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International audience; Background: Organophosphate pesticides (OP) are widely used for both agricultural and domestic purposes. Epidemiological studies suggest neurotoxicity in children after exposure to organophosphates pesticides (OP) at low levels but possible mechanism is still unclear.Objectives: We aimed at investigating the effects of prenatal exposure to OPs on inhibitory control of 10-12 year-old-children assessed by a motor inhibition task during functional magnetic resonance imaging (fMRI).Methods: Ninety-five children from the PELAGIE cohort (Brittany-France, from 2002) underwent a fMRI examination during which inhibition was assessed by a Go/No-Go task. Task performance was assessed by average response latency, commission rate and composite performance score (PS). Whole brain activation was estimated by modeling the hemodynamic response related to inhibition demand and successful inhibition. OP exposure was assessed by measuring six dialkylphosphate (DAP) metabolites in the urine of women in early pregnancy (

Visual scenes are processed in terms of spatial frequencies. Low spatial frequencies (LSF) carry coarse information, whereas high spatial frequencies (HSF) subsequently carry information about fine details. The present magnetic resonance imaging study investigated how cortical thickness covaried with LSF/HSF processing abilities in ten-year-old children and adults. Participants indicated whether natural scenes that were filtered in either LSF or HSF represented outdoor or indoor scenes, while reaction times (RTs) and accuracy measures were recorded. In adults, faster RTs for LSF and HSF images were consistently associated with a thicker cortex (parahippocampal cortex, middle frontal gyrus, and precentral and insula regions for LSF, parahippocampal cortex and fronto-marginal and supramarginal gyri for HSF). On the other hand, in children, faster RTs for HSF were associated with a thicker cortex (posterior cingulate, supramarginal and calcarine cortical regions), whereas faster RTs for LSF were associated with a thinner cortex (subcallosal and insula regions). Increased cortical thickness in adults and children could correspond to an expansion mechanism linked to visual scene processing efficiency. In contrast, lower cortical thickness associated with LSF efficiency in children could correspond to a pruning mechanism reflecting an ongoing maturational process, in agreement with the view that LSF efficiency continues to be refined during childhood. This differing pattern between children and adults appeared to be particularly significant in anterior regions of the brain, in line with the proposed existence of a postero-anterior gradient of brain development. Taken together, our results highlight the dynamic brain processes that allow children and adults to perceive a visual natural scene in a coherent way.

Background Hallucinations are the most common and debilitating symptom in schizophrenia, affecting more than 70% of patients. The superior temporal sulcus (STS) is involved in the language process notably in the perception of the human voice and several studies show its implication in auditory verbal hallucinations (AVHs). Sulcal patterns in the white matter can reflect an early vulnerability, probably genetic since they set up at a very early stage and are stable over the life course. In contrast, the cortical thickness is dynamic and variable over the development and so can reflect the impact of environmental factors on the maturation of the brain. The aim of this study is therefore to determine whether AVHs are associated with morphological changes of the STS and in particular, whether these changes concern sulcal patterns or cortical thickness reflecting early (genetic) or late (environmental) vulnerability respectively. Methods Seventy-three schizophrenia patients (DSM-IV) with a proneness of AVH (53 AVH+) and without AVH (20 AVH-) and 100 healthy volunteers (HC) had a 3T MRI brain scan. Cortical reconstructions were generated using Freesurfer. Mean cortical thickness was measured over the entire brain in each participant. Number of sulcal pits, which represents the position with the maximum depth in the sulcus, was automatically counted on the white matter surface. Both measures were compared between groups and related to the Auditory Hallucination Rating Scale (AHRS). Results AVH+ patients compared to HC showed a significantly thinner cortical thickness in the left temporal and frontal regions and especially in the STS (p ≤ 0.05 FDR corrected). A negative correlation (r²=0.25) between the cortical thickness in the central part of the left STS and the AHRS score was found (p = 0.01 uncorrected). A different distribution of the number of pits in the left STS is found in AVH+ patients compared to HC (p = 0.05). Discussion The results suggest that AVH+ patients compared to HC have a lower cortical thickness in the left STS, but also have a specific white matter pattern of the left STS. These results support the hypothesis that a particular morphology of the STS related with auditory hallucinations might be due to both early (genetic) and late (environmental) factors.

