2024
Aging-dependent loss of functional connectivity in a mouse model of Alzheimer’s disease and reversal by mGluR5 modulator
Mandino F, Shen X, Desrosiers-Grégoire G, O’Connor D, Mukherjee B, Owens A, Qu A, Onofrey J, Papademetris X, Chakravarty M, Strittmatter S, Lake E. Aging-dependent loss of functional connectivity in a mouse model of Alzheimer’s disease and reversal by mGluR5 modulator. Molecular Psychiatry 2024, 1-16. PMID: 39424929, DOI: 10.1038/s41380-024-02779-z.Peer-Reviewed Original ResearchFunctional connectivity deficitsConnectivity deficitsFunctional connectivityBrain connectivityAllosteric modulators of mGluR5Alzheimer's diseaseDefault-mode networkModulation of mGluR5Loss of functional connectivityResting-state fMRIApplication of fMRIWild-type controlsAged AD miceMouse model of Alzheimer's diseaseAD-related changesAD miceModel of Alzheimer's diseaseAssociated with synaptic damageMGluR5 modulationMonths of ageFMRI measurementsAmyloid accumulationDecreased connectivityBrain networksSilent allosteric modulatorsRepetitive Mild Closed-Head Injury Induced Synapse Loss and Increased Local BOLD-fMRI Signal Homogeneity
Markicevic M, Mandino F, Toyonaga T, Cai Z, Fesharaki-Zadeh A, Shen X, Strittmatter S, Lake E. Repetitive Mild Closed-Head Injury Induced Synapse Loss and Increased Local BOLD-fMRI Signal Homogeneity. Journal Of Neurotrauma 2024 PMID: 39096127, DOI: 10.1089/neu.2024.0095.Peer-Reviewed Original ResearchChronic variable stressRegional homogeneityFunctional brain abnormalitiesSynapse densityMild closed-head injuryClosed-head injuryTraumatic brain injuryTreat traumatic brain injuryNeurobiological alterationsMild head injuryVariable stressBrain abnormalitiesPositron emission tomographyMultimodal studiesSynaptic densityMagnetic resonance imagingBrain imagingBrain injuryInduce synapse lossFMRIInjured miceMouse modelEmission tomographyResonance imagingCompensatory mechanismsVentricular-subventricular zone stem cell niche adaptations in a mouse model of post-infectious hydrocephalus
Herman J, Rittenhouse N, Mandino F, Majid M, Wang Y, Mezger A, Kump A, Kadian S, Lake E, Verardi P, Conover J. Ventricular-subventricular zone stem cell niche adaptations in a mouse model of post-infectious hydrocephalus. Frontiers In Neuroscience 2024, 18: 1429829. PMID: 39145299, PMCID: PMC11322059, DOI: 10.3389/fnins.2024.1429829.Peer-Reviewed Original ResearchPost-infectious hydrocephalusVentricular-subventricular zoneInfluenza virusMouse modelMouse-adapted influenza virusIntact ependymaStem cellsPostnatal day 4Stem cell numbersStem cell nicheCell-to-cell transmissionOlfactory bulbMultiorgan hemorrhageLateral ventricleIntracerebroventricular injectionVentriculomegalyEmbryonic dayVentricular systemDay 4Cell nicheNo significant reductionHydrocephalusSignificant reductionVentricleCell numberPathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics
DeSpenza T, Singh A, Allington G, Zhao S, Lee J, Kiziltug E, Prina M, Desmet N, Dang H, Fields J, Nelson-Williams C, Zhang J, Mekbib K, Dennis E, Mehta N, Duy P, Shimelis H, Walsh L, Marlier A, Deniz E, Lake E, Constable R, Hoffman E, Lifton R, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper S, Jin S, Kahle K, Luikart B. Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314702121. PMID: 38916997, PMCID: PMC11228466, DOI: 10.1073/pnas.2314702121.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventriculomegalyPathogenic variantsPrefrontal pyramidal neuronsGenetic subsets of patientsDevelopment of ventriculomegalyRadial gliaSubsets of patientsHigh-frequency firingNeuronal connectivityHeterozygous germline variantsAutism spectrum disorderVentricular-subventricular zoneMicrotubule dynamicsImpaired spermatogenesisCSF shuntingExcitatory driveMicrotubule-severing ATPasePyramidal neuronsDisrupt neuronal connectivityGermline variantsVentriculomegalyCSF homeostasisDisrupt microtubule dynamicsPlanar cell polarity184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry
DeSpenza T, Kizlitug E, Allington G, Barson D, O'Connor D, Robert S, Mekbib K, Singh A, Phan D, Nanda P, Mandino F, Constable T, Lake E, Carter B, Gunel M, Lifton R, Luikart B, Kahle K. 184 PTEN Mutations Portend Cerebral Ventriculomegaly With Autism-Like Deficits in Cortical Circuitry. Neurosurgery 2024, 70: 46-46. DOI: 10.1227/neu.0000000000002809_184.Peer-Reviewed Original ResearchWhole-exome sequencingFetal ventriculomegalyCongenital hydrocephalusExome sequencingChoroid plexus hyperplasiaMutated genesCa2+ imagingMutant mouse modelsPTEN mutantsHuman fetal brainPten mutant miceSporadic CHCerebral ventriculomegalyCSF diversionObstructive hydrocephalusCH patientsCSF secretionPharmacological mTORC1 inhibitionNeurodevelopmental assessmentRadiographic biomarkersFetal brainPTEN mutationsAqueductal stenosisPTEN deletionVentriculomegalyWhat N Is N-ough for MRI-Based Animal Neuroimaging?
