2023
Fluorescent liposomal nanocarriers for targeted drug delivery in ischemic stroke therapy
Arul M, Alahmadi I, Turro D, Ruikar A, Abdulmalik S, Williams J, Sanganahalli B, Liang B, Verma R, Kumbar S. Fluorescent liposomal nanocarriers for targeted drug delivery in ischemic stroke therapy. Biomaterials Science 2023, 11: 7856-7866. PMID: 37902365, PMCID: PMC10697427, DOI: 10.1039/d3bm00951c.Peer-Reviewed Original ResearchConceptsSurgical clot removalPEGylated liposomal formulationPreclinical mouse modelsShorter treatment durationPurinergic receptor P2X4Reduced infarct volumeAcute CNS injuryCNS infiltrationLong-term disabilitySystemic deliveryTreatment optionsLiposomal formulationIschemic stroke therapyVulnerable brain regionsAdministered 4Clot removalInfarct volumeLow dosesTreatment durationMouse modelNeuroprotective therapiesCNS injuryLiposomal nanocarriersStroke therapyIschemic strokeA consensus protocol for functional connectivity analysis in the rat brain
Grandjean J, Desrosiers-Gregoire G, Anckaerts C, Angeles-Valdez D, Ayad F, Barrière D, Blockx I, Bortel A, Broadwater M, Cardoso B, Célestine M, Chavez-Negrete J, Choi S, Christiaen E, Clavijo P, Colon-Perez L, Cramer S, Daniele T, Dempsey E, Diao Y, Doelemeyer A, Dopfel D, Dvořáková L, Falfán-Melgoza C, Fernandes F, Fowler C, Fuentes-Ibañez A, Garin C, Gelderman E, Golden C, Guo C, Henckens M, Hennessy L, Herman P, Hofwijks N, Horien C, Ionescu T, Jones J, Kaesser J, Kim E, Lambers H, Lazari A, Lee S, Lillywhite A, Liu Y, Liu Y, López -Castro A, López-Gil X, Ma Z, MacNicol E, Madularu D, Mandino F, Marciano S, McAuslan M, McCunn P, McIntosh A, Meng X, Meyer-Baese L, Missault S, Moro F, Naessens D, Nava-Gomez L, Nonaka H, Ortiz J, Paasonen J, Peeters L, Pereira M, Perez P, Pompilus M, Prior M, Rakhmatullin R, Reimann H, Reinwald J, Del Rio R, Rivera-Olvera A, Ruiz-Pérez D, Russo G, Rutten T, Ryoke R, Sack M, Salvan P, Sanganahalli B, Schroeter A, Seewoo B, Selingue E, Seuwen A, Shi B, Sirmpilatze N, Smith J, Smith C, Sobczak F, Stenroos P, Straathof M, Strobelt S, Sumiyoshi A, Takahashi K, Torres-García M, Tudela R, van den Berg M, van der Marel K, van Hout A, Vertullo R, Vidal B, Vrooman R, Wang V, Wank I, Watson D, Yin T, Zhang Y, Zurbruegg S, Achard S, Alcauter S, Auer D, Barbier E, Baudewig J, Beckmann C, Beckmann N, Becq G, Blezer E, Bolbos R, Boretius S, Bouvard S, Budinger E, Buxbaum J, Cash D, Chapman V, Chuang K, Ciobanu L, Coolen B, Dalley J, Dhenain M, Dijkhuizen R, Esteban O, Faber C, Febo M, Feindel K, Forloni G, Fouquet J, Garza-Villarreal E, Gass N, Glennon J, Gozzi A, Gröhn O, Harkin A, Heerschap A, Helluy X, Herfert K, Heuser A, Homberg J, Houwing D, Hyder F, Ielacqua G, Jelescu I, Johansen-Berg H, Kaneko G, Kawashima R, Keilholz S, Keliris G, Kelly C, Kerskens C, Khokhar J, Kind P, Langlois J, Lerch J, López-Hidalgo M, Manahan-Vaughan D, Marchand F, Mars R, Marsella G, Micotti E, Muñoz-Moreno E, Near J, Niendorf T, Otte W, Pais-Roldán P, Pan W, Prado-Alcalá R, Quirarte G, Rodger J, Rosenow T, Sampaio-Baptista C, Sartorius A, Sawiak S, Scheenen T, Shemesh N, Shih Y, Shmuel A, Soria G, Stoop R, Thompson G, Till S, Todd N, Van Der Linden A, van der Toorn A, van Tilborg G, Vanhove C, Veltien A, Verhoye M, Wachsmuth L, Weber-Fahr W, Wenk P, Yu X, Zerbi V, Zhang N, Zhang B, Zimmer L, Devenyi G, Chakravarty M, Hess A. A consensus protocol for functional connectivity analysis in the rat brain. Nature Neuroscience 2023, 26: 673-681. PMID: 36973511, PMCID: PMC10493189, DOI: 10.1038/s41593-023-01286-8.Peer-Reviewed Original Research
