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1. Ensemble feature selection with data-driven thresholding for Alzheimer's disease biomarker discovery

Author: Annette Spooner, Gelareh Mohammadi, Perminder S. Sachdev, Henry Brodaty, Arcot Sowmya, and for the Sydney Memory and Ageing Study and the Alzheimer’s Disease Neuroimaging Initiative
Subjects: Ensemble feature selection, Stability, Data-driven thresholding, Alzheimer's disease, Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract: Abstract Background Feature selection is often used to identify the important features in a dataset but can produce unstable results when applied to high-dimensional data. The stability of feature selection can be improved with the use of feature selection ensembles, which aggregate the results of multiple base feature selectors. However, a threshold must be applied to the final aggregated feature set to separate the relevant features from the redundant ones. A fixed threshold, which is typically used, offers no guarantee that the final set of selected features contains only relevant features. This work examines a selection of data-driven thresholds to automatically identify the relevant features in an ensemble feature selector and evaluates their predictive accuracy and stability. Ensemble feature selection with data-driven thresholding is applied to two real-world studies of Alzheimer's disease. Alzheimer's disease is a progressive neurodegenerative disease with no known cure, that begins at least 2–3 decades before overt symptoms appear, presenting an opportunity for researchers to identify early biomarkers that might identify patients at risk of developing Alzheimer's disease. Results The ensemble feature selectors, combined with data-driven thresholds, produced more stable results, on the whole, than the equivalent individual feature selectors, showing an improvement in stability of up to 34%. The most successful data-driven thresholds were the robust rank aggregation threshold and the threshold algorithm threshold from the field of information retrieval. The features identified by applying these methods to datasets from Alzheimer's disease studies reflect current findings in the AD literature. Conclusions Data-driven thresholds applied to ensemble feature selectors provide more stable, and therefore more reproducible, selections of features than individual feature selectors, without loss of performance. The use of a data-driven threshold eliminates the need to choose a fixed threshold a-priori and can select a more meaningful set of features. A reliable and compact set of features can produce more interpretable models by identifying the factors that are important in understanding a disease.
Published: 2023
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2. Lifestyle, Exercise and Diet: The LEAD Study (LEAD)

Author: Sunnybrook Health Sciences Centre, Toronto Rehabilitation Institute, The Centre for Memory and Aging, University of Waterloo, and Carol Greenwood, Senior Scientist
Published: 2020

3. Cognitive subtypes of probable Alzheimer's disease robustly identified in four cohorts

Author: Scheltens, Nienke ME, Tijms, Betty M, Koene, Teddy, Barkhof, Frederik, Teunissen, Charlotte E, Wolfsgruber, Steffen, Wagner, Michael, Kornhuber, Johannes, Peters, Oliver, Cohn‐Sheehy, Brendan I, Rabinovici, Gil D, Miller, Bruce L, Kramer, Joel H, Scheltens, Philip, van der Flier, Wiesje M, Network, German Dementia Competence, San Francisco Memory and Aging Center, University of California, and Cohort, Amsterdam Dementia
Subjects: Biological Psychology, Psychology, Alzheimer's Disease, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurosciences, Behavioral and Social Science, Brain Disorders, Dementia, Acquired Cognitive Impairment, Neurodegenerative, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Apolipoprotein E4, Cluster Analysis, Cognition Disorders, Cohort Studies, Denmark, Disease Progression, Female, Germany, Humans, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Neuropsychological Tests, Peptide Fragments, United States, Alzheimer's disease, Cognition, Heterogeneity, Subtypes, Atypical, Neuropsychology, German Dementia Competence Network, University of California San Francisco Memory and Aging Center, Amsterdam Dementia Cohort, Clinical Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract: IntroductionPatients with Alzheimer's disease (AD) show heterogeneity in profile of cognitive impairment. We aimed to identify cognitive subtypes in four large AD cohorts using a data-driven clustering approach.MethodsWe included probable AD dementia patients from the Amsterdam Dementia Cohort (n = 496), Alzheimer's Disease Neuroimaging Initiative (n = 376), German Dementia Competence Network (n = 521), and University of California, San Francisco (n = 589). Neuropsychological data were clustered using nonnegative matrix factorization. We explored clinical and neurobiological characteristics of identified clusters.ResultsIn each cohort, a two-clusters solution best fitted the data (cophenetic correlation >0.9): one cluster was memory-impaired and the other relatively memory spared. Pooled analyses showed that the memory-spared clusters (29%-52% of patients) were younger, more often apolipoprotein E (APOE) ɛ4 negative, and had more severe posterior atrophy compared with the memory-impaired clusters (all P
Published: 2017

4. Genetically predicted body mass index and Alzheimer's disease–related phenotypes in three large samples: Mendelian randomization analyses

Author: Mukherjee, Shubhabrata, Walter, Stefan, Kauwe, John SK, Saykin, Andrew J, Bennett, David A, Larson, Eric B, Crane, Paul K, Glymour, M Maria, Investigators, Adult Changes in Thought Study, Investigators, Religious Orders Study Memory and Aging Project, and Consortium, Alzheimer's Disease Genetics
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Alzheimer's Disease, Neurodegenerative, Prevention, Aging, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Genetics, Dementia, Human Genome, Acquired Cognitive Impairment, Brain Disorders, 2.1 Biological and endogenous factors, 4.1 Discovery and preclinical testing of markers and technologies, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Body Mass Index, Female, Genotype, Humans, Linear Models, Male, Mendelian Randomization Analysis, Obesity, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Alzheimer's disease, Mendelian randomization, Adult Changes in Thought Study Investigators, Religious Orders Study/Memory and Aging Project Investigators, Alzheimer's Disease Genetics Consortium, Geriatrics, Clinical sciences, Biological psychology
Abstract: Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.
Published: 2015

5. Protective variant for hippocampal atrophy identified by whole exome sequencing

Author: Nho, Kwangsik, Kim, Sungeun, Risacher, Shannon L, Shen, Li, Corneveaux, Jason J, Swaminathan, Shanker, Lin, Hai, Ramanan, Vijay K, Liu, Yunlong, Foroud, Tatiana M, Inlow, Mark H, Siniard, Ashley L, Reiman, Rebecca A, Aisen, Paul S, Petersen, Ronald C, Green, Robert C, Jack, Clifford R, Weiner, Michael W, Baldwin, Clinton T, Lunetta, Kathryn L, Farrer, Lindsay A, Study, for the MIRAGE, Furney, Simon J, Lovestone, Simon, Simmons, Andrew, Mecocci, Patrizia, Vellas, Bruno, Tsolaki, Magda, Kloszewska, Iwona, Soininen, Hilkka, Consortium, for the AddNeuroMed, McDonald, Brenna C, Farlow, Martin R, Ghetti, Bernardino, Study, for the Indiana Memory and Aging, Huentelman, Matthew J, Saykin, Andrew J, and Initiative, for the Alzheimer's Disease Neuroimaging
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Neurodegenerative, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer's Disease, Brain Disorders, Acquired Cognitive Impairment, Human Genome, Aging, Dementia, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Mental health, Neurological, Aged, Alzheimer Disease, Amnesia, Atrophy, Cognitive Dysfunction, Disease Progression, Exome, Hippocampus, Humans, Male, Mutation, Missense, Protective Factors, Repressor Proteins, Sequence Analysis, DNA, MIRAGE (Multi-Institutional Research on Alzheimer Genetic Epidemiology) Study, AddNeuroMed Consortium, Indiana Memory and Aging Study, Alzheimer's Disease Neuroimaging Initiative, Neurology & Neurosurgery, Clinical sciences
Abstract: We used whole-exome sequencing to identify variants other than APOE associated with the rate of hippocampal atrophy in amnestic mild cognitive impairment. An in-silico predicted missense variant in REST (rs3796529) was found exclusively in subjects with slow hippocampal volume loss and validated using unbiased whole-brain analysis and meta-analysis across 5 independent cohorts. REST is a master regulator of neurogenesis and neuronal differentiation that has not been previously implicated in Alzheimer's disease. These findings nominate REST and its functional pathways as protective and illustrate the potential of combining next-generation sequencing with neuroimaging to discover novel disease mechanisms and potential therapeutic targets.
Published: 2015

6. Factors predicting reversion from mild cognitive impairment to normal cognitive functioning: a population-based study.

Author: Perminder S Sachdev, Darren M Lipnicki, John Crawford, Simone Reppermund, Nicole A Kochan, Julian N Trollor, Wei Wen, Brian Draper, Melissa J Slavin, Kristan Kang, Ora Lux, Karen A Mather, Henry Brodaty, and Sydney Memory, Ageing Study Team
Subjects: Medicine, Science
Abstract: Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition.Our analyses considered 223 participants (48.9% male) aged 71-89 years, drawn from the prospective, population-based Sydney Memory and Ageing Study. All were diagnosed with MCI at baseline and subsequently classified with either normal cognition or repeat diagnosis of MCI after two years (a further 11 participants who progressed from MCI to dementia were excluded). Associations with reversion were investigated for (1) baseline factors that included diagnostic features, personality, neuroimaging, sociodemographics, lifestyle, and physical and mental health; (2) longitudinal change in potentially modifiable factors.There were 66 reverters to normal cognition and 157 non-reverters (stable MCI). Regression analyses identified diagnostic features as most predictive of prognosis, with reversion less likely in participants with multiple-domain MCI (p = 0.011), a moderately or severely impaired cognitive domain (p = 0.002 and p = 0.006), or an informant-based memory complaint (p = 0.031). Reversion was also less likely for participants with arthritis (p = 0.037), but more likely for participants with higher complex mental activity (p = 0.003), greater openness to experience (p = 0.041), better vision (p = 0.014), better smelling ability (p = 0.040), or larger combined volume of the left hippocampus and left amygdala (p
Published: 2013
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7. Prominent Non-Memory Deficits in Alzheimer’s Disease Are Associated with Faster Disease Progression

Author: Scheltens, Nienke ME, Tijms, Betty M, Heymans, Martijn W, Rabinovici, Gil D, Cohn-Sheehy, Brendan I, Miller, Bruce L, Kramer, Joel H, Wolfsgruber, Steffen, Wagner, Michael, Kornhuber, Johannes, Peters, Oliver, Scheltens, Philip, van der Flier, Wiesje M, Amsterdam Dementia Cohort, Alzheimer’s Disease Neuroimaging Initiative, German Dementia Competence Network, University of San Francisco Memory and Aging Center, Neurology, Amsterdam Neuroscience - Neurodegeneration, Epidemiology and Data Science, APH - Personalized Medicine, and APH - Methodology
Subjects: Male, cognition, 0301 basic medicine, Aging, psychology [Alzheimer Disease], Time Factors, Kaplan-Meier Estimate, Disease, Neuropsychological Tests, Neurodegenerative, Alzheimer's Disease, 0302 clinical medicine, Risk of mortality, 2.1 Biological and endogenous factors, Aetiology, mortality [Memory Disorders], medicine.diagnostic_test, subtypes, General Neuroscience, phenotypes, General Medicine, Neuropsychological test, Psychiatry and Mental health, Clinical Psychology, University of San Francisco Memory and Aging Center, Phenotype, Neurological, Cohort, Disease Progression, Female, Mental health, Cognitive Sciences, Superior Sagittal Sinus, Alzheimer’s disease, clustering, Alzheimer's Disease Neuroimaging Initiative, medicine.medical_specialty, Clinical Dementia Rating, Clinical Sciences, Amsterdam Dementia Cohort, German Dementia Competence Network, Article, 03 medical and health sciences, disease progression, Alzheimer Disease, Clinical Research, Internal medicine, mental disorders, Acquired Cognitive Impairment, medicine, Humans, Dementia, Memory impairment, ddc:610, Aged, Memory Disorders, Neurology & Neurosurgery, business.industry, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Alzheimer’s Disease Neuroimaging Initiative, medicine.disease, mortality, Brain Disorders, Cross-Sectional Studies, Good Health and Well Being, 030104 developmental biology, mortality [Alzheimer Disease], Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Background: Alzheimer's disease (AD) is a heterogeneous disorder. Objective: To investigate whether cognitive AD subtypes are associated with different rates of disease progression. Methods: We included 1,066 probable AD patients from the Amsterdam Dementia Cohort (n = 290), Alzheimer's Disease Neuroimaging Initiative (n = 268), Dementia Competence Network (n = 226), and University of California, San Francisco (n = 282) with available follow-up data. Patients were previously clustered into two subtypes based on their neuropsychological test results: one with most prominent memory impairment (n = 663) and one with most prominent non-memory impairment (n = 403). We examined associations between cognitive subtype and disease progression, as measured with repeated Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear mixed models. Furthermore, we investigated mortality risk associated with subtypes using Cox proportional hazard analyses. Results: Patients were 71±9 years old; 541 (51%) were female. At baseline, pooled non-memory patients had worse MMSE scores (23.1±0.1) and slightly worse CDR sob (4.4±0.1) than memory patients (MMSE 24.0±0.1; p < 0.001; CDR sob 4.1±0.1; p < 0.001). During follow-up, pooled non-memory patients showed steeper annual decline in MMSE (-2.8±0.1) and steeper annual increase in CDR sob (1.8±0.1) than memory patients (MMSE - 1.9±0.1; p interaction
Published: 2018
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8. Cognitive subtypes of probable Alzheimer's disease robustly identified in four cohorts

Author: Scheltens, Nienke M E, Tijms, Betty M, Rabinovici, Gil D, Miller, Bruce L, Kramer, Joel H, Scheltens, Philip, van der Flier, Wiesje M, Initiative, Alzheimer's Disease Neuroimaging, Network, German Dementia Competence, Center, University of California San Francisco Memory and Aging, Cohort, Amsterdam Dementia, Koene, Teddy, Barkhof, Frederik, Teunissen, Charlotte E, Wolfsgruber, Steffen, Wagner, Michael, Kornhuber, Johannes, Peters, Oliver, Cohn-Sheehy, Brendan I, Neurology, Amsterdam Neuroscience - Neurodegeneration, Medical psychology, Radiology and nuclear medicine, Laboratory Medicine, APH - Personalized Medicine, APH - Methodology, and Epidemiology and Data Science
Subjects: 0301 basic medicine, Apolipoprotein E, Oncology, Male, Epidemiology, Denmark, Apolipoprotein E4, genetics [Alzheimer Disease], cerebrospinal fluid [Amyloid beta-Peptides], Disease, Neuropsychological Tests, diagnostic imaging [Cognition Disorders], Cohort Studies, 0302 clinical medicine, Germany, Cluster Analysis, genetics [Apolipoprotein E4], Aged, 80 and over, Health Policy, Neuropsychology, complications [Alzheimer Disease], Cognition, Middle Aged, amyloid beta-protein (1-42), classification [Cognition Disorders], Magnetic Resonance Imaging, cerebrospinal fluid [Alzheimer Disease], Psychiatry and Mental health, Cohort, Disease Progression, Female, Psychology, medicine.medical_specialty, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Atrophy, Developmental Neuroscience, Neuroimaging, Alzheimer Disease, Internal medicine, medicine, Dementia, Humans, ddc:610, cerebrospinal fluid [Peptide Fragments], Psychiatry, Aged, Amyloid beta-Peptides, etiology [Cognition Disorders], medicine.disease, Peptide Fragments, United States, 030104 developmental biology, Neurology (clinical), Geriatrics and Gerontology, Cognition Disorders, Mental Status Schedule, diagnostic imaging [Alzheimer Disease], 030217 neurology & neurosurgery
Abstract: Patients with Alzheimer's disease (AD) show heterogeneity in profile of cognitive impairment. We aimed to identify cognitive subtypes in four large AD cohorts using a data-driven clustering approach.We included probable AD dementia patients from the Amsterdam Dementia Cohort (n = 496), Alzheimer's Disease Neuroimaging Initiative (n = 376), German Dementia Competence Network (n = 521), and University of California, San Francisco (n = 589). Neuropsychological data were clustered using nonnegative matrix factorization. We explored clinical and neurobiological characteristics of identified clusters.In each cohort, a two-clusters solution best fitted the data (cophenetic correlation0.9): one cluster was memory-impaired and the other relatively memory spared. Pooled analyses showed that the memory-spared clusters (29%-52% of patients) were younger, more often apolipoprotein E (APOE) ɛ4 negative, and had more severe posterior atrophy compared with the memory-impaired clusters (all P .05).We could identify two robust cognitive clusters in four independent large cohorts with distinct clinical characteristics.Alzheimer's disease (AD) is a heterogeneous disorder. We identified two cognitive AD subtypes in four cohorts with a data-driven approach. Nonamnestic AD is associated with distinct neurobiological characteristics.
Published: 2016
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9. Unexpected abundance of pathological tau in progressive supranuclear palsy white matter