Grandjean J, Lake E, Pagani M, Mandino F. What N Is N-ough for MRI-Based Animal Neuroimaging? ENeuro 2024, 11: eneuro.0531-23.2024. PMID: 38499355, PMCID: PMC10950324, DOI: 10.1523/eneuro.0531-23.2024.Peer-Reviewed Original ResearchMultimodal measures of spontaneous brain activity reveal both common and divergent patterns of cortical functional organization
Vafaii H, Mandino F, Desrosiers-Grégoire G, O’Connor D, Markicevic M, Shen X, Ge X, Herman P, Hyder F, Papademetris X, Chakravarty M, Crair M, Constable R, Lake E, Pessoa L. Multimodal measures of spontaneous brain activity reveal both common and divergent patterns of cortical functional organization. Nature Communications 2024, 15: 229. PMID: 38172111, PMCID: PMC10764905, DOI: 10.1038/s41467-023-44363-z.Peer-Reviewed Original Research
2023
SMC5 Plays Independent Roles in Congenital Heart Disease and Neurodevelopmental Disability
O'Brien M, Pryzhkova M, Lake E, Mandino F, Shen X, Karnik R, Atkins A, Xu M, Ji W, Konstantino M, Brueckner M, Ment L, Khokha M, Jordan P. SMC5 Plays Independent Roles in Congenital Heart Disease and Neurodevelopmental Disability. International Journal Of Molecular Sciences 2023, 25: 430. PMID: 38203602, PMCID: PMC10779392, DOI: 10.3390/ijms25010430.Peer-Reviewed Original ResearchWhere do we stand on fMRI in awake mice?
Mandino F, Vujic S, Grandjean J, Lake E. Where do we stand on fMRI in awake mice? Cerebral Cortex 2023, 34: bhad478. PMID: 38100331, PMCID: PMC10793583, DOI: 10.1093/cercor/bhad478.Peer-Reviewed Original ResearchAutism spectrum disorder-specific changes in white matter connectome edge density based on functionally defined nodes
Weber C, Lake E, Haider S, Mozayan A, Bobba P, Mukherjee P, Scheinost D, Constable R, Ment L, Payabvash S. Autism spectrum disorder-specific changes in white matter connectome edge density based on functionally defined nodes. Frontiers In Neuroscience 2023, 17: 1285396. PMID: 38075286, PMCID: PMC10702224, DOI: 10.3389/fnins.2023.1285396.Peer-Reviewed Original ResearchWhite matterPositive symptom correlationAutism spectrum disorderSymptom severity scoresBetween-group differencesAbnormal connectivity patternsCortical nodesVoxel-wise analysisDiffusion tensor imagingSeverity scoreWM fiber tractsSymptom correlationClinical dataConnectome disruptionConnectome changesEarly changesCortical regionsInfantsED reductionWM disruptionDisorder-specific changesTensor imagingFunctional imagingFiber tractsProbabilistic tractographyLongitudinal simultaneous fMRI and mesoscale calcium imaging in a mouse model of Alzheimer’s disease
Mandino F, Shen X, Desrosiers-Gregoire G, O'Connor D, Mukherjee B, DeLuca K, Hamodi A, Owens A, Ha Y, Qu A, Onofrey J, Papademetris X, Chakravarty M, Crair M, Strittmatter S, Lake E. Longitudinal simultaneous fMRI and mesoscale calcium imaging in a mouse model of Alzheimer’s disease. Proceedings Of The International Society For Magnetic Resonance In Medicine ... Scientific Meeting And Exhibition. 2023 DOI: 10.58530/2023/3914.Peer-Reviewed Original ResearchMouse model of Alzheimer's diseaseModel of Alzheimer's diseaseMesoscale calcium imagingAlzheimer's diseaseBehavioral deficitsExcitatory neural activityMultimodal neuroimagingBOLD signalSimultaneous fMRINeuroimaging changesNeural activityBOLD fMRIPreliminary evidenceCalcium imagingClinically accessible biomarkersMesoscopic calcium imagingSpontaneous activityFMRINeuroimagingBOLDDeficitsComplex relationship
2022
A generalizable connectome-based marker of in-scan sustained attention in neurodiverse youth
