2024
In vivo neuropil density from anatomical MRI and machine learning
Akif A, Staib L, Herman P, Rothman D, Yu Y, Hyder F. In vivo neuropil density from anatomical MRI and machine learning. Cerebral Cortex 2024, 34: bhae200. PMID: 38771239, PMCID: PMC11107380, DOI: 10.1093/cercor/bhae200.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingSynaptic densityNeuropil densityCellular densityArtificial neural networkNeural networkPositron emission tomographyAnatomical magnetic resonance imagingHealthy subjectsSynaptic activityMRI scansMachine learning algorithmsBrain's energy budgetEmission tomographyIn vivo MRI scansResonance imagingTissue cellularityLearning algorithmsDiffusion magnetic resonance imagingMachine learningMicroscopic interpretationInterpretation of functional neuroimaging dataIndividual predictionsSubjects
2023
A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke
Lyden P, Diniz M, Bosetti F, Lamb J, Nagarkatti K, Rogatko A, Kim S, Cabeen R, Koenig J, Akhter K, Arbab A, Avery B, Beatty H, Bibic A, Cao S, Simoes Braga Boisserand L, Chamorro A, Chauhan A, Diaz-Perez S, Dhandapani K, Dhanesha N, Goh A, Herman A, Hyder F, Imai T, Johnson C, Khan M, Kamat P, Karuppagounder S, Kumskova M, Mihailovic J, Mandeville J, Morais A, Patel R, Sanganahalli B, Smith C, Shi Y, Sutariya B, Thedens D, Qin T, Velazquez S, Aronowski J, Ayata C, Chauhan A, Leira E, Hess D, Koehler R, McCullough L, Sansing L. A multi-laboratory preclinical trial in rodents to assess treatment candidates for acute ischemic stroke. Science Translational Medicine 2023, 15: eadg8656. PMID: 37729432, DOI: 10.1126/scitranslmed.adg8656.Peer-Reviewed Original ResearchConceptsPreclinical assessmentFocal cerebral ischemic insultAcute ischemic strokeCerebral ischemic insultLarge clinical trialsDiet-induced obesityNew clinical interventionsIntravascular thrombectomyIschemic strokeStroke treatmentHypertensive ratsIschemic insultBlinded assessmentClinical trialsYoung miceTreatment candidatesExclusion criteriaAnimal modelsYoung ratsFutile interventionsPreclinical trialsClinical interventionsFutility boundariesMiceDisease areasDecreased but diverse activity of cortical and thalamic neurons in consciousness-impairing rodent absence seizures
McCafferty C, Gruenbaum B, Tung R, Li J, Zheng X, Salvino P, Vincent P, Kratochvil Z, Ryu J, Khalaf A, Swift K, Akbari R, Islam W, Antwi P, Johnson E, Vitkovskiy P, Sampognaro J, Freedman I, Kundishora A, Depaulis A, David F, Crunelli V, Sanganahalli B, Herman P, Hyder F, Blumenfeld H. Decreased but diverse activity of cortical and thalamic neurons in consciousness-impairing rodent absence seizures. Nature Communications 2023, 14: 117. PMID: 36627270, PMCID: PMC9832004, DOI: 10.1038/s41467-022-35535-4.Peer-Reviewed Original ResearchConceptsThalamic neuronsAbsence seizuresSeizure onsetNeuronal firingConsciousness-impairing seizuresFemale rat modelLow-frequency electroencephalographic activityFunctional magnetic resonanceBehavioral arrestRat modelRhythmic firingTransient initial peakFiring increasesSeizuresNeuronal mechanismsElectroencephalographic activityNeuronsBrain state changesBrief episodesFiring decreasesInitial peakFiringMagnetic resonanceDistinct patternsOnset
2015
Decreased Subcortical Cholinergic Arousal in Focal Seizures