Author: Michigan Alzheimer's Disease Research Center, University of Michigan Health Center, Ann Arbor, MI ; Ann Arbor Affairs Medical Center Geriatric Research Education and Clinical Center, Ann Arbor, MI, Michigan Alzheimer's Disease Research Center, University of Michigan Health Center, Ann Arbor, MI, Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Philadelphia, PA, Department of Neurology, University of Pennsylvania, Philadelphia, PA, Department of Pathology, University of Utah, Salt Lake City, UT, Memory and Aging Center of the University of California, San Francisco, CA, Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Philadelphia, PA ; The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, HUP/Maloney 3, 3600 Spruce Street, Philadelphia, PA 19104-4283, Zhukareva, Victoria, Joyce, Sonali, Schuck, Teresa, Van Deerlin, Vivianna, Hurtig, Howard, Albin, Roger, Gilman, Sid, Chin, Steven, Miller, Bruce, Trojanowski, John Q., Lee, Virginia M-Y., Michigan Alzheimer's Disease Research Center, University of Michigan Health Center, Ann Arbor, MI ; Ann Arbor Affairs Medical Center Geriatric Research Education and Clinical Center, Ann Arbor, MI, Michigan Alzheimer's Disease Research Center, University of Michigan Health Center, Ann Arbor, MI, Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Philadelphia, PA, Department of Neurology, University of Pennsylvania, Philadelphia, PA, Department of Pathology, University of Utah, Salt Lake City, UT, Memory and Aging Center of the University of California, San Francisco, CA, Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Philadelphia, PA ; The Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, HUP/Maloney 3, 3600 Spruce Street, Philadelphia, PA 19104-4283, Zhukareva, Victoria, Joyce, Sonali, Schuck, Teresa, Van Deerlin, Vivianna, Hurtig, Howard, Albin, Roger, Gilman, Sid, Chin, Steven, Miller, Bruce, Trojanowski, John Q., and Lee, Virginia M-Y.
Abstract: Objective To investigate whether biochemical insoluble tau with 4 (4R) and/or 3 (3R) microtubule-binding repeats accumulate in white as well as gray matter in progressive supranuclear palsy (PSP), a neurodegenerative tauopathy. Methods To assess tau pathology in PSP white matter, we combined Western blot (WB) and immunohistochemical methods to analyze 23 autopsy-confirmed PSP brains. Results WBs showed an unexpected abundance of insoluble tau in white and gray matter of PSP brains, but biochemical tau pathology in white matter was not correlated with immunohistochemistry using the same panel of epitope-specific anti-tau antibodies used for WB. Despite heterogeneity in the representation of pathological 3R and 4R tau isoforms in cortical versus subcortical regions, biochemically detectable white matter tau pathology is a constant feature of PSP. Interpretation These studies show additional similarities between PSP and corticobasal degeneration, but unlike corticobasal degeneration, more abundant white matter tau pathology in PSP is detectable by WB than by immunohistochemistry. The differential detection of abnormal tau by biochemistry versus microscopy in PSP may reflect distinct pathological mechanisms, and elucidation of these processes will augment efforts to develop better strategies for the diagnosis and treatment of PSP and related neurodegenerative tauopathies. Ann Neurol 2006
Published: 2007

10. BioFINDER-Brown: Examination of Alzheimer's Disease Biomarkers

Author: The Warren Alpert Foundation, Brown University, University of Rhode Island, Hoffmann-La Roche, Eli Lilly and Company, GE Healthcare, and Edward Huey, Director, Memory and Aging Program, Butler Hospital; Martin M. Zucker Professor of Psychiatry and Human Behavior, Associate Director for Clinical Research, Brown Center for Alzheimer's Disease Research Alpert Medical School of Brown University
Published: 2024

11. Repurposing Nucleoside Reverse Transcriptase Inhibitors for Treatment of AD (LINE-AD)

Author: Alzheimer's Association, Brown University, The Miriam Hospital, and Meghan Riddle, Director of Neurology and the Memory and Aging Program
Published: 2024

12. Accurate prediction of histologically confirmed Alzheimer's disease and the differential diagnosis of dementia: the use of NINCDS-ADRDA and DSM-III-R criteria, SPECT, X-ray CT, and Apo E4 in medial temporal lobe dementias. Oxford Project to Investigate Memory and Aging.

Author: Jobst KA, Barnetson LPD, Shepstone BJ, Oxford Project to Investigate Memory and Aging, Jobst, K A, Barnetson, L P, and Shepstone, B J
Published: 1998

13. Validation of memory assessment in the Starmaze task: Data from 14 month-old APPPS1 mice and controls

Author: Anne-Lise Paradis, Mathieu Boucher, Julien Schmitt, Laure Rondi-Reig, Pascal Barneoud, Laurent Andrieu, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurodegeneration Cluster, Rare & Neurologic Diseases Research, Sanofi Aventis R&D [Chilly-Mazarin], IT&M STATS, Groupe IT&M, Biostatistics & Programming Department, Non-Clinical Efficacy & Safety team, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Paradis, Anne-Lise, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Aging, medicine.medical_specialty, Science (General), Computer applications to medicine. Medical informatics, R858-859.7, Navigation behavior, Normal aging, Audiology, Task (project management), Sequence memory, Q1-390, 03 medical and health sciences, 0302 clinical medicine, medicine, Spatio-temporal memory, Cognitive decline, Alzheimer’s Disease (AD), Data Article, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Familial form, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, robustness assessment, Flexibility (personality), medicine.disease, transgenic mouse model, 030220 oncology & carcinogenesis, Alzheimer's disease (AD), Spatial learning, APPPS1, Alzheimer's disease, Psychology, sequence memory
Abstract: International audience; This article describes navigation data of 14 month-old APPPS1 and C57Bl6 in the Starmaze task. These data were acquired as positive controls of memory deficit in a model of the familial form of Alzheimers’s disease (see Schmitt et al., Flexibility as a marker of early cognitive decline in humanized Apolipoprotein E ε4 (ApoE4) mice, Neurobiol Aging, 2021). They were acquired in a reduced version of the Starmaze environment and accompanied by a number of acquisitions in different control groups at 6 and 14 months to assess the robustness of the procedure and its associated memory scores. These data illustrate the extraction of a variety of navigation scores (including search strategy, spatial learning and memory) and provide a reference of navigation data in the Starmaze task for healthy 6-month-old controls, normal aging and a model of pathological memory deficit.
Published: 2021
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14. Amyloid in dementia associated with familial FTLD: not an innocent bystander

Author: Rosen, Howard [University of California, San Francisco, CA (United States). Memory and Aging Center, Dept. of Neurology]
Published: 2015
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15. A hippocampo-cerebellar centred network for the learning and execution of sequence-based navigation

Author: Babayan, Benedicte M., Watilliaux, Aurélie, Viejo, Guillaume, Paradis, Anne-Lise, Girard, Benoît, Rondi-Reig, Laure, Girard, Benoît, Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des Systèmes Intelligents et de Robotique (ISIR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), AMAC, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, lcsh:R, [SCCO.NEUR] Cognitive science/Neuroscience, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, lcsh:Medicine, lcsh:Q, [INFO.INFO-LG] Computer Science [cs]/Machine Learning [cs.LG], lcsh:Science, Article
Abstract: International audience; How do we translate self-motion into goal-directed actions? Here we investigate the cognitive architecture underlying self-motion processing during exploration and goal-directed behaviour. The task, performed in an environment with limited and ambiguous external landmarks, constrained mice to use self-motion based information for sequence-based navigation. The post-behavioural analysis combined brain network characterization based on c-Fos imaging and graph theory analysis as well as computational modelling of the learning process. The study revealed a widespread network centred around the cerebral cortex and basal ganglia during the exploration phase, while a network dominated by hippocampal and cerebellar activity appeared to sustain sequence-based navigation. The learning process could be modelled by an algorithm combining memory of past actions and model-free reinforcement learning, which parameters pointed toward a central role of hippocampal and cerebellar structures for learning to translate self-motion into a sequence of goal-directed actions.
Published: 2017
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16. The Effects of the Rivastigmine Patch on Parkinson's Disease With Memory and/or Thinking Problems

Author: Novartis and Bruce Miller, Director of the Memory & Aging Center
Published: 2014

17. A Liaison Brought to Light: Cerebellum-Hippocampus, Partners for Spatial Cognition

Author: Laure Rondi-Reig, Anne-Lise Paradis, Mehdi Fallahnezhad, Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), The National Agency for Research ANR-17-CE16-0019-03 (SynPredict), and ANR-18-CE16-0010-02 (RewInhib) supported LRR and MF. ANR-17-CE37-0015-02 (Navi-GPS) and SATT Lutech supported LRR and ALP., ANR-17-CE37-0015,NaviGPS,la Navigation au delà de l'hippocampe: Comment coder ses déplacements propres en tenant compte de l'environnement ?(2017), ANR-18-CE16-0010,RewInhib,Etude du circuit cérébelleux inhibiteur lors d'une tâche orienté vers la récompense(2018), ANR-17-CE16-0019,SynPredict,Rôle de la synapse pour le codage prédictif dans le cortex cérébelleux(2017), Paradis, Anne-Lise, la Navigation au delà de l'hippocampe: Comment coder ses déplacements propres en tenant compte de l'environnement ? - - NaviGPS2017 - ANR-17-CE37-0015 - AAPG2017 - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Etude du circuit cérébelleux inhibiteur lors d'une tâche orienté vers la récompense - - RewInhib2018 - ANR-18-CE16-0010 - AAPG2018 - VALID, and Rôle de la synapse pour le codage prédictif dans le cortex cérébelleux - - SynPredict2017 - ANR-17-CE16-0019 - AAPG2017 - VALID
Subjects: Neurons, Hippocampus Introduction: Cerebellum and Spatial Cognition, Cognition, Multimodal sensory information, Neurology, Cerebellum, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Neurology (clinical), Hippocampus, Navigation, Spatial cognition, Spatial Navigation
Abstract: International audience; This review focuses on the functional and anatomical links between the cerebellum and the hippocampus and the role of their interplay in goal-directed navigation and spatial cognition. We will describe the interactions between the cerebellum and the hippocampus at different scales: a macroscopic scale revealing the joint activations of these two structures at the level of neuronal circuits, a mesoscopic scale highlighting the synchronization of neuronal oscillations, and finally a cellular scale where we will describe the activity of hippocampal neuronal assemblies following a targeted manipulation of the cerebellar system. We will take advantage of this framework to summarize the different anatomical pathways that may sustain this multiscale interaction. We will finally consider the possible influence of the cerebellum on pathologies traditionally associated with hippocampal dysfunction.
Published: 2022
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18. Excessive self-grooming of $Shank3$ mutant mice is associated with gene dysregulation and imbalance between the striosome and matrix compartments in the striatum

Author: Ferhat, Allain-Thibeault, Biton, Anne, Verpy, Elisabeth, Forget, Benoit, de Chaumont, Fabrice, Mueller, Florian, Le Sourd, Anne-Marie, Coqueran, Sabrina, Schmitt, Julien, Rochefort, Christelle, Rondi-Reig, Laure, Leboucher, Aziliz, Boland, Anne, Fin, Bertrand, Deleuze, Jean François, Boeckers, Tobias, Ey, Elodie, Bourgeron, Thomas, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Columbia University Medical Center (CUMC), Columbia University [New York], Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Modélisation - Imaging and Modeling, Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre d'Etude du Polymorphisme Humain (CEPH), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Fondation Jean Dausset-Université Paris Cité (UPCité), Universität Ulm - Ulm University [Ulm, Allemagne], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-10-LABX-BioPsy, ANR-10-LABX-0013,GENMED,Medical Genomics(2010), ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Ey, Elodie, Medical Genomics - - GENMED2010 - ANR-10-LABX-0013 - LABX - VALID, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, and Développment d'une infrastructure française distribuée coordonnée - - France-BioImaging2010 - ANR-10-INBS-0004 - INBS - VALID
Subjects: [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Abstract: Autism spectrum disorders (ASD) are characterised by atypical social communication and stereotyped behaviours. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are detected in 1-2% of patients with ASD and intellectual disability (ID), but the mechanisms underpinning the symptoms remain largely unknown. Here, we characterized the behaviour of Shank3 mutant mice deleted for exon 11 ( Shank3 $^{Δ11/Δ11}$ ) from three to twelve months of age. We observed decreased locomotor activity, increased stereotyped self-grooming and atypical socio-sexual interaction compared to wild-type littermates. We then used RNAseq on four brain regions of the same animals to identify differentially expressed genes (DEG). DEGs were identified mainly in the striatum and were associated with synaptic transmission (e.g. Grm2 , Dlgap1 ), G-protein-signalling pathways (e.g. Gnal , Prkcg1 , and Camk2g ), as well as excitation/inhibition balance (e.g. Gad2 ). Downregulated and upregulated genes were respectively enriched in the gene clusters of medium-sized spiny neurons expressing the dopamine 1 (D1-MSN) and the dopamine 2 receptor (D2-MSN). Moreover, expression of DEGs reported as striosome markers within the striatum ( Cnr1 , Gnal1 , Gad2 , and Drd4 ) were positively correlated with excessive self-grooming. Finally, we showed that the striosome compartment of Shank3 Shank3 $^{Δ11/Δ11}$ mice was enlarged and displayed higher expression of GAD65 compared to wild-type mice. Altogether, these results shed light on a possible role of the striosomes/matrix imbalance in excessive self-grooming in Shank3Shank3 $^{Δ11/Δ11}$ mice. Such striatal alterations could be present in a subgroup of patients with ASD and ID and could open the way to new therapeutic approaches.
Published: 2022

19. SimulAD: A dynamical model for personalized simulation and disease staging in Alzheimer's disease

Author: Clément Abi Nader, Federica Ribaldi, Giovanni B. Frisoni, Valentina Garibotto, Philippe Robert, Nicholas Ayache, Marco Lorenzi, E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Côte d'Azur (UCA), Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Geneva University Hospitals and Geneva University, Cognition Behaviour Technology (CobTek), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice), MNC3 UCA, ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Côte d'Azur (UCA)
Subjects: Aging, tau Proteins, Disease progression models, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Clinical trials, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], Alzheimer Disease, mental disorders, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Cognitive Dysfunction, Amyloid beta-Peptides, General Neuroscience, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Alzheimer's disease, [STAT]Statistics [stat], Disease Progression, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Neurology (clinical), Geriatrics and Gerontology, Atrophy, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Biomarkers, Developmental Biology
Abstract: International audience; SimulAD is a computational disease progression model (DPM) originally developed on the ADNI database to simulate the evolution of clinical and imaging markers characteristic of AD, and to quantify the disease severity (DS) of a subject. In this work, we assessed the validity of this estimated DS, as well as the generalization of the DPM, by applying SimulAD on a new cohort from the Geneva Memory Center (GMC). The differences between the estimated DS of healthy, mild cognitive impairment and AD dementia groups were statistically significant (p-values < 0.05; d ≥ 0.8). DS correlated with MMSE (ρ =-0.55), hippocampal atrophy (ρ =-0.62), glucose hypometabolism (ρ =-0.67), amyloid burden (ρ = 0.31) and tau deposition (ρ = 0.62) (p-values < 0.01). Based on the dynamics estimated on the ADNI cohort, we simulated a DPM for the subjects of the GMC cohort. The difference between the temporal evolution of similar biomarkers simulated on the ADNI and GMC cohorts remained below 10%. This study illustrates the robustness and good generalization of SimulAD, highlighting its potential for clinical and pharmaceutical studies.
Published: 2022
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20. Preserved Navigation abilities and Spatio-Temporal Memory in individuals with Autism Spectrum Disorder

Author: Charles Laidi, Nathan Neu, Aurélie Watilliaux, Axelle Martinez‐Teruel, Mihoby Razafinimanana, Jennifer Boisgontier, Sevan Hotier, Marc‐Antoine d'Albis, Richard Delorme, Anouck Amestoy, Štefan Holiga, Myriam Ly‐Le Moal, Pierrick Coupé, Marion Leboyer, Josselin Houenou, Laure Rondi‐Reig, Anne‐Lise Paradis, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Unité de recherche en NeuroImagerie Applicative Clinique et Translationnelle (UNIACT), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Cerebellum Navigation and Memory Team [IBPS] (CeZaMe), Neurosciences Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Robert Debré, Institut Roche [Boulogne-Billancourt, France], Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Investissements d'Avenir programs managed by the ANR under references ANR-11-IDEX-004-02 (Labex BioPsy) and ANR-10-COHO-10-01 and CNRS, and via collaboration with the Roche Institute for Research and Translational Medicine., CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Neuroscience Paris Seine (NPS), Fondation FondaMental [Créteil], Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Charles PERRENS, Patch-based processing for medical and natural images (PICTURA), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Autism Spectrum Disorder, Memory, General Neuroscience, Cerebellum, [SCCO.NEUR]Cognitive science/Neuroscience, Adults, Neurology (clinical), Genetics (clinical), Spatial Navigation
Abstract: International audience; Cerebellar abnormalities have been reported in autism spectrum disorder (ASD). Beyond its role in hallmark features of ASD, the cerebellum and its connectivity with forebrain structures also play a role in navigation. However, the current understanding of navigation abilities in ASD is equivocal, as is the impact of the disorder on the functional anatomy of the cerebellum. In the present study, we investigated the navigation behavior of a population of ASD and typically developing (TD) adults related to their brain anatomy as assessed by structural and functional MRI at rest. We used the Starmaze task, which permits assessing and distinguishing two complex navigation behaviors, one based on allocentric and the other on egocentric learning of a route with multiple decision points. Compared to TD controls, individuals with ASD showed similar exploration, learning, and strategy performance and preference. In addition, there was no difference in the structural or functional anatomy of the cerebellar circuits involved in navigation between the two groups. The findings of our work suggest that navigation abilities, spatio-temporal memory, and their underlying circuits are preserved in individuals with ASD.
Published: 2022
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21. SUSD4 controls GLUA2 degradation, synaptic plasticity and motor learning