2022
Thalamic activations in rat brain by fMRI during tactile (forepaw, whisker) and non-tactile (visual, olfactory) sensory stimulations
Sanganahalli BG, Thompson GJ, Parent M, Verhagen JV, Blumenfeld H, Herman P, Hyder F. Thalamic activations in rat brain by fMRI during tactile (forepaw, whisker) and non-tactile (visual, olfactory) sensory stimulations. PLOS ONE 2022, 17: e0267916. PMID: 35522646, PMCID: PMC9075615, DOI: 10.1371/journal.pone.0267916.Peer-Reviewed Original ResearchConceptsDorsal lateral geniculate nucleusVentral posterior medialVentral posterior lateralThalamic activationFunctional MRIPosterior medial thalamic nucleusMedial thalamic nucleiSensory stimuliLateral geniculate nucleusPost-mortem humanOlfactory stimuliHigh-field functional MRIField functional MRIWhisker stimuliDeep brain regionsRat thalamusThalamic nucleiGeniculate nucleusMediodorsal nucleusRat brainInferior colliculusThalamusDifferent sensory stimuliCortical activationCortical activityThe Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results
Lyden PD, Bosetti F, Diniz MA, Rogatko A, Koenig JI, Lamb J, Nagarkatti KA, Cabeen RP, Hess DC, Kamat PK, Khan MB, Wood K, Dhandapani K, Arbab AS, Leira EC, Chauhan AK, Dhanesha N, Patel RB, Kumskova M, Thedens D, Morais A, Imai T, Qin T, Ayata C, Boisserand LSB, Herman AL, Beatty HE, Velazquez SE, Diaz-Perez S, Sanganahalli BG, Mihailovic JM, Hyder F, Sansing LH, Koehler RC, Lannon S, Shi Y, Karuppagounder SS, Bibic A, Akhter K, Aronowski J, McCullough LD, Chauhan A, Goh A, Siddiqui S, Sheth K, Matouk C, Cruz C, Zhou J, Dawson V, Dawson T, Liang J, van Zijl P, Zeiler S, Taylor Kimberly W, Erdogan T, Yu L, Mandeville J, Whittier J. The Stroke Preclinical Assessment Network: Rationale, Design, Feasibility, and Stage 1 Results. Stroke 2022, 53: 1802-1812. PMID: 35354299, PMCID: PMC9038686, DOI: 10.1161/strokeaha.121.038047.Peer-Reviewed Original ResearchConceptsPreclinical assessmentStroke treatmentCandidate treatmentMiddle cerebral artery occlusion (MCAO) surgeryClinical stroke trialsSuccessful stroke treatmentInclusion/exclusion criteriaStroke clinical trialsClinical trial designYoung male animalsComorbid diseasesOcclusion surgeryCerebral ischemiaNeurological disabilityComorbid conditionsStroke trialsProtocol adherenceBlinded assessmentSuch therapyClinical trialsClinical studiesExclusion criteriaTrial designAged animalsOutcome assessment
2021
Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity
Farina MG, Sandhu MRS, Parent M, Sanganahalli BG, Derbin M, Dhaher R, Wang H, Zaveri HP, Zhou Y, Danbolt NC, Hyder F, Eid T. Small loci of astroglial glutamine synthetase deficiency in the postnatal brain cause epileptic seizures and impaired functional connectivity. Epilepsia 2021, 62: 2858-2870. PMID: 34536233, PMCID: PMC9006438, DOI: 10.1111/epi.17072.Peer-Reviewed Original ResearchConceptsPostnatal brainFunctional connectivityContinuous video-electroencephalographic recordingSpontaneous recurrent seizuresPathogenesis of epilepsyGlutamine synthetase deficiencyVideo-electroencephalographic recordingsSpecific animal modelsEx vivo studySeizure thresholdAdult patientsRecurrent seizuresFocal epilepsyAdeno-associated virusHippocampal formationAnimal modelsFocal mannerEpileptic seizuresGS deficiencySmall lociSynthetase deficiencyEpilepsyGradual returnVivo studiesBrain