Horien C, Greene A, Shen X, Fortes D, Brennan-Wydra E, Banarjee C, Foster R, Donthireddy V, Butler M, Powell K, Vernetti A, Mandino F, O'Connor D, Lake E, McPartland J, Volkmar F, Chun M, Chawarska K, Rosenberg M, Scheinost D, Constable R. A generalizable connectome-based marker of in-scan sustained attention in neurodiverse youth. Cerebral Cortex 2022, 33: 6320-6334. PMID: 36573438, PMCID: PMC10183743, DOI: 10.1093/cercor/bhac506.Peer-Reviewed Original ResearchConceptsAttention taskAttentional stateConnectome-based predictive modelingNeurodiverse conditionsSustained attention taskAttention network modelSample of youthNeurotypical participantsSustained attentionBrain correlatesNeurobiological correlatesAttention networkIndividual participantsSeparate samplesYouthParticipantsHead motionTaskCorrelatesAttentionAutismConfoundsNetwork modelGeneralizesHealthcare settingsAge-associated White Matter Microstructure and Connectome Abnormalities in Autism Spectrum Disorder
Weber C, Haider S, Mukherjee P, Lake E, Scheinost D, Bamford N, Ment L, Constable T, Payabvash S. Age-associated White Matter Microstructure and Connectome Abnormalities in Autism Spectrum Disorder. Proceedings Of The International Society For Magnetic Resonance In Medicine ... Scientific Meeting And Exhibition. 2022 DOI: 10.58530/2022/2100.Peer-Reviewed Original Research
2019
Trim71 Links an Ancient MicroRNA Pathway to Neural Stem Cell Development and Human Congenital Hydrocephalus
Phan D, Foster D, Jux B, Lake E, Constable T, Kolanus W, Slack F, Kahle K. Trim71 Links an Ancient MicroRNA Pathway to Neural Stem Cell Development and Human Congenital Hydrocephalus. Neurosurgery 2019, 66: 310-649. DOI: 10.1093/neuros/nyz310_649.Peer-Reviewed Original ResearchThe Functional Brain Organization of an Individual Allows Prediction of Measures of Social Abilities Transdiagnostically in Autism and Attention-Deficit/Hyperactivity Disorder
Lake EMR, Finn ES, Noble SM, Vanderwal T, Shen X, Rosenberg MD, Spann MN, Chun MM, Scheinost D, Constable RT. The Functional Brain Organization of an Individual Allows Prediction of Measures of Social Abilities Transdiagnostically in Autism and Attention-Deficit/Hyperactivity Disorder. Biological Psychiatry 2019, 86: 315-326. PMID: 31010580, PMCID: PMC7311928, DOI: 10.1016/j.biopsych.2019.02.019.Peer-Reviewed Original ResearchConceptsAttention-deficit/hyperactivity disorderAutism spectrum disorderSpectrum disorderFunctional connectivity profilesHyperactivity disorderBrain organizationAutism Brain Imaging Data ExchangeConnectome-based predictive modelingAutism Diagnostic Observation ScheduleAutism spectrum disorder traitsAutism spectrum disorder severitySocial Responsiveness Scale scoresADHD Rating Scale scoresFunctional magnetic resonance imagingBrain-behavior associationsSocial Responsiveness ScaleResting-state functional magnetic resonanceFunctional brain organizationFunctional magnetic resonanceADHD traitsNeurofunctional basisADHD symptomsSplit-half analysisResponsiveness ScaleSocial abilitiesTen simple rules for predictive modeling of individual differences in neuroimaging
Scheinost D, Noble S, Horien C, Greene AS, Lake EM, Salehi M, Gao S, Shen X, O’Connor D, Barron DS, Yip SW, Rosenberg MD, Constable RT. Ten simple rules for predictive modeling of individual differences in neuroimaging. NeuroImage 2019, 193: 35-45. PMID: 30831310, PMCID: PMC6521850, DOI: 10.1016/j.neuroimage.2019.02.057.Peer-Reviewed Original Research
2018
Imaging the Effects of &bgr;-Hydroxybutyrate on Peri-Infarct Neurovascular Function and Metabolism