Author: González-Calvo, I., Iyer, K., Carquin, M., Khayachi, A., Giuliani, F.A., Sigoillot, S.M., Vincent, J., Seveno, M., Veleanu, M., Tahraoui, S., Albert, M., Vigy, Oana, Bosso-Lefèvre, Célia, Nadjar, Y., Dumoulin, A., Triller, A., Bessereau, J.-L., Rondi-Reig, L., Isope, P., Selimi, Fekrije, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Cerebellum Navigation and Memory Team (CeZaMe), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Selimi, Fekrije
Subjects: neuroscience, proteostasis, cerebellum, synapse, plasticity, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, mouse
Abstract: At excitatory synapses, the choice between recycling or degradation of glutamate AMPA receptors controls the direction of synaptic plasticity. In this context, how the degradation machinery is targeted to specific synaptic substrates in an activity-dependent manner is not understood. Here we show that SUSD4, a complement-related transmembrane protein, is a tether for HECT ubiquitin ligases of the NEDD4 subfamily, which promote the degradation of a large number of cellular substrates. SUSD4 is expressed by many neuronal populations starting at the time of synapse formation. Loss-of-function of Susd4 in the mouse prevents activity-dependent degradation of the GLUA2 AMPA receptor subunit and long-term depression at cerebellar synapses, and leads to impairment in motor coordination adaptation and learning. SUSD4 could thus act as an adaptor targeting NEDD4 ubiquitin ligases to AMPA receptors during long-term synaptic plasticity. These findings shed light on the potential contribution of SUSD4 mutations to the etiology of neurodevelopmental diseases.
Published: 2021

22. Cerebellar Control of a Unitary Head Direction Sense

Author: Julia Le Méro, Xhensjana Zenelaj, Christelle Rochefort, Laure Rondi-Reig, Jean Vincent, Mehdi Fallahnezhad, Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Cerebellum Navigation and Memory Team (CeZaMe), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Rondi-Reig, Laure, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS)
Subjects: Cerebellum, Head (linguistics), Sensory system, Head direction cell, Biology, Unitary state, 03 medical and health sciences, 0302 clinical medicine, medicine, Premovement neuronal activity, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Control (linguistics), Angular head velocity, Attractor network, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Representation (systemics), Retrosplenial cortex, Continuous attractor network, medicine.anatomical_structure, Anterodorsal thalamus, Speed cell, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience, 030217 neurology & neurosurgery
Abstract: The head-direction (HD) system, a key neural circuit for navigation, consists of several anatomical structures containing neurons selective to the animal’s head direction. HD cells exhibit ubiquitous temporal coordination across brain regions, independently of the animal’s behavioral state or sensory inputs. Such temporal coordination mediates a single, stable, and persistent HD signal, which is essential for intact orientation. However, the mechanistic processes behind the temporal organization of HD cells are unknown. By manipulating the cerebellum, we identify pairs of HD cells recorded from two brain structures (anterodorsal thalamus and retrosplenial cortex) that lose their temporal coordination, specifically during the removal of the external sensory inputs. Further, we identify distinct cerebellar mechanisms that participate in the spatial stability of the HD signal depending on sensory signals. We show that while cerebellar protein phosphatase 2B-dependent mechanisms facilitate the anchoring of the HD signal on the external cues, the cerebellar protein kinase C-dependent mechanisms are required for the stability of the HD signal by self-motion cues. These results indicate that the cerebellum contributes to the preservation of a single and stable sense of direction.
Published: 2021

23. Combining Multi-Task Learning and Multi-Channel Variational Auto-Encoders to Exploit Datasets with Missing Observations -Application to Multi-Modal Neuroimaging Studies in Dementia

Author: ANTELMI, Luigi, AYACHE, Nicholas, ROBERT, Philippe, RIBALDI, Federica, GARIBOTTO, Valentina, FRISONI, Giovanni, LORENZI, Marco, E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Cognition Behaviour Technology (CobTek), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Côte d'Azur (UCA), Centre Mémoire de Ressources et de Recherche [Nice] (CMRR Nice), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), IRCCS Fatebenefratelli - Brescia, Università degli Studi di Brescia = University of Brescia (UniBs), Laboratory of Alzheimer’s Neuroimaging and Epidemiology (LANE), Saint John of God Clinical Research Centre, Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMT-lab), Geneva University Hospital (HUG), Nuclear Medicine and Molecular Imaging Division, Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019), Université Côte d'Azur (UCA)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Côte d'Azur (UCA), Università degli Studi di Brescia [Brescia], ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI (2016), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice), Université Côte d'Azur (UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), and COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)
Subjects: [STAT]Statistics [stat], [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Missing Data, Multi Task Learning, Variational Autoencoders, Multimodal Data Analysis, OPAL-Meso
Abstract: The joint modeling of neuroimaging data across multiple datasets requires to consistently analyze high-dimensional and heterogeneous information in presence of often non-overlapping sets of views across data samples (e.g. imaging data, clinical scores, biological measurements). This analysis is associated with the problem of missing information across datasets, which can happen in two forms: missing at random (MAR), when the absence of a view is unpredictable and does not depend on the dataset (e.g. due to data corruption); missing not at random (MNAR), when a specific view is absent by design for a specific dataset. In order to take advantage of the increased variability and sample size when pooling together observations from many cohorts and at the same time cope with the ubiquitous problem of missing information, we propose here a multi-task generative latent-variable model where the common variability across datasets stems from the estimation of a shared latent representation across views. Our formulation allows to retrieve a consistent latent representation common to all views and datasets, even in the presence of missing information. Simulations on synthetic data show that our method is able to identify a common latent representation of multi-view datasets, even when the compatibility across datasets is minimal. When jointly analyzing multi-modal neuroimaging and clinical data from real independent dementia studies, our model is able to mitigate the absence of modalities without having to discard any available information. Moreover, the common latent representation inferred with our model can be used to define robust classifiers gathering the combined information across different datasets. To conclude, both on synthetic and real data experiments, our model compared favorably to state of the art benchmark methods, providing a more powerful exploitation of multi-modal observations with missing views.
Published: 2021

24. Intepirdine as adjunctive therapy to donepezil for mild‐to‐moderate Alzheimer's disease: A randomized, placebo‐controlled, phase 3 clinical trial (MINDSET)

Author: Giovanni B. Frisoni, Frederick M. Lang, Roy W. Jones, Jeffrey L. Cummings, Timo Grimmer, Mark Harnett, Bruno Dubois, Paul Solomon, Sarah R. Friedhoff, Shari Coslett, Mercè Boada, Marwan N. Sabbagh, Yi Mo, Columbia University [New York], Sio Gene Therapies, Lou Ruvo Center for Brain Health [Las Vegas], Cleveland Clinic, Boston University [Boston] (BU), Clínica Universidad de Navarra [Pamplona], University of Bath [Bath], Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Nevada [Las Vegas] (WGU Nevada), and Technical University of Munich (TUM)
Subjects: 0301 basic medicine, medicine.medical_specialty, Activities of daily living, 5-HT6, Phases of clinical research, 5‐HT6, Placebo, 03 medical and health sciences, intepirdine, 0302 clinical medicine, Internal medicine, mental disorders, medicine, Dementia, RC346-429, Donepezil, Research Articles, business.industry, RC952-954.6, clinical trial, Alzheimer's disease, medicine.disease, Confidence interval, Clinical trial, Psychiatry and Mental health, 030104 developmental biology, Geriatrics, phase 3, Intepirdine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology. Diseases of the nervous system, Neurology (clinical), business, 030217 neurology & neurosurgery, Research Article, medicine.drug
Abstract: International audience; Introduction: A previous phase 2b study supported the use of the 5-HT6 receptor antagonist intepirdine as adjunctive therapy to donepezil for Alzheimer's disease (AD) dementia. A phase 3 study, MINDSET, was performed to test this hypothesis. Methods: MINDSET was a global, double-blind, randomized, placebo-controlled trial in 1315 mild-to-moderate AD dementia patients on stable donepezil. Patients received 35 mg/day intepirdine or placebo for 24 weeks. The co-primary endpoints were change from baseline to week 24 on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL). Results: There were no statistically significant differences between intepirdine and placebo groups (adjusted mean [95% confidence interval]) on the co-primary endpoints ADAS-Cog (−0.36 [−0.95, 0.22], P = 0.2249) and ADCS-ADL (−0.09 [−0.90, This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Published: 2021
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25. Sushi domain-containing protein 4 controls synaptic plasticity and motor learning

Author: Keerthana Iyer, Fernando A Giuliani, Laure Rondi-Reig, Philippe Isope, Yann Nadjar, Antoine Triller, Jean-Louis Bessereau, Mélanie Albert, Andréa Dumoulin, Séverine M. Sigoillot, Oana Vigy, Maxime Veleanu, Jean Vincent, Mélanie Carquin, Anouar Khayachi, Célia Bosso-Lefèvre, Martial Séveno, Fekrije Selimi, Inés González-Calvo, Sylvana Tahraoui, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie de l'ENS Paris (IBENS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département de Biologie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, Hal Sorbonne Université, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Sushi domain, cerebellum, QH301-705.5, Science, [SDV]Life Sciences [q-bio], Protein subunit, AMPA receptor, Motor Activity, General Biochemistry, Genetics and Molecular Biology, neuroscience, Synapse, Mice, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, synapse, Animals, Learning, Biology (General), mouse, Complement Inactivator Proteins, Neuronal Plasticity, proteostasis, General Immunology and Microbiology, biology, General Neuroscience, Membrane Proteins, General Medicine, Transmembrane protein, [SDV] Life Sciences [q-bio], 030104 developmental biology, Proteostasis, plasticity, Synaptic plasticity, biology.protein, Medicine, Neuroscience, 030217 neurology & neurosurgery, Research Article
Abstract: Fine control of protein stoichiometry at synapses underlies brain function and plasticity. How proteostasis is controlled independently for each type of synaptic protein in a synapse-specific and activity-dependent manner remains unclear. Here, we show that Susd4, a gene coding for a complement-related transmembrane protein, is expressed by many neuronal populations starting at the time of synapse formation. Constitutive loss-of-function of Susd4 in the mouse impairs motor coordination adaptation and learning, prevents long-term depression at cerebellar synapses, and leads to misregulation of activity-dependent AMPA receptor subunit GluA2 degradation. We identified several proteins with known roles in the regulation of AMPA receptor turnover, in particular ubiquitin ligases of the NEDD4 subfamily, as SUSD4 binding partners. Our findings shed light on the potential role of SUSD4 mutations in neurodevelopmental diseases.
Published: 2021
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26. Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study

Author: Bernhard W. Müller, Daniele Altomare, Marco Salvatore, Renaud Lopes, Paolo Maria Rossini, Jens Wiltfang, Moira Marizzoni, Martina Montalti, Stéphanie Bombois, Giovanni B. Frisoni, Clarissa Ferrari, Karl Titus Hoffmann, Camillo Marra, Massimo Caulo, Francesca B. Pizzini, David Bartrés-Faz, Ute Fiedler, Antonio Ferretti, Mira Didic, Manos Constantinidis, Andrea Soricelli, Federica Ribaldi, Joost P.A. Kuijer, Carlo Cavaliere, Antonios Drevelegas, Flavio Nobili, Piero Floridi, Luca Roccatagliata, Julien Sein, Régis Bordet, Franco Alessandrini, Pierre Payoux, Roberto Tarducci, Jorge Jovicich, Olivier Blin, Agnese Picco, Jean-Philippe Ranjeva, Frederik Barkhof, Beatriz Bosch, Magda Tsolaki, Pieter Jelle Visser, Lucilla Parnetti, Tilman Hensch, Jill C. Richardson, Núria Bargalló, Anna Mega, Helene Gros-Dagnac, Marco Aiello, Peter Schönknecht, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Center for Mind/Brain Sciences (CIMEC), University of Trento [Trento], Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili [Genova] (DINOGMI), Universita degli studi di Genova, Department of Diagnostics and Public Health [Verona] (UNIVR | DDSP), University of Verona (UNIVR), IRCCS SDN Napoli, Department of Clinic Sciences and Bioimaging, University G. d'Annunzio Chieti-Pescara, Interbalkan Medical Center of Thessaloniki, Dept. of Child and Adolescent Psychiatry and Psychology, Institut Clinic of Neurosciences IDIBAPS (Institut d'Investigacions Biomèdiques August Pi Sunyer), Hospital Clínic Universitari of Barcelona, Department of Child and Adolescent Psychiatry and Psychotherapy, LVR-Klinikum Essen, Universität Duisburg-Essen [Essen], Department of Neuroscience, Catholic University, Roma, Centre for Medical Image Computing (CMIC), University College of London [London] (UCL), Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), University Medical Center Göttingen (UMG), Department of Neuroradiology, University Hospital Leipzig, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Neurology Department, Hospital Clinic, IDIBAPS, Facultad de Medicina, Barcelona, Dept. Neuroscience & Neurorehabilitation, IRCCS-San Raffaele-Pisana, Rome, University of Leipzig Medical Center, Neuroradiology Unit, Perugia General Hospital, Perugia, Alzheimer Center Amsterdam, Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Medical Physics Unit, Perugia General Hospital, Perugia, Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Università degli Studi di Brescia = University of Brescia (UniBs), Università degli studi di Genova = University of Genoa (UniGe), Università degli studi di Verona = University of Verona (UNIVR), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Leipzig University, Università degli Studi di Perugia = University of Perugia (UNIPG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Adult, Male, Aging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Image Processing, Medizin, Biomedical Engineering, Biophysics, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Automation, 0302 clinical medicine, Computer-Assisted, Sørensen–Dice coefficient, Image Processing, Computer-Assisted, White matter hyperintensities, Medicine, Humans, Radiology, Nuclear Medicine and imaging, Segmentation, Lesion segmentation toolbox, ComputingMilieux_MISCELLANEOUS, Accuracy, Reproducibility, Lesion segmentation, business.industry, Lesion growth, Automated segmentation algorithms, Multi site, Reproducibility of Results, Gold standard (test), White Matter, Magnetic Resonance Imaging, Hyperintensity, Settore MED/26 - NEUROLOGIA, Cross-Sectional Studies, Algorithms, Female, Nuclear medicine, business, 030217 neurology & neurosurgery
Abstract: Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was −0.22[IQR = 0.50] for LGA-SPM8, −0.12[0.57] for LGA-SPM12, −0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies.
Published: 2021
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27. MOND-like behavior in the Dirac-Milne universe -- Flat rotation curves and mass/velocity relations in galaxies and clusters

Author: Clément Stahl, Bruce N. Miller, Yohan Dubois, Gabriel Chardin, Giovanni Manfredi, AstroParticule et Cosmologie (APC (UMR_7164)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Oxford, Memory and Aging Center [San Francisco, CA, États-Unis], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), University of Oxford [Oxford], University of California [San Francisco] (UCSF), University of California-University of California, Institut d'Astrophysique de Paris (IAP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Réseau nanophotonique et optique, and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)
Subjects: cosmological model, Cosmology and Nongalactic Astrophysics (astro-ph.CO), media_common.quotation_subject, Dark matter, FOS: Physical sciences, Lambda-CDM model, Astrophysics, dark matter: velocity: dispersion, Astrophysics::Cosmology and Extragalactic Astrophysics, 01 natural sciences, rotation, Cosmology, dark matter, Gravitation, General Relativity and Quantum Cosmology, velocity: dispersion, 0103 physical sciences, MOND, antimatter, cloud, structure, cluster, dark energy, 010303 astronomy & astrophysics, Galaxy rotation curve, media_common, gravitation: surface, Physics, polarization, 010308 nuclear & particles physics, Computer Science::Information Retrieval, formation, nucleosynthesis, Astronomy and Astrophysics, acceleration, redshift, Astrophysics - Astrophysics of Galaxies, Universe, Modified Newtonian dynamics, Space and Planetary Science, gravitation, Astrophysics of Galaxies (astro-ph.GA), Dark energy, cosmology: miscellaneous, galaxy: velocity: dispersion, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], fundamental constant, Astrophysics - Cosmology and Nongalactic Astrophysics
Abstract: Aims.Observational data show that the observed luminous matter is not sufficient to explain several features of the present universe, from gravitational structure formation to the rotational velocities in galaxies and clusters. The mainstream explanation is that the missing mass, although gravitationally active, interacts very weakly with ordinary matter. Competing explanations involve changing the laws of gravity at low accelerations, as in MOdified Newtonian Dynamics (MOND). Here, we suggest that the Dirac-Milne cosmology, a matter-antimatter symmetric cosmology where the two components repel each other, is capable of accounting for such an apparent modification of the Newtonian law, without invoking dark matter.Methods.Using a simple analytical approximation and 1D and 3D simulations, we study rotation curves and virial velocities and compare the mass observed in the simulations to the mass derived assuming Newtonian gravity. Using a modified version of theRAMSEScode, we study the Faber-Jackson scaling relation and the intensity of the additional gravitational field created by antimatter clouds.Results.We show that, in the Dirac-Milne universe, rotation curves are generically flat beyond a characteristic distance of ≈2.5 virial radii, and that the Tully-Fisher and Faber-Jackson scaling relations with an exponent ≈3 are satisfied. We show that the mass derived from the rotation curves assuming Newtonian gravity is systematically overestimated compared to the mass really present. In addition, the Dirac-Milne universe, featuring a polarization between its matter and antimatter components, presents a behavior similar to that of MOND, characterized by an additional surface gravity compared to the Newtonian case. We show that in the Dirac-Milne universe, at the present epoch, the intensity of the additional gravitational fieldgamdue to the presence of clouds of antimatter is on the order of a few 10−11m s−2, similar to the characteristic acceleration of MOND. We study the evolution of this additional accelerationgamand show that it depends on the redshift, and it is therefore not a fundamental constant.Conclusions.Combined with its known concordance properties on the SNIa luminosity distance, age, nucleosynthesis, and structure formation, the Dirac-Milne cosmology may then represent an interesting alternative to the standard cosmological model ΛCDM, MOND, and other scenarios for explaining the dark matter (or missing gravity) and dark energy conundrum.
Published: 2021
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28. Flexibility as a marker of early cognitive decline in humanized Apolipoprotein E ε4 (ApoE4) mice: Early flexibility deficit in ApoE4 mice

