to the enhancement of cognitive reserve and brain plasticity, thereby preserving brain functions from alterations during aging.

Background: Cognitive impairment and Alzheimer's disease (AD) are increasingly considered a major public health problem. The MemoVie cohort study aims to investigate the living conditions or risk factors under which the normal cognitive capacities of the senior population in Luxembourg (≥ 65 year-old) evolve (1) to mild cognitive impairment (MCI) - transitory non-clinical stage - and (2) to AD. Identifying MCI and AD predictors undeniably constitutes a challenge in public health in that it would allow interventions which could protect or delay the occurrence of cognitive disorders in elderly people. In addition, the MemoVie study sets out to generate hitherto unavailable data, and a comprehensive view of the elderly population in the country., Methods/design: The study has been designed with a view to highlighting the prevalence in Luxembourg of MCI and AD in the first step of the survey, conducted among participants selected from a random sample of the general population. A prospective cohort is consequently set up in the second step, and appropriate follow-up of the non-demented participants allows improving the knowledge of the preclinical stage of MCI. Case-control designs are used for cross-sectional or retrospective comparisons between outcomes and biological or clinical factors. To ensure maximal reliability of the information collected, we decided to opt for structured face to face interviews. Besides health status, medical and family history, demographic and socio-cultural information are explored, as well as education, habitat network, social behavior, leisure and physical activities. As multilingualism is expected to challenge the cognitive alterations associated with pathological ageing, it is additionally investigated. Data relative to motor function, including balance, walk, limits of stability, history of falls and accidents are further detailed. Finally, biological examinations, including ApoE genetic polymorphism are carried out. In addition to standard blood parameters, the lipid status of the participants is subsequently determined from the fatty acid profiles in their red blood cells. The study obtained the legal and ethical authorizations., Discussion: By means of the multidisciplinary MemoVie study, new insights into the onset of cognitive impairment during aging should be put forward, much to the benefit of intervention strategies as a whole.

Background: Aged patients (>50 years old) with residual schizophrenic symptoms differ from young patients. They represent a subpopulation with a more unfavorable Kraepelinian course and have an increased risk (up to 30%) for dementia of unknown origin. However, our current understanding of age-related brain changes in schizophrenia is derived from studies that included less than 17% of patients who were older than 50 years of age. This study investigated the anatomical distribution of gray matter (GM) brain deficits in aged patients with ongoing schizophrenia., Methods: Voxel-based morphometry was applied to 3D-T1 magnetic resonance images obtained from 27 aged patients with schizophrenia (mean age of 60 years) and 40 age-matched normal controls., Results: Older patients with schizophrenia showed a bilateral reduction of GM volume in the thalamus, the prefrontal cortex, and in a large posterior region centered on the occipito-temporo-parietal junction. Only the latter region showed accelerated GM volume loss with increasing age. None of these results could be accounted for by institutionalization, antipsychotic medication, or cognitive scores., Conclusions: This study replicated most common findings in patients with schizophrenia with regard to thalamic and frontal GM deficits. However, it uncovered an unexpected large region of GM atrophy in the posterior tertiary cortices. The latter observation may be specific to this aged and chronically symptomatic subpopulation, as atrophy in this region is rarely reported in younger patients and is accelerated with age.

Although it is generally acknowledged that familiar face recognition is fast, mandatory, and proceeds outside conscious control, it is still unclear whether processes leading to familiar face recognition occur in a linear (i.e., gradual) or a nonlinear (i.e., all-or-none) manner. To test these two alternative accounts, we recorded scalp ERPs while participants indicated whether they recognize as familiar the faces of famous and unfamiliar persons gradually revealed in a descending sequence of frames, from the noisier to the least noisy. This presentation procedure allowed us to characterize the changes in scalp ERP responses occurring prior to and up to overt recognition. Our main finding is that gradual and all-or-none processes are possibly involved during overt recognition of familiar faces. Although the N170 and the N250 face-sensitive responses displayed an abrupt activity change at the moment of overt recognition of famous faces, later ERPs encompassing the N400 and late positive component exhibited an incremental increase in amplitude as the point of recognition approached. In addition, famous faces that were not overtly recognized at one trial before recognition elicited larger ERP potentials than unfamiliar faces, probably reflecting a covert recognition process. Overall, these findings present evidence that recognition of familiar faces implicates spatio-temporally complex neural processes exhibiting differential pattern activity changes as a function of recognition state.

