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
2019
Neural computations of threat in the aftermath of combat trauma
Homan P, Levy I, Feltham E, Gordon C, Hu J, Li J, Pietrzak RH, Southwick S, Krystal JH, Harpaz-Rotem I, Schiller D. Neural computations of threat in the aftermath of combat trauma. Nature Neuroscience 2019, 22: 470-476. PMID: 30664770, PMCID: PMC6829910, DOI: 10.1038/s41593-018-0315-x.Peer-Reviewed Original ResearchConceptsPTSD symptomsPost-traumatic stress disorder symptomsHigher PTSD symptom severityThreat-predictive cuesPTSD symptom severityAssociative threatPredictive cuesNeural trackingDisorder symptomsPrediction errorCombat veteransDynamic learning rateNegative outcomesCombat traumaSmaller amygdala volumesNeural computationLatent markersSymptomatic veteransSymptom severityAmygdala volumeAssociabilityCuesLearning rateVeteransSymptoms
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 modelDistractibility
2015
Functional hierarchy underlies preferential connectivity disturbances in schizophrenia
Yang GJ, Murray JD, Wang XJ, Glahn DC, Pearlson GD, Repovs G, Krystal JH, Anticevic A. Functional hierarchy underlies preferential connectivity disturbances in schizophrenia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 113: e219-e228. PMID: 26699491, PMCID: PMC4720350, DOI: 10.1073/pnas.1508436113.Peer-Reviewed Original ResearchMeSH KeywordsBrainComputer SimulationFrontal LobeHumansModels, NeurologicalNerve NetNeural InhibitionParietal LobeSchizophreniaConceptsFunctional connectivityResting-state functional MRIExcitation/inhibition ratioElevated functional connectivityLarge-scale functional connectivityFronto-parietal control networkI elevationConnectivity disturbancesHealthy subjectsPreferential vulnerabilityAssociation cortexSchizophrenia patientsBipolar disorderFunctional MRIPatientsSymptom levelsSchizophreniaCortical microcircuitsInhibition ratioNeural modelControl networkNeuronal dynamicsHierarchical differencesParsimonious mechanismDysconnectivity
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 deficitsDeficitsNMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia
Anticevic A, Gancsos M, Murray JD, Repovs G, Driesen NR, Ennis DJ, Niciu MJ, Morgan PT, Surti TS, Bloch MH, Ramani R, Smith MA, Wang XJ, Krystal JH, Corlett PR. NMDA receptor function in large-scale anticorrelated neural systems with implications for cognition and schizophrenia. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16720-16725. PMID: 23012427, PMCID: PMC3478611, DOI: 10.1073/pnas.1208494109.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlgorithmsBrainCognitionDouble-Blind MethodExcitatory Amino Acid AntagonistsFemaleHumansInfusions, IntravenousKetamineMagnetic Resonance ImagingMaleMemoryModels, NeurologicalPattern Recognition, VisualPsychomotor PerformanceReceptors, N-Methyl-D-AspartateSchizophreniaSynaptic TransmissionYoung AdultConceptsNeural systemsLarge-scale brain systemsTask-dependent activationN-methyl-D-aspartate receptorsRealistic computational modelingSevere neuropsychiatric illnessNMDA glutamate receptor antagonistGlutamate receptor antagonistsBrain systemsNMDA receptor functionTask performanceMultiple interacting regionsCognitionCortical disinhibitionGlutamatergic neurotransmissionReceptor antagonistCortical computationGlutamate's roleReciprocal relationshipNeuropsychiatric illnessLocal circuitsReceptor functionSchizophreniaPresent findingsComputational modeling
2010
Glutamatergic Model Psychoses: Prediction Error, Learning, and Inference
Corlett PR, Honey GD, Krystal JH, Fletcher PC. Glutamatergic Model Psychoses: Prediction Error, Learning, and Inference. Neuropsychopharmacology 2010, 36: 294-315. PMID: 20861831, PMCID: PMC3055519, DOI: 10.1038/npp.2010.163.Peer-Reviewed Original ResearchToward a neurobiology of delusions