Motelow JE, Li W, Zhan Q, Mishra AM, Sachdev RN, Liu G, Gummadavelli A, Zayyad Z, Lee HS, Chu V, Andrews JP, Englot DJ, Herman P, Sanganahalli BG, Hyder F, Blumenfeld H. Decreased Subcortical Cholinergic Arousal in Focal Seizures. Neuron 2015, 85: 561-572. PMID: 25654258, PMCID: PMC4319118, DOI: 10.1016/j.neuron.2014.12.058.Peer-Reviewed Original ResearchConceptsTemporal lobe seizuresFocal temporal lobe seizuresReduced cholinergic neurotransmissionBilateral temporal lobesLoss of consciousnessPedunculopontine tegmental nucleusQuality of lifeBrainstem arousal systemsFunctional magnetic resonanceSeizure spreadCholinergic neuronsImpaired consciousnessFocal seizuresBasal forebrainAnterior hypothalamusCholinergic neurotransmissionTegmental nucleusLateral septumCortical functionRodent modelsTemporal lobeSubcortical regionsSeizuresImpair consciousnessSubcortical arousal
2013
Glutamatergic Function in the Resting Awake Human Brain is Supported by Uniformly High Oxidative Energy
Hyder F, Fulbright RK, Shulman RG, Rothman DL. Glutamatergic Function in the Resting Awake Human Brain is Supported by Uniformly High Oxidative Energy. Cerebrovascular And Brain Metabolism Reviews 2013, 33: 339-347. PMID: 23299240, PMCID: PMC3587823, DOI: 10.1038/jcbfm.2012.207.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingMagnetic resonance spectroscopy studyAwake resting stateFuture clinical investigationsMagnetic resonance imagingHigh resting activityAwake human brainGray matter regionsGlutamatergic functionGlutamatergic signalingMetabolic measuresClinical investigationAwake stateResting activityVisual cortexGlucose utilizationResonance imaging
2012
Neural Progenitor Cells Regulate Capillary Blood Flow in the Postnatal Subventricular Zone
Lacar B, Herman P, Platel JC, Kubera C, Hyder F, Bordey A. Neural Progenitor Cells Regulate Capillary Blood Flow in the Postnatal Subventricular Zone. Journal Of Neuroscience 2012, 32: 16435-16448. PMID: 23152626, PMCID: PMC3520061, DOI: 10.1523/jneurosci.1457-12.2012.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsAnimals, NewbornAstrocytesCalcium SignalingCapillariesCerebral VentriclesCerebrovascular CirculationElectric StimulationElectroporationFemaleFluorescent Antibody TechniqueImage Processing, Computer-AssistedLaser-Doppler FlowmetryMaleMiceMuscle TonusMuscle, Smooth, VascularNeural Stem CellsPericytesVasoconstrictionVasodilationConceptsNeural progenitor cellsSubventricular zoneB cellsBlood flowSVZ cellsPurinergic receptorsPostnatal subventricular zoneVascular responsesCapillary constrictionTransgenic miceElectrical stimulationCalcium increaseBlood flow increasesLaser Doppler flowmetryCapillary blood flowAstrocyte-like cellsReceptor agonist UTPNeonatal electroporationNeurometabolic couplingIntraventricular injectionVasodilating factorsAcute slicesYoung miceDoppler flowmetryHemodynamic response
2001
Homocarnosine and seizure control in juvenile myoclonic epilepsy and complex partial seizures
Petroff O, Hyder F, Rothman D, Mattson R. Homocarnosine and seizure control in juvenile myoclonic epilepsy and complex partial seizures. Neurology 2001, 56: 709-715. PMID: 11274303, DOI: 10.1212/wnl.56.6.709.Peer-Reviewed Original ResearchConceptsComplex partial seizuresJuvenile myoclonic epilepsyGamma-aminobutyric acidHigher homocarnosine levelsGood seizure controlSeizure controlPoor seizure controlHomocarnosine levelsPartial seizuresMyoclonic epilepsyBrain gamma-aminobutyric acidLower GABA levelsType of epilepsyLower gamma-aminobutyric acidGABA levelsOccipital cortexPatientsVisual cortexEpilepsyValproateLamotrigineSeizuresCortexHomocarnosineMR spectrometer