Author: Schmitt, Julien, Paradis, Anne-Lise, Boucher, Mathieu, Andrieu, Laurent, Barnéoud, Pascal, Rondi-Reig, Laure, Neurodegeneration Cluster, Rare & Neurologic Diseases Research, Sanofi Aventis R&D [Chilly-Mazarin], Cerebellum Navigation and Memory Team (CeZaMe), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), IT&M STATS, Groupe IT&M, Biostatistics & Programming Department, Non-Clinical Efficacy & Safety team, Paradis, Anne-Lise, CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: ApoE4, Aging, Spatial memory, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SCCO.NEUR] Cognitive science/Neuroscience, mental disorders, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Navigation behavior, lipids (amino acids, peptides, and proteins), Reversal Learning, Flexibility, human activities
Abstract: International audience; To test the hypothesis that ApoE4 may be involved in cognitive deficits associated with aging, we investigated the impact of APOE4 status and aging on the flexibility and memory components of spatial learning in mice. Young adult (6 months) and middle-aged (14 months) ApoE4, ApoE3 and C57BL/6 adult male mice were tested for flexibility in an aquatic Y-maze, and for spatio-temporal memory acquisition in the Starmaze. Our results revealed a flexibility deficit of the 6-month-old ApoE4 mice compared to controls. However, this deficit was not associated with spatio-temporal memory deficit at the same age. Importantly, the ApoE4 flexibility deficit did not increase with age, nor turn into memory deficit, or was able to predict individual variations of memory performance at 14 months. By contrast, control ApoE3 mice showed a decline of flexibility at 14 months resulting in performance similar to that of ApoE4. Overall, our results suggest that ApoE4 could be associated with an acceleration of the flexibility decrease otherwise observed in normal aging.
Published: 2021
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29. Simulating the outcome of amyloid treatments in Alzheimer's Disease from multi-modal imaging and clinical data

Author: Abi Nader, Clément, Ayache, Nicholas, Frisoni, Giovanni, Robert, Philippe, Lorenzi, Marco, E-Patient : Images, données & mOdèles pour la médeciNe numériquE (EPIONE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Cognition Behaviour Technology (CobTek), Université Côte d'Azur (UCA)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice), Institut Claude Pompidou [Nice] (ICP - Nice), ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI (2016), ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Côte d'Azur (UCA), ANR-15-IDEX-0001,UCA JEDI,Idex UCA JEDI(2015), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Centre Hospitalier Universitaire de Nice (CHU Nice)-Institut Claude Pompidou [Nice] (ICP - Nice)-Université Côte d'Azur (UCA), ANR: JEDI,ANR-15-IDEX-01, and ANR-19-P3IA-0002,3IA Côte d'Azur,Nice - Interdisciplinary Institute for Artificial Intelligence(2019)
Subjects: Disease progression, CDRSB = Clinical Dementia Rating Scale Sum of Boxes, Clinical trials, Mental State Examination, [STAT.ML]Statistics [stat]/Machine Learning [stat.ML], Amyloid hypothesis, [SCCO.NEUR]Cognitive science/Neuroscience, FAQ = Functional Assessment Questionnaire, RAVLT = Rey Auditory Verbal Learning Test, Alzheimer's Disease, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation
Abstract: International audience; In this study we investigate a novel quantitative instrument for the development of intervention strategies for disease modifying drugs in Alzheimer's disease. Our framework is based on the modeling of the spatio-temporal dynamics governing the joint evolution of imaging and clinical biomarkers along the history of the disease, and allows the simulation of the effect of intervention time and drug dosage on the biomarkers' progression. When applied to multi-modal imaging and clinical data from the Alzheimer's Disease Neuroimaging Initiative our method enables to generate hypothetical scenarios of amyloid lowering interventions. The results quantify the crucial role of intervention time, and provide a theoretical justification for testing amyloid modifying drugs in the pre-clinical stage. Our experimental simulations are compatible with the outcomes observed in past clinical trials, and suggest that anti-amyloid treatments should be administered at least 7 years earlier than what is currently being done in order to obtain statistically powered improvement of clinical endpoints.
Published: 2020
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30. Mouse Visual Cortex Is Modulated by Distance Traveled and by Theta Oscillations

Author: Julien Fournier, Aman B. Saleem, Miles J. Wells, E. Mika Diamanti, Matteo Carandini, Kenneth D. Harris, University College of London [London] (UCL), Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des systèmes perceptifs (LSP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institute of Ophthalmology [London], Institute of Neurology [London], Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), and Gestionnaire, Hal Sorbonne Université
Subjects: Male, 0301 basic medicine, Sensory processing, hippocampus, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Phase (waves), theta oscillation, Action Potentials, Spatial Behavior, Hippocampus, Hippocampal formation, Biology, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, 0302 clinical medicine, Reward, Report, Oscillation (cell signaling), medicine, Animals, Theta Rhythm, navigation, CA1 Region, Hippocampal, primary visual cortex, Visual Cortex, Neurons, Pyramidal Cells, Theta oscillations, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], 030104 developmental biology, Visual cortex, medicine.anatomical_structure, distance coding, virtual reality, Female, General Agricultural and Biological Sciences, Licking, Neuroscience, 030217 neurology & neurosurgery
Abstract: Summary The visual responses of neurons in the primary visual cortex (V1) are influenced by the animal’s position in the environment [1, 2, 3, 4, 5]. V1 responses encode positions that co-fluctuate with those encoded by place cells in hippocampal area CA1 [2, 5]. This correlation might reflect a common influence of non-visual spatial signals on both areas. Place cells in CA1, indeed, do not rely only on vision; their place preference depends on the physical distance traveled [6, 7, 8, 9, 10, 11] and on the phase of the 6–9 Hz theta oscillation [12, 13]. Are V1 responses similarly influenced by these non-visual factors? We recorded V1 and CA1 neurons simultaneously while mice performed a spatial task in a virtual corridor by running on a wheel and licking at a reward location. By changing the gain that couples the wheel movement to the virtual environment, we found that ∼20% of V1 neurons were influenced by the physical distance traveled, as were ∼40% of CA1 place cells. Moreover, the firing rate of ∼24% of V1 neurons was modulated by the phase of theta oscillations recorded in CA1 and the response profiles of ∼7% of V1 neurons shifted spatially across the theta cycle, analogous to the phase precession observed in ∼37% of CA1 place cells. The influence of theta oscillations on V1 responses was more prominent in putative layer 6. These results reveal that, in a familiar environment, sensory processing in V1 is modulated by the key non-visual signals that influence spatial coding in the hippocampus., Graphical Abstract, Highlights • We compared responses of mouse V1 and CA1 during navigation in virtual reality • Similar to CA1 neurons, V1 neurons are influenced by physical distance traveled • V1 responses are modulated by theta oscillations recorded in hippocampus • Positions encoded by V1 shift spatially with the phase of the theta oscillation, Fournier et al. compare responses of hippocampus and visual cortex in mice navigating a virtual reality. They find that, similar to hippocampus, activity in visual cortex is influenced by the physical distance traveled in an environment. In addition, theta oscillations modulate the activity of visual cortical neurons and their position coding.
Published: 2020
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31. Amygdalar nuclei and hippocampal subfields on MRI

Author: Michela Pievani, Agnese Picco, Jean-Philippe Ranjeva, Giovanni B. Frisoni, Lucilla Parnetti, Piero Floridi, Frederik Barkhof, Jens Wiltfang, Marco Salvatore, Helene Gros-Dagnac, Antonio Ferretti, Julien Sein, Massimo Caulo, Alberto Beltramello, Pierre Payoux, Marco Aiello, Joost P.A. Kuijer, Roberto Tarducci, Tilman Hensch, Renaud Lopes, Björn H. Schott, Peter Schönknecht, Luca Roccatagliata, Camillo Marra, David Bartrés-Faz, Jill C. Richardson, Jorge Jovicich, Flavio Nobili, Antonios Drevelegas, Pieter Jelle Visser, Olivier Blin, Paolo Maria Rossini, Karl Titus Hoffmann, Mira Didic, Régis Bordet, Bernhard W. Müller, Francesca B. Pizzini, Magda Tsolaki, Ute Fiedler, Manos Constantinides, Giulia Quattrini, Moira Marizzoni, Andrea Soricelli, Núria Bargalló, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Center for Mind/Brain Sciences, University of Trento, Corso Bettini, 31, 38068, Rovereto, TN, Italy, IRCCS SDN Napoli, Department of Neuroradiology and Image Research Platform, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], Institute of Neurology, Queen Square, London, Department of Medicine and Health Sciences, Faculty of Medicine, Universitat de Barcelona and IDIBAPS, Barcelona, Department of Radiology, IRCCS 'Sacro Cuore-Don Calabria', Negrar, Verona, Radiology, Department of Diagnostic and Public Health, University of Verona, Verona, Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University 'G. d'Annunzio' of Chieti-Pescara [Chieti], Interbalkan Medical Center of Thessaloniki, LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, Neuroradiology Unit, Perugia General Hospital, Perugia, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Department of Neuroradiology, University Hospital Leipzig, LVR-Hospital Essen, Department for Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Università degli Studi di Genova, 16132 Genova, Section of Neurology, Department of Medicine, University of Perugia, Perugia, Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), IRCCS, Ospedale Policlinico San Martino, Genova, Italy, Department of Health Science (DISSAL), University of Genoa, Genoa, Dept. Neuroscience & Rehabilitation, IRCCS San Raffaele-Pisana, Rome, Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Göttingen, Leibniz Institute for Neurobiology, Magdeburg, Center for Neurodegenerative Diseases (DZNE), Goettingen, Medical Physics Unit, Perugia General Hospital, Perugia, Aristotle University of Thessaloniki, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Netherlands, Maastricht University, Maastricht, Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, German Center for Neurodegenerative Diseases (DZNE), Goettingen, GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Amsterdam Neuroscience - Brain Imaging, Radiology and nuclear medicine, Neurology, Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Trento (UNITN), Università degli studi di Verona = University of Verona (UNIVR), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lille Neurosciences & Cognition - U 1172 (LilNCog), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Leipzig University, Università degli studi di Genova = University of Genoa (UniGe), Università degli Studi di Perugia = University of Perugia (UNIPG), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), and Leibniz Institute for Neurobiology [Magdeburg] (LIN)
Subjects: Male, STRUCTURAL DIFFERENCES, Neurology, genetic structures, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, FreeSurfer, Medizin, Hippocampus, Hippocampal formation, Amygdalar nuclei, Hippocampal subfields, Multicenter MRI study, Reliability analysis, 0302 clinical medicine, methods [Magnetic Resonance Imaging], hippocampal subfields, multicenter MRI study, reliability analysis, methods [Image Processing, Computer-Assisted], Image Processing, Computer-Assisted, METHODS FREESURFER, ELDERLY-PATIENTS, ComputingMilieux_MISCELLANEOUS, 05 social sciences, Subiculum, BORDERLINE PERSONALITY-DISORDER, Middle Aged, Amygdala, HUMAN BRAIN, Magnetic Resonance Imaging, ALZHEIMERS-DISEASE, standards [Image Processing, Computer-Assisted], Settore MED/26 - NEUROLOGIA, MANUAL SEGMENTATION, medicine.anatomical_structure, Brain size, Cohort, Female, methods [Neuroimaging], Adult, medicine.medical_specialty, Cognitive Neuroscience, anatomy & histology [Hippocampus], Neuroimaging, Cognitive neuroscience, SURFACE-BASED ANALYSIS, 050105 experimental psychology, lcsh:RC321-571, 03 medical and health sciences, medicine, Humans, 0501 psychology and cognitive sciences, ddc:610, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, standards [Magnetic Resonance Imaging], business.industry, Reproducibility of Results, SAMPLE-SIZE CALCULATIONS, ddc:616.8, nervous system, anatomy & histology [Amygdala], Nuclear medicine, business, 030217 neurology & neurosurgery, standards [Neuroimaging], Software, FUNCTIONAL-ORGANIZATION
Abstract: Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults.Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (epsilon) and spatial overlapping coefficient (DICE) between test and retest session.Results: Significant MRI site and vendor effects (p 0.43, p 0.80).Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.
Published: 2020
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32. CSF cutoffs for MCI due to AD depend on APOEε4 carrier status

Author: Jean-Philippe Ranjeva, Frederik Barkhof, Jorge Jovicich, Régis Bordet, Jill C. Richardson, Elena Rolandi, Magda Tsolaki, Andrea Soricelli, Olivier Blin, Lucilla Parnetti, Marco Salvatore, Claudio Babiloni, Tilman Hensch, Jens Wiltfang, Camillo Marra, José Luis Molinuevo, Libera Cavaliere, Samantha Galluzzi, Moira Marizzoni, Diego Albani, Mira Didic, Clarissa Ferrari, Flavio Nobili, Federica Fusco, Paolo Maria Rossini, Giovanni B. Frisoni, Gianluigi Forloni, Federica Ribaldi, Pierre Payoux, Pieter Jelle Visser, Centro San Giovanni di Dio, Fatebenefratelli, Brescia (IRCCS), Università degli Studi di Brescia [Brescia], Department of Physiology and Pharmacology 'Vittorio Erspamer', Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Neuroscience Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milano, Department of Radiology and Nuclear Medicine [Amsterdam], VU University Medical Center [Amsterdam], Institutes of Neurology and Healthcare Engineering, UCL, London, Institut de Neurosciences des Systèmes (INS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Center for Mind/Brain Sciences, University of Trento, Corso Bettini, 31, 38068, Rovereto, TN, Italy, Department of Gerontology, Neurosciences & Orthopedics, Catholic University, Rome, Alzheimer's Disease Unit and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Dipartimento di Neuroscienze, riabilitazione, oftalmologia, genetica e scienze materno-infantili [Genova] (DINOGMI), Universita degli studi di Genova, Section of Neurology, Centre for Memory Disturbances, University of Perugia, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre de résonance magnétique biologique et médicale (CRMBM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Area Neuroscience, IRCCS San Raffaele, Rome, IRCCS SDN Napoli, Department of Neurology (Aristotle University of Thessaloniki), Aristotle University of Thessaloniki, Alzheimer Center Amsterdam, LVR-Clinic for Psychiatry and Psychotherapy, Institutes and Clinics of the University Duisburg-Essen, GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Università degli Studi di Brescia = University of Brescia (UniBs), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Leipzig University, Università degli Studi di Trento (UNITN), Università degli studi di Genova = University of Genoa (UniGe), Università degli Studi di Perugia = University of Perugia (UNIPG), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), and Lille Neurosciences & Cognition - U 1172 (LilNCog)
Subjects: Male, 0301 basic medicine, Oncology, Apolipoprotein E, Aging, Medizin, Cohort Studies, 0302 clinical medicine, Cerebrospinal fluid, Cutoff, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, biology, General Neuroscience, Alzheimer's disease, 3. Good health, Settore MED/26 - NEUROLOGIA, Biomarker (medicine), Female, Heterozygote, medicine.medical_specialty, CSF cutoff, Disease progression, Mild cognitive impairment, Tau protein, tau Proteins, 03 medical and health sciences, Apolipoproteins E, Neuroimaging, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Cognitive Dysfunction, Aged, Amyloid beta-Peptides, Receiver operating characteristic, business.industry, medicine.disease, Peptide Fragments, ddc:616.8, 030104 developmental biology, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, biology.protein, Neurology (clinical), Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Amyloid and tau pathological accumulation should be considered for Alzheimer's disease (AD) definition and before subjects' enrollment in disease-modifying trials. Although age, APOEε4, and sex influence cerebrospinal fluid (CSF) biomarker levels, none of these variables are considered by current normality/abnormality cutoffs. Using baseline CSF data from 2 independent cohorts (PharmaCOG/European Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Neuroimaging Initiative), we investigated the effect of age, APOEε4 status, and sex on CSF Aβ42/P-tau distribution and cutoff extraction by applying mixture models with covariates. The Aβ42/P-tau distribution revealed the presence of 3 subgroups (AD-like, intermediate, control-like) and 2 cutoffs. The identification of the intermediate subgroup and of the higher cutoff was APOEε4 dependent in both cohorts. APOE-specific classification (higher cutoff for APOEε4+, lower cutoff for APOEε4-) showed higher diagnostic accuracy in identifying MCI due to AD compared to single Aβ42 and Aβ42/P-tau cutoffs. APOEε4 influences amyloid and tau CSF markers and AD progression in MCI patients supporting i) the use of APOE-specific cutoffs to identify MCI due to AD and ii) the utility of considering APOE genotype for early AD diagnosis.
Published: 2020
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33. Progress update from the hippocampal subfields group

