2021
Effects of Altered Excitation-Inhibition Balance on Decision Making in a Cortical Circuit Model
Lam NH, Borduqui T, Hallak J, Roque A, Anticevic A, Krystal JH, Wang XJ, Murray JD. Effects of Altered Excitation-Inhibition Balance on Decision Making in a Cortical Circuit Model. Journal Of Neuroscience 2021, 42: 1035-1053. PMID: 34887320, PMCID: PMC8824494, DOI: 10.1523/jneurosci.1371-20.2021.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCerebral CortexComputer SimulationDecision MakingHumansModels, NeurologicalNeural PathwaysConceptsCortical circuitsCognitive deficitsCortical circuit modelAltered excitation-inhibition balanceExcitatory pyramidal neuronsNMDA receptor hypofunctionCerebral cortical circuitsExcitation-inhibition balancePyramidal neuronsReceptor hypofunctionDistinct time coursesSynaptic excitationInhibitory interneuronsMultiple neuropsychiatric disordersBehavioral deficitsSynaptic balanceSynaptic levelLatest evidenceNeuropsychiatric disordersCognitive functionCircuit mechanismsBehavioral effectsPsychometric performanceBehavioral levelTask paradigm
2020
Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis
Wang X, Xie H, Chen T, Cotton AS, Salminen LE, Logue MW, Clarke-Rubright EK, Wall J, Dennis EL, O’Leary B, Abdallah CG, Andrew E, Baugh LA, Bomyea J, Bruce SE, Bryant R, Choi K, Daniels JK, Davenport ND, Davidson RJ, DeBellis M, deRoon-Cassini T, Disner SG, Fani N, Fercho KA, Fitzgerald J, Forster GL, Frijling JL, Geuze E, Gomaa H, Gordon EM, Grupe D, Harpaz-Rotem I, Haswell CC, Herzog JI, Hofmann D, Hollifield M, Hosseini B, Hudson AR, Ipser J, Jahanshad N, Jovanovic T, Kaufman ML, King AP, Koch SBJ, Koerte IK, Korgaonkar MS, Krystal JH, Larson C, Lebois LAM, Levy I, Li G, Magnotta VA, Manthey A, May G, McLaughlin KA, Mueller SC, Nawijn L, Nelson SM, Neria Y, Nitschke JB, Olff M, Olson EA, Peverill M, Phan K, Rashid FM, Ressler K, Rosso IM, Sambrook K, Schmahl C, Shenton ME, Sierk A, Simons JS, Simons RM, Sponheim SR, Stein MB, Stein DJ, Stevens JS, Straube T, Suarez-Jimenez B, Tamburrino M, Thomopoulos SI, van der Wee NJA, van der Werff SJA, van Erp TGM, van Rooij SJH, van Zuiden M, Varkevisser T, Veltman DJ, Vermeiren RRJM, Walter H, Wang L, Zhu Y, Zhu X, Thompson PM, Morey RA, Liberzon I. Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis. Molecular Psychiatry 2020, 26: 4331-4343. PMID: 33288872, PMCID: PMC8180531, DOI: 10.1038/s41380-020-00967-1.Peer-Reviewed Original ResearchMeSH KeywordsCerebral CortexGenomicsHumansMagnetic Resonance ImagingStress Disorders, Post-TraumaticTemporal LobeConceptsPosttraumatic stress disorderLateral orbitofrontal gyrusPTSD patientsCortical regionsComorbid depressionCortical volumeVolume abnormalitiesStress disorderSuperior parietal gyrusRegional cortical volumesSuperior temporal gyrusPrefrontal regulatory regionsCerebral cortexControl subjectsRight insularLimbic regionsParietal gyrusPosttraumatic stress symptom severityStress symptom severityDepression symptomsOrbitofrontal gyrusSymptom severityTemporal gyrusPatientsAbnormalities
2019
Schizophrenia Exhibits Bi-directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits
Ji JL, Diehl C, Schleifer C, Tamminga CA, Keshavan MS, Sweeney JA, Clementz BA, Hill SK, Pearlson G, Yang G, Creatura G, Krystal JH, Repovs G, Murray J, Winkler A, Anticevic A. Schizophrenia Exhibits Bi-directional Brain-Wide Alterations in Cortico-Striato-Cerebellar Circuits. Cerebral Cortex 2019, 29: 4463-4487. PMID: 31157363, PMCID: PMC6917525, DOI: 10.1093/cercor/bhy306.Peer-Reviewed Original ResearchConceptsBrain-wide alterationsResting-state functional magnetic resonanceSensory-motor cortexFunctional magnetic resonanceNeural dysconnectivityPolysynaptic connectionsCortico-striatoFunctional disturbancesChronic patientsAssociation cortexFocal disruptionNeural effectsCerebellar circuitsPatientsDysconnectivityStriatal componentsSchizophreniaCortexSpecific alterationsHallmark featureCognitive performanceAlterationsFunctional pathwaysQuestion accountsMagnetic resonanceAltered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments
Duman RS, Sanacora G, Krystal JH. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron 2019, 102: 75-90. PMID: 30946828, PMCID: PMC6450409, DOI: 10.1016/j.neuron.2019.03.013.Peer-Reviewed Original ResearchConceptsAltered connectivityDepressed patientsExcitatory glutamate neuronsMajor neuronal typesRapid-acting agentsAtrophy of neuronsTreatment of depressionLimbic brain regionsChronic stress exposureStress-related disordersBrain imaging studiesImportant sex differencesNeurotransmitter deficitsGABA interneuronsImmunologic mechanismsGlutamate neuronsCurrent antidepressantsExcitotoxic effectsNeurochemical deficitsGlutamate dysfunctionPathophysiological mechanismsGABA systemInflammatory cytokinesAdrenal glucocorticoidsHippocampal regionAltered functional connectivity and low-frequency signal fluctuations in early psychosis and genetic high risk
Tang Y, Zhou Q, Chang M, Chekroud A, Gueorguieva R, Jiang X, Zhou Y, He G, Rowland M, Wang D, Fu S, Yin Z, Leng H, Wei S, Xu K, Wang F, Krystal JH, Driesen NR. Altered functional connectivity and low-frequency signal fluctuations in early psychosis and genetic high risk. Schizophrenia Research 2019, 210: 172-179. PMID: 30685394, DOI: 10.1016/j.schres.2018.12.041.Peer-Reviewed Original ResearchConceptsFunctional connectivityHigh-risk individualsAltered functional connectivityHealthy comparison subjectsGenetic high riskGenetic high-risk individualsLow-frequency signal fluctuationsFunctional magnetic resonanceALFF abnormalitiesALFF measuresFunctional connectivity measuresBasal gangliaFirst episodeHigh riskEarly psychosisComparison subjectsSchizophrenia diathesisSchizophrenia vulnerabilityFESzGenetic riskLow-frequency fluctuationsIllnessSchizophreniaVoxel connectivityGHR
2018
Alcohol Expectancy and Cerebral Responses to Cue-Elicited Craving in Adult Nondependent Drinkers
Zhornitsky S, Zhang S, Ide JS, Chao HH, Wang W, Le TM, Leeman RF, Bi J, Krystal JH, Li CR. Alcohol Expectancy and Cerebral Responses to Cue-Elicited Craving in Adult Nondependent Drinkers. Biological Psychiatry Cognitive Neuroscience And Neuroimaging 2018, 4: 493-504. PMID: 30711509, PMCID: PMC6500759, DOI: 10.1016/j.bpsc.2018.11.012.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlcohol DrinkingCerebral CortexCravingCuesFemaleHumansMagnetic Resonance ImagingMaleMotivationThalamusConceptsAlcohol Use Disorders Identification Test (AUDIT) scoresFrontal cortical connectivityCerebral responsesCortical connectivityPositive scoreAlcohol cuesNondependent drinkersAlcohol Use Disorders Identification TestLeft caudate headCue activityCue responsesAlcohol expectanciesProblem drinkingDisorders Identification TestNeutral cuesMedial orbitofrontal cortexAlcohol Expectancy QuestionnaireFunctional magnetic resonanceBilateral thalamusThalamic processingCaudate headRisk drinkingThalamic responsesRed nucleusImaging studiesDefault mode network abnormalities in posttraumatic stress disorder: A novel network-restricted topology approach