Bazzigaluppi P, Lake EM, Beckett TL, Koletar MM, Weisspapir I, Heinen S, Mester J, Lai A, Janik R, Dorr A, McLaurin J, Stanisz GJ, Carlen PL, Stefanovic B. Imaging the Effects of &bgr;-Hydroxybutyrate on Peri-Infarct Neurovascular Function and Metabolism. Stroke 2018, 49: 2173-2181. PMID: 30354983, DOI: 10.1161/strokeaha.118.020586.Peer-Reviewed Original ResearchMeSH Keywords3-Hydroxybutyric AcidAcetoacetatesAnimalsAstrocytesBlood GlucoseBrainBrain IschemiaCell DeathCerebrovascular CirculationDisease Models, AnimalElectrophysiological PhenomenaEndothelin-1HemodynamicsMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMicroinjectionsNeuronsRatsReactive Oxygen SpeciesSensorimotor CortexConceptsBody β-hydroxybutyrateFunctional recoveryMagnetic resonance imagingIschemic insultNeuronal deathResonance imagingFocal cortical strokeVehicle-administered animalsNeurological deficit scoresKetone body β-hydroxybutyrateNeuronal glucose uptakeContinuous arterial spinReduced oxidative stressPurpose Recent evidenceReactive oxygen species productionCortical microinjectionsCortical strokePostischemic hyperglycemiaDeficit scoresNeurovascular functionAcute phaseCerebrovascular reactivitySensorimotor cortexCerebral hemodynamicsEndothelin-1
2017
Reduced Cerebrovascular Reactivity and Increased Resting Cerebral Perfusion in Rats Exposed to a Cafeteria Diet
Gomez-Smith M, Janik R, Adams C, Lake EM, Thomason LAM, Jeffers MS, Stefanovic B, Corbett D. Reduced Cerebrovascular Reactivity and Increased Resting Cerebral Perfusion in Rats Exposed to a Cafeteria Diet. Neuroscience 2017, 371: 166-177. PMID: 29229555, DOI: 10.1016/j.neuroscience.2017.11.054.Peer-Reviewed Original ResearchConceptsRat endothelial cell antigen-1Cerebrovascular reactivityCafeteria dietMagnetic resonance imagingCerebral perfusionStandard chowAnimals fed standard chowEndothelial cell antigen-1Arterial spin labeling magnetic resonance imagingContinuous arterial spin labeling (CASL) magnetic resonance imagingEndothelin-1 injectionReduced Cerebrovascular ReactivityUltra-processed dietFed standard chowSprague-Dawley ratsShort-term consumptionCell antigen-1CAF ratsCerebrovascular functionIschemic lesionsCerebral microvasculatureDiet ratsSensorimotor cortexBrain perfusionDawley rats
2016
Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition
Lake EMR, Mester J, Thomason LA, Adams C, Bazzigaluppi P, Koletar M, Janik R, Carlen P, McLaurin J, Stanisz GJ, Stefanovic B. Modulation of the peri‐infarct neurogliovascular function by delayed COX‐1 inhibition. Journal Of Magnetic Resonance Imaging 2016, 46: 505-517. PMID: 28703413, DOI: 10.1002/jmri.25541.Peer-Reviewed Original ResearchConceptsNeuronal survivalMicroglia/macrophage recruitmentExerts multiple beneficial effectsChronic ischemic injuryAdult male ratsCOX-1 inhibitionMultiple beneficial effectsMost patientsAstrocytic activationEndothelial densityNeuronal lossChronic stageFocal ischemiaHemodynamic changesIschemic injuryAdult disabilityMacrophage recruitmentMale ratsPerfusion responseMore effective interventionsNeurogliovascular unitCOX-1Novel treatmentsPerfusionBeneficial effectsFunctional magnetic resonance imaging in chronic ischaemic stroke
Lake EM, Bazzigaluppi P, Stefanovic B. Functional magnetic resonance imaging in chronic ischaemic stroke. Philosophical Transactions Of The Royal Society B Biological Sciences 2016, 371: 20150353. PMID: 27574307, PMCID: PMC5003855, DOI: 10.1098/rstb.2015.0353.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingIschemic strokeInjury progressionLevel-dependent functional magnetic resonance imagingBlood oxygenation level-dependent functional magnetic resonance imagingChronic ischemic strokeBOLD functional magnetic resonance imagingBOLD signal contrastMagnetic resonance imagingFunctional magnetic resonanceBOLD fMRI measurementsVascular reactivityStroke progressionAdult disabilityChronic stageVascular functionPreclinical modelsStroke researchNeuronal activityNew treatmentsResonance imagingVivo markerClinical researchPreclinical researchBrain function