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The assessment of resting state (rs) neurophysiological dynamics relies on the control of sensory, perceptual, and behavioral environments to minimize variability and rule-out confounding sources of activation during testing conditions. Here, we investigated how temporally-distal environmental inputs, specifically metal exposures experienced up to several months prior to scanning, affect functional dynamics measured using rs functional magnetic resonance imaging (rs-fMRI). We implemented an interpretable XGBoost-Shapley Additive Explanation (SHAP) model that integrated information from multiple exposure biomarkers to predict rs dynamics in typically developing adolescents. In 124 participants (53% females, ages: 13-25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of six metals (manganese, lead, chromium, cupper, nickel and zinc) in biological matrices (saliva, hair, fingernails, toenails, blood and urine) and acquired rs-fMRI scans. Using graph theory metrics, we computed global efficiency (GE) in 111 brain areas (Harvard Oxford Atlas). We used a predictive model based on ensemble gradient boosting to predict GE from metal biomarkers, adjusting for age and biological sex. Model performance was evaluated by comparing predicted versus measured GE. SHAP scores were used to evaluate feature importance. Measured versus predicted rs dynamics from our model utilizing chemical exposures as inputs were significantly correlated (p< 0.001,r= 0.36). Lead, chromium, and copper contributed most to the prediction of GE metrics. Our results indicate that a significant component of rs dynamics, comprising approximately 13% of observed variability in GE, is driven by recent metal exposures. These findings emphasize the need to estimate and control for the influence of past and current chemical exposures in the assessment and analysis of rs functional connectivity.

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders characterized by abnormal social interactions. Eye-tracking studies have objectively reported social perception abnormalities in ASD, characterized by a decrease of gaze towards social stimuli. Brain imaging studies, using PET and SPECT methods, have revealed a decrease in cerebral blood flow (CSF) at rest in the temporal regions, particularly in the superior temporal sulcus (STS), in children with ASD. Nowadays, it is possible to measure rest CBF with MRI using arterial spin labeling (ASL) sequence. In this thesis, we confirmed the decreased in rest CBF within the STS in children with ASD using MRI-ASL, which could allow its use as a biomarker in ASD. We also suggest that rest CBF could be a more relevant index for studying basic brain function in ASD. In addition, we performed a cross-sectional eye-tracking study using the same stimuli over a wide age-range and showed the impact of age on social perception in ASD and in typical development. Finally, we showed social perception abnormalities, using eye-tracking, and cortical functioning abnormalities within the STS using MRI-ASL, in children with posterior fossa arachnoid cyst. A better understanding of the social difficulties underlying this disorder could have a major impact on patient outcome.; Les troubles du spectre autistique (TSA) sont des troubles neuro-développementaux caractérisés notamment par des anomalies des interactions sociales. Des études en eye-tracking ont permis de mettre en évidence de façon objective des anomalies de la perception sociale dans les TSA, caractérisées par une diminution du regard vers des stimuli sociaux. Des études sur le fonctionnement cérébral, par des méthodes TEP et SPECT, ont mis en évidence une diminution du débit sanguin cérébral (DSC) au repos au niveau des régions temporales, notamment au niveau du sillon temporal supérieur (STS), chez des enfants avec TSA. Nous avons aujourd’hui la possibilité de mesurer le DSC au repos en IRM avec la séquence arterial spin labelling (ASL). Dans cette thèse nous avons confirmé la diminution du DSC au repos au niveau du STS chez des enfants avec TSA par la méthode IRM-ASL, ce qui pourraient permettre son utilisation en tant que biomarqueur dans les TSA. Nous suggérons également que le DSC au repos pourrait être un indice plus pertinent pour l’étude du fonctionnement cérébral de base dans les TSA. De plus, par une étude transversale en eye-tracking utilisant les mêmes stimuli sur une large tranche d’âge, nous avons montré l’impact de l’âge sur la perception sociale chez des participants avec TSA et des témoins. Enfin, nous avons mis en évidence des anomalies de perception sociale par l’eye-tracking et de fonctionnement cortical au niveau du STS par l’IRM-ASL, chez des enfants ayant un kyste arachnoïdien de la fosse postérieure. Une meilleure connaissance des difficultés sociales subjacentes à ce trouble peut avoir un impact majeur sur la prise en charge de ces enfants.