Author: Trevor A. Steve, Katrin Amunts, Olga Kedo, Rosanna K. Olsen, Elliott G. Johnson, Joshua K. Lee, Martina Bocchetta, Ulman Lindenberger, Craig E.L. Stark, Ricardo Insausti, Daniela J. Palombo, Naftali Raz, Margaret L. Schlichting, Gaël Chételat, Valerie A. Carr, Markus Werkle-Bergner, Nanthia Suthana, Paul A. Yushkevich, Jordan DeKraker, Attila Keresztes, Andrew R. Bender, Noa Ofen, John Pluta, Arnold Bakker, David Berron, Karen M. Rodrigue, Kristen M. Kennedy, Robert S. C. Amaral, Prabesh Kanel, Renaud La Joie, Mirjam I. Geerlings, Susanne G. Mueller, Qijing Yu, Songlin Ding, Jean C. Augustinack, Laura E.M. Wisse, Marina Boccardi, Lei Wang, Lorenzo Pasquini, Yee Lee Shing, Ana M. Daugherty, Elizabeth M. Mulligan, Robin de Flores, Yushan Huang, M. Mallar Chakravarty, Alison C. Burggren, Rotman Research Institute at the Baycrest Centre (RRI), University of Toronto, San Jose State University [San José] (SJSU), Wayne State University [Detroit], Memory and Aging Center [San Francisco, CA, États-Unis], University of California [San Francisco] (UCSF), University of California-University of California, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Institute of Neuroscience and Medicine [Jülich] (INM-1), Massachusetts General Hospital [Boston], Johns Hopkins University School of Medicine [Baltimore], Lund University [Lund], German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Neuroimaging and Telemedicine (LENITEM), IRCCS Fatebenefratelli - Brescia, Dementia Research Centre [London] (DRC), University College of London [London] (UCL), University of Oregon [Eugene], Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU), University of Western Ontario (UWO), Allen Institute for Brain Science [Seattle, WA, USA], University Medical Center [Utrecht], University of Alberta, Human Neuroanatomy Laboratory [Albacete, Spain] (School of Medicine - CRIB), University of Castilla-La Mancha (UCLM)-Centro Regional de Investigaciones Biomédicas (CRIB), University of California, University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], University of Texas at Dallas [Richardson] (UT Dallas), Max Planck Institute for Human Development, Max-Planck-Gesellschaft, University of California [Davis] (UC Davis), Freie Universität Berlin, Florida State University [Tallahassee] (FSU), Weizmann Institutes of Science [Rehovot, Israel], University of British Columbia (UBC), University of Pennsylvania [Philadelphia], Goethe-University Frankfurt am Main, University of California [Irvine] (UCI), University of California [Los Angeles] (UCLA), Northwestern University Feinberg School of Medicine, Penn Image Computing & Science Lab [Philadelphia] (PICSL), The work on this article was also supported by NIH grant R01 AG-011230 to Naftali Raz, NIH grant R01 AG-055121 to Lei Wang, NIH grant R01 AG-056014 to Paul Yushkevich, and NIH grant R01 AG-034613 to Craig Stark. M.M.C. receives salary support from the Fonds du Recherches Santes Quebec and also acknowledges support from NSERC, Weston Brain Institute, and CIHR., Hippocampal Subfields Group, San Jose State University [San Jose] (SJSU), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM)-Centro Regional de Investigaciones Biomédicas (CRIB), University of California (UC), University of Pennsylvania, University of California [Irvine] (UC Irvine), and CHETELAT, Gaëlle
Subjects: Histology, Standardization, Computer science, Clinical Neurology, Structural imaging, Neuroimaging, lcsh:Geriatrics, Hippocampal formation, Hippocampus, lcsh:RC346-429, Special Section: Working Group Summaries for the European Joint Programme for Neurodegenerative Disease Research (JPND). (Guest Editors: Jorge Jovicich & Giovanni B. Frisoni), Temporal lobe, ddc:616.89, 03 medical and health sciences, 0302 clinical medicine, Volumetry, Segmentation, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:610, lcsh:Neurology. Diseases of the nervous system, Reliability (statistics), 030304 developmental biology, Protocol (science), 0303 health sciences, ex vivo, International working group, Data science, Ex vivo, 3. Good health, lcsh:RC952-954.6, Psychiatry and Mental health, Neuroanatomy, Cytoarchitec- ture, Cytoarchitecture, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), 030217 neurology & neurosurgery, Human
Abstract: Introduction Heterogeneity of segmentation protocols for medial temporal lobe regions and hippocampal subfields on in vivo magnetic resonance imaging hinders the ability to integrate findings across studies. We aim to develop a harmonized protocol based on expert consensus and histological evidence. Methods Our international working group, funded by the EU Joint Programme–Neurodegenerative Disease Research (JPND), is working toward the production of a reliable, validated, harmonized protocol for segmentation of medial temporal lobe regions. The working group uses a novel postmortem data set and online consensus procedures to ensure validity and facilitate adoption. Results This progress report describes the initial results and milestones that we have achieved to date, including the development of a draft protocol and results from the initial reliability tests and consensus procedures. Discussion A harmonized protocol will enable the standardization of segmentation methods across laboratories interested in medial temporal lobe research worldwide., Highlights • Harmonization of MRI-based segmentation of medial temporal regions is needed. • The Hippocampal Subfield Group includes >200 imaging and anatomy experts worldwide. • Reliable and valid protocol based on specialized histology data set in development. • A modified Delphi procedure is used to determine consensus on protocol rules. • Final protocol will provide subfield delineation in hippocampal body, head, and tail.
Published: 2019
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34. Cross-sectional and longitudinal characterization of SCD patients recruited from the community versus from a memory clinic: subjective cognitive decline, psychoaffective factors, cognitive performances, and atrophy progression over time

Author: Denis Vivien, Audrey Perrotin, Clémence Tomadesso, Béatrice Desgranges, Alexandre Bejanin, Siya Sherif, Renaud La Joie, Brigitte Landeau, Inès Moulinet, Géraldine Poisnel, Elizabeth Kuhn, Vincent de la Sayette, G. Chételat, Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurology [San Francisco, CA, États-Unis], Memory and Aging Center [San Francisco, CA, États-Unis], University of California [San Francisco] (UCSF), University of California-University of California-University of California [San Francisco] (UCSF), University of California-University of California, Neuropsychologie et imagerie de la mémoire humaine (NIMH), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre de recherche clinique [CHU Caen] (CRC), Normandie Université (NU)-Normandie Université (NU)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), The study was supported by Fondation Plan Alzheimer (Alzheimer Plan 2008–2012), Programme Hospitalier de Recherche Clinique (PHRCN 2011-A01493-38 and PHRCN 2012 12-006-0347), Agence Nationale de la Recherche (LONGVIE 2007), Région Basse-Normandie, Association France Alzheimer et maladies apparentées AAP 2013, the Institut National de la Santé et de la Recherche Médicale (INSERM), and the University of Caen Normandy., University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC)-University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Normandie Université (NU)-Normandie Université (NU)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, and Bodescot, Myriam
Subjects: 0301 basic medicine, Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Neocortex, Anxiety, lcsh:RC346-429, 0302 clinical medicine, hemic and lymphatic diseases, Longitudinal Studies, Cognitive decline, Gray Matter, Depression (differential diagnoses), Subclinical infection, Aged, 80 and over, education.field_of_study, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Depression, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Cognition, Middle Aged, Mental Status and Dementia Tests, Magnetic Resonance Imaging, Neurology, Disease Progression, Female, medicine.symptom, Pathological ageing, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Cognitive Neuroscience, Population, Prodromal Symptoms, Neuroimaging, lcsh:RC321-571, 03 medical and health sciences, Diagnostic Self Evaluation, Atrophy, Alzheimer Disease, Internal medicine, medicine, Humans, Cognitive Dysfunction, cardiovascular diseases, education, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Preclinical Alzheimer’s disease, Aged, Memory Disorders, business.industry, Research, Memory clinic, medicine.disease, 030104 developmental biology, [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, Cross-Sectional Studies, Positron-Emission Tomography, Psychoaffective factors, Subjective cognitive decline, Neurology (clinical), business, 030217 neurology & neurosurgery, Biomarkers, Follow-Up Studies
Abstract: Background Subjective cognitive decline (SCD) defines a heterogeneous population, part of which having Alzheimer’s disease (AD). We aimed at characterizing SCD populations according to whether or not they referred to a memory clinic, by assessing the factors associated with increased AD risk. Methods Seventy-eight cognitively unimpaired older adults from the IMAP+ study (Caen) were included, amongst which 28 healthy controls (HC) and 50 SCD recruited from the community (SCD-community; n = 23) or from a memory clinic (SCD-clinic; n = 27). Participants underwent cognitive, psychoaffective, structural MRI, FDG-PET, and amyloid-PET assessments. They were followed up over a mean period of 2.4 ± 0.8 years. The groups were compared in terms of baseline and follow-up levels of SCD (self- and informant-reported), cognition, subclinical anxiety and depression, and atrophy progression over time. We also investigated SCD substrates within each SCD group through the correlations between self-reported SCD and other psychometric and brain measures. Results Compared to HC, both SCD groups showed similar cognitive performances but higher informant-reported SCD and anxiety. Compared to SCD-community, SCD-clinic showed higher informant-reported SCD, depression score, and atrophy progression over time but similar brain amyloid load. A significant increase over time was found for depression in the SCD-community and for self-reported praxis-domestic activities SCD factor in the SCD-clinic. Higher self-reported SCD correlated with (i) lower grey matter volume and higher anxiety in SCD-community, (ii) greater informant-reported SCD in SCD-clinic, and (iii) lower glucose metabolism in both SCD groups. Conclusions Higher subclinical depression and informant-reported SCD specifically characterize the SCD group that refers to a memory clinic. The same group appears as a frailer population than SCD-community as they show greater atrophy progression over time. Yet, both the SCD groups were quite similar otherwise including for brain amyloid load and the SCD-community showed increased depression score over time. Altogether, our findings highlight the relevance of assessing psychoaffective factors and informant-reported SCD in SCD populations and point to both differences and similarities in SCD populations referring or not to a memory clinic. Electronic supplementary material The online version of this article (10.1186/s13195-019-0514-z) contains supplementary material, which is available to authorized users.
Published: 2019
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35. Anatomical and physiological foundations of cerebello-hippocampal interaction

Author: Patrice Coulon, Arturo Torres-Herraez, Christelle Rochefort, Pauline Obiang, Laure Rondi-Reig, Thomas C. Watson, Aurélie Watilliaux, Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), ANR-17-CE16-0019,SynPredict,Rôle de la synapse pour le codage prédictif dans le cortex cérébelleux(2017), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Male, Cerebellum, anatomy, cerebellum, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Rabies, hippocampus, QH301-705.5, Science, Hippocampus, spatial navigation, Local field potential, Hippocampal formation, Biology, Spatial memory, General Biochemistry, Genetics and Molecular Biology, neuroscience, 03 medical and health sciences, 0302 clinical medicine, Neural Pathways, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Premovement neuronal activity, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biology (General), mouse, Neurons, General Immunology and Microbiology, General Neuroscience, Motor control, General Medicine, Electric Stimulation, Mice, Inbred C57BL, Brain region, 030104 developmental biology, medicine.anatomical_structure, nervous system, Rabies virus, physiology, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nerve Net, Neuroscience, 030217 neurology & neurosurgery, Research Article
Abstract: International audience; Multiple lines of evidence suggest that functionally intact cerebello-hippocampal interactions are required for appropriate spatial processing. However, how the cerebellum anatomically and physiologically engages with the hippocampus to sustain such communication remains unknown. Using rabies virus as a retrograde transneuronal tracer in mice, we reveal that the dorsal hippocampus receives input from topographically restricted and disparate regions of the cerebellum. By simultaneously recording local field potential from both the dorsal hippocampus and anatomically connected cerebellar regions, we additionally suggest that the two structures interact, in a behaviorally dynamic manner, through subregion-specific synchronization of neuronal oscillations in the 6-12 Hz frequency range. Together, these results reveal a novel neural network macro-architecture through which we can understand how a brain region classically associated with motor control, the cerebellum, may influence hippocampal neuronal activity and related functions, such as spatial navigation.
Published: 2019
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36. Transmission of Predictable Sensory Signals to the Cerebellum via Climbing Fiber Pathways Is Gated during Exploratory Behavior

Author: Richard Apps, Charlotte Lawrenson, Thomas C. Watson, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), United Kingdom Medical Research Council, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Cerebellum, cerebellum, Behavioral/Cognitive, Motor behaviour, Sensation, Stimulation, Sensory system, sensory, Gating, Evoked field, Olivary Nucleus, motor behaviour, 03 medical and health sciences, 0302 clinical medicine, Neural Pathways, medicine, Animals, Learning, Neurons, Afferent, Inferior olive, Rats, Wistar, exploratory, Feedback, Physiological, Afferent Pathways, Sensory, learning, General Neuroscience, Exploratory, Neural Inhibition, Articles, Climbing fiber, Rats, 030104 developmental biology, medicine.anatomical_structure, inferior olive, Climbing, Cerebellar cortex, Exploratory Behavior, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: Pathways arising from the periphery that target the inferior olive [spino-olivocerebellar pathways (SOCPs)] are a vital source of information to the cerebellum and are modulated (gated) during active movements. This limits their ability to forward signals to climbing fibers in the cerebellar cortex. We tested the hypothesis that the temporal pattern of gating is related to the predictability of a sensory signal. Low-intensity electrical stimulation of the ipsilateral hindlimb in awake rats evoked field potentials in the C1 zone in the copula pyramidis of the cerebellar cortex. Responses had an onset latency of 12.5 ± 0.3 ms and were either short or long duration (8.7 ± 0.1 vs 31.2 ± 0.3 ms, respectively). Both types of response were shown to be mainly climbing fiber in origin and therefore evoked by transmission in hindlimb SOCPs. Changes in response size (area of field, millivolts per millisecond) were used to monitor differences in transmission during rest and three phases of rearing: phase 1, rearing up; phase 2, upright; and phase 3, rearing down. Responses evoked during phase 2 were similar in size to rest but were smaller during phases 1 and 3, i.e., transmission was reduced during active movement when self-generated (predictable) sensory signals from the hindlimbs are likely to occur. To test whether the pattern of gating was related to the predictability of the sensory signal, some animals received the hindlimb stimulation only during phase 2. Over ∼10 d, the responses became progressively smaller in size, consistent with gating-out transmission of predictable sensory signals relayed via SOCPs. SIGNIFICANCE STATEMENT A major route for peripheral information to gain access to the cerebellum is via ascending climbing fiber pathways. During active movements, gating of transmission in these pathways controls when climbing fiber signals can modify cerebellar activity. We investigated this phenomenon in rats during their exploratory behavior of rearing. During rearing up and down, transmission was reduced at a time when self-generated, behaviorally irrelevant (predictable) signals occur. However, during the upright phase of rearing, transmission was increased when behaviorally relevant (unpredictable) signals may occur. When the peripheral stimulation was delivered only during the upright phase, so its occurrence became predictable over time, transmission was reduced. Therefore, the results indicate that the gating is related to the level of predictability of a sensory signal.
Published: 2016
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37. Cerebellar Volume in Autism: Literature Meta-analysis and Analysis of the Autism Brain Imaging Data Exchange Cohort