Background: Blood-brain barrier (BBB) breakdown is an early event in the pathogenesis of multiple sclerosis (MS). In a previous study we have found a direct stabilization of barrier characteristics after treatment of bovine brain capillary endothelial cells (BCECs) with human recombinant interferon-beta-1a (IFN-beta-1a) in an in vitro BBB model. In the present study we examined the effect of human recombinant IFN-beta-1a on the barrier properties of BCECs derived from four different species including humans to predict treatment efficacy of IFN-beta-1a in MS patients., Methods: We used primary bovine and porcine BCECs, as well as human and murine BCEC cell lines. We investigated the influence of human recombinant IFN-beta-1a on the paracellular permeability for 3H-inulin and 14C-sucrose across monolayers of bovine, human, and murine BCECs. In addition, the transendothelial electrical resistance (TEER) was determined in in vitro systems applying porcine and murine BCECS., Results: We found a stabilizing effect on the barrier characteristics of BCECs after pretreatment with IFN-beta-1a in all applied in vitro models: addition of IFN-beta-1a resulted in a significant decrease of the paracellular permeability across monolayers of human, bovine, and murine BCECs. Furthermore, the TEER was significantly increased after pretreatment of porcine and murine BCECs with IFN-beta-1a., Conclusion: Our data suggest that BBB stabilization by IFN-beta-1a may contribute to its beneficial effects in the treatment of MS. A human in vitro BBB model might be useful as bioassay for testing the treatment efficacy of drugs in MS.

Background: Children with pervasive developmental disorder (PDD) show behavioral abnormalities in gaze and face processing, but recent studies have indicated that normal activation of face-specific brain areas in response to faces is possible in this group. It is not clear whether the brain activity related to gaze processing is also normal in children with PDD., Methods: Event-related brain potentials (ERPs) were measured during two spatial attention tasks in which a centrally presented stimulus served as cue for the location of a forthcoming target. In one task faces were used as cues, and in the other arrows. Seventeen children with PDD and 18 age- and IQ-matched control children were tested., Results: Face stimuli elicited the same specific ERP activity in both groups. Also, both children with PDD and controls showed shorter reaction times as well as larger amplitudes and shorter latency times of several ERP peaks to congruently cued targets than to incongruently cued targets in both tasks. However, children with PDD showed abnormally small occipital ERPs in response to both face and arrow stimuli., Conclusions: The results provide evidence for the capability of normal processing of face and gaze change in children with PDD. The smaller occipital activity might be related to more general abnormalities in perception.

Objective: The detection of a lateralized visual target is faster when preceded by a face gazing to the location of this stimulus. Here we aimed to clarify the time-course of the visual processing modulated by these reflexive shifts of attention., Methods: ERPs were measured on 16 subjects performing a speeded location task on a circular checkerboard. The checkerboard target appeared either on the left or right of the upper or lower visual field, and was preceded by a central face orienting its gaze obliquely to one of the four possible corner locations for the target to appear., Results: Congruently cued targets were located faster than incongruently cued targets and were associated with larger and earlier occipital P1 (approximately 110 ms) and occipito-parieto-temporal N1 (approximately 150 ms) components. However, no such attentional modulations were found on the earlier C1 visual component, best observed with a negative polarity for upper visual field stimulations, and thought to originate largely from primary visual cortex., Conclusions and Significance: These results show that reflexive shifts of attention following oblique eye gaze to upper and lower visual fields increase and speed up the processing of visual information beyond the feedforward flow of information in primary visual cortex.