2020
Kaempferol Treatment after Traumatic Brain Injury during Early Development Mitigates Brain Parenchymal Microstructure and Neural Functional Connectivity Deterioration at Adolescence
Parent M, Chitturi J, Santhakumar V, Hyder F, Sanganahalli BG, Kannurpatti SS. Kaempferol Treatment after Traumatic Brain Injury during Early Development Mitigates Brain Parenchymal Microstructure and Neural Functional Connectivity Deterioration at Adolescence. Journal Of Neurotrauma 2020, 37: 966-974. PMID: 31830867, PMCID: PMC7175625, DOI: 10.1089/neu.2019.6486.Peer-Reviewed Original ResearchConceptsTraumatic brain injuryKaempferol treatmentDiffusion tensor imagingFractional anisotropyBrain injuryParenchymal microstructureCallosal fractional anisotropyInterhemispheric structural connectivityH post-TBINeural connectivitySelect brain regionsFunctional magnetic resonance imagingMagnetic resonance imagingTBI prognosisCerebrovascular reactivityFunctional outcomeImaging outcomesNeurovascular couplingPost-TBITBI outcomesTBI pathophysiologyMetabolic benefitsResting-state functional connectivity networksRsFC changesWhole brain
2016
Hypofrontality and Posterior Hyperactivity in Early Schizophrenia: Imaging and Behavior in a Preclinical Model
Kaneko G, Sanganahalli BG, Groman SM, Wang H, Coman D, Rao J, Herman P, Jiang L, Rich K, de Graaf RA, Taylor JR, Hyder F. Hypofrontality and Posterior Hyperactivity in Early Schizophrenia: Imaging and Behavior in a Preclinical Model. Biological Psychiatry 2016, 81: 503-513. PMID: 27450031, PMCID: PMC5130616, DOI: 10.1016/j.biopsych.2016.05.019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalBiomarkersBrainDecision MakingDiffusion Tensor ImagingDisease Models, AnimalFemaleMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMaleMethylazoxymethanol AcetateMultimodal ImagingPrefrontal CortexRatsRats, Sprague-DawleyReversal LearningRewardSchizophreniaSchizophrenic PsychologyConceptsMAM ratsEarly schizophreniaReversal-learning taskEarly behavioral markersResting-state functional magnetic resonanceFunctional magnetic resonanceMethylazoxymethanol acetate (MAM) rat modelFunctional brain biomarkersPerceptual problemsBehavioral markersOrbitofrontal cortexLate adolescenceFunctional connectivityRat modelEarly diagnosisThree-choiceBehavioral studiesBehavioral symptomsPosterior corpus callosumSubstance abuseProdromal patientsSubthreshold symptomsVisual cortexBrain biomarkersSaline-treated controlsChapter 5 New horizons in neurometabolic and neurovascular coupling from calibrated fMRI
Shu CY, Sanganahalli BG, Coman D, Herman P, Hyder F. Chapter 5 New horizons in neurometabolic and neurovascular coupling from calibrated fMRI. Progress In Brain Research 2016, 225: 99-122. PMID: 27130413, DOI: 10.1016/bs.pbr.2016.02.003.Peer-Reviewed Original ResearchConceptsNeurovascular couplingFunctional MRINeuronal activityBlood oxygenation level-dependent (BOLD) signalFunctional brain activationLevel-dependent signalNeurometabolic couplingEffective therapyBlood flowNeuroimaging toolsHealth conditionsPowerful neuroimaging toolBrain activationBOLD signalNeural activityBOLD contrastMetabolic demandsOxygen consumptionDependent signalsTherapyMicrovesselsMRIActivityBiomarkers
2015
Brain region and activity-dependent properties of M for calibrated fMRI