Corlett PR, Taylor JR, Wang X, Fletcher PC, Krystal JH. Toward a neurobiology of delusions. Progress In Neurobiology 2010, 92: 345-369. PMID: 20558235, PMCID: PMC3676875, DOI: 10.1016/j.pneurobio.2010.06.007.Peer-Reviewed Original ResearchMeSH KeywordsBrainCognitionComputer SimulationCultureDelusionsHumansLearningMemoryModels, NeurologicalNervous System DiseasesNeurobiologyPerceptionConceptsFundamental brain mechanismsFronto-striatal circuitsTerms of cognitionPsychological processesBrain mechanismsComputational mechanismsCortical hierarchyPrediction errorSocial learningParietal cortexExternal worldBrain circuitsNeurobiological abnormalitiesNeurobiology of delusionsBrain functionHierarchical predictionBodily agencyDelusionsMemoryReinforcement learningPerceptionMental illnessTranslational understandingLearningCognition
2005
γ-Aminobutyric Acid–Serotonin Interactions in Healthy Men: Implications for Network Models of Psychosis and Dissociation
D’Souza D, Gil RB, Zuzarte E, MacDougall LM, Donahue L, Ebersole JS, Boutros NN, Cooper T, Seibyl J, Krystal JH. γ-Aminobutyric Acid–Serotonin Interactions in Healthy Men: Implications for Network Models of Psychosis and Dissociation. Biological Psychiatry 2005, 59: 128-137. PMID: 16140281, DOI: 10.1016/j.biopsych.2005.06.020.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnxietyCross-Over StudiesDissociative DisordersDouble-Blind MethodDrug SynergismFlumazenilGABA ModulatorsGamma-Aminobutyric AcidHumansMaleModels, NeurologicalPerceptual DisordersPiperazinesPsychoses, Substance-InducedReceptors, GABA-AReceptors, Serotonin, 5-HT2Reference ValuesSerotoninSerotonin Receptor Agonists
2003
NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development
Krystal JH, D'Souza DC, Mathalon D, Perry E, Belger A, Hoffman R. NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development. Psychopharmacology 2003, 169: 215-233. PMID: 12955285, DOI: 10.1007/s00213-003-1582-z.Peer-Reviewed Original ResearchConceptsTreatment of schizophreniaReceptor antagonistN-methyl-D-aspartate (NMDA) glutamate receptor antagonistPharmacotherapy of schizophreniaGlutamate receptor antagonistsReceptor antagonist effectsNMDA receptor antagonistNMDA receptor antagonist effectsNMDA receptor contributionTranslational Neuroscience ApproachGlutamatergic activityGlutamatergic functionNew medicationsClinical studiesReceptor contributionTherapeutic implicationsMedication developmentCortical connectivityAntagonist effectsAntagonist responseNew treatment insightsSchizophreniaModel psychosisTreatment insightsAntagonist
2002
Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments
Krystal JH, Sanacora G, Blumberg H, Anand A, Charney DS, Marek G, Epperson CN, Goddard A, Mason GF. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Molecular Psychiatry 2002, 7: s71-s80. PMID: 11986998, DOI: 10.1038/sj.mp.4001021.Peer-Reviewed Original ResearchMeSH KeywordsAntidepressive AgentsGamma-Aminobutyric AcidGlutamic AcidHumansModels, NeurologicalMood DisordersSynaptic TransmissionConceptsCortical GABA levelsMood-stabilizing treatmentMood disordersGABA levelsΓ-amino-butyric acid (GABA) systemMood-stabilizing agentsGlutamate receptor functionDevelopment of medicationsGABA deficitAvailable antidepressantsGABAergic modulationAntimanic effectsGlutamatergic activityClinical evidenceNovel antidepressantsGABA systemAntidepressant drugsNew agentsReceptor functionAvailable evidenceReceptor targetsAntidepressantsDisordersGlutamateTreatment
1999
Comparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report
Boutros N, Belger A, Campbell D, D’Souza C, Krystal J. Comparison of four components of sensory gating in schizophrenia and normal subjects: a preliminary report. Psychiatry Research 1999, 88: 119-130. PMID: 10622348, DOI: 10.1016/s0165-1781(99)00074-8.Peer-Reviewed Original ResearchConceptsNormal control subjectsSchizophrenia patientsSensory gatingControl subjectsNormal subjectsSex-matched normal control subjectsPathophysiology of schizophreniaStimulus repetitionStable schizophrenia patientsSchizophrenia subjectsSimilar abnormalitiesPatientsPreliminary reportDysfunctionDegree of attenuationSchizophreniaLate phaseSubjectsDeviant stimuliStimulus changeIrrelevant stimuliPathophysiologyStimuliPotential paradigmAbnormalities