The adhesion of highly activated neutrophils to cerebral microvascular endothelial cells (MVECs) may contribute to disruption and hyperpermeability of the blood-brain barrier (BBB) after cardiac surgery with prolonged cardiopulmonary bypass (CPB). A correlation between CPB duration and neutrophil-mediated BBB damage has not been investigated on the cellular level yet. Therefore, we studied the effects of neutrophils from cardiac surgery patients with CPB time <80 min (group I; n=8) and >80 min (group II; n=8) on the integrity of cultured porcine MVEC. Ex vivo, neutrophils of group II but not of group I significantly degraded the zonula adherens molecule beta-catenin whereas VE-cadherin and occludin were not modified. The transendothelial electric resistance as a measure for the integrity of the endothelial monolayers was reduced over time in both groups. In conclusion, prolonged CPB time entails neutrophil-mediated decrease in MVEC beta-catenin expression, and thus may be an important trigger for BBB disruption.

Objective: Cardiac surgery with cardiopulmonary bypass is associated with aberrant neutrophil activation and potentially severe pathogenic sequelae. This experimental study was done to evaluate a leukocyte inhibition module that rapidly inactivates neutrophils through CD95 stimulation., Methods: German landrace pigs (4 groups, each n = 5) underwent cardiac surgery without cardiopulmonary bypass (group I), with cardiopulmonary bypass (group II), with cardiopulmonary bypass plus a leukocyte filter (group III), and with cardiopulmonary bypass plus a leukocyte inhibition module (group IV). The leukocyte filter or leukocyte inhibition module was introduced into the arterial line of the heart-lung machine., Results: Leukocyte counts were decreased by up to 43% in group IV compared with values in group II (P =.023). In group IV, but not in groups I to III, no delay in spontaneous neutrophil apoptosis was observed after annexin V-propidium iodide staining. Late apoptotic (11.7%) or necrotic neutrophils (9.3%) were detected in 2 animals (group IV). Tumor necrosis factor alpha serum levels increased over time in groups I to III (>2-fold) but remained at baseline levels in group IV (P <.05). Interleukin 8-mediated chemotactic neutrophil transmigration activity increased over time in groups I to III but was totally abrogated in group IV at any time point. The perioperative increase of creatine kinase and creatine kinase MB levels was lower in groups III (1.5-fold and 1.3-fold, respectively) and IV (1.2-fold and 1.5-fold, respectively) compared with values in group II (both 1.9-fold)., Conclusions: The leukocyte inhibition module downregulated cardiopulmonary bypass-related neutrophil activity and thus might be beneficial in cardiac surgery and other clinical settings with unappreciated neutrophil activation.

Objective: Using event-related potentials (ERPs), it has been recently shown that a reflexive shift of attention following the observation of a dynamic eye gaze cue enhances and speeds up early visual processing of a target presented at the gazed-at location. Here we investigate whether similar early sensory modulations are also elicited by static gaze cues, or if previously described attentional effects were caused mainly by visual motion cues and not by eye gaze direction per se. Furthermore, we explore if these possible attentional orienting effects reflect facilitation of the processing of cued stimuli, inhibition of the unattended stimuli, or both., Methods: Subjects were presented with a face looking to the right or left visual field (VF), or straight away, before the occurrence of a lateralized target to detect. There were 3 conditions in this nonpredictive cueing task: (1) target presented in the VF indicated by the eye gaze direction (congruent); (2) opposite to the eye gaze direction (incongruent); or (3) preceded by a straight gazing face (neutral)., Results: Subjects were faster at detecting congruently than incongruently and neutrally cued targets. Facilitation effects were observed on early ERP components: the occipital P1 and occipito-temporal N1 components were speeded up as early as approximately 100 ms following stimulus onset (P1), and enhanced (P1 and N1) in response to congruent trials, particularly in the right hemisphere., Conclusions: Spatial attention triggered by static eye gaze direction produces response facilitations - predominantly lateralized to the right hemisphere - from the early sensory stages of visual processing., Significance: This study provides the first evidence of a speeding up and amplification of early visual processing following attention triggered by static eye gaze perception.

