Biology subjects

Abdallah, M.

Publications and source records attributed to Abdallah, M..

4 recordsLinked to original sources

bioRxiv2022

Meta-Analysis of the Functional Neuroimaging Literature with Probabilistic Logic Programming

Inferring reliable brain-behavior associations requires synthesizing evidence from thousands of functional neuroimaging studies through meta-analysis. However, existing meta-analysis tools are limited to investigating simple neuroscience concepts and expressing a restricted range of questions. Here, we expand the scope of neuroimaging meta-analysis by designing NeuroLang: a domain-specific language to express and test hypotheses using probabilistic first-order logic programming. By leveraging formalisms found at the crossroads of artificial intelligence and knowledge representation, NeuroLang provides the expressivity to address a larger repertoire of hypotheses in a meta-analysis, while seamlessly modelling the uncertainty inherent to neuroimaging data. We demonstrate the languages capabilities in conducting comprehensive neuroimaging meta-analysis through use-case examples that address questions of structure-function associations. Specifically, we infer the specific functional roles of three canonical brain networks, support the role of the visual word-form area in visuospatial attention, and investigate the heterogeneous organization of the fronto-parietal control network.

neuroscience↗

bioRxiv2022

Functional gradients in the human lateral prefrontal cortex revealed by a comprehensive coordinate-based meta-analysis

The human lateral prefrontal cortex (LPFC) enables flexible goal-directed behavior. Yet, its organizing principles remain actively debated despite decades of research. Meta-analysis efforts to map the LPFC have either been restricted in scope or suffered from limited expressivity in meta-analysis tools. The latter short-coming hinders the complexity of questions that can be expressed in a meta-analysis and hence limits the specificity of structure-function associations. Here, we adopt NeuroLang, a novel approach to meta-analysis based on first-order probabilistic logic programming, to infer the organizing principles of the LPFC with greater specificity from 14,371 neuroimaging publications. Our results reveal a rostrocaudal and a dorsoventral gradient, respectively explaining the most and second-most variance in whole-brain meta-analytic connectivity in the LPFC. Moreover, we find a cross-study agreement on a spectrum of increasing abstraction from caudal to rostral LPFC both in specific network connectivity and structure-function associations that supports a domain-general role for the mid-LPFC. Furthermore, meta-analyzing inter-hemispheric asymmetries along the rostrocaudal gradient reveals specific associations with topics of language, memory, response inhibition, and error processing. Overall, we provide a comprehensive mapping of the organizing principles of task-dependent activity in the LPFC, grounding future hypothesis generation on a quantitative overview of past findings.

neuroscience↗

bioRxiv2020

Static and Dynamic Aspects of Cerebro-Cerebellar Functional Connectivity are Associated with Self-reported Measures of Impulsivity: A Resting-State fMRI Study

Converging evidence from human and animal studies predict a possible role of the cerebellum in impulsivity. However, this hypothesis has not been thoroughly investigated within the framework of functional connectivity (FC). To address this issue, we employed resting-state fMRI data and two self-reports of impulsivity (UPPS-P and BIS/BAS) from a large group of healthy young individuals (N=134). We identified cerebral and cerebellar resting-state networks, and evaluated the association of static (strength) and dynamic (temporal variability) aspects of cerebro-cerebellar FC with different elements of self-reported impulsivity. Our results revealed that the behavioral inhibition and approach systems (BIS/BAS) were inversely associated with basal ganglia-cerebellar and fronto-cerebellar FC strength, respectively. In addition, we found that lack of premeditation was inversely associated with the temporal variability of FC between the cerebellum and top-down control networks that included sub-regions of the prefrontal cortex, precuneus, and posterior cingulate cortex. Moreover, we found that sensation seeking was associated with the temporal variability of FC between the cerebellum and networks that included cortical control regions and sub-cortical reward regions: the basal ganglia and the thalamus. Together, these findings indicate that the cerebellum may contribute to different forms of impulsivity through its connections to large-scale control and reward networks.

neuroscience↗

bioRxiv2019

In vivo characterisation of the toxicological properties of DPhP, one of the main degradation product of aryl phosphate esters.

BackgroundAryl phosphate esters (APEs), a main class of organophosphorus ester molecules, are widely used and commonly present in the environment. Health hazards associated with these compounds remain largely unknown and the effects of diphenyl phosphate (DPhP), one of their most frequent derivatives in human samples, are poorly characterised. ObjectiveOur aim was to investigate whether DPhP per se may represent a more relevant marker of exposure to APEs and determine its potential deleterious biological effects in chronically exposed mice. MethodsConventional animals (FVB mice) were acutely (intravenous or oral gavage) or chronically (0.1 mg.mL-1, 1 mg.mL-1, 10 mg.mL-1 in drink water) exposed to relevant doses of DPhP or triphenyl phosphate (TPhP), one of its main precursors in the environment. Both molecules were measured in blood and other relevant tissues by liquid chromatography-mass spectrometry (LC-MS). Biological effects of chronic DPhP exposure were addressed through liver multi-omics analysis combining mRNA extraction and sequencing to high resolution LC-MS to determine the corresponding metabolic profile. Deep statistical exploration was performed to extract correlated information, guiding further physiological analyses (immunohistochemistry (IHC) and animal growth measurement). ResultsAcute and chronic exposure to DPhP led to significant levels of this molecule in blood and other tissues, an effect missing with TPhP. Multi-omics analysis confirmed the existence of biological effects of DPhP, even at a very low dose of 0.1 mg.mL-1 in drinking water. Chemical structural homology and pathway mapping demonstrated a clear reduction of the fatty-acid catabolic processes centred on acylcarnitine and mitochondrial {beta}-oxidation. Interestingly, mRNA expression confirmed and extended these observations by demonstrating at all tested doses the overall repression of genes involved in lipid catabolic processes and regulated by PPAR, a master regulator of {beta}-oxidation and its associated ketogenesis. IHC analysis confirmed the alteration of these pathways by showing a specific downregulation of Hmgcs2, a kernel target gene of PPAR, at all doses tested, and surprisingly, a strong reduction of the lipid droplet content only at the highest dose. Overall, DPhP absorption led to weight loss, which was significant using the highest dose. ConclusionsOur results suggest that in mice, the effects of chronic exposure to DPhP, even at a low dose, are not negligible. Fatty acid metabolism in the liver in particular is essential for controlling fast and feast periods with adverse consequences on the overall physiology. Therefore, the impact of DPhP on circulating fat, cardiovascular and metabolic disease incidence deserves, in light of our results, further investigations.

pharmacology and toxicology↗