1996
Neural Mechanisms in dissociative amnesia for childhood abuse: relevance to the current controversy surrounding the "false memory syndrome"
Bremner JD, Krystal JH, Charney DS, Southwick SM. Neural Mechanisms in dissociative amnesia for childhood abuse: relevance to the current controversy surrounding the "false memory syndrome". American Journal Of Psychiatry 1996, 153: 71-82. PMID: 8659644, DOI: 10.1176/ajp.153.7.71.Peer-Reviewed Original ResearchConceptsFalse memory syndromeMemory tracesChildhood abuseDissociative amnesiaEffects of stressMemory functionMemory syndromeNeurobiology of memoryBrain regionsNormal memory functionChildren's memoryTraumatic stressorsSpecific brain regionsNeural mechanismsStressful eventsMemoryAmnesiaExtreme stressBrain chemistryAbuseRecallPsychiatric disordersLong-term alterationsLong-term effectsNormal persons
1993
Abnormal Noradrenergic Function in Posttraumatic Stress Disorder
Southwick SM, Krystal JH, Morgan CA, Johnson D, Nagy LM, Nicolaou A, Heninger GR, Charney DS. Abnormal Noradrenergic Function in Posttraumatic Stress Disorder. JAMA Psychiatry 1993, 50: 266-274. PMID: 8466387, DOI: 10.1001/archpsyc.1993.01820160036003.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderYohimbine-induced panic attacksUncontrollable stressStress disorderYohimbine-induced increasesSystolic blood pressureSubgroup of patientsHealthy male subjectsCore PTSD symptomsCardiovascular effectsBlood pressureMale patientsPathophysiological relationshipNoradrenergic functionPreclinical dataNeurobiological sequelaeHealthy subjectsHeart rateNeuronal regulationPanic disorderMale subjectsNeuronal functionPanic attacksPatientsYohimbine hydrochloridePsychobiologic Mechanisms of Posttraumatic Stress Disorder
Charney DS, Deutch AY, Krystal JH, Southwick SM, Davis M. Psychobiologic Mechanisms of Posttraumatic Stress Disorder. JAMA Psychiatry 1993, 50: 294-305. PMID: 8466391, DOI: 10.1001/archpsyc.1993.01820160064008.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderStress disorderPathophysiology of PTSDAvoidance of stimuliFailure of extinctionFear conditioningTraumatic memoriesMemory processesAutonomic hyperarousalTraumatic eventsEffects of stressCore symptomsPersistent reexperiencingPsychobiologic mechanismsAdaptive behavioralBrain structuresNeurochemical systemsNeurobiologic mechanismsReexperiencingParallel activationHyperarousalDisordersChronic courseTrauma resultsBehavioral sensitization
1990
Noradrenergic function in panic disorder.
Charney DS, Woods SW, Nagy LM, Southwick SM, Krystal JH, Heninger GR. Noradrenergic function in panic disorder. The Journal Of Clinical Psychiatry 1990, 51 Suppl A: 5-11. PMID: 2258377.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnxiety DisordersCatsHumansLocus CoeruleusMacacaModels, NeurologicalNorepinephrinePanicSympathetic Nervous SystemConceptsLocus ceruleusNoradrenergic functionPanic disorderBrain noradrenergic functionNoradrenergic neuronal activityPanic disorder patientsNoradrenergic neuronsPreclinical evidenceNatural courseNoradrenergic nucleusDevelopment of anxietyAnxiogenic effectsClinical investigationDisorder patientsNeuronal activityUncontrollable stressNeuron firingNonhuman primatesNeurodevelopmental perspectiveLaboratory animalsSystem regulationFear responsesDisordersAnxietyElectrical activation
1988
A review of behavioral and pharmacologic studies relevant to the application of CO2 as a human subject model of anxiety.
Woods SW, Krystal JH, D'Amico CL, Heninger GR, Charney DS. A review of behavioral and pharmacologic studies relevant to the application of CO2 as a human subject model of anxiety. Psychopharmacology Bulletin 1988, 24: 149-53. PMID: 3133718.Peer-Reviewed Original Research