Shu CY, Herman P, Coman D, Sanganahalli BG, Wang H, Juchem C, Rothman DL, de Graaf RA, Hyder F. Brain region and activity-dependent properties of M for calibrated fMRI. NeuroImage 2015, 125: 848-856. PMID: 26529646, PMCID: PMC4691415, DOI: 10.1016/j.neuroimage.2015.10.083.Peer-Reviewed Original ResearchRole of mitochondrial calcium uptake homeostasis in resting state fMRI brain networks
Kannurpatti SS, Sanganahalli BG, Herman P, Hyder F. Role of mitochondrial calcium uptake homeostasis in resting state fMRI brain networks. NMR In Biomedicine 2015, 28: 1579-1588. PMID: 26439799, PMCID: PMC4621005, DOI: 10.1002/nbm.3421.Peer-Reviewed Original ResearchConceptsSimilar dose-dependent decreaseDose-dependent decreaseCaudate putamenBrain regionsBlood oxygen level-dependent fluctuationsBrain energy metabolismLevel-dependent fluctuationsBrain functional organizationSomatosensory cortexAnesthetized ratsDifferent functional networksFunctional organizationDrug treatmentVascular densityHippocampal regionThalamic regionsDifferent physiological impactsBOLD fluctuationsRSFC networksIntrinsic activityState fMRINeural signalingBrain networksPutamenFMRI brain networksDistribution of temperature changes and neurovascular coupling in rat brain following 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) exposure
Coman D, Sanganahalli BG, Jiang L, Hyder F, Behar KL. Distribution of temperature changes and neurovascular coupling in rat brain following 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) exposure. NMR In Biomedicine 2015, 28: 1257-1266. PMID: 26286889, PMCID: PMC4573923, DOI: 10.1002/nbm.3375.Peer-Reviewed Original ResearchConceptsNeurovascular couplingBlood flowNeuronal activityNeural activityWhole-body hyperthermiaAbused psychostimulantMethylenedioxymethamphetamine (MDMA) exposureNeurovascular responseCortex temperatureMDMA effectsRat cortexRat brainBrain temperatureSubcortical regionsBrain regionsCortexSubcortexMDMA actionSkeletal muscleMonoaminergic stimulationBrainMDMACBFBody temperatureThermogenesisRhythmic 3–4Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures
Youngblood MW, Chen WC, Mishra AM, Enamandram S, Sanganahalli BG, Motelow JE, Bai HX, Frohlich F, Gribizis A, Lighten A, Hyder F, Blumenfeld H. Rhythmic 3–4Hz discharge is insufficient to produce cortical BOLD fMRI decreases in generalized seizures. NeuroImage 2015, 109: 368-377. PMID: 25562830, PMCID: PMC4340775, DOI: 10.1016/j.neuroimage.2014.12.066.Peer-Reviewed Original ResearchConceptsHz spike-wave dischargesSpike-wave dischargesFMRI decreasesSpike-wave seizuresAnimal modelsHuman patientsMagnetic resonance imaging studyTonic-clonic seizuresBlood oxygen level-dependent (BOLD) signalResonance imaging studyFunctional magnetic resonance imaging studyHuman functional magnetic resonance imaging (fMRI) studiesGeneralized seizuresFerret modelCortical decreasesAbsence seizuresCortical developmentAnesthetic regimeSeizuresTransient episodesHuman seizuresImaging studiesPatientsBOLD fMRISimultaneous electroencephalography
2014
DYNAmic Multi‐coIl TEchnique (DYNAMITE) shimming of the rat brain at 11.7 T
Juchem C, Herman P, Sanganahalli BG, Brown PB, McIntyre S, Nixon TW, Green D, Hyder F, Graaf R. DYNAmic Multi‐coIl TEchnique (DYNAMITE) shimming of the rat brain at 11.7 T. NMR In Biomedicine 2014, 27: 897-906. PMID: 24839167, PMCID: PMC4120278, DOI: 10.1002/nbm.3133.Peer-Reviewed Original Research
2013
Mapping phosphorylation rate of fluoro-deoxy-glucose in rat brain by 19F chemical shift imaging