Akiki TJ, Averill CL, Wrocklage KM, Scott JC, Averill LA, Schweinsburg B, Alexander-Bloch A, Martini B, Southwick SM, Krystal JH, Abdallah CG. Default mode network abnormalities in posttraumatic stress disorder: A novel network-restricted topology approach. NeuroImage 2018, 176: 489-498. PMID: 29730491, PMCID: PMC5976548, DOI: 10.1016/j.neuroimage.2018.05.005.Peer-Reviewed Original Research
2017
Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD
Wrocklage KM, Averill LA, Scott J, Averill CL, Schweinsburg B, Trejo M, Roy A, Weisser V, Kelly C, Martini B, Harpaz-Rotem I, Southwick SM, Krystal JH, Abdallah CG. Cortical thickness reduction in combat exposed U.S. veterans with and without PTSD. European Neuropsychopharmacology 2017, 27: 515-525. PMID: 28279623, PMCID: PMC5429865, DOI: 10.1016/j.euroneuro.2017.02.010.Peer-Reviewed Original ResearchConceptsClinician-Administered PTSD ScalePTSD symptom dimensionsPTSD diagnosisCombat exposureCortical thicknessSymptom dimensionsMagnetic resonance imagingPosttraumatic stress disorder (PTSD) symptomsU.S. veteransCortical thinningUnique brain regionsLeft lateral prefrontalAnxious arousalPTSD dimensionsNeural correlatesHigh-resolution magnetic resonance imagingCortical thickness reductionsLateral prefrontalPTSD symptomsDisorder symptomsCombat severityCurrent PTSDPTSD ScalePrefrontal cortexPotential confoundsImpaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A Translational and Computational Neuroscience Perspective
Krystal JH, Anticevic A, Yang GJ, Dragoi G, Driesen NR, Wang XJ, Murray JD. Impaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A Translational and Computational Neuroscience Perspective. Biological Psychiatry 2017, 81: 874-885. PMID: 28434616, PMCID: PMC5407407, DOI: 10.1016/j.biopsych.2017.01.004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCerebral CortexComputer SimulationHumansNerve NetNeuronsNeurosciencesSchizophreniaConceptsNeural activityNeural ensemblesComputational neuroscience perspectiveHigher cognitive functionsNeuroscience perspectiveDevelopmental perspectiveDevelopmental correlatesCognitive functionNegative functional consequencesCortical networksComputational neuroscienceNeural codeCortical activityCognitive impairmentNeural dysfunctionAspartate glutamate receptor antagonistTemporal tuningSpatial tuningGlutamate receptor antagonistsPathophysiology of schizophreniaNeural network functionSchizophreniaPsychiatric disordersBalance of excitationInput-output curves
2016
Schizophrenia is associated with a pattern of spatial working memory deficits consistent with cortical disinhibition
Starc M, Murray JD, Santamauro N, Savic A, Diehl C, Cho YT, Srihari V, Morgan PT, Krystal JH, Wang XJ, Repovs G, Anticevic A. Schizophrenia is associated with a pattern of spatial working memory deficits consistent with cortical disinhibition. Schizophrenia Research 2016, 181: 107-116. PMID: 27745755, PMCID: PMC5901719, DOI: 10.1016/j.schres.2016.10.011.Peer-Reviewed Original ResearchConceptsHealthy comparison subjectsSpatial WM taskSchizophrenia patientsSevere cognitive deficitsSpecific spatial locationsComputational modelContinuous response measuresWM precisionWM representationsSpatial WMWM taskDistractor distanceWM impairmentWM tracesNeural mechanismsCognitive deficitsMemory deficitsBehavioral consequencesDelay periodDelay durationCortical disinhibitionSpatial locationComparison subjectsMicrocircuit modelDistractibilityRole of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia
Kort NS, Ford JM, Roach BJ, Gunduz-Bruce H, Krystal JH, Jaeger J, Reinhart RM, Mathalon DH. Role of N-Methyl-D-Aspartate Receptors in Action-Based Predictive Coding Deficits in Schizophrenia. Biological Psychiatry 2016, 81: 514-524. PMID: 27647218, PMCID: PMC5203970, DOI: 10.1016/j.biopsych.2016.06.019.Peer-Reviewed Original ResearchConceptsEvent-related potentialsPredictive codingN1 suppressionN1 amplitudePredictive coding deficitsSelf-generated speechSchizophrenia patientsAuditory cortical responsesAuditory predictive codingSelf-produced vocalizationsNMDAR hypofunctionEffects of schizophreniaSpeech soundsTheorized contributionN1 componentHealthy volunteersPassive playbackCognitive deficitsN-methyl-D-aspartate receptorsPutative measureTalk/Cortical responsesHealthy control volunteersCase-control studySaline days
2013
Characterizing Thalamo-Cortical Disturbances in Schizophrenia and Bipolar Illness
Anticevic A, Cole MW, Repovs G, Murray JD, Brumbaugh MS, Winkler AM, Savic A, Krystal JH, Pearlson GD, Glahn DC. Characterizing Thalamo-Cortical Disturbances in Schizophrenia and Bipolar Illness. Cerebral Cortex 2013, 24: 3116-3130. PMID: 23825317, PMCID: PMC4224238, DOI: 10.1093/cercor/bht165.Peer-Reviewed Original ResearchConceptsThalamo-cortical systemThalamic connectivityBipolar illnessResting-state functional magnetic resonance imagingSensory-motor cortexSevere mental illnessFunctional magnetic resonance imagingMagnetic resonance imagingThalamic dysconnectivityThalamic seedsClinical presentationNeuropsychiatric syndromeBrain dysconnectivityThalamic nucleiBipolar patientsSchizophrenia patientsSensory gatingMental illnessResonance imagingDysconnectivityCerebellar regionsDiagnostic membershipPrefrontal cortexSchizophreniaIllnessNeural Correlates of Impulsivity in Healthy Males and Females with Family Histories of Alcoholism
DeVito EE, Meda SA, Jiantonio R, Potenza MN, Krystal JH, Pearlson GD. Neural Correlates of Impulsivity in Healthy Males and Females with Family Histories of Alcoholism. Neuropsychopharmacology 2013, 38: 1854-1863. PMID: 23584260, PMCID: PMC3746701, DOI: 10.1038/npp.2013.92.Peer-Reviewed Original ResearchConceptsAlcohol use measuresNeural correlatesFHP individualsImpulse controlHigher self-reported impulsivityGreater BOLD signalFHN groupSelf-reported impulsivityAlcohol useInferior frontal gyrusLeft anterior insulaUse measuresImpulsivity factorsAnterior insulaFrontal gyrusGreater activationImpulsivityAddictive disordersNeural systemsScanner measuresSuccessful inhibitionBOLD signalSex differencesBehavioral traitsAddictionRelationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans
Driesen NR, McCarthy G, Bhagwagar Z, Bloch M, Calhoun V, D'Souza DC, Gueorguieva R, He G, Ramachandran R, Suckow RF, Anticevic A, Morgan PT, Krystal JH. Relationship of resting brain hyperconnectivity and schizophrenia-like symptoms produced by the NMDA receptor antagonist ketamine in humans. Molecular Psychiatry 2013, 18: 1199-1204. PMID: 23337947, PMCID: PMC3646075, DOI: 10.1038/mp.2012.194.Peer-Reviewed Original ResearchConceptsFunctional connectivityNegative symptomsGamma-aminobutyric acid (GABA) neuronsNMDA receptor antagonist ketamineAspartate glutamate receptor antagonistContinuous ketamine infusionGlutamate receptor antagonistsNMDA-R antagonistsCortical functional connectivityNMDA-R antagonist ketamineSchizophrenia-like symptomsHealthy human subjectsNegative Syndrome ScaleBrain functional connectivityPrimary samplesRegion-specific mannerFunctional magnetic resonanceKetamine infusionReceptor antagonistPathological increaseSyndrome ScaleSymptomsPreclinical researchKetamineBrain oscillations