Recently, we showed that the arterial in-line application of the leukocyte inhibition module (LIM) within the heart-lung machine limits overshooting leukocyte activity and cardiac tissue damage. Moreover, significantly better cardiac function was found in an experimental animal model when LIM was used. In the meantime, the first promising clinical data exist. LIM has to be regarded as an essential tool in extracorporeal circulation, in the future, to improve postoperative clinical outcome and to reduce costs. This review summarizes the biological background of LIM and the current experience obtained in experimental models and clinical studies.

The present study used a parametric design to characterize early event-related potentials (ERP) to face stimuli embedded in gradually decreasing random noise levels. For both N170 and the vertex positive potential (VPP) there was a linear increase in amplitude and decrease in latency with decreasing levels of noise. In contrast, the earlier visual P1 component was stable across noise levels. The P1/N170 dissociation suggests not only a functional dissociation between low and high-level visual processing of faces but also that the N170 reflects the integration of sensorial information into a unitary representation. In addition, the N170/VPP association supports the view that they reflect the same processes operating when viewing faces.

Neuroimaging studies have identified at least two bilateral areas of the visual extrastriate cortex that respond more to pictures of faces than objects in normal human subjects in the middle fusiform gyrus [the 'fusiform face area' (FFA)] and, more posteriorly, in the inferior occipital cortex ['occipital face area' (OFA)], with a right hemisphere dominance. However, it is not yet clear how these regions interact which each other and whether they are all necessary for normal face perception. It has been proposed that the right hemisphere FFA acts as an isolated ('modular') processing system for faces or that this region receives its face-sensitive inputs from the OFA in a feedforward hierarchical model of face processing. To test these proposals, we report a detailed neuropsychological investigation combined with a neuroimaging study of a patient presenting a deficit restricted to face perception, consecutive to bilateral occipito-temporal lesions. Due to the asymmetry of the lesions, the left middle fusiform gyrus and the right inferior occipital cortex were damaged but the right middle fusiform gyrus was structurally intact. Using functional MRI, we disclosed a normal activation of the right FFA in response to faces in the patient despite the absence of any feedforward inputs from the right OFA, located in a damaged area of cortex. Together, these findings show that the integrity of the right OFA is necessary for normal face perception and suggest that the face-sensitive responses observed at this level in normal subjects may arise from feedback connections from the right FFA. In agreement with the current literature on the anatomical basis of prosopagnosia, it is suggested that the FFA and OFA in the right hemisphere and their re-entrant integration are necessary for normal face processing.

What are the neuronal correlates of reflexive shifts of attention triggered by eye gaze direction? Event related potentials (ERPs) were measured on 14 subjects performing a spatial attention task where eye gaze direction of a face cued the location of a forthcoming target. Subjects were faster in detecting a validly cued target, i.e. one appearing at the location the eye was gazing at, compared to invalidly cued targets, despite the non-predictive value of the eye cues. ERP results showed an enhanced and earlier occipito-parietal P1 and N1 for valid trials, demonstrating the early modulation of visual input by attentional allocation. These findings provide the first evidence that social attention can rapidly modify the processing of visual information in extrastriate cortex.

Immunocompromised individuals are susceptible to a variety of esophageal infections. Organisms responsible for esophagitis in patients with the acquired immunodeficiency syndrome (AIDS) are briefly reviewed. Usually confined to the esophageal mucosa, pathogens known to have the potential for transmural invasion are identified. The first report of tracheoesophageal fistulization in an AIDS patient with herpes esophagitis is presented.