Coman D, Sanganahalli BG, Cheng D, McCarthy T, Rothman DL, Hyder F. Mapping phosphorylation rate of fluoro-deoxy-glucose in rat brain by 19F chemical shift imaging. Magnetic Resonance Imaging 2013, 32: 305-313. PMID: 24581725, PMCID: PMC3965601, DOI: 10.1016/j.mri.2013.10.015.Peer-Reviewed Original ResearchMeSH KeywordsAlgorithmsAnimalsBrainFluorodeoxyglucose F18Glucose-6-PhosphateMagnetic Resonance ImagingMagnetic Resonance SpectroscopyMetabolic Clearance RateMolecular ImagingPhosphorylationPhosphotransferasesRadionuclide ImagingRadiopharmaceuticalsRatsRats, Inbred LewReproducibility of ResultsSensitivity and SpecificityTissue DistributionConceptsRat brainChemical shift imagingHalothane-anesthetized ratsMagnetic resonance spectroscopy studyTotal glucose metabolismMinimal side effectsMagnetic resonance imaging (MRI) measurementsFunctional magnetic resonance imaging (fMRI) measurementsFDG phosphorylationFMRI BOLD responsesCerebral physiologyForepaw stimulationShift imagingGlucose metabolismSide effectsBrain tissueFDGExtracted tissuesTumor pathophysiologyBrainMRS measurementsTissue componentsVivo detectionVivoD-glucoseIncreased resting functional connectivity in spike‐wave epilepsy in WAG/Rij rats
Mishra AM, Bai X, Motelow JE, DeSalvo MN, Danielson N, Sanganahalli BG, Hyder F, Blumenfeld H. Increased resting functional connectivity in spike‐wave epilepsy in WAG/Rij rats. Epilepsia 2013, 54: 1214-1222. PMID: 23815571, PMCID: PMC3703864, DOI: 10.1111/epi.12227.Peer-Reviewed Original ResearchConceptsSpike-wave dischargesWAG/RijFunctional connectivityNonepileptic controlsAbsence epilepsyEpileptic WAG/RijBrain networksWAG/Rij ratsChronic seizure activitySpike-wave epilepsyHuman absence seizuresChildhood absence epilepsyWistar Albino GlaxoActivity-dependent plasticityCortical-cortical connectivityFunctional magnetic resonance imagingMagnetic resonance imagingNonepileptic animalsSeizure activitySpontaneous episodesWistar controlsAbsence seizuresAdjacent cortexChronic changesAnimal modelsFunctional MRI and neural responses in a rat model of Alzheimer's disease
Sanganahalli BG, Herman P, Behar KL, Blumenfeld H, Rothman DL, Hyder F. Functional MRI and neural responses in a rat model of Alzheimer's disease. NeuroImage 2013, 79: 404-411. PMID: 23648961, PMCID: PMC3700380, DOI: 10.1016/j.neuroimage.2013.04.099.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseFunctional magnetic resonance imagingCerebral cortexAD brainSomatosensory cortexRat modelCortical functionNeural responsesAge-matched healthy controlsAD rat modelContralateral somatosensory cortexSensory-evoked responsesHigh-field functional magnetic resonance imagingBrain functional responsesMagnetic resonance imagingAD ratsControl ratsHealthy controlsThalamic responsesNormal ratsCortical responsesAD modelSubcortical functionBrain plaquesElectrical stimulationLactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia
Herzog RI, Jiang L, Herman P, Zhao C, Sanganahalli BG, Mason GF, Hyder F, Rothman DL, Sherwin RS, Behar KL. Lactate preserves neuronal metabolism and function following antecedent recurrent hypoglycemia. Journal Of Clinical Investigation 2013, 123: 1988-1998. PMID: 23543056, PMCID: PMC3638906, DOI: 10.1172/jci65105.Peer-Reviewed Original ResearchConceptsAntecedent recurrent hypoglycemiaRecurrent hypoglycemiaHypoglycemic conditionsIntensive insulin therapyTight glycemic controlType 2 diabetesInsulin therapyGlycemic controlBrain metabolismElevated lactateNeuronal metabolismRodent modelsNeuronal activityGlucose metabolismHypoglycemiaLactate uptakeNeuronal functionType 1Metabolic regulatorOxidative capacityModest incrementLactateMetabolismUnexpected findingBrain
