Neural correlates of visual hallucinations in dementia with Lewy bodies.

NTRODUCTION: The aim of this study was to investigate the association between visual hallucinations in dementia with Lewy bodies (DLB) and brain perfusion using single-photon emission computed tomography. METHODS: We retrospectively included 66 patients with DLB, 36 of whom were having visual hallucinations (DLB-hallu) and 30 of whom were not (DLB-c). We assessed visual hallucination severity on a 3-point scale of increasing severity: illusions, simple visual hallucinations and complex visual hallucinations. We performed voxel-level comparisons between the two groups and assessed correlations between perfusion and visual hallucinations severity. RESULTS: We found a significant decrease in perfusion in the left anterior cingulate cortex, the left orbitofrontal cortex and the left cuneus in the DLB-hallu group compared with the DLB-c group. We also found a significant correlation between decreased bilateral anterior cingulate cortex, left orbitofrontal cortex, right parahippocampal gyrus, right inferior temporal cortex and left cuneus perfusion with the severity of hallucinations. CONCLUSIONS: Visual hallucinations seem to be associated with the impairment of anterior and posterior regions (secondary visual areas, orbitofrontal cortex and anterior cingulate cortex) involved in a top-down and bottom-up mechanism, respectively. Furthermore, involvement of the bilateral anterior cingulate cortex and right parahippocampal gyrus seems to lead to more complex hallucinations.journal article20152015 02 17importe

Mise en évidence de marqueurs moléculaires de sources primaires et secondaires de particules atmosphériques : intérêt de l'approche analytique non ciblée par spectrométrie de masse haute résolution

The impact of particulate matter (PM, aerosols) on air quality is widely recognized and the implementation of measures to reduce their concentrations in ambient air requires knowledge of their origins. The study of the PM sources can be achieved by monitoring molecular markers or chemical signatures used in statistical source-receptor models. However, some sources remain unresolved due to the lack of specific molecular markers. High resolution mass spectrometry (HRMS) provides a means to obtain a more complete characterization of environmental matrices. Non-target screening (NTS) approaches combined with multivariate statistical analysis allow a comparison of sample chemical fingerprints to highlight substances of interest. The objective of this thesis was to evaluate the potential of the chemical fingerprinting approach to identify specific molecular markers of currently unresolved PM sources. Two sources of PM were studied because of their important contributions to the observed ambient air concentrations: biomass combustion and vehicular emissions. The objective was to distinguish between residential wood burning and green waste burning (garden fires) and to discriminate between primary and secondary sources of PM from light-duty diesel and gasoline vehicle emissions. Different tests under controlled real conditions were performed to collect PM samples from the two targeted sources. Biomass combustion tests, residential wood heating (fireplace, log stove) and green waste burning (hedge trimmings, fallen leaves), were performed in a large combustion chamber to simulate real ambient air dilution conditions. Vehicular samples were obtained from chassis dynamometer tests with two current-in-use (EURO 5 standard) gasoline and diesel vehicles. Their emissions were also aged in an oxidation reactor to simulate photochemical processes (with OH radical) taking place in the atmosphere. The work was based on chemical characterization using targeted and non-targeted analytical methods using HRMS coupled with liquid- and gas- chromatography (LC and GC). In addition to evaluate emission factors of particulate species of interest emitted from green waste burning, results obtained from targeted analyses highlighted indicators of both biomass combustion sources (carbon preference index, levoglucosan/mannosan ratio, sinapylaldehyde, erythritol and sorbitol abundances) which was ultimately not specific enough to allow their clear discrimination in ambient air. From multivariate statistical analyses (e.g. partial least squares discriminant analysis (PLS-DA) and clustering analysis) of NTS data obtained by LC- and GC-HRMS, about thirty entities specific to green waste burning and four to residential wood heating, were highlighted and some of them could be identified. Similarly, about ten chemical entities of each the primary and secondary emissions of gasoline and diesel vehicles could be determined. This work has shown the potential of the NTS approach and the chemical fingerprinting to highlight chemical entities of atmospheric interest and in particular markers of PM sources. In the long term, they could be used in studies of PM sources in ambient air.L'impact délétère des particules (PM, aérosols) sur la qualité de l'air est largement reconnu et la mise en place de mesures de réduction de leurs concentrations dans l'air ambiant requiert de connaitre leurs origines. L'étude des sources des PM peut être réalisée à partir du suivi de composés marqueurs ou de signatures chimiques utilisés dans des modèles statistiques sources-récepteurs. Cependant, certaines sources demeurent non résolues actuellement par manque de marqueurs moléculaires spécifiques. La spectrométrie de masse haute résolution (HRMS) apporte un moyen d'obtenir une caractérisation plus complète des matrices environnementales. Par ce biais, les approches d'analyses non-ciblées (non-target screening, NTS) combinées à des analyses statistiques multivariées, permettent de réaliser une comparaison d'empreintes chimiques d'échantillons afin de mettre en évidence des substances d'intérêt. Ainsi, l'objectif de ce travail de thèse était d'évaluer le potentiel de l'approche de comparaisons d'empreintes chimiques afin de mettre en évidence des marqueurs moléculaires spécifiques de sources de PM non résolues actuellement. Deux sources de PM ont été étudiées compte tenu de l'importance de leurs contributions sur les concentrations observées dans l'air ambiant : la combustion de biomasse et les émissions véhiculaires avec pour objectif d'une part, la distinction du chauffage résidentiel au bois et du brûlage à l'air libre de déchets vert (feux de jardin) et d'autre part, la discrimination des sources de PM primaires et secondaires provenant des émissions de véhicules routiers légers diesel et essence. Différents essais en conditions réelles contrôlées ont été réalisés afin de collecter des échantillons de PM des deux sources ciblées. Les essais de combustion de biomasse, chauffage résidentiel au bois (cheminée, poêle bûches) et brûlage à l'air libre de déchets verts de jardin (tailles de haies, feuilles mortes), ont été réalisés dans une large chambre de combustion permettant de simuler les conditions réelles de dilution de l'air ambiant. Les échantillons véhiculaires ont été obtenus à partir d'essais sur banc à rouleaux avec deux véhicules modernes (norme EURO 5) essence et diesel. Leurs émissions ont également été vieillies au moyen d'un réacteur d'oxydation permettant de simuler les processus photochimiques (réactivé avec le radical OH) ayant lieu dans l'atmosphère. Le travail était basé sur une caractérisation chimique au moyen de méthodes d'analyses ciblées et non ciblées utilisant la HRMS couplée à la chromatographie en phase liquide et gazeuse (LC et GC). Outre l'évaluation des facteurs d'émission d'espèces particulaires d'intérêt émises par le brûlage de déchets verts, les résultats obtenus à partir des analyses ciblées ont permis de mettre en avant des indicateurs des deux sources de combustion de biomasse (indice de parité des alcanes, rapport lévoglucosan/mannosan, abondance du sinapylaldéhyde, érythritol et sorbitol) mais finalement pas assez spécifiques pour permettre leur discrimination claire dans l'air ambiant. A partir d'analyses statistiques multivariées (e.g. analyse discriminante par les moindres carrés partiels (PLS-DA) et analyse de regroupement) des données NTS obtenues par LC- et GC-HRMS, une trentaine d'entités ou composés chimiques spécifiques du brûlage à l'air libre de déchets verts de jardin et quatre du chauffage résidentiel au bois, ont été mis en évidence et dont certains ont pu être identifiés. De façon similaire, une dizaine d'entités chimiques singulières de chacune des émissions primaires ou secondaires des véhicules essence et diesel ont pu être déterminées. Ce travail a permis de montrer le potentiel de l'approche NTS et de la comparaison d'empreintes chimiques afin de mettre en évidence des entités chimiques d'intérêt atmosphériques et notamment marqueurs de sources de PM. A terme, elles pourront être utilisées lors d'études de sources de PM dans l'air ambiant