National audience; Some economic transactions require people to trust strangers, whose trustworthiness is unknown. In these circumstances, behavioral studies have shown that adults (but not young adolescents) seem to have some minimal ability to detect the trustworthiness of adult strangers based on their facial features. In this study, we explored the neural correlates of this facial trustworthiness detection. A group of adolescents and adults played a series of economic Trust Games with adult trustees of which we had previously recorded the strategy. Results showed that when adult investors were looking at the picture of a trust-abusing trustee, the left amygdala was relatively more activated than when they were looking at a trust-honoring player. Younger adolescents did not show this pattern and responded with a more pronounced deactivation when facing a trust-abusing trustee. An exploratory whole-brain analysis detected a similar age shift for mentalizing regions of the brain. Our results fit with an emerging model suggesting that the amygdala is implicated in an associative learning process that progressively refines a mapping of faces onto trustworthy behavior and may result in avoiding to be exploited by untrustworthy strangers.

Purpose The Time to First Metastatic Recurrence (TFMR) could be considered as an indirect reflection of the tumour growth kinetics which plays an important role in cancer. Molecular subtypes such as expression of estrogen receptor are known predictive factors of TFMR. The CinéBreast study aimed to identify predictive factors of the time to TFMR. Methods The French Epidemiological Strategy and Medical Economics (ESME) Metastatic Breast Cancer (MBC) Database (NCT03275311) was used, which contains data from a cohort of metastatic breast cancer patients from 2008 to 2016 using retrospective data collection. It is a national multi-centre database. The impact of TFMR on overall survival (OS) since first metastasis was also evaluated. Results Among 16 702 patients recorded in the ESME MBC database, 10 595 had an initially localised breast cancer with hormone receptor (HR) and HER2 status available, with a metastatic recurrence. Median follow up was 56 months. Median TFMR was 59 months (120: 24%). HER2+ and TNBC were respectively 4 times and 12 times (p, Highlights • ESME is a large-scale real-life database of 16 702 metastatic breast cancer patients. • A short time to first metastatic recurrence is associated with poor overall survival. • Triple-negative tumours were more likely to recur early than HR+ and HER2+ tumours.

Adolescents have been shown to be more likely to engage in risky behaviors in daily life. Many studies have indicated that adolescents could make advantageous choices when they receive explicit information but could fail to choose advantageously when they are not informed about risks. The current study aimed to examine the influence of explicit risk information (i.e., when risk information is directly available) versus implicit risk information (i.e., when risk information has to be learned from feedback) on risk-taking engagement, in order to clarify whether the enhanced risk-taking observed in decision making under ambiguity in adolescents results from either a greater exploration of ambiguous situations (i.e., a higher ambiguity tolerance) or a specific difficulty associated with learning based on previous choices' outcomes. Adolescents and young adults completed a new adaptation of the Balloon Analogue Risk Task. They were required to accumulate as many points as possible by inflating balloons associated with variable break points and avoiding explosions. This adaptation involved a manipulation of the information level with two conditions, an " informed " condition and a " noninformed " condition, in which the participants had to learn the matching of colors with balloons' resistances based on feedback. The results demonstrated that providing explicit risk information allows adolescents to be as efficient as adults at the end of the game. In contrast, adolescents failed to adjust risk-taking to the balloon resistance in the noninformed condition. These findings critically suggest that this failure reflects a specific impairment of feedback-based learning ability but not a global excess of risk-taking during adolescence.

Since reasoning is often biased by intuitive heuristics, the development of sound reasoning has long been postulated to depend on successful bias monitoring and inhibition. The present fMRI study aimed to identify neural correlates of developmental changes in these processes. A group of adults and young adolescents were presented with ratio-bias problems in which an intuitively cued heuristic response could be incongruent (conflict item) or congruent (no-conflict item) with the correct response. Results showed that successfully avoiding biased responding on conflict items across both age groups was associated with increased activation in Anterior Cingulate Cortex (ACC) and the right Lateral Prefrontal Cortex (LPFC) regions of interest. Critically, the right LPFC activation decreased with age. Biased responding did not result in right LPFC or ACC modulation and failed to show any developmental activation changes. We discuss implications for ongoing debates on the nature of heuristic bias and its development.