Author: Traut, Nicolas, Beggiato, Anita, Bourgeron, Thomas, Delorme, Richard, Rondi-Reig, Laure, Paradis, Anne-Lise, Toro, Roberto, CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fondation FondaMental [Créteil], This work was supported by the Fondation de France project 'Développement du plissement cortical dans les troubles du spectre autistique: caractérisation morphométrique et génétique' (NT, AB, TB, RD, RT). The Institut Pasteur group (NT, AB, TB, RD, RT) was funded by the European Research Area Networks Network of European Funding for Neuroscience Research Cofund Programme under 'Horizon 2020' (SynPathy project), Institut Pasteur, Bettencourt-Schueller Foundation, Centre National de la Recherche Scientifique, University Paris Diderot, Agence Nationale de la Recherche programme 'Investissements d’avenir,' Laboratoire d'excellence de Biologie pour la Psychiatrie (BioPsy, reference: ANR-11-IDEX-0004-02), Laboratoire d'excellence en Génomique Médicale, Conny-Maeva Charitable Foundation, Cognacq Jay Foundation, Orange Foundation, and Fondamental Foundation. The Neuroscience Paris Seine group (NT, LR-R, A-LP) is a member of BioPsy and École de Neuroscience de Paris foundation., ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), ANR-15-NEUR-0007,SynPathy,Key Determinants of Synaptic Excitation-Inhibition Imbalance in Autism Spectrum Disorders - From Genetic Animal Models to Human Patients(2015), ANR-11-LABX-0035,BIOPSY,Laboratoire de Psychiatrie Biologique(2011), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, ANR-11-IDEX-0004-02/11-LABX-0035,BIOPSY,Laboratoire de Psychiatrie Biologique(2011), Gestionnaire, Hal Sorbonne Université, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, Key Determinants of Synaptic Excitation-Inhibition Imbalance in Autism Spectrum Disorders - From Genetic Animal Models to Human Patients - - SynPathy2015 - ANR-15-NEUR-0007 - NEURON II - VALID, Laboratoire de Psychiatrie Biologique - - BIOPSY2011 - ANR-11-LABX-0035 - LABX - VALID, and Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: Adult, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Adolescent, Databases, Factual, Autism Spectrum Disorder, Autism, Neuroimaging, Cohort Studies, Young Adult, Meta-analysis, Cerebellum, Computational neuroanatomy, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Child, Cohort study, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUND: The neuroanatomical bases of autism spectrum disorder remain largely unknown. Among the most widely discussed candidate endophenotypes, differences in cerebellar volume have been often reported as statistically significant.METHODS: We aimed at objectifying this possible alteration by performing a systematic meta-analysis of the literature and an analysis of the ABIDE (Autism Brain Imaging Data Exchange) cohort. Our meta-analysis sought to determine a combined effect size of autism spectrum disorder diagnosis on different measures of the cerebellar anatomy as well as the effect of possible factors of variability across studies. We then analyzed the cerebellar volume of 328 patients and 353 control subjects from the ABIDE project.RESULTS: The meta-analysis of the literature suggested a weak but significant association between autism spectrum disorder diagnosis and increased cerebellar volume (p = .049, uncorrected), but the analysis of ABIDE did not show any relationship. The studies meta-analyzed were generally underpowered; however, the number of statistically significant findings was larger than expected.CONCLUSIONS: Although we could not provide a conclusive explanation for this excess of significant findings, our analyses would suggest publication bias as a possible reason. Finally, age, sex, and IQ were important sources of cerebellar volume variability, although independent of autism diagnosis.
Published: 2018
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38. Prevalence of amyloid‐β pathology in distinct variants of primary progressive aphasia

Author: Philip Scheltens, Ellen Gelpi, Raquel Sánchez-Valle, María Nieves Cabrera-Martín, Rik Ossenkoppele, Olivier Piguet, William W. Seeley, Gaël Chételat, Harro Seelaar, M.-Marsel Mesulam, Willemijn J. Jansen, Miguel A. Santos-Santos, M. Antoinette Keulen, David J. Irwin, Julia Keith, Kristensen Nora, Janine Diehl-Schmid, Edmond Teng, Jordi A. Matías-Guiu, Mario Masellis, Marie Sarazin, Yolande A.L. Pijnenburg, Bradford C. Dickerson, Murray Grossman, Ismael Calandri, Claire Paquet, Timo Grimmer, Roberto Santangelo, Ian R. A. Mackenzie, Robert Laforce, Jeéreémie Pariente, Cristian E. Leyton, Lejla Koric, Jennifer M. Harris, Jason D. Warren, Rik Vandenberghe, John C. van Swieten, Wiesje M. van der Flier, Ging-Yuek Robin Hsiung, Elias Granadillo, Rémi W. Bouchard, Vincent Deramecourt, Niklas Mattsson, Sandra E. Black, Christopher C. Rowe, Jonathan M. Schott, Philipp T. Meyer, David G. Mann, Marc Teichmann, Colin Groot, Florence Pasquier, Alejandra A. Amengual, Victor L. Villemagne, Patricio Chrem-Méndez, Nick C. Fox, Giuseppe Magnani, Jonathan D. Rohrer, Bart N.M. van Berckel, Eloi Magnin, John R. Hodges, Mario F. Mendez, Janne M. Papma, Pieter Jelle Visser, Oskar Hansson, Michel Bottlaender, Matthew Jones, Bruce L. Miller, Julien Dumurgier, Emily Rogalski, Alberto Lleó, Sang Won Seo, Rafael Blesa, Juan Fortea, Oriol Grau-Rivera, David Bergeron, Kristian Steen Frederiksen, Maria Luisa Gorno-Tempini, Gil D. Rabinovici, David A. Wolk, Bruno Dubois, Christer Nilsson, Lars Frings, Serge Belliard, Julie S. Snowden, Pascual Sánchez-Juan, Carole Miguet-Alfonsi, Duchange, Nathalie, Interdisciplinary Clinic of Memory of the Child Jesus, Université Laval [Québec] (ULaval), Alzheimer Center Amsterdam, VU University Medical Center [Amsterdam], Memory and Aging Center [San Francisco, CA, États-Unis], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Llobregat Hospital [Barcelona], Institute of Neurology [London], University College of London [London] (UCL), August Pi i Sunyer Biomedical Research Institute [Barcelona], Medizinische Universität Wien = Medical University of Vienna, Erasmus University Medical Center [Rotterdam] (Erasmus MC), The University of Sydney, University of New South Wales [Sydney] (UNSW), Australian Research Council Centre of Excellence in Cognition and its Disorders [Sidney], Massachusetts Alzheimer's Disease Research Center, Harvard Medical School [Boston] (HMS), Rush University [Chicago], Northwestern University Medical School [Chicago], Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, University of British Columbia (UBC), University of Pennsylvania, Greater Manchester Neurosciences Centre, University of Manchester [Manchester], Neurological Research Institute [Buenos Aires], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Vita Salute University [Milan], IRCCS Ospedale San Raffaele [Milan, Italy], Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lund University [Lund], Skane University Hospital [Malmo], University of Toronto, Sunnybrook Research Institute [Toronto] (SRI), Sunnybrook Health Sciences Centre, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), San Carlos Clinical Hospital [Madrid], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Austin Health, University of Melbourne, University Hospitals Leuven [Leuven], University of California [Los Angeles] (UCLA), University of California (UC), VA Greater Los Angeles Healthcare System, West Los Angeles VA Medical Center, University Hospital of Freiburg, Universitat Autònoma de Barcelona (UAB), Santa Cruz and Saint Paul Hospital [Barcelona], Center for Biomedical Network Research on Neurodegenerative Diseases [Barcelona], Samsung Medical Center Sungkyunkwan University School of Medicine, Institute Division of Hematology/Oncology, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Danish Dementia Research Center [Copenhagen], Marqués de Valdecilla University Hospital [Santander], Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), School for Mental Health and Neuroscience - Alzheimer Center Limburg (MUMC), Maastricht University [Maastricht], Banner Alzheimer's Institute [Phoenix], Clinique Interdisciplinaire de Mémoire de l'Enfant-Jésus, Centre Hospitalier de l'Université de Laval (CHUL), Vrije Universiteit Amsterdam [Amsterdam] (VU), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), University Hospital Freiburg, Neurology, Divisions, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, APH - Personalized Medicine, APH - Methodology, Epidemiology and Data Science, Human genetics, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of California [San Francisco] (UCSF), University of California-University of California, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], University of Pennsylvania [Philadelphia], Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of California, VU University Amsterdam, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU)
Subjects: Male, NATIONAL INSTITUTE, 0301 basic medicine, Apolipoprotein E, Aging, Pathology, Neurology, LANGUAGE, Autopsy, Neurodegenerative, Alzheimer's Disease, Primary progressive aphasia, 0302 clinical medicine, 80 and over, Prevalence, 2.1 Biological and endogenous factors, Medicine, HETEROGENEITY, Aetiology, Alzheimer's Disease Related Dementias (ADRD), ALZHEIMER-DISEASE, Aged, 80 and over, screening and diagnosis, DEMENTIA, Age Factors, Brain, Frontotemporal lobar degeneration, Middle Aged, respiratory system, 3. Good health, Frontotemporal Dementia (FTD), Detection, Neurological, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, medicine.symptom, 4.2 Evaluation of markers and technologies, medicine.medical_specialty, Genotype, Primary Progressive, Clinical Sciences, BIOMARKERS, DIAGNOSIS, Article, 03 medical and health sciences, Rare Diseases, Apolipoproteins E, Clinical Research, Aphasia, mental disorders, Acquired Cognitive Impairment, Genetics, Humans, Dementia, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Aged, Neurology & Neurosurgery, Amyloid beta-Peptides, business.industry, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, Brain Disorders, Aphasia, Primary Progressive, PET, 030104 developmental biology, FRONTOTEMPORAL PATHOLOGY, Neurology (clinical), CONSENSUS, business, 030217 neurology & neurosurgery
Abstract: Objective Methods To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-beta pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) epsilon 4 status was determined using generalized estimating equation models. Results Interpretation Amyloid-beta positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p
Published: 2018
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39. Abnormalities of resting-state functional cortical connectivity in patients with dementia due to Alzheimer's and Lewy body diseases: an EEG study

Author: Franco Giubilei, Ute Gschwandtner, Raffaella Franciotti, Roberta Lizio, Gerhard Ransmayr, Fabrizio Stocchi, Dag Aarsland, John-Paul Taylor, Giuseppe Noce, Bahar Güntekin, Laura Vacca, Claudio Babiloni, Raffaele Ferri, Peter Fuhr, Antonio Ivano Triggiani, Dario Arnaldi, Lucia Fraioli, Claudio Del Percio, Paola Stirpe, Susanna Lopez, Lutfu Hanoglu, Francesco Orzi, Marco Onofrj, Laura Bonanni, Maria Francesca De Pandis, Carlo de Lena, Flavio Nobili, Andrea Soricelli, Michela Pievani, Giovanni B. Frisoni, Derya Durusu Emek-Savaş, Carla Buttinelli, Francesco Famà, Erol Başar, Heinrich Garn, Görsev Yener, Fabrizia D'Antonio, Babiloni, Claudio, Lizio, Roberta, Lopez, Susanna Univ Roma La Sapienza, Dept Physiol & Pharmacol Vittorio Erspamer, Rome, Italy, Stocchi, Fabrizio, Stirpe, Paola, Vacca, Laura IRCCS San Raffaele Pisana, Inst Res & Med Care, Rome, Italy, Del Percio, Claudio, Noce, Giuseppe, Soricelli, Andrea IRCCS, SDN, Dept Integrated Imaging, Naples, Italy, Soricelli, Andrea Univ Naples Parthenope, Dept Motor Sci & Healthiness, Naples, Italy, Ferri, Raffaele IRCCS, Oasi Inst Res Mental Retardat & Brain Aging, Dept Neurol, Troina, Enna, Italy, Nobili, Flavio, Arnaldi, Dario, Fama, Francesco Univ Genoa, Dept Neurosci DiNOGMI, Clin Neurol, Genoa, Italy, Fama, Francesco IRCCS, AOU S Martino IST, Genoa, Italy, Aarsland, Dag Kings Coll Univ, Dept Old Age Psychiat, London, England, Orzi, Francesco, Buttinelli, Carla, Giubilei, Franco Univ Roma La Sapienza, Dept Neurosci Mental Hlth & Sensory Organs, Rome, Italy, Onofrj, Marco, Franciotti, Raffaella, Bonanni, Laura Univ G Annunzio Chieti Pescara, Dept Neurosci Imaging & Clin Sci, Chieti, Italy, Bonanni, Laura Univ G Annunzio Chieti Pescara, CESI, Chieti, Italy, Fuhr, Peter, Gschwandtner, Ute Univ Spita Basel, Abt Neurophysiol, Basel, Switzerland, Ransmayr, Gerhard Johannes Kepler Univ Linz, Gen Hosp City Linz, Dept Neurol & Psychiat, Linz, Austria, Ransmayr, Gerhard Johannes Kepler Univ Linz, Gen Hosp City Linz, Fac Med, Linz, Austria, Garn, Heinrich AIT Austrian Inst Technol GmbH, Vienna, Austria, Fraioli, Lucia, De Pandis, Maria Francesca Hosp San Raffaele Cassino, Cassino, Italy, Pievani, Michela, Frisoni, Giovanni B. IRCCS, Ist Ctr San Giovanni Dio Fatebenefratelli, Lab Alzheimers Neuroimaging & Epidemiol, Brescia, Italy, Frisoni, Giovanni B. Univ Hosp, Lab Neuroimaging Aging, Memory Clin, Geneva, Switzerland, Frisoni, Giovanni B. Univ Hosp, Lab Neuroimaging Aging, LANVIE, Geneva, Switzerland, Frisoni, Giovanni B. Univ Geneva, Geneva, Switzerland, D'Antonio, Fabrizia, De Lena, Carlo Sapienza Univ Rome, Dept Neurol & Psychiat, Rome, Italy, Guntekin, Bahar Istanbul Medipol Univ, Dept Biophys, Istanbul, Turkey, Hanoglu, Lutfu Univ Istanbul Medipol, Dept Neurol, Istanbul, Turkey, Bazar, Erol, Yener, Gorsev Dokuz Eyliil Univ, IBG, Dept Neurol, Izmir, Turkey, Yener, Gorsev Dokuz Eyliil Univ, IBG, Dept Neurosci, Izmir, Turkey, Emek-Savas, Derya Durusu Dokuz Eyliil Univ, Dept Psychol, Izmir, Turkey, Emek-Savas, Derya Durusu Dokuz Eyliil Univ, Dept Neurosci, Izmir, Turkey, Triggiani, Antonio Ivano Univ Foggia, Dept Clin & Expt Med, Foggia, Italy, Taylor, John Paul Newcastle Univ, Inst Neurosci, Newcastle, NSW, Australia, Vacca, Laura Casa Cura Privata Policlin CCPP Milano SpA, Milan, Italy, Guntekin, Bahar -- 0000-0002-0860-0524, Pievani, Michela -- 0000-0002-1794-8987, triggiani, antonio ivano -- 0000-0003-3291-9452, Ferri, Raffaele -- 0000-0001-6937-3065, Stocchi, Fabrizio -- 0000-0002-5763-0033, Babiloni, Claudio -- 0000-0002-5245-9839, Emek-Savas, Derya Durusu -- 0000-0001-7042-697X, Taylor, John-Paul -- 0000-0001-7958-6558, nobili, flavio -- 0000-0001-9811-0897, and Aarsland, Dag -- 0000-0001-6314-216X
Subjects: 0301 basic medicine, Male, Aging, Parkinson's disease, Resting-state EEG rhythms, Dementia with Lewy bodies, Audiology, Electroencephalography, neuroscience, 0302 clinical medicine, Cognition, Resting State EEG Rhythms, Cortical Synchronization, Cognition/physiology, Cerebral Cortex, medicine.diagnostic_test, General Neuroscience, Neurodegenerative diseases, Alzheimer's disease, 16. Peace & justice, Dementia/diagnosis/etiology/physiopathology/psychology, Cortical Synchronization/physiology, Female, Alzheimer’s disease, Lewy Body Disease, medicine.medical_specialty, animal structures, Alzheimer Disease/complications, Rest, Alpha (ethology), behavioral disciplines and activities, 03 medical and health sciences, Lewy Body Disease/complications, Alzheimer Disease, mental disorders, medicine, Dementia, Humans, Dementia with Lewy Bodies, Functional brain connectivity, Neuroscience (all), Neurology (clinical), Developmental Biology, Geriatrics and Gerontology, Resting state EEG rhythms, dementia, dementia with Lewy bodies, functional brain connectivity, neurodegenerative diseases, resting-state EEG rhythms, aging, neurology (clinical), developmental biology, geriatrics and gerontology, Aged, Mini–Mental State Examination, Lewy body, Resting state fMRI, Rest/physiology, medicine.disease, nervous system diseases, 030104 developmental biology, ddc:618.97, Parkinson’s disease, Cerebral Cortex/diagnostic imaging/physiology, 030217 neurology & neurosurgery
Abstract: WOS: 000428233700003 PubMed ID: 29407464 Previous evidence showed abnormal posterior sources of resting-state delta (< 4 Hz) and alpha (8-12 Hz) rhythms in patients with Alzheimer's disease with dementia (ADD), Parkinson's disease with dementia (PDD), and Lewy body dementia (DLB), as cortical neural synchronization markers in quiet wakefulness. Here, we tested the hypothesis of additional abnormalities in functional cortical connectivity computed in those sources, in ADD, considered as a "disconnection cortical syndrome", in comparison with PDD and DLB. Resting-state eyes-closed electroencephalographic (rsEEG) rhythms had been collected in 42 ADD, 42 PDD, 34 DLB, and 40 normal healthy older (Hold) participants. Exact low-resolution brain electromagnetic tomography (eLORETA) freeware estimated the functional lagged linear connectivity (LLC) from rsEEG cortical sources in delta, theta, alpha, beta, and gamma bands. The area under receiver operating characteristic (AUROC) curve indexed the classification accuracy between Nold and diseased individuals (only values > 0.7 were considered). Interhemispheric and intrahemispheric LLCs in widespread delta sources were abnormally higher in the ADD group and, unexpectedly, normal in DLB and PDD groups. Intrahemispheric LLC was reduced in widespread alpha sources dramatically in ADD, markedly in DLB, and moderately in PDD group. Furthermore, the interhemispheric LLC in widespread alpha sources showed lower values in ADD and DLB than PDD groups. At the individual level, AUROC curves of LLC in alpha sources exhibited better classification accuracies for the discrimination of ADD versus Nold individuals (0.84) than for DLB versus Nold participants (0.78) and PDD versus Nold participants (0.75). Functional cortical connectivity markers in delta and alpha sources suggest a more compromised neurophysiological reserve in ADD than DLB, at both group and individual levels. (C) 2017 Elsevier Inc. All rights reserved. H2020 Marie S. Curie ITN-ETN project The present study was developed based on the data of the informal European Consortium PDWAVES and European Consortium of Dementia with Lewy Body. The members and institutional affiliations of the consortia are reported in the cover page of this manuscript. The research activities of the Unit of University of Rome "La Sapienza" were partially supported by the H2020 Marie S. Curie ITN-ETN project with the short title "BBDiag" (http://bddiag-itn-etn.eu). We thank Mrs. Jessica Janson and Mrs. Marina Selivanova for their support to those activities in the framework of the BBDiag project.
Published: 2018
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40. Cerebellar Contribution to Spatial Navigation: New Insights into Potential Mechanisms

