Professional Education

  • Master of Science, Imperial College London, Bioengineering with neurotechnology (2015)
  • Diplome d'ingénieur, Télécom Paristech, Computer Science, Electronic (2015)
  • Doctor of Philosophy, Neurospin, CEA, Université Paris-Saclay, MR imaging, Neuroscience, Imaging-genetic (2018)

Stanford Advisors


All Publications

  • Association of Klotho-VS Heterozygosity With Risk of Alzheimer Disease in Individuals Who Carry APOE4. JAMA neurology Belloy, M. E., Napolioni, V., Han, S. S., Le Guen, Y., Greicius, M. D. 2020


    Identification of genetic factors that interact with the apolipoprotein e4 (APOE4) allele to reduce risk for Alzheimer disease (AD) would accelerate the search for new AD drug targets. Klotho-VS heterozygosity (KL-VSHET+ status) protects against aging-associated phenotypes and cognitive decline, but whether it protects individuals who carry APOE4 from AD remains unclear.To determine if KL-VSHET+ status is associated with reduced AD risk and ?-amyloid (A?) pathology in individuals who carry APOE4.This study combined 25 independent case-control, family-based, and longitudinal AD cohorts that recruited referred and volunteer participants and made data available through public repositories. Analyses were stratified by APOE4 status. Three cohorts were used to evaluate conversion risk, 1 provided longitudinal measures of A? CSF and PET, and 3 provided cross-sectional measures of A? CSF. Genetic data were available from high-density single-nucleotide variant microarrays. All data were collected between September 2015 and September 2019 and analyzed between April 2019 and December 2019.The risk of AD was evaluated through logistic regression analyses under a case-control design. The risk of conversion to mild cognitive impairment (MCI) or AD was evaluated through competing risks regression. Associations with A?, measured from cerebrospinal fluid (CSF) or brain positron emission tomography (PET), were evaluated using linear regression and mixed-effects modeling.Of 36?530 eligible participants, 13?782 were excluded for analysis exclusion criteria or refusal to participate. Participants were men and women aged 60 years and older who were non-Hispanic and of Northwestern European ancestry and had been diagnosed as being cognitively normal or having MCI or AD. The sample included 20?928 participants in case-control studies, 3008 in conversion studies, 556 in A? CSF regression analyses, and 251 in PET regression analyses. The genotype KL-VSHET+ was associated with reduced risk for AD in individuals carrying APOE4 who were 60 years or older (odds ratio, 0.75 [95% CI, 0.67-0.84]; P?=?7.4?×?10-7), and this was more prominent at ages 60 to 80 years (odds ratio, 0.69 [95% CI, 0.61-0.79]; P?=?3.6?×?10-8). Additionally, control participants carrying APOE4 with KL-VS heterozygosity were at reduced risk of converting to MCI or AD (hazard ratio, 0.64 [95% CI, 0.44-0.94]; P?=?.02). Finally, in control participants who carried APOE4 and were aged 60 to 80 years, KL-VS heterozygosity was associated with higher A? in CSF (?, 0.06 [95% CI, 0.01-0.10]; P?=?.03) and lower A? on PET scans (?, -0.04 [95% CI, -0.07 to -0.00]; P?=?.04).The genotype KL-VSHET+ is associated with reduced AD risk and A? burden in individuals who are aged 60 to 80 years, cognitively normal, and carrying APOE4. Molecular pathways associated with KL merit exploration for novel AD drug targets. The KL-VS genotype should be considered in conjunction with the APOE genotype to refine AD prediction models used in clinical trial enrichment and personalized genetic counseling.

    View details for DOI 10.1001/jamaneurol.2020.0414

    View details for PubMedID 32282020

  • "Plis de passage" Deserve a Role in Models of the Cortical Folding Process BRAIN TOPOGRAPHY Mangin, J., Le Guen, Y., Labra, N., Grigis, A., Frouin, V., Guevara, M., Fischer, C., Riviere, D., Hopkins, W. D., Regis, J., Sun, Z. 2019


    Cortical folding is a hallmark of brain topography whose variability across individuals remains a puzzle. In this paper, we call for an effort to improve our understanding of the pli de passage phenomenon, namely annectant gyri buried in the depth of the main sulci. We suggest that plis de passage could become an interesting benchmark for models of the cortical folding process. As an illustration, we speculate on the link between modern biological models of cortical folding and the development of the Pli de Passage Frontal Moyen (PPFM) in the middle of the central sulcus. For this purpose, we have detected nine interrupted central sulci in the Human Connectome Project dataset, which are used to explore the organization of the hand sensorimotor areas in this rare configuration of the PPFM.

    View details for DOI 10.1007/s10548-019-00734-8

    View details for Web of Science ID 000488894700001

    View details for PubMedID 31583493

  • eQTL of KCNK2 regionally influences the brain sulcal widening: evidence from 15,597 UK Biobank participants with neuroimaging data. Brain structure & function Le Guen, Y., Philippe, C., Riviere, D., Lemaitre, H., Grigis, A., Fischer, C., Dehaene-Lambertz, G., Mangin, J., Frouin, V. 2018


    The grey and white matter volumes are known to reduce with age. This cortical shrinkage is visible on magnetic resonance images and is conveniently identified by the increased volume of cerebrospinal fluid in the sulci between two gyri. Here, we replicated this finding using the UK Biobank dataset and studied the genetic influence on these cortical features of aging. We divided all individuals genetically confirmed of British ancestry into two sub-cohorts (12,162 and 3435 subjects for discovery and replication samples, respectively). We found that the heritability of the sulcal opening ranges from 15 to 45% (SE = 4.8%). We identified 4 new loci that contribute to this opening, including one that also affects the sulci grey matter thickness. We identified the most significant variant (rs864736) on this locus as being an expression quantitative trait locus (eQTL) for the KCNK2 gene. This gene regulates the immune-cell into the central nervous system (CNS) and controls the CNS inflammation, which is implicated in cortical atrophy and cognitive decline. These results expand our knowledge of the genetic contribution to cortical shrinking and promote further investigation into these variants and genes in pathological context such as Alzheimer's disease in which brain shrinkage is a key biomarker.