Cet article presente la situation clinique d’une caledonienne d’origine polynesienne souffrant d’un deuil dit « complique » l’ayant desequilibree dans sa totalite bio-psycho-sociale avec apparition de passages a l’acte auto- et hetero-agressifs. Les modeles cliniques du deuil actuels admettent que le maintien des liens avec l’etre aime puisse etre source de souffrance mais aussi de resilience pour l’endeuille et que le mode de resolution du deuil par rupture ou maintien des liens varie selon la culture et peut meme osciller pour un meme individu. La demarche clinique de cet article s’attache a penser le mort comme un etre concerne par des processus de transformation reciproques avec le vivant. A partir de la pragmatique du langage qui permet de poser que les manifestations semantiques des morts constituent l’un de leur mode d’existence, cet article propose de presenter comment l’instauration d’une prosopopee, soit le fait de s’interesser a une intentionnalite supposee du defunt, peut constituer un acte therapeutique. Au final, la resolution du deuil engageant un soin du mort « pour guerir le vif », necessite ici le deploiement d’actes necessaires a cet effet de la part de l’endeuille. Cette presentation pose la question de la categorisation du mode d’existence des morts apparaissant comme une forme de realite pour l’endeuille. D’autre part, cette situation clinique interroge la « capacite » des morts a pouvoir participer activement a un dispositif de soin dans le cadre d’une psychotherapie d’un deuil complique.

Reading relies on a left-lateralized network of brain areas that include the pre-lexical processing regions of the ventral stream. Specifically, a region in the left lateral occipitotemporal sulcus (OTS) is consistently more activated for visual presentations of words than for other categories of stimuli. This region undergoes dramatic changes at the functional and structural levels when children learn to read, but little is known about the effects of early cerebral constraints on reading skills. Using anatomical magnetic resonance imaging, we investigated whether the sulcal pattern of the lateral OTS—a stable brain feature—was associated with oral reading skills. The sulcal pattern of the left but not the right lateral OTS was associated with the number of words correctly read in 3 min. This study is the first to evidence that reading is affected by early cerebral constraints, such as the sulcal morphology of the left lateral OTS.

Background Repetitive transcranial magnetic stimulation (rTMS) shows high inter-subject variability in its efficacy for treating resistant auditory verbal hallucinations in schizophrenia. Currently, the response of an individual patient to rTMS treatment cannot be predicted. It is possible that cortical anatomical characteristics could affect the therapeutic response. Objective We hypothesized that rTMS efficacy is related to anatomical variations underlying the stimulation target in the left temporal cortex. We investigated two regions of interest (ROIs) that have been implicated in rTMS: the left temporal cortex, where the stimulation is delivered, and the primary hand motor cortex, where the stimulation strength is determined by the resting motor threshold (rMT). Methods Fifteen patients with schizophrenia (DSM IV) underwent rTMS and magnetic resonance imaging. The scalp-to-cortex distance (SCD) and the grey matter density (GMD) were measured in both ROIs. Linear regression models were used to investigate the relationships between these measures and the clinical efficacy of rTMS. Results Treatment efficacy was highly predicted by the temporal SCD and the GMD in the temporal and primary hand motor cortex regions. In contrast, the rMT was not predicted by the primary hand motor cortex SCD or GMD. Conclusion These results suggest that rTMS treatment efficacy could be related to the depth of the temporal target. The data raise the question of whether rMT is the best measure for assessing the stimulation intensity in treating patients with schizophrenia.

International audience

Long-latency auditory event potentials (LLAEPs) involving local and global auditory processes have been investigated to examine the impact of low-frequency (LF) and high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) on the cortical excitability of the temporal cortex. We hypothesized that both stimulation frequencies have the same modulation effect, in accordance with clinical data showing a reduction in auditory verbal hallucinations (AVHs) after LF and HF temporal rTMS in patients with schizophrenia. With 30 right-handed healthy volunteer participants enrolled in a crossover trial, we analyzed LLAEPs before and after LF- and HF-rTMS of the left temporal cortex. While we observed no changes in latencies, we did observe a similar inhibitory action of both rTMS frequencies on LLAEP amplitudes. Analysis of surface potential maps and cortical generators revealed some differences regarding auditory processes: HF-rTMS produced earlier, more diffuse, and more right-lateralized effects than LF-rTMS. Beyond a local impact, rTMS exerted a remote modulation influence on the frontal cortex that might be involved in attentional processes. This association could explain the therapeutic effect of temporal HF-rTMS on AVH.