Author: Julie M. Lefort, Laure Rondi-Reig, Christelle Rochefort, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cerebellum, Plasticity, Place cell, Hippocampus, Hippocampal formation, Spatial memory, Task (project management), 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, 030304 developmental biology, Cued speech, 0303 health sciences, Navigation, Electrophysiology, medicine.anatomical_structure, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), Psychology, Neuroscience, 030217 neurology & neurosurgery, Spatial Navigation, L7-PKCI
Abstract: SIXTH INTERNATIONAL SYMPOSIUM OF SRC, Rome, ITALY, JUL 03-04, 2014; International audience; The contribution of the cerebellum to the non-motor aspects of spatial navigation is now established, but the mechanisms of its participation remain unclear. The L7-PKCI mouse model, in which inhibited PKC activity suppresses parallel fiber-Purkinje cell long-term depression (LTD), provides the opportunity to study their spatial abilities in the absence of any motor impairment. L7-PKCI mice are deficient in the spatial but not the cued version of the watermaze task. Their performances are preserved when alleys guide their trajectories in the starmaze task, suggesting that cerebellar PKC-dependent mechanisms are required for the production of an optimal trajectory toward a goal. Furthermore, electrophysiological recordings in freely moving L7-PKCI mice revealed that their hippocampal place cell properties are affected when they have to rely on self motion information: in the absence of external information as well as in a conflicting situation between self-motion and external information. This suggests that the cerebellum is involved in the processing of self-motion information and is required for the construction of the spatial representation in the hippocampus.
Published: 2015
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41. FROM VISUAL MOTION PERCEPTION TO SPATIAL COGNITION: Study of behavior and brain activity

Author: Anne-Lise Paradis, Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université, UPMC, Olivier Bertrand, Neurosciences Paris Seine (NPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Paradis, Anne-Lise, CeZaMe - Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS)
Subjects: Behavior, Structure à partir du mouvement, MEG, functional brain imaging, Forme, Visual perception, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, fMRI, Comportement, Shape, Mémoire, 3D structure form motion, Perception visuelle, Navigation, Motion, Memory, Mouvement, Cognition spatiale, Spatial cognition, Imagerie cérébrale fonctionnelle, IRMf
Published: 2017

42. Oscillatory Dynamics and Place Field Maps Reflect Hippocampal Ensemble Processing of Sequence and Place Memory under NMDA Receptor Control

Author: Cyriel M. A. Pennartz, Martin Vinck, Henrique Cabral, Celine Fouquet, Laure Rondi-Reig, Francesco P. Battaglia, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), STW [AET7613], EU [270108], European Commission [ENLIGHTENMENT 284801], Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cognitive and Systems Neuroscience (SILS, FNWI), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Neuroinformatics, Patch-Clamp Techniques, Neuroscience(all), Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Action Potentials, Hippocampus, Nerve Tissue Proteins, Sensory system, Serial Learning, Hippocampal formation, Receptors, N-Methyl-D-Aspartate, Mice, 03 medical and health sciences, 0302 clinical medicine, Biological Clocks, Memory, Animals, Maze Learning, Control (linguistics), 030304 developmental biology, Sequence (medicine), Mice, Knockout, Neurons, Analysis of Variance, 0303 health sciences, Spectrum Analysis, General Neuroscience, Dynamics (mechanics), Brain Waves, Nonlinear Dynamics, nervous system, Space Perception, Forebrain, NMDA receptor, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Carrier Proteins, Psychology, Neuroscience, 030217 neurology & neurosurgery
Abstract: International audience; Place coding in the hippocampus requires flexible combination of sensory inputs (e.g., environmental and self-motion information) with memory of past events. We show that mouse CA1 hippocampal spatial representations may either be anchored to external landmarks (place memory) or reflect memorized sequences of cell assemblies depending on the behavioral strategy spontaneously selected. These computational modalities correspond to different CA1 dynamical states, as expressed by theta and low- and high-frequency gamma oscillations, when switching from place to sequence memory-based processing. These changes are consistent with a shift from entorhinal to CA3 input dominance on CA1. In mice with a deletion of forebrain NMDA receptors, the ability of place cells to maintain a map based on sequence memory is selectively impaired and oscillatory dynamics are correspondingly altered, suggesting that oscillations contribute to selecting behaviorally appropriate computations in the hippocampus and that NMDA receptors are crucial for this function.
Published: 2014
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43. Cerebellar volume in autism: Meta-analysis and analysis of the ABIDE cohort

Author: Richard Delorme, Nicolas Traut, Anne-Lise Paradis, Roberto Toro, Laure Rondi-Reig, Anita Beggiato, Thomas Bourgeron, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Autism brain imaging data exchange, business.industry, Publication bias, medicine.disease, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, Autism spectrum disorder, Endophenotype, Meta-analysis, Cohort, medicine, Autism, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], 10. No inequality, Association (psychology), business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Cerebellar volume abnormalities have been often suggested as a possible endophenotype for autism spectrum disorder (ASD). We aimed at objectifying this possible alteration by performing a systematic meta-analysis of the literature, and an analysis of the Autism Brain Imaging Data Exchange (ABIDE) cohort. Our meta-analysis sought to determine a combined effect size of ASD diagnosis on different measures of the cerebellar anatomy, as well as the effect of possible factors of variability across studies. We then analysed the cerebellar volume of 328 patients and 353 controls from the ABIDE project. The meta-analysis of the literature suggested a weak but significant association between ASD diagnosis and increased cerebellar volume (p=0.049, uncorrected), but the analysis of ABIDE did not show any relationship. The studies in the literature were generally underpowered, however, the number of statistically significant findings was larger than expected. Although we could not provide a conclusive explanation for this excess of significant findings, our analyses would suggest publication bias as a possible reason. Finally, age, sex and IQ were important sources of cerebellar volume variability, however, independent of autism diagnosis.
Published: 2017
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44. Vitamin D and the mechanisms, circumstances and consequences of falls in older adults: A case-control study

Author: Pierre-Yves Paré, Stéphane Walrand, Mickael Dinomais, Jennifer Gautier, Cédric Annweiler, Guillaume T. Duval, Department of Neuroscience and Aging, Division of Geriatric Medicine and Memory Clinic, Research Centre on Autonomy and Longevity, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), LUNAM, Médecine Physique et Réadaptation, PRES Université Nantes Angers Le Mans (UNAM), Research Office, Schulich Medicine and Dentistry, University of Western Ontario (UWO), Unité de Nutrition Humaine (UNH), and Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], vitamine D, Medicine (miscellaneous), Parathyroid hormone, Poison control, Falls in older adults, complication, carence en vitamines, vitamin D deficiency, personne âgée, Hypotension, Orthostatic, 03 medical and health sciences, Orthostatic vital signs, 0302 clinical medicine, Recurrence, Internal medicine, falls, Prevalence, medicine, Vitamin D and neurology, Humans, 030212 general & internal medicine, Vitamin D, older adults, senior citizens, Aged, 80 and over, 2. Zero hunger, Polypharmacy, Inpatients, mechanisms, Nutrition and Dietetics, business.industry, Vitamin D Deficiency, medicine.disease, Case-Control Studies, Physical therapy, concentration sérique, Accidental Falls, Female, France, Geriatrics and Gerontology, business, Body mass index, 030217 neurology & neurosurgery
Abstract: To determine i) whether cases of elderly fallers had lower serum 25-hydroxyvitamin D (25OHD) concentration than controls without history of falls; and ii) whether serum 25OHD concentration was associated with specific mechanisms, circumstances and consequences of falls. Case-control study with a 1:2 ratio. Geriatric ward of the University Hospital of Angers, France, between February 2012 and March 2014. 216 inpatients (72 cases and 144 age- and gender-matched controls). Falls were defined as involuntary events causing the person to the ground or other lower level. The main mechanisms, circumstances and consequences of falls were identified using standardized questionnaires. Vitamin D deficiency was defined as serum 25OHD concentration 25nmol/L. Age, gender, body mass index, polypharmacy, use antihypertensive drugs, use psychoactive drugs, disability, cognitive performance, serum concentrations of parathyroid hormone, creatinine and albumin, and season of evaluation were used as potential confounders. 216 participants (72 cases and 144 controls) were included in the study. There was no between-group difference in the prevalence of vitamin D deficiency (P=0.176). After adjusting for confounding factors, vitamin D deficiency was positively associated with falls (OR=4.03, P=0.014). Finally, the fallers with vitamin D deficiency exhibited more often orthostatic hypotension (68.8% against 33.3%, P=0.039) and a history of recurrent falls (85% against 50%, P=0.002) than those without vitamin D deficiency. This casecontrol study reported that vitamin D deficiency was associated with falls in older inpatients. There was a greater prevalence of orthostatic hypotension and of the reccurrence of falls among fallers with vitamin D deficiency, suggesting that vitamin D may influence the conditions predisposing to falls rather than the fall by itself.
Published: 2017
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45. Anatomic Correlation of the Mini-Mental State Examination: A Voxel-Based Morphometric Study in Older Adults

Author: Frédéric Roche, Robert Bartha, Olivier Beauchet, Mickael Dinomais, Cédric Annweiler, Sébastien Celle, Samir Henni, Guillaume T. Duval, Laboratoire Angevin de Recherche en Ingénierie des Systèmes (LARIS), Université d'Angers (UA), Hôpital Nord - Faculté de MédecineJacques Lisfranc, Service de Physiologie Clinique et de l'Exercice, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Department of Neuroscience and Aging, Division of Geriatric Medicine and Memory Clinic, Research Centre on Autonomy and Longevity, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Department of Sports Medicine and Vascular Investigations, Department of Medical Biophysics, Robarts Research Institute [Canada], University of Western Ontario (UWO)-University of Western Ontario (UWO), Department of Medicine, Division of Geriatric Medicine, Sir Mortimer B. Davis—Jewish General Hospital and Lady Davis Institute for Medical Research, and Robarts Research Institute, Department of Medical Biophysics
Subjects: 0301 basic medicine, Male, Central Nervous System, Pathology, [SDV]Life Sciences [q-bio], lcsh:Medicine, Audiology, Hippocampus, Nervous System, Diagnostic Radiology, 0302 clinical medicine, Limbic system, Cognition, Learning and Memory, Medicine and Health Sciences, Gray Matter, 10. No inequality, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Cognitive Impairment, Brain Mapping, Multidisciplinary, medicine.diagnostic_test, Cognitive Neurology, Radiology and Imaging, Brain, Neurodegenerative Diseases, Middle Aged, Amygdala, Magnetic Resonance Imaging, White Matter, Cognitive test, medicine.anatomical_structure, Neurology, Brain size, Female, Anatomy, Parahippocampal gyrus, Research Article, medicine.medical_specialty, Imaging Techniques, Cognitive Neuroscience, Brain Morphometry, Neuroimaging, Statistical parametric mapping, Research and Analysis Methods, White matter, 03 medical and health sciences, Alzheimer Disease, Memory, Diagnostic Medicine, Mental Health and Psychiatry, mental disorders, medicine, Humans, Cognitive Dysfunction, Aged, Mini–Mental State Examination, business.industry, Morphometry, lcsh:R, Biology and Life Sciences, Voxel-based morphometry, 030104 developmental biology, Cross-Sectional Studies, Cognitive Science, Dementia, lcsh:Q, business, Mental Status Schedule, Voxel-Based Morphometry, 030217 neurology & neurosurgery, Neuroscience
Abstract: The clinical utility of the Mini-Mental State Examination (MMSE) and its shorter version (SMMSE) is still debated. There is a need to better understand the neuroanatomical correlates of these cognitive tests. The objective of this cross-sectional study was to determine whether lower MMSE and SMMSE scores correlated with focal brain volume reduction in older adults. Participants from the GAIT study (n = 207; mean, 70.9±5.9 years; 57% female; mean MMSE 26.2±3.9; mean SMMSE 5.1±1.1) were evaluated using the MMSE and SMMSE and received a 1.5-Tesla MRI scan of the brain. Cortical gray and white matter subvolumes were automatically segmented using Statistical Parametric Mapping. Age, gender, education level, and total intracranial volume were included as potential confounders. We found correlations between the MMSE score and specific cortical regions of the limbic system including the hippocampus, amygdala, cingulate gyrus, and parahippocampal gyrus, independently of the diagnostic category (i.e., mild cognitive impairment or Alzheimer disease or controls). Regarding correlations with the SMMSE score, only one cluster in the left hippocampus was identified, which overlapped with the cluster that was positively correlated with the MMSE score. There were no correlations with the volume of white matter. In conclusion, worse MMSE and SMMSE scores were associated with gray matter atrophy mainly in the limbic system. This finding highlights that atrophy of specific brain regions are related to performance on the MMSE and the SMMSE tests, and provides new insights into the cognitive function probed by these tests.
Published: 2016
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46. An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease

Author: Brian H. Chen, Michael S. Kobor, Devin Absher, Morgan E. Levine, Michael Gurven, Lluis Quintana-Murci, Wei Chen, Maud Fagny, Beate Ritz, Hillard Kaplan, Hooman Allayee, Benjamin C. Trumble, Steve Horvath, Philip S. Tsao, Kerstin L. Edlefsen, Shengxu Li, Tammy M. Rickabaugh, Alexander P. Reiner, Ake T. Lu, Beth D. Jamieson, Themistocles L. Assimes, Dianjianyi Sun, University of California [Los Angeles] (UCLA), University of California (UC), University of California [Santa Barbara] (UC Santa Barbara), The University of New Mexico [Albuquerque], University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Tulane University, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Dana-Farber Cancer Institute [Boston], Harvard T.H. Chan School of Public Health, University of British Columbia (UBC), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, University of Washington [Seattle], HudsonAlpha Institute for Biotechnology [Huntsville, AL], and This study was supported by NIH/NHLBI 60442456 BAA23 (Assimes, Absher, Horvath), National Institutes of Health NIH/NIA 1U34AG051425-01 (Horvath). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. The PEG data were supported by NIEHS RO1ES10544 (Ritz) and NIEHS R21 ES024356 (Horvath, Ritz). Gurven and Trumble were funded by NIH/NIA R01AG024119 and R56AG02411. The Religious Order study and Rush Memory and Aging Project (brain dataset 6) were funded by P30AG10161, R01AG17917, RF1AG15819, and R01AG36042.
Subjects: Male, 0301 basic medicine, Aging, Epigenetic clock, Ethnic group, Coronary Disease, Disease, Cardiovascular, Epigenesis, Genetic, MESH: DNA Methylation, MESH: Risk Factors, Risk Factors, MESH: Aging, MESH: Epigenesis, Genetic, MESH: Hispanic or Latino, MESH: Aged, African Americans, Genetics, Sex Characteristics, Hispanic paradox, DNA methylation, Continental Population Groups, Mortality rate, Incidence (epidemiology), Hispanic or Latino, Biological Sciences, 3. Good health, Black/white mortality cross-over, Coronary heart disease, Heart Disease, Female, Hispanic Americans, MESH: Sex Characteristics, Sex characteristics, Race, Bioinformatics, MESH: Whites, European Continental Ancestry Group, Biology, White People, 03 medical and health sciences, Genetic, Clinical Research, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Information and Computing Sciences, MESH: United States, Humans, Epigenetics, Heart Disease - Coronary Heart Disease, Aged, MESH: Humans, Prevention, Research, Racial Groups, Gender, MESH: Male, United States, Black or African American, MESH: Racial Groups, Good Health and Well Being, 030104 developmental biology, MESH: African Americans, Life expectancy, MESH: Coronary Disease, MESH: Female, Environmental Sciences, Epigenesis, Demography
Abstract: Background Epigenetic biomarkers of aging (the “epigenetic clock”) have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors. Results We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue. Conclusions Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1030-0) contains supplementary material, which is available to authorized users.
Published: 2016
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47. Clinical and biomarker profiling of prodromal Alzheimer's disease in workpackage 5 of the Innovative Medicines Initiative PharmaCog project: a ‘European ADNI study’