2000
Effects of Gabapentin on Brain GABA, Homocarnosine, and Pyrrolidinone in Epilepsy Patients
Petroff O, Hyder F, Rothman D, Mattson R. Effects of Gabapentin on Brain GABA, Homocarnosine, and Pyrrolidinone in Epilepsy Patients. Epilepsia 2000, 41: 675-680. PMID: 10840398, DOI: 10.1111/j.1528-1157.2000.tb00227.x.Peer-Reviewed Original ResearchConceptsBrain gamma-aminobutyric acidGamma-aminobutyric acidFirst oral doseFirst doseOral doseAntiepileptic drugsEffect of gabapentinStandard daily doseSingle high doseGBP therapyDaily therapyNeuropathic painAnticonvulsant effectsFurther seizuresDaily doseEpilepsy patientsOccipital cortexHigh doseGabapentinPatientsPartial protectionDoseHomocarnosineTherapyVivo measurements
1999
Effects of Vigabatrin on the GABAergic System as Determined by [123I]Iomazenil SPECT and GABA MRS
Verhoeff N, Petroff O, Hyder F, Zoghbi S, Fujita M, Rajeevan N, Rothman D, Seibyl J, Mattson R, Innis R. Effects of Vigabatrin on the GABAergic System as Determined by [123I]Iomazenil SPECT and GABA MRS. Epilepsia 1999, 40: 1433-1438. PMID: 10528940, DOI: 10.1111/j.1528-1157.1999.tb02016.x.Peer-Reviewed Original ResearchConceptsEffects of vigabatrinGABA levelsTissue GABA levelsMR imagingCentral gamma-aminobutyric acidGABA magnetic resonance spectroscopyDistribution volumeHealthy age-matched controlsOccipital GABA levelsAge-matched controlsGamma-aminobutyric acidVolume of interestSingle photon emissionMagnetic resonance spectroscopyTotal plasma activityT1-weighted MR imagingPartial seizuresGABAergic systemOccipital cortexConstant infusion methodPlasma activityVigabatrinOccipital activityEffective doseWilcoxon testAcute Effects of Vigabatrin on Brain GABA and Homocarnosine in Patients with Complex Partial Seizures
Petroff O, Hyder F, Collins T, Mattson R, Rothman D. Acute Effects of Vigabatrin on Brain GABA and Homocarnosine in Patients with Complex Partial Seizures. Epilepsia 1999, 40: 958-964. PMID: 10403220, DOI: 10.1111/j.1528-1157.1999.tb00803.x.Peer-Reviewed Original ResearchConceptsBrain gamma-aminobutyric acidGamma-aminobutyric acidDose of vigabatrinComplex partial seizuresPartial seizuresRefractory complex partial seizuresFirst oral doseVGB therapyFirst doseFurther seizuresAdjunct therapyDay dosingOral doseAcute effectsOral administrationOccipital cortexMedian increasePatientsVigabatrinChronic effectsNormal levelsPartial protectionSeizuresDoseHomocarnosineLocalized 1H NMR measurements of 2‐pyrrolidinone in human brain in vivo
Hyder F, Petroff O, Mattson R, Rothman D. Localized 1H NMR measurements of 2‐pyrrolidinone in human brain in vivo. Magnetic Resonance In Medicine 1999, 41: 889-896. PMID: 10332870, DOI: 10.1002/(sici)1522-2594(199905)41:5<889::aid-mrm6>3.0.co;2-r.Peer-Reviewed Original ResearchGABA Changes with Vigabatrin in the Developing Human Brain
Novotny E, Hyder F, Shevell M, Rothman D. GABA Changes with Vigabatrin in the Developing Human Brain. Epilepsia 1999, 40: 462-466. PMID: 10219272, DOI: 10.1111/j.1528-1157.1999.tb00741.x.Peer-Reviewed Original ResearchConceptsBrain GABA levelsGABA levelsBrain GABAVGB treatmentRole of GABASeizure controlGABA changesSeizure susceptibilityPediatric epilepsyEpileptic focusOccipital lobeNervous systemEpileptic regionsVigabatrinEpilepsyGABAGABA metabolismTreatmentAge 1Noninvasive measurementHuman brainSubjectsDrugsFivefold increaseChildrenTopiramate increases brain GABA, homocarnosine, and pyrrolidinone in patients with epilepsy