International audience; Liquid vaccine formulations present some disadvantages such as stability problems, cold chain requirement or administration by trained personnel. Vaccine formulated as tablets would present a wide range of progress such as an increase stability that would facilitate the administration, the distribution and the storage of vaccine formulations. This work investigates the possibility to develop a mucosal tablet vaccine for human influenza viruses. The tablets were tested in vitro for biological efficacy and stability and in vivo in swine as a model for influenza A virus immunity. First, the ability to produce by compaction a stable vaccine with a preserved antigen was demonstrated. In a second part, vaccine tablets were used to immunize pigs. After positioning the tablets on the buccal mucosa, the animals were challenged by inoculation of the A/H1N1 pandemic virus. The responses were compared to those observed in animals vaccinated intramuscularly with the commercial liquid vaccine. It was observed signs of priming of the pig's immune system with vaccine tablets, even if the immune response stayed lower than vaccination by intramuscular route. Thus, we present attractive results that indicate a promising potential for mucosal vaccine tablets.

Human reasoning is often biased by heuristic thinking. A key question is whether people detect that their heuristic answer conflicts with logical considerations. Empirical studies suggest that the detection is typically successful but the generality of these findings has been questioned. The present study focuses on this issue. A response confidence measure was used to validate conflict sensitivity findings in the classical ratio bias task and identify individual differences in conflict detection efficiency. Participants were asked to indicate how confident they were after solving problems for which a cued heuristic response could be inconsistent or consistent with the correct response. Results confirmed that most reasoners showed a confidence decrease when they were biased, suggesting that they acknowledge that their intuitive answers are not fully warranted. However, there were also subgroups of reasoners who failed to show a confidence effect. Implications for the debate on conflict detection during th...

The acquisition of number conservation is a critical step in children’s numerical and mathematical development. Classic developmental studies have established that children’s number conservation is often biased by misleading intuitions. However, the precise nature of these conservation errors is not clear. A key question is whether conservation errors result from a failure to inhibit the misleading intuitions or from a failure to detect that these intuitions are erroneous in the first place. The present paper focuses on this fundamental conservation error or conflict sensitivity issue. We review behavioral and neuroimaging work that suggests that non-conserving preschoolers detect that their response is questionable and are less ignorant about conservation than their well-documented errors might have previously suggested.

Few studies have examined the impact of repetitive transcranial magnetic stimulation (rTMS) on the cortical excitability of nonmotor cortices; current treatments often target the temporal or prefrontal cortex. We used auditory evoked potentials recorded in 24 healthy subjects to evaluate the neuromodulatory effects of low- and high-frequency rTMS in the temporal lobe. Both auditory evoked potential P50 amplitude, a marker of cortical excitability, and P50 ratio, a marker of sensory gating known to be impaired in patients with auditory verbal hallucinations, were compared before and after rTMS. We observed a similar effect after both stimulation frequencies, with a decrease in P50 amplitude and no significant effect on P50 ratio. Low- and high-frequency rTMS applied to the temporal lobe seemed to exert the same cortical neuromodulation effect, while auditory sensory gating may not be modulated by temporal rTMS.

Highlights • Difficulties in cognitive control are related to several psychiatric conditions. • Inhibitory control (IC) of children predicts academic and professional successes. • ACC sulcal patterns at age 5 were related to IC efficiency at age 5 (Stroop scores). • ACC sulcal patterns at age 5 explained IC efficiency at age 9 (Stroop scores). • ACC sulcal patterns constrain IC efficiency during childhood., Difficulties in cognitive control including inhibitory control (IC) are related to the pathophysiology of several psychiatric conditions. In healthy subjects, IC efficiency in childhood is a strong predictor of academic and professional successes later in life. The dorsal anterior cingulate cortex (ACC) is one of the core structures responsible for IC. Although quantitative structural characteristics of the ACC contribute to IC efficiency, the qualitative structural brain characteristics contributing to IC development are less-understood. Using anatomical magnetic resonance imaging, we investigated whether the ACC sulcal pattern at age 5, a stable qualitative characteristic of the brain determined in utero, explains IC at age 9. 18 children performed Stroop tasks at age 5 and age 9. Children with asymmetrical ACC sulcal patterns (n = 7) had better IC efficiency at age 5 and age 9 than children with symmetrical ACC sulcal patterns (n = 11). The ACC sulcal patterns appear to affect specifically IC efficiency given that the ACC sulcal patterns had no effect on verbal working memory. Our study provides the first evidence that the ACC sulcal pattern – a qualitative structural characteristic of the brain not affected by maturation and learning after birth – partially explains IC efficiency during childhood.