Chemical characterization of SOA from diesel and gasoline vehicles with untargeted approaches

Recent studies have shown that the PM emissions of modern cars equipped with the newest after-treatment technologies are mainly related to the production of secondary organic aerosols (SOA) especially in the case of gasoline vehicles. The objective of this work is to identify specific molecular markers or chemical patterns that can be further used in PM source apportionment studies to discriminate SOA from diesel and gasoline vehicles. Experiments were performed on a chassis dynamometer with a gasoline and diesel Euro 5 vehicles. Exhaust emissions were diluted before introduction into a potential aerosol mass (PAM) oxidation flow reactor (OFR) for aging and SOA formation. About 50 filter samples were collected upstream and downstream the PAM-OFR and analyzed using innovative non-targeted approaches with high-resolution mass spectrometry coupled to gas or liquid chromatography. The data treatment and statistical analysis will allow to highlight features or chemical patterns specific of gasoline and diesel SOA

Aerosolomics based approach to discover source molecular markers: A case study for discriminating residential wood heating vs garden green waste burning emission sources

International audienceBiomass burning is a significant source of particulate matter (PM) in ambient air and its accurate source apportionment is a major concern for air quality. The discrimination between residential wood heating (RWH) and garden green waste burning (GWB) particulate matter (PM) is rarely achieved. The objective of this work was to evaluate the potential of non-targeted screening (NTS) analyses using HRMS (high resolution mass spectrometry) data to reveal discriminating potential molecular markers of both sources. Two residential wood combustion appliances (wood log stove and fireplace) were tested under different output conditions and wood moisture content. GWB experiments were carried out using two burning materials (fallen leaves and hedge trimming). PM samples were characterized using NTS approaches with both LC- and GC-HRMS (liquid and gas chromatography-HRMS). The analytical procedures were optimized to detect as many species as possible. Chemical fingerprints obtained were compared combining several multivariate statistical analyses (PCA, HCAand PLS-DA). Results showed a strong impact of the fuel nature and the combustion quality on the chemical fingerprints. 31 and 4 possible markers were discovered as characteristic of GWB and RWH, respectively. Complementary work was attempted to identify potential molecular formulas of the different potential marker candidates. The combination of HRMS NTS chemical characterization with multivariate statistical analyses shows promise for uncovering organic aerosol fingerprinting and discovering potential PM source markers