In the aftermath of the World Trade Center (WTC) attack, rescue and recovery workers faced hazardous conditions and toxic agents. Prior research linked these exposures to adverse health effects, but mainly examined individual factors, overlooking complex mixture effects. This study applies an exposomic approach encompassing the totality of responders' experience, defined as the WTC exposome. We analyzed data from 34,096 members of the WTC Health Program General Responder, including mental and physical health, occupational history, traumatic and environmental exposures using generalized weighted quantile sum regression. We find a significant association between the exposure mixture index all investigated health outcomes. Factors identified as risk factors include working in an enclosed heavily contaminated area, construction occupation, and exposure to blood and body fluids. Conversely, full-time employment emerged as a protective factor. This exposomics study emphasizes the importance of considering combined exposures. In an era marked by more frequent and severe natural disasters due to the evolving climate crisis, the exposomic framework holds promise as a valuable tool for disaster preparedness., Competing Interests: Declaration of interests The authors declare no competing interests.

Coronavirus disease 2019 (COVID-19) has been associated with brain functional, structural, and cognitive changes that persist months after infection. Most studies of the neurologic outcomes related to COVID-19 focus on severe infection and aging populations. Here, we investigated the neural activities underlying COVID-19 related outcomes in a case-control study of mildly infected youth enrolled in a longitudinal study in Lombardy, Italy, a global hotspot of COVID-19. All participants (13 cases, 27 controls, mean age 24 years) completed resting state functional (fMRI), structural MRI, cognitive assessments (CANTAB spatial working memory) at baseline (pre-COVID) and follow-up (post-COVID). Using graph theory eigenvector centrality (EC) and data-driven statistical methods, we examined differences in EC delta (i.e., the difference in EC values pre- and post-COVID-19) and volumetric delta (i.e., the difference in cortical volume of cortical and subcortical areas pre- and post-COVID) between COVID-19 cases and controls. We found that EC delta significantly between COVID-19 and healthy participants in five brain regions; right intracalcarine cortex, right lingual gyrus, left hippocampus, left amygdala, left frontal orbital cortex. The left hippocampus showed a significant decrease in volumetric delta between groups (p=0.041). The reduced EC delta in the right amygdala associated with COVID-19 status mediated the association between COVID-19 and disrupted spatial working memory. Our results show persistent structural, functional and cognitive brain changes in key brain areas associated with olfaction and cognition. These results may guide treatment efforts to assess the longevity, reversibility and impact of the observed brain and cognitive changes following COVID-19., Competing Interests: Conflict of Interest: None.

The assessment of resting state (rs) neurophysiological dynamics relies on the control of sensory, perceptual, and behavioral environments to minimize variability and rule-out confounding sources of activation during testing conditions. Here, we investigated how temporally-distal environmental inputs, specifically metal exposures experienced up to several months prior to scanning, affect functional dynamics measured using rs functional magnetic resonance imaging (rs-fMRI). We implemented an interpretable XGBoost-Shapley Additive Explanation (SHAP) model that integrated information from multiple exposure biomarkers to predict rs dynamics in typically developing adolescents. In 124 participants (53% females, ages: 13-25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of six metals (manganese, lead, chromium, cupper, nickel and zinc) in biological matrices (saliva, hair, fingernails, toenails, blood and urine) and acquired rs-fMRI scans. Using graph theory metrics, we computed global efficiency (GE) in 111 brain areas (Harvard Oxford Atlas). We used a predictive model based on ensemble gradient boosting to predict GE from metal biomarkers, adjusting for age and biological sex. Model performance was evaluated by comparing predicted versus measured GE. SHAP scores were used to evaluate feature importance. Measured versus predicted rs dynamics from our model utilizing chemical exposures as inputs were significantly correlated ( p < 0.001, r = 0.36). Lead, chromium, and copper contributed most to the prediction of GE metrics. Our results indicate that a significant component of rs dynamics, comprising approximately 13% of observed variability in GE, is driven by recent metal exposures. These findings emphasize the need to estimate and control for the influence of past and current chemical exposures in the assessment and analysis of rs functional connectivity.