2012
Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of Disinhibition Associated with Schizophrenia in a Cortical Working Memory Model
Murray JD, Anticevic A, Gancsos M, Ichinose M, Corlett PR, Krystal JH, Wang XJ. Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of Disinhibition Associated with Schizophrenia in a Cortical Working Memory Model. Cerebral Cortex 2012, 24: 859-872. PMID: 23203979, PMCID: PMC3948492, DOI: 10.1093/cercor/bhs370.Peer-Reviewed Original ResearchConceptsWorking memoryNeural levelSpatial WM taskWorking Memory ModelSpatial working memoryPersistent activity patternsWM representationsWM taskWM maintenanceBrain mechanismsWM deficitsMicrocircuit dysfunctionPrefrontal cortexCognitive deficitsBehavioral dataMemory modelBehavioral variabilityWM deteriorationCognitive impairmentCortical disinhibitionExcitation-inhibition balanceMain model predictionsDisinhibitionBehavioral deficitsDeficitsCapturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans
Moghaddam B, Krystal JH. Capturing the Angel in “Angel Dust”: Twenty Years of Translational Neuroscience Studies of NMDA Receptor Antagonists in Animals and Humans. Schizophrenia Bulletin 2012, 38: 942-949. PMID: 22899397, PMCID: PMC3446228, DOI: 10.1093/schbul/sbs075.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsAntipsychotic AgentsBrief Psychiatric Rating ScaleCerebral CortexDisease Models, AnimalDopamineEmotionsGlutamic AcidHumansKetamineNeurosciencesPhencyclidinePsychoses, Substance-InducedReceptor, Metabotropic Glutamate 5Receptors, Dopamine D2Receptors, Metabotropic GlutamateReceptors, N-Methyl-D-AspartateSchizophreniaSynapsesTranslational Research, BiomedicalConceptsNMDA receptor antagonistReceptor antagonistDopamine hypothesisN-methyl-D-aspartate receptor antagonistGlutamate synaptic functionTranslational neuroscience studiesTreatment of schizophreniaPathophysiology of schizophreniaPotential treatment targetPotential new targetsDopamine antagonistsCortical functionAnimal studiesTreatment targetsClinical testingSynaptic functionAntagonistTranslational toolSchizophreniaTranslational research fundingTranslational researchPotential mechanismsNew targetsAngel dustSystems neuroscience
2011
Intravenous Ethanol Infusion Decreases Human Cortical γ-Aminobutyric Acid and N-Acetylaspartate as Measured with Proton Magnetic Resonance Spectroscopy at 4 Tesla
Gomez R, Behar KL, Watzl J, Weinzimer SA, Gulanski B, Sanacora G, Koretski J, Guidone E, Jiang L, Petrakis IL, Pittman B, Krystal JH, Mason GF. Intravenous Ethanol Infusion Decreases Human Cortical γ-Aminobutyric Acid and N-Acetylaspartate as Measured with Proton Magnetic Resonance Spectroscopy at 4 Tesla. Biological Psychiatry 2011, 71: 239-246. PMID: 21855054, PMCID: PMC3227760, DOI: 10.1016/j.biopsych.2011.06.026.Peer-Reviewed Original ResearchConceptsIntravenous ethanol infusionProton magnetic resonance spectroscopyEthanol infusionNAA levelsN-acetylaspartateCortical γ-aminobutyric acidAcute pharmacologic effectsLevels of GABAHealthy social drinkersBreath alcohol levelsN-acetylaspartyl-glutamateCortical GABAEthanol modulatesFirst infusionΓ-aminobutyric acidGABA levelsPharmacologic effectsBrain ethanolOccipital GABAInfusionAlcohol levelsMagnetic resonance spectroscopyReceptor functionBreath ethanolHuman cortex