Discrimination of biomass burning sources using innovative non-targeted approaches

To date, the evaluation of the contributions of wood burning, used for residential heating, and green waste burning on the PM concentrations is rarely achieved. The objective of the research project SODEMASS is to identify specific organic molecular markers or chemical patterns of both biomass burning sources that can be further used in PM source apportionment studies. Several experiments have been performed in a combustion chamber to simulate the ambient air dilution conditions. Different wood combustion appliances (residential wood stove, fireplace) were tested and green waste burning experiments were performed using different burning materials (leaves and branches). About 50 PM samples have been characterized using both targeted and non-targeted (high-resolution mass spectrometry analyses) approaches. As targeted results were not enough to discriminate between wood and green waste burning sources in ambient air, non-targeted strategies were applied. After statistical analysis, several features specific of each biomass burning source were finally highlighted

Chemical characterization of biomass burning sources using targeted and untargeted approaches

International audienc

Cognitive and affective theory of mind in dementia with Lewy bodies and Alzheimer's disease

Background: Theory of mind (ToM) refers to the ability to attribute mental states, thoughts (cognitive component) or feelings (affective component) to others. This function has been studied in many neurodegenerative diseases; however, to our knowledge, no studies investigating ToM in dementia with Lewy bodies (DLB) have been published. The aim of our study was to assess ToM in patients with DLB and to search for neural correlates of potential deficits.Methods: Thirty-three patients with DLB (DLB group) and 15 patients with Alzheimer’s disease (AD group), all in the early stage of the disease, as well as 16 healthy elderly control subjects (HC group), were included in the study. After a global cognitive assessment, we used the Faux Pas Recognition (FPR) test, the Reading the Mind in the Eyes (RME) test and Ekman’s Facial Emotion Recognition test to assess cognitive and affective components of ToM. Patients underwent cerebral 3-T magnetic resonance imaging, and atrophy of grey matter was analysed using voxel-based morphometry. We performed a one-sample t test to investigate the correlation between each ToM score and grey matter volume and a two-sample t test to compare patients with DLB impaired with those non-impaired for each test.Results: The DLB group performed significantly worse than the HC group on the FPR test (P = 0.033) and the RME test (P = 0.015). There was no significant difference between the AD group and the HC group or between the DLB group and the AD group. Some brain regions were associated with ToM impairments. The prefrontal cortex, with the inferior frontal cortex and the orbitofrontal cortex, was the main region, but we also found correlations with the temporoparietal junction, the precuneus, the fusiform gyrus and the insula.Conclusions: This study is the first one to show early impairments of ToM in DLB. The two cognitive and affective components both appear to be affected in this disease. Among patients with ToM difficulties, we found atrophy in brain regions classically involved in ToM, which reinforces the neuronal network of ToM. Further studies are now needed to better understand the neural basis of such impairment

Emission factors and chemical characterization of particulate emissions from garden green waste burning

International audienceThis work provides an evaluation of the emission factors (EFs) of typical garden waste burning (fallen leaves and hedge trimming) in terms of particulate matter (PM), elemental and organic carbon (EC-OC) together with a detailed chemical characterization of 88 particle-bound organic species including polycyclic aromatic hydrocarbons (PAHs), levoglucosan and its isomers, lignin breakdown products (methoxyphenols), cholesterol, alkanes, polyols and sugars. Furthermore, wood-log based burning experiments have been performed to highlight key indicators or chemical patterns of both, green waste and wood burning (residential heating) sources, that may be used for PM source apportionment purposes. Two residential log wood combustion appliances, wood stove (RWS) and fireplace, under different output conditions (nominal and reduced) and wood log moisture content (mix of beech, oak and hornbeam), have been tested. Open wood burning experiments using wood logs were also performed. Green waste burning EFs obtained were comparable to the available literature data for open-air biomass burning. For PM and for most of the organic species studied, they were about 2 to 30 times higher than those observed for wood log combustion experiments. Though, poor performance wood combustions (open-air wood log burning, fireplace and RWS in reduced output) showed comparable EFs for levoglucosan and its isomers, methoxyphenols, polyols, PAHs and sugars. Toxic PAH equivalent benzo[a]pyrene EFs were even 3–10 times higher for the fireplace and open-air wood log burning. These results highlighted the impact of the nature of the fuel burnt and the combustion performances on the emissions. Different chemical fingerprints between both biomass burning sources were highlighted with notably a predominance of odd high-molecular weight n-alkanes (higher carbon preference index, CPI), lower levoglucosan/mannosan ratio and lower sinapylaldehyde abundance for green waste burning. However, the use of such indicators seems limited, especially if applied alone, for a clear discrimination of both sources in ambient air