    View details for DOI 10.1007/s00429-018-1808-9

    View details for PubMedID 30519892

  • Shared genetic aetiology between cognitive performance and brain activations in language and math tasks SCIENTIFIC REPORTS Le Guen, Y., Amalric, M., Pinel, P., Pallier, C., Frouin, V. 2018; 8: 17624


    Cognitive performance is highly heritable. However, little is known about common genetic influences on cognitive ability and brain activation when engaged in a cognitive task. The Human Connectome Project (HCP) offers a unique opportunity to study this shared genetic etiology with an extended pedigree of 785 individuals. To investigate this common genetic origin, we took advantage of the HCP dataset, which includes both language and mathematics activation tasks. Using the HCP multimodal parcellation, we identified areals in which inter-individual functional MRI (fMRI) activation variance was significantly explained by genetics. Then, we performed bivariate genetic analyses between the neural activations and behavioral scores, corresponding to the fMRI task accuracies, fluid intelligence, working memory and language performance. We observed that several parts of the language network along the superior temporal sulcus, as well as the angular gyrus belonging to the math processing network, are significantly genetically correlated with these indicators of cognitive performance. This shared genetic etiology provides insights into the brain areas where the human-specific genetic repertoire is expressed. Studying the association of polygenic risk scores, using variants associated with human cognitive ability and brain activation, would provide an opportunity to better understand where these variants are influential.

    View details for DOI 10.1038/s41598-018-35665-0

    View details for Web of Science ID 000452084600032

    View details for PubMedID 30514932

    View details for PubMedCentralID PMC6279777

  • The chaotic morphology of the left superior temporal sulcus is genetically constrained NEUROIMAGE Le Guen, Y., Leroy, F., Auzias, G., Riviere, D., Grigis, A., Mangin, J., Coulon, O., Dehaene-Lambertz, G., Frouin, V. 2018; 174: 297?307


    The asymmetry of the superior temporal sulcus (STS) has been identified as a species-specific feature of the human brain. The so-called superior temporal asymmetrical pit (STAP) area is observed from the last trimester of gestation onwards and is far less pronounced in the chimpanzee brain. This asymmetry is associated with more frequent sulcal interruptions, named plis de passage (PPs), leading to the irregular morphology of the left sulcus. In this paper, we aimed to characterize the variability, asymmetry, and heritability of these interruptions in the STS in comparison with the other main sulci. We developed an automated method to extract PPs across the cortex based on a highly reproducible grid of sulcal pits across individuals, which we applied to a subset of Human Connectome Project (HCP) subjects (N?=?820). We report that only a few PPs across the cortex are genetically constrained, namely in the collateral, postcentral and superior temporal sulci and the calcarine fissure. Moreover, some PPs occur more often in one hemisphere than the other, namely in the precentral, postcentral, intraparietal sulci, as well as in both inferior and superior temporal sulci. Most importantly, we found that only the interruptions within the STAP region are both asymmetric and genetically constrained. Because this morphological pattern is located in an area of the left hemisphere related to speech, our results suggest structural constraints on the architecture of the linguistic network.

    View details for DOI 10.1016/j.neuroimage.2018.03.046

    View details for Web of Science ID 000438609100026

    View details for PubMedID 29571714

  • Genetic Influence on the Sulcal Pits: On the Origin of the First Cortical Folds CEREBRAL CORTEX Le Guen, Y., Auzias, G., Leroy, F., Noulhiane, M., Dehaene-Lambertz, G., Duchesnay, E., Mangin, J., Coulon, O., Frouin, V. 2018; 28 (6): 1922?33
  • PyPNS: Multiscale Simulation of a Peripheral Nerve in Python. Neuroinformatics Lubba, C. H., Le Guen, Y., Jarvis, S., Jones, N. S., Cork, S. C., Eftekhar, A., Schultz, S. R. 2018


    Bioelectronic Medicines that modulate the activity patterns on peripheral nerves have promise as a new way of treating diverse medical conditions from epilepsy to rheumatism. Progress in the field builds upon time consuming and expensive experiments in living organisms. To reduce experimentation load and allow for a faster, more detailed analysis of peripheral nerve stimulation and recording, computational models incorporating experimental insights will be of great help. We present a peripheral nerve simulator that combines biophysical axon models and numerically solved and idealised extracellular space models in one environment. We modelled the extracellular space as a three-dimensional resistive continuum governed by the electro-quasistatic approximation of the Maxwell equations. Potential distributions were precomputed in finite element models for different media (homogeneous, nerve in saline, nerve in cuff) and imported into our simulator. Axons, on the other hand, were modelled more abstractly as one-dimensional chains of compartments. Unmyelinated fibres were based on the Hodgkin-Huxley model; for myelinated fibres, we adapted the model proposed by McIntyre et al. in 2002 to smaller diameters. To obtain realistic axon shapes, an iterative algorithm positioned fibres along the nerve with a variable tortuosity fit to imaged trajectories. We validated our model with data from the stimulated rat vagus nerve. Simulation results predicted that tortuosity alters recorded signal shapes and increases stimulation thresholds. The model we developed can easily be adapted to different nerves, and may be of use for Bioelectronic Medicine research in the future.

    View details for DOI 10.1007/s12021-018-9383-z

    View details for PubMedID 29948844

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