2011
Where fMRI and Electrophysiology Agree to Disagree: Corticothalamic and Striatal Activity Patterns in the WAG/Rij Rat
Mishra AM, Ellens DJ, Schridde U, Motelow JE, Purcaro MJ, DeSalvo MN, Enev M, Sanganahalli BG, Hyder F, Blumenfeld H. Where fMRI and Electrophysiology Agree to Disagree: Corticothalamic and Striatal Activity Patterns in the WAG/Rij Rat. Journal Of Neuroscience 2011, 31: 15053-15064. PMID: 22016539, PMCID: PMC3432284, DOI: 10.1523/jneurosci.0101-11.2011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainBrain MappingBrain WavesCerebral CortexCerebrovascular CirculationCorpus StriatumDisease Models, AnimalElectroencephalographyElectrophysiologyEpilepsyImage Processing, Computer-AssistedLaser-Doppler FlowmetryMagnetic Resonance ImagingNicotinic AntagonistsOxygenRatsRats, WistarThalamusTubocurarineVibrissaeConceptsCerebral blood flowCerebral blood volumeLocal field potentialsNeuronal activityLaser Doppler cerebral blood flowSubcortical structuresWAG/Rij ratsNeuronal activity decreasesHuman absence epilepsySpike-wave dischargesWAG/RijMultiunit activity recordingsFMRI signalsFunctional magnetic resonance imaging (fMRI) signalsMagnetic resonance imaging signalsFMRI decreasesCBF decreaseHemodynamic changesCerebral cortexBasal gangliaSomatosensory cortexAbsence epilepsyWhisker stimulationBlood flowAnimal modelsRole of Ongoing, Intrinsic Activity of Neuronal Populations for Quantitative Neuroimaging of Functional Magnetic Resonance Imaging–Based Networks
Hyder F, Herman P, Sanganahalli BG, Coman D, Blumenfeld H, Rothman DL. Role of Ongoing, Intrinsic Activity of Neuronal Populations for Quantitative Neuroimaging of Functional Magnetic Resonance Imaging–Based Networks. Brain Connectivity 2011, 1: 185-193. PMID: 22433047, PMCID: PMC3621320, DOI: 10.1089/brain.2011.0032.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingEnergy/activityMagnetic resonance imagingBOLD signalNeuronal activityQuantitative neuroimagingNeuronal populationsResonance imagingBaseline BOLD signalsTotal neuronal activityBlood oxygenation level-dependent (BOLD) signalLevel-dependent signalResting-state fMRI experimentsAnimal modelsFMRI experimentMagnetic resonance spectroscopy measurementsBrain networksBaselineNeuroimagingPrimary objectiveImagingIntrinsic activityActivityPopulation
2009
Tactile and Non-tactile Sensory Paradigms for fMRI and Neurophysiologic Studies in Rodents
Sanganahalli BG, Bailey CJ, Herman P, Hyder F. Tactile and Non-tactile Sensory Paradigms for fMRI and Neurophysiologic Studies in Rodents. Methods In Molecular Biology 2009, 489: 213-242. PMID: 18839094, PMCID: PMC3703391, DOI: 10.1007/978-1-59745-543-5_10.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingBlood oxygenation level-dependent (BOLD) signal changesDifferent peripheral stimuliSensory paradigmsLevel-dependent signal changesFunctional imaging toolMagnetic resonance imagingBOLD signal changesDependent signal changesCortical perceptionSignal changesNeurophysiologic studiesAnesthetized ratsNeuronal activityStimulation protocolPeripheral stimuliPharmacological agentsHuman studiesAnimal modelsFuture diagnostic useVariety of modalitiesResonance imagingInvasive natureNeurophysiologic markersSensory systems