Petroff O, Hyder F, Mattson R, Rothman D. Topiramate increases brain GABA, homocarnosine, and pyrrolidinone in patients with epilepsy. Neurology 1999, 52: 473-478. PMID: 10025774, DOI: 10.1212/wnl.52.3.473.Peer-Reviewed Original ResearchConceptsBrain gamma-aminobutyric acidGamma-aminobutyric acidComplex partial seizuresAntiepileptic actionPartial seizuresRefractory complex partial seizuresNew antiepileptic medicationsEffects of topiramateNew antiepileptic drugsDrug-free volunteersMultiple putative mechanismsPotent antiepileptic actionAntiepileptic medicationsAdditional patientsAntiepileptic drugsControl subjectsOccipital cortexTopiramatePatientsPutative mechanismsHomocarnosineEpilepsySeizuresVivo measurementsSurface coil
1998
Vigabatrin increases human brain homocarnosine and improves seizure control
Petroff O, Mattson R, Behar K, Hyder F, Rothman D. Vigabatrin increases human brain homocarnosine and improves seizure control. Annals Of Neurology 1998, 44: 948-952. PMID: 9851440, DOI: 10.1002/ana.410440614.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidSeizure controlGABA concentrationAddition of vigabatrinLow-dose vigabatrinImproved seizure controlMean GABA concentrationAntiepileptic drug vigabatrinInhibitory neuromodulatorDaily doseGABAergic neuronsGABA levelsLarge dosesHomocarnosine concentrationsVigabatrinDrug vigabatrinHomocarnosinePatientsHuman brainMagnetic resonance spectroscopyControlNeuromodulatorsNeuronsDoseDoses
1997
“Willed action”: A functional MRI study of the human prefrontal cortex during a sensorimotor task
Hyder F, Phelps E, Wiggins C, Labar K, Blamire A, Shulman R. “Willed action”: A functional MRI study of the human prefrontal cortex during a sensorimotor task. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 6989-6994. PMID: 9192679, PMCID: PMC21272, DOI: 10.1073/pnas.94.13.6989.Peer-Reviewed Original ResearchConceptsDorsolateral prefrontal cortexPrefrontal cortexVerbal fluency taskFunctional MRISensorimotor tasksPositron emission tomography studyLeft dorsolateral prefrontal cortexEmission tomography studiesFunctional MRI studyFluency taskWilled actionHuman prefrontal cortexHealthy subjectsPET resultsMRI studiesBilateral activationCoronal slicesPET studiesTomography studyCortexFMRI dataFMRI studyActivation fociBrain activityHuman brain activityFMRI of the prefrontal cortex during overt verbal fluency
Phelps E, Hyder F, Blamire A, Shulman R. FMRI of the prefrontal cortex during overt verbal fluency. Neuroreport 1997, 8: 561-565. PMID: 9080448, DOI: 10.1097/00001756-199701200-00036.Peer-Reviewed Original Research
1991
Applications of nuclear magnetic cross‐relaxation spectroscopy to tissues
Grad J, Mendelson D, Hyder F, Bryant R. Applications of nuclear magnetic cross‐relaxation spectroscopy to tissues. Magnetic Resonance In Medicine 1991, 17: 452-459. PMID: 2062216, DOI: 10.1002/mrm.1910170216.Peer-Reviewed Original ResearchConceptsCross-relaxation spectroscopyFundamental relaxation timeMagnetic imagingMagnetic imagesMagnetic relaxationDecay constantsAqueous heterogeneous systemsRelaxation timeWater spinsSpinNMR spectraRelaxationFrequency responseSpectroscopySpectraExperimental approachSignal intensitySystem mixtureIntensityConstantsImaging