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
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 resonance
2018
Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor
Preller KH, Burt JB, Ji JL, Schleifer CH, Adkinson BD, Stämpfli P, Seifritz E, Repovs G, Krystal JH, Murray JD, Vollenweider FX, Anticevic A. Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. ELife 2018, 7: e35082. PMID: 30355445, PMCID: PMC6202055, DOI: 10.7554/elife.35082.Peer-Reviewed Original ResearchConceptsLysergic acid diethylamideLSD effectsResting-state functional connectivityCortical gene expressionHealthy human participantsThalamic connectivityDopamine receptorsReceptor contributionNeurobiological effectsAgonist activityFunctional connectivityBrain connectivityAcid diethylamideReceptorsKetanserinNeuropharmacologyLSD mechanismCritical roleGene expressionAltered statesHuman participantsRational developmentSerotoninProblem Drinking, Alcohol Expectancy, and Thalamic Resting-State Functional Connectivity in Nondependent Adult Drinkers
Zhornitsky S, Ide J, Wang W, Chao H, Zhang S, Hu S, Krystal J, Li C. Problem Drinking, Alcohol Expectancy, and Thalamic Resting-State Functional Connectivity in Nondependent Adult Drinkers. Brain Connectivity 2018, 8: 487-502. PMID: 30198312, PMCID: PMC6207153, DOI: 10.1089/brain.2018.0633.Peer-Reviewed Original ResearchConceptsAlcohol Use Disorders Identification TestResting-state functional connectivityThalamic connectivityCaudate connectivityFrontal associationThalamic dysfunctionCaudate headProblem drinkingWhole-brain linear regressionAE scoreSubcortical structuresFunctional connectivityBilateral caudate headRight caudate headDisorders Identification TestSex differencesThalamic subdivisionsThalamic subregionsParietal associationAlcohol misuseThalamusWhite matter tractographyAUDIT scoresNondependent drinkersAlcohol expectancies
2017
Targeted neural network interventions for auditory hallucinations: Can TMS inform DBS?
Taylor JJ, Krystal JH, D'Souza DC, Gerrard JL, Corlett PR. Targeted neural network interventions for auditory hallucinations: Can TMS inform DBS? Schizophrenia Research 2017, 195: 455-462. PMID: 28969932, PMCID: PMC8141945, DOI: 10.1016/j.schres.2017.09.020.Peer-Reviewed Original ResearchMeSH KeywordsBrainDeep Brain StimulationHallucinationsHumansNeural PathwaysTranscranial Magnetic StimulationConceptsDeep brain stimulationTranscranial magnetic stimulationAuditory hallucinationsBrain stimulationCombination of TMSTreatment-refractory schizophreniaAberrant neural networksRelevant neural networksNon-invasive formNeuromodulatory interventionsMagnetic stimulationPsychiatric disordersSymptom clusteringTherapeutic interventionsClinical decisionInvasive formNeurophysiological dataCausal evidencePsychiatric constructsStimulationNetwork modulationInterventionNeural networkSafety concernsInvestigational probesMultimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder
Scheinost D, Holmes SE, DellaGioia N, Schleifer C, Matuskey D, Abdallah CG, Hampson M, Krystal JH, Anticevic A, Esterlis I. Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder. Neuropsychopharmacology 2017, 43: 1119-1127. PMID: 28944772, PMCID: PMC5854800, DOI: 10.1038/npp.2017.229.Peer-Reviewed Original ResearchConceptsMajor depressive disorderAnterior cingulate cortexIntrinsic functional connectivityMedial prefrontal cortexFunctional connectivityLarge-scale brain networksDepressive disorderMDD groupAnatomical covarianceBrain networksUnmedicated major depressive disorderWhole-brain intrinsic functional connectivitySystem-level disorderIntrinsic connectivity distributionRegional brain structureMultiple brain networksAltered connectivityCommon findingHealthy comparison participantsDepressive symptomsAltered volumeUnmedicated individualsLocal circuitryCingulate cortexDepressive symptomatology
2016
Altered Global Signal Topography in Schizophrenia
Yang GJ, Murray JD, Glasser M, Pearlson GD, Krystal JH, Schleifer C, Repovs G, Anticevic A. Altered Global Signal Topography in Schizophrenia. Cerebral Cortex 2016, 27: 5156-5169. PMID: 27702810, PMCID: PMC6075538, DOI: 10.1093/cercor/bhw297.Peer-Reviewed Original ResearchConceptsSCZ patientsGS topographyