Biology subjects

Dumas, G.

Publications and source records attributed to Dumas, G..

25 records · Page 2Linked to original sources

bioRxiv2019

Neuropsychiatric mutations delineate functional brain connectivity dimensions contributing to autism and schizophrenia

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. We analyzed resting-state functional magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We used CNV FC-signatures to identify dimensions contributing to complex idiopathic conditions. CNVs had large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions played a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibited worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.

neuroscience↗

bioRxiv2019

Systematic detection of divergent brain proteins in human evolution and their roles in cognition

The human brain differs from that of other primates, but the genetic basis of these differences remains unclear. We investigated the evolutionary pressures acting on almost all human protein-coding genes (N=11,667; 1:1 orthologs in primates) based on their divergence from those of early hominins, such as Neanderthals, and non-human primates. We confirm that genes encoding brain-related proteins are among the most strongly conserved protein-coding genes in the human genome. Combining our evolutionary pressure metrics for the protein-coding genome with recent datasets, we found that this conservation applied to genes functionally associated with the synapse and expressed in brain structures such as the prefrontal cortex and the cerebellum. Conversely, several genes presenting signatures commonly associated with positive selection appear as causing brain diseases or conditions, such as micro/macrocephaly, Joubert syndrome, dyslexia, and autism. Among those, a number of DNA damage response genes associated with microcephaly in humans such as BRCA1, NHEJ1, TOP3A, and RNF168 show strong signs of positive selection and might have played a role in human brain size expansion during primate evolution. We also showed that cerebellum granule neurons express a set of genes also presenting signatures of positive selection and that may have contributed to the emergence of fine motor skills and social cognition in humans. This resource is available online and can be used to estimate evolutionary constraints acting on a set of genes and to explore their relative contributions to human traits.

genetics↗

bioRxiv2019

The Human Dynamic Clamp reveals the fronto-parietal network linking real-time social coordination and cognition

How does the brain allow us to interact with others, and above all how does it handle situations when the goals of the interactors overlap (i.e. cooperation) or differ (i.e. competition)? Social neuroscience has already provided some answers to these questions but has tended to treat high-level, cognitive interpretations of social behavior separately from the sensorimotor mechanisms upon which they rely. The goal here is to identify the underlying neural processes and mechanisms linking sensorimotor coordination and intention attribution. We combine the Human Dynamic Clamp (HDC), a novel paradigm for studying realistic social behavior between self and other in well-controlled laboratory conditions, with high resolution electroencephalography (EEG). The collection of humanness and intention attribution reports, kinematics and neural data affords an opportunity to relate brain activity to the behavior of the HDC as well as to what the human is doing. Behavioral results demonstrate that sensorimotor coordination influences judgements of cooperativeness and humanness. Analysis of brain dynamics reveals two distinct networks related to integration of visuo-motor information from self and other. The two networks overlap over the right parietal region, an area known to be important for interpersonal motor interactions. Furthermore, connectivity analysis highlights how the judgement of humanness and cooperation of others modulate the connection between the right parietal hub and prefrontal cortex. These results reveal how distributed neural dynamics integrates information from low-level sensorimotor mechanisms and high-level social cognition to support the realistic social behaviors that play out in real time during interactive scenarios.\n\nSignificance StatementDaily social interactions require us to coordinate with others and to reflect on their potential motives. This study investigates the brain and behavioral dynamics of these two key aspects of social cognition. Combining high-density electroencephalography and the Human Dynamic Clamp (a Virtual Partner endowed with human-based coordination dynamics), we show first, that several features of sensorimotor coordination influence attribution of intention and judgement of humanness; second, that the right parietal lobe is a key integration hub between information related to self- and other-behavior; and third, that the posterior online social hub is functionally coupled to anterior offline brain structures to support mentalizing about others. Our results stress the complementary nature of low-level and high-level mechanisms that underlie social cognition.

neuroscience↗

bioRxiv2019

Binaural Beats through the auditory pathway: from brainstem to connectivity patterns

Binaural beating is a perceptual auditory illusion occurring when presenting two neighboring frequencies to each ear separately. Binaural beats have been attributed to several controversial claims regarding their ability to modulate brain activity and mood, in both the scientific literature and the marketing realm. Here, we sought to address those questions in a robust fashion using a single-blind, sham-controlled protocol. To do so, we characterized responses to theta and gamma binaural beats and \"sham\" stimulation (monaural beats) across four distinct levels: subcortical and cortical entrainment, scalp-level Functional Connectivity and self-reports. Both stimuli elicited standard subcortical responses at the pure tone frequencies of the stimulus (i.e., Frequency Following Response), and entrained the cortex at the beat frequency (i.e., Auditory Steady State Response). Furthermore, Functional Connectivity patterns were modulated differentially by both kinds of stimuli, with binaural beats being the only one eliciting cross-frequency activity. Despite this, we did not find any mood modulation related to our experimental manipulation. Our results provide evidence that binaural beats elicit cross frequency connectivity patterns, but weakly entrain the cortex when compared to a sham stimulus. Whether these patterns have an impact in cognitive performance or other mood measurements remains to be seen.\n\nSignificance StatementBinaural beats have been a source of speculation and debate in the scientific community. Our study addresses pseudo-scientific marketing claims and approaches them using proper experimental control and state-of-the-art signal processing techniques. Here we show that binaural beats can both entrain the cortex and elicit specific connectivity patterns. Regardless of this, our sham condition was able to entrain the cortex more strongly, and both binaural beats and the sham condition failed to regulate mood. All in all, though binaural beats weakly entrain cortical activity and elicit complex patterns of connectivity, the functional significance (if any) of these patterns remains an open question.

neuroscience↗

bioRxiv2018

Dissecting the heterogeneous cortical anatomy of autism spectrum disorder using normative models

BackgroundThe neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly due to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort towards understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous.\n\nMethodsHere, we used an innovative normative modelling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertex-wise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this we employed a heterogeneous cross-sectional sample of 206 typically developing (TD) individuals (127 male), and 321 individuals (232 male) with ASD (aged 6-31).\n\nResultsWe found few case-control differences but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing.\n\nConclusionsOur results: (i) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and (ii) show that by focusing on common effects (i.e. the average ASD participant), the case-control approach disguises considerable inter-individual variation crucial for precision medicine.

neuroscience↗

bioRxiv2017

Experimenting with reproducibility in bioinformatics

Reproducibility has been shown to be limited in many scientific fields. This question is a fundamental tenet of the scientific activity, but the related issues of reusability of scientific data are poorly documented. Here, we present a case study of our attempt to reproduce a promising bioinformatics method [1] and illustrate the challenges to use a published method for which code and data were available. First, we tried to re-run the analysis with the code and data provided by the authors. Second, we reimplemented the method in Python to avoid dependency on a MATLAB licence and ease the execution of the code on HPCC (High-Performance Computing Cluster). Third, we assessed reusability of our reimplementation and the quality of our documentation. Then, we experimented with our own software and tested how easy it would be to start from our implementation to reproduce the results, hence attempting to estimate the robustness of the reproducibility. Finally, in a second part, we propose solutions from this case study and other observations to improve reproducibility and research efficiency at the individual and collective level.\n\nAvailabilitylast version of StratiPy (Python) with two examples of reproducibility are available at GitHub [2].\n\nContactyang-min.kim@pasteur.fr

bioinformatics↗

bioRxiv2017

Dark Control: A Unified Account of Default Mode Function by Control Theory and Reinforcement Learning

The default mode network (DMN) is believed to subserve the baseline mental activity in humans. Its highest energy consumption compared to other brain networks and its intimate coupling with conscious awareness are both pointing to an overarching function. Many research streams speak in favor of an evolutionarily adaptive role in envisioning experience to anticipate the future. In the present work, we propose a process model that tries to explain how the DMN may implement continuous evaluation and prediction of the environment to guide behavior. Specifically, we answer the question whether the neurobiological properties of the DMN collectively provide the computational building blocks necessary for a Markov Decision Process. We argue that our formal account of DMN function naturally accommodates as special cases previous interpretations based on (1) predictive coding, (2) semantic associations, and (3) a sentinel role. Moreover, this process model for the neural optimization of complex behavior in the DMN offers parsimonious explanations for recent experimental findings in animals and humans.

neuroscience↗