Author: Diego Albani, Jean-Philippe Ranjeva, Olivier Blin, Andrea Soricelli, Flavio Nobili, Samantha Galluzzi, Elena Rolandi, Jens Wiltfang, C. Del Percio, David Bartrés-Faz, Jérémie Pariente, Susanna Cordone, Lucia Farotti, Pierre Payoux, Camillo Marra, Cristina Bagnoli, Nicola Girtler, Jorge Jovicich, Paolo Maria Rossini, Claudio Babiloni, Mira Didic, Moira Marizzoni, Magda Tsolaki, Pieter Jelle Visser, Régis Bordet, Giovanni B. Frisoni, Peter Schönknecht, Tilman Hensch, Gianluigi Forloni, Luigi Antelmi, José Luis Molinuevo, Ute Fiedler, Lucilla Parnetti, Jill C. Richardson, Anna E. Leeuwis, Laboratory of Alzheimer's Neuroimaging & Epidemiology, Saint John of God Clinical Research Centre, Brescia, Department of Physiology and Pharmacology, University of Rome 'La Sapienza', Rome, IRCCS-Hospital San Raffaele Pisana of Rome and Cassino, Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Department of Psychiatry and Clinical Psychobiology, Faculty of Medicine, University of Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Clinica Neurologica, Università di Perugia, Ospedale Santa Maria della Misericordia, Perugia, Department of Psychiatry and Psychotherapy, Faculty of Medicine, LVR-Hospital Essen, University of Duisburg-Essen, Essen, Clinical Neurology, Department of Neurosciences, Rehabilitation, Ophthalmology and Maternal-Fetal Medicine, University of Genoa, Genoa, Department of Psychiatry and Psychotherapy, University of Leipzig Medical Center, Leipzig, Center for Mind/Brain Sciences, University of Trento, Corso Bettini, 31, 38068, Rovereto, TN, Italy, Alzheimer Center Amsterdam, VU University Medical Center [Amsterdam], Department of Gerontology, Neurosciences & Orthopedics, Catholic University, Rome, Alzheimer's Disease Unit and Other Cognitive Disorders Unit, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Clinical Neurology, Department of Neurosciences, Rehabilitation, Ophthalmology and Maternal-Fetal Medicine, University of Genoa, Toulouse Neuro Imaging Center (ToNIC), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], SDN Istituto di Ricerca Diagnostica e Nucleare, Napoli, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - AP-HM] (CEMEREM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Third Neurologic Clinic, Medical School, G. Papanikolaou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, GlaxoSmithKline [Stevenage, UK] (GSK), GlaxoSmithKline [Headquarters, London, UK] (GSK), Lille Neurosciences & Cognition - U 1172 (LilNCog (ex-JPARC)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre investigation clinique - Unité de pharmacologie clinique et d'évaluations thérapeutiques (CIC-UPCET), Assistance Publique - Hôpitaux de Marseille (APHM), Laboratory of Neuroimaging of aging, Memory clinic and LANVIE, Geneva University Hospital and Geneva University, Frisoni, Giovanni, Università degli Studi di Perugia = University of Perugia (UNIPG), Università degli studi di Genova = University of Genoa (UniGe), Leipzig University, Università degli Studi di Trento (UNITN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre d'Exploration Métabolique par Résonance Magnétique [Hôpital de la Timone - APHM] (CEMEREM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Lille Neurosciences & Cognition - U 1172 (LilNCog), Neurology, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Male, 0301 basic medicine, Oncology, Pathology, Medizin, Neuropsychological Tests, Electroencephalography, Corpus callosum, Spinal Puncture, prodromal AD, ddc:616.89, 0302 clinical medicine, magnetic resonance imaging, ComputingMilieux_MISCELLANEOUS, biomarkers, electroencephalography, mild cognitive impairment, internal medicine, medicine.diagnostic_test, Neuropsychology, Brain, 3. Good health, Settore MED/26 - NEUROLOGIA, Biomarker (medicine), Female, Alzheimer's disease, medicine.medical_specialty, Genotype, tau Proteins, Prodromal AD, 03 medical and health sciences, Magnetic resonance imaging, Apolipoproteins E, Neuroimaging, Alzheimer Disease, Internal medicine, mental disorders, medicine, Humans, Aged, Amyloid beta-Peptides, Surrogate endpoint, business.industry, Mild cognitive impairment, medicine.disease, Peptide Fragments, 030104 developmental biology, Posterior cingulate, business, Biomarkers, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. Objective To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). Methods A total of 147 aMCI patients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid β peptide 1–42 (Aβ42), tau and p‐tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusion MRI) and EEG (with resting‐state and auditory oddball event‐related potential (AO‐ERP) paradigm) biomarkers were evaluated. Results Prodromal AD was found in 55 aMCI patients defined by low Aβ42 in the cerebrospinal fluid (Aβ positive). Compared to the aMCI group with high Aβ42 levels (Aβ negative), Aβ positive patients showed poorer visual (P = 0.001), spatial recognition (P < 0.0005) and working (P = 0.024) memory, as well as a higher frequency of APOE4 (P < 0.0005), lower hippocampal volume (P = 0.04), reduced thickness of the parietal cortex (P < 0.009) and structural connectivity of the corpus callosum (P < 0.05), higher amplitude of delta rhythms at rest (P = 0.03) and lower amplitude of posterior cingulate sources of AO‐ERP (P = 0.03). Conclusion These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.
Published: 2016
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48. Interaction Between Hippocampus and Cerebellum Crus I in Sequence-Based but not Place-Based Navigation

Author: Anne-Lise Paradis, Christian F. Doeller, Karim Benchenane, Kinga Igloi, Neil Burgess, Alain Berthoz, Laure Rondi-Reig, Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), EU, Agence Nationale de la Recherche, Fondation pour la Recherche Medicale (France), Medical Research Council, Wellcome Trust (UK), European Research Council [ERC-StG RECONTEXT 261177], Netherlands Organisation for Scientific Research (NWO-Vidi) [452-12-009], Collège de France (CdF (institution)), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Cerebellum, Cognitive Neuroscience, Posterior parietal cortex, Hippocampus, Hippocampal formation, Sequence learning, Spatial memory, Functional Laterality, Virtual reality, User-Computer Interface, Young Adult, Functional connectivity, Cellular and Molecular Neuroscience, Neural Pathways, Image Processing, Computer-Assisted, medicine, Humans, Maze Learning, Prefrontal cortex, sequence learning, medicine.diagnostic_test, fMRI, functional connectivity, Parietal lobe, Articles, spatial memory, Magnetic Resonance Imaging, Oxygen, ddc:128.37, medicine.anatomical_structure, nervous system, virtual reality, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychology, Functional magnetic resonance imaging, 120 Memory and Space, Neuroscience, Spatial Navigation
Abstract: International audience; To examine the cerebellar contribution to human spatial navigation we used functional magnetic resonance imaging and virtual reality. Our findings show that the sensory-motor requirements of navigation induce activity in cerebellar lobules and cortical areas known to be involved in the motor loop and vestibular processing. By contrast, cognitive aspects of navigation mainly induce activity in a different cerebellar lobule (VIIA Crus I). Our results demonstrate a functional link between cerebellum and hippocampus in humans and identify specific functional circuits linking lobule VIIA Crus I of the cerebellum to medial parietal, medial prefrontal, and hippocampal cortices in nonmotor aspects of navigation. They further suggest that Crus I belongs to 2 nonmotor loops, involved in different strategies: placebased navigation is supported by coherent activity between left cerebellar lobule VIIA Crus I and medial parietal cortex along with right hippocampus activity, while sequence-based navigation is supported by coherent activity between right lobule VIIA Crus I, medial prefrontal cortex, and left hippocampus. These results highlight the prominent role of the human cerebellum in both motor and cognitive aspects of navigation, and specify the cortico-cerebellar circuits by which it acts depending on the requirements of the task.
Published: 2015
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49. The Periaqueductal Gray Orchestrates Sensory and Motor Circuits at Multiple Levels of the Neuraxis

Author: Koutsikou, Stella, Watson, Thomas C., Crook, Jonathan J., Leith, J. Lianne, Lawrenson, Charlotte L., Apps, Richard, Lumb, Bridget M., Cervelet, navigation et mémoire = Memory, Navigation and Aging (NPS-13), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biotechnology and Biological Sciences Research Council UK, Medical Research Council, Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Nociception, Spinal cord, cerebellum, proprioception, spinal cord, periaqueductal grey, Fear, Proprioception, nervous system, Cerebellum, Periaqueductal grey, fear, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], nociception
Abstract: International audience; The periaqueductal gray (PAG) coordinates behaviors essential to survival, including striking changes in movement and posture (e.g., escape behaviors in response to noxious stimuli vs freezing in response to fear-evoking stimuli). However, the neural circuits underlying the expression of these behaviors remain poorly understood. We demonstrate in vivo in rats that activation of the ventrolateral PAG (vlPAG) affects motor systems at multiple levels of the neuraxis through the following: (1) differential control of spinal neurons that forward sensory information to the cerebellum via spino-olivo-cerebellar pathways (nociceptive signals are reduced while proprioceptive signals are enhanced); (2) alterations in cerebellar nuclear output as revealed by changes in expression of Fos-like immunoreactivity; and (3) regulation of spinal reflex circuits, as shown by an increase in alpha-motoneuron excitability. The capacity to coordinate sensory and motor functions is demonstrated in awake, behaving rats, in which natural activation of the vlPAG in fear-conditioned animals reduced transmission in spino-olivo-cerebellar pathways during periods of freezing that were associated with increased muscle tone and thus motor outflow. The increase in spinal motor reflex excitability and reduction in transmission of ascending sensory signals via spino-olivo-cerebellar pathways occurred simultaneously. We suggest that the interactions revealed in the present study between the vlPAG and sensorimotor circuits could form the neural substrate for survival behaviors associated with vlPAG activation.
Published: 2015
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50. Multiethnic Genome-Wide Association Study of Cerebral White Matter Hyperintensities on MRI

Author: Susan H. Blanton, Ashley Beecham, Pamela J. Schreiner, Ralph L. Sacco, Stéphanie Debette, Ben A. Oostra, Marian Beekman, M. Arfan Ikram, Edith Hofer, Anna Maria Töglhofer, Alexander Teumer, Ganesh Chauhan, Clinton B. Wright, Meike W. Vernooij, Wiro J. Niessen, Aad van der Lugt, Cornelia M. van Duijn, Christophe Tzourio, Matthias Nauck, Bernard Mazoyer, Bettina von Sarnowski, Alexa S. Beiser, Susan R. Heckbert, André G. Uitterlinden, Alex P. Zijdenbos, David S. Knopman, Paul Freudenberger, Myriam Fornage, Maaike Schuur, Stephen Turner, Matthew Traylor, Qiong Yang, Fabrice Crivello, P. Eline Slagboom, Ian J. Deary, Sharon L.R. Kardia, Cora E. Lewis, Stella Trompet, Mike A. Nalls, Jennifer A. Smith, Katrin Hegenscheid, Hans J. Grabe, Lenore J. Launer, Reinhold Schmidt, Albert V. Smith, M. Kamran Ikram, Kumar B. Rajan, Mariza de Andrade, Sudha Seshadri, Lorna M. Lopez, Philip L. De Jager, Albert Hofman, Joshua C. Bis, Gerardo Heiss, Neelum T. Aggarwal, Elizabeth J. Atkinson, Carla A. Ibrahim-Verbaas, David C. Liewald, Anton J. M. de Craen, Jing Wang, David J. Stott, Sandra Barral, Adam M. Brickman, Mohamad Habes, Eric Boerwinkle, Katharina Wittfeld, Jerome I. Rotter, Saima Hilal, R. Nick Bryan, Charles C. DeCarli, Mark A. van Buchem, Mitchell S.V. Elkind, Rebecca F. Gottesman, Christiane Wolf, Vincent Chouraki, Jeroen van der Grond, Jiemin Liao, Joris Deelen, Stephen Sidney, Kenneth Rice, Vilmundur Guðnason, Hieab H.H. Adams, Benjamin F.J. Verhaaren, Tien Yin Wong, Oliver Martinez, Denis A. Evans, Helena Schmidt, W. T. Longstreth, J. Wouter Jukema, Richard Mayeux, Joanna M. Wardlaw, Thomas H. Mosley, Michelle Luciano, Sigurdur Sigurdsson, Carole Dufouil, Christopher Chen, Philippe Amouyel, Wei Zhao, John C. van Swieten, Bruce M. Psaty, Hae-Won Uh, B. Gwen Windham, Erasmus University Medical Center [Rotterdam] (Erasmus MC), INSERM U897, University of Bordeaux, France, University of Washington [Seattle], University of Michigan [Ann Arbor], University of Michigan System, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), John P. Hussman Institute for Human Genomics, University of Miami Leonard M. Miller School of Medicine (UMMSM), Rush University Medical Center [Chicago], University of Edinburgh, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands, Depts of Radiology, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Department of Materials Science and Metallurgy [Cambridge University] (DMSM), University of Cambridge [UK] (CAM), JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), Greifswald University Hospital, Division of Biomedical Statistics and Informatics, Mayo Clinic, Division of Biomedical Statistics and Informatics, Mayo Clinic, Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Genetics, The University of Texas Health Science Center at Houston (UTHealth), Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University [New York], Perelman School of Medicine, University of Pennsylvania, INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, Systèmes et Applications des Technologies de l'Information et de l'Energie (SATIE), École normale supérieure - Cachan (ENS Cachan)-Université Paris-Sud - Paris 11 (UP11)-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-École normale supérieure - Rennes (ENS Rennes)-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre National de la Recherche Scientifique (CNRS), Université Lille Nord de France (COMUE), Department of neurology, Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Dept of Psychology, Molecular Epidemiology, Harvard Medical School [Boston] (HMS), Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Columbia Mailman School of Public Health, Laboratoire pharmaceutique Lilly France [Neuilly-sur-Seine], Institute of Molecular Biology & Biochemistry, Johns Hopkins University School of Medicine [Baltimore], Faculty of Medicine, University of Iceland [Reykjavik], The Icelandic Heart Association, Kopavogur, Iceland, Institutes for Community Medicine, Department of Epidemiology, University of Washington, Group Health Research Institute, Group Health Cooperative, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), National University of Singapore (NUS), Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes - UFR Langage, lettres et arts du spectacle, information et communication - Dpt Sciences de l'information et de la communication (UGA UFR LLASIC SIC), Mayo Clinic [Rochester], Academic Unit of Inflammation and Tumour Targeting, Dept. of Oncology, University of Sheffield Medical School, East China University of Science and Technology, Medstar Research Institute, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Bioinformatics, GlaxoSmithKline, National Institutes of Health [Bethesda] (NIH), Institute of Clinical Chemistry and Laboratory Medicine, Universität Greifswald - University of Greifswald, Delft University of Technology (TU Delft), Cardiovascular Health Research Unit, University of Washington, Department of Medicine, University of Washington, Department of Health Services, University of Washington, Department of Biostatistics, University of Washington, Cedars-Sinai Medical Center, Dept of Neurology, Univ Medicine of Greifswald, Germany, Department of Physics [Stockholm], Stockholm University, University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Kaiser Permanente, Broad Institute [Cambridge], Harvard University-Massachusetts Institute of Technology (MIT), Department of Medical Biochemistry and Microbiology, Uppsala University, Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, King‘s College London, Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria, Research Centre for Stroke & Dementia, St George 's Univ of London, Interuniversity Cardiology Institute Netherlands, SAC, Bush Estate, School Medicine, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Singapore Eye Research Institute, Singapore National Eye Centre, University of Oslo (UiO), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, Dundee Technopole, CXR Biosciences Ltd, Department of Atmospheric, Oceanic, and Space Sciences [Ann Arbor] (AOSS), University of Michigan System-University of Michigan System, University of Miami [Coral Gables], Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biospective [Montréal], Dept of Epidemiology & Public Health Sciences, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Mississippi Medical Center (UMMC), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California (UC)-University of California (UC), Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Austrian Institute of Technology [Vienna] (AIT), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Human Genetics Center, University of Pennsylvania [Philadelphia], Université Paris-Seine-Université Paris-Seine-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Memory Aging & Cognition Centre, National Univ of Singapore, Singapore, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), Dept of Ophthalmology, National Univ of Singapore & National Univ Health System, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), University of California-University of California, Radboud university [Nijmegen], Epidemiology, Radiology & Nuclear Medicine, General Practice, Neurology, Medical Informatics, Clinical Genetics, Internal Medicine, Human genetics, NCA - neurodegeneration, Hal, GIN, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), and HESAM Université (HESAM)-HESAM Université (HESAM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, Male, single nucleotide, Pathology, Genome-wide association study, leukoencephalopathies, polymorphisms, single nucleotide, Chromosomes, Human, Genetics (clinical), Aged, 80 and over, education.field_of_study, Continental Population Groups, cerebrovascular disorders, Middle Aged, White Matter, 3. Good health, Stroke, genetics [Stroke], Female, cerebral small vessel diseases, Alzheimer's disease, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, hypertension, Population, genetics [Chromosomes, Human], Article, Meta-Analysis as Topic, Internal medicine, Genetics, medicine, Dementia, Humans, ddc:610, 1000 Genomes Project, education, Genetic association, Aged, Intracerebral hemorrhage, genome-wide association study, Models, Genetic, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Racial Groups, medicine.disease, ethnology [Stroke], Hyperintensity, Genetic Loci, pathology [Stroke], business, polymorphisms, Genome-Wide Association Study
Abstract: Background— The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. Methods and Results— We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 ( P =2.7×10 −19 ) and identified novel loci on chr10q24 ( P =1.6×10 −9 ) and chr2p21 ( P =4.4×10 −8 ). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 ( P =2.0×10 −8 ) and chr2p16 ( P =1.5×10 −8 ). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). Conclusions— We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
Published: 2015
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