2008
Modulation of the cortical processing of novel and target stimuli by drugs affecting glutamate and GABA neurotransmission
Watson TD, Petrakis IL, Edgecombe J, Perrino A, Krystal JH, Mathalon DH. Modulation of the cortical processing of novel and target stimuli by drugs affecting glutamate and GABA neurotransmission. The International Journal Of Neuropsychopharmacology 2008, 12: 357-370. PMID: 18771605, PMCID: PMC2900256, DOI: 10.1017/s1461145708009334.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceCerebral CortexDouble-Blind MethodElectroencephalographyEvoked PotentialsFemaleGABA ModulatorsHumansKetamineMalePain MeasurementPattern Recognition, VisualPhotic StimulationReaction TimeReceptors, GABA-BReceptors, N-Methyl-D-AspartateStatistics as TopicThiopentalYoung AdultConceptsPlacebo-controlled studyNMDA receptor systemSubanaesthetic dosesGABA neurotransmissionChallenge sessionsDrug effectsNMDA antagonismHealthy adultsNovel stimuliCortical processingReceptor systemPlaceboDrugsCounterbalanced orderKetaminePotential correlatesNeural correlatesP3a amplitudeNovelty processingP300 componentStandard stimuliStimulus processingStimuliTarget stimuliN2 amplitude
2007
Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation
Hoffman RE, Hampson M, Wu K, Anderson AW, Gore JC, Buchanan RJ, Constable RT, Hawkins KA, Sahay N, Krystal JH. Probing the Pathophysiology of Auditory/Verbal Hallucinations by Combining Functional Magnetic Resonance Imaging and Transcranial Magnetic Stimulation. Cerebral Cortex 2007, 17: 2733-2743. PMID: 17298962, PMCID: PMC2634833, DOI: 10.1093/cercor/bhl183.Peer-Reviewed Original ResearchConceptsRepetitive transcranial magnetic stimulationTranscranial magnetic stimulationFunctional magnetic resonance imagingMagnetic resonance imagingMagnetic stimulationSham stimulationTemporoparietal repetitive transcranial magnetic stimulationAuditory/verbal hallucinationsResonance imagingWernicke's areaVerbal hallucinationsBOLD signal time coursesBroca's areaSchizophrenia spectrum disordersGreater rateInferior frontal regionsPatientsTemporoparietal areasSignal time courseCortical sitesPathophysiologySupramarginal gyrusHallucinationsRight homologueStimulation
2006
γ-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment
Krystal JH, Staley J, Mason G, Petrakis IL, Kaufman J, Harris RA, Gelernter J, Lappalainen J. γ-Aminobutyric Acid Type A Receptors and Alcoholism: Intoxication, Dependence, Vulnerability, and Treatment. JAMA Psychiatry 2006, 63: 957-968. PMID: 16952998, DOI: 10.1001/archpsyc.63.9.957.Peer-Reviewed Original ResearchConceptsBrain GABA systemsGABA systemAlcohol dependenceWithdrawal symptomsGABA functionGamma-aminobutyric acid (GABA) functionCortical GABA levelsAlcohol withdrawal symptomsΓ-Aminobutyric Acid Type A ReceptorsEnvironmental risk factorsLong-term alcohol effectsType A ReceptorsAlcohol-dependent individualsLong-term sobrietyGABA releaseNeurosteroid levelsAcute withdrawalAlcoholism vulnerabilityGABA neurotransmissionRisk factorsGABA levelsExtrasynaptic locationsLow chloride conductanceReceptor densityTonic component