2024
Pathogenic 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 polarity
2019
The 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 abilities
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 effectsNeurovascular unit remodelling in the subacute stage of stroke recovery
Lake EMR, Bazzigaluppi P, Mester J, Thomason LAM, Janik R, Brown M, McLaurin J, Carlen PL, Corbett D, Stanisz GJ, Stefanovic B. Neurovascular unit remodelling in the subacute stage of stroke recovery. NeuroImage 2016, 146: 869-882. PMID: 27664828, DOI: 10.1016/j.neuroimage.2016.09.016.Peer-Reviewed Original ResearchConceptsPeri-lesional cortexVascular reactivityNeuronal lossSubacute stageEndothelin-1LFP activityLong-term functional outcomeLocal field potential responsesPeripheral somatosensory stimulationActivation of microgliaET-1 injectionFocal ischemic strokeFocal cerebral ischaemiaPeri-infarct zoneSensori-motor cortexSpontaneous neuronal activityAdult Sprague-DawleyField potential responsesExtended temporal windowDynamic functional changesIschemic strokeAstrocytic activationCerebral ischaemiaNeurovascular unitIschemic insultAltered intracortical myelin staining in the dorsolateral prefrontal cortex in severe mental illness
Lake EMR, Steffler EA, Rowley CD, Sehmbi M, Minuzzi L, Frey BN, Bock NA. Altered intracortical myelin staining in the dorsolateral prefrontal cortex in severe mental illness. European Archives Of Psychiatry And Clinical Neuroscience 2016, 267: 369-376. PMID: 27629158, DOI: 10.1007/s00406-016-0730-5.Peer-Reviewed Original ResearchConceptsMajor depressive disorderSevere mental illnessMiddle frontal gyrusBipolar disorderDorsolateral prefrontal cortexMental illnessWhite matterIntracortical myelinDiagnosis of MDDPrefrontal cortexDeep white matter tractsDeep white matterTissue attenuationSuperficial white matterAmount of myelinWhite matter tractsCerebral cortexDepressive disorderFast BlueMyelinated fibersPsychiatric illnessMyelin stainingIllnessCortexCortical depth
2015
The Effects of Delayed Reduction of Tonic Inhibition on Ischemic Lesion and Sensorimotor Function
Lake E, Chaudhuri J, Thomason L, Janik R, Ganguly M, Brown M, McLaurin J, Corbett D, Stanisz GJ, Stefanovic B. The Effects of Delayed Reduction of Tonic Inhibition on Ischemic Lesion and Sensorimotor Function. Cerebrovascular And Brain Metabolism Reviews 2015, 35: 1601-1609. PMID: 25966952, PMCID: PMC4640317, DOI: 10.1038/jcbfm.2015.86.Peer-Reviewed Original ResearchConceptsIschemic lesionsFocal ischemiaEndothelin-1Rat modelMontoya staircase testWeeks of treatmentTotal stroke volumeCortical microinjectionsIschemic strokeChronic stageSensorimotor deficitsStroke recoveryTonic inhibitionSensorimotor functionStroke volumeGABAA antagonismGABA antagonismStaircase testPerilesional regionsDelayed reductionInverse agonistNecrotic coreBrain structuresBeneficial effectsStroke
2014
A non-surgical model of cervical spinal cord injury induced with focused ultrasound and microbubbles
Oakden W, Kwiecien JM, O’Reilly M, Lake EM, Akens MK, Aubert I, Whyne C, Finkelstein J, Hynynen K, Stanisz GJ. A non-surgical model of cervical spinal cord injury induced with focused ultrasound and microbubbles. Journal Of Neuroscience Methods 2014, 235: 92-100. PMID: 24970578, DOI: 10.1016/j.jneumeth.2014.06.018.Peer-Reviewed Original ResearchConceptsSpinal cord injuryCervical spinal cord injuryMagnetic resonance imagingNon-surgical modelCord injurySpinal cordModel of SCIHuman spinal cord injuryT2-weighted magnetic resonance imagingFocused ultrasoundSpinal cord contusionCervical spinal cord damageSurgical incision siteSpinal cord damagePost-operative imagingCervical spinal cordDorsal spinal cordPost-operative careExtent of injuryDegree of injuryCord contusionAcute phaseCord damageVertebral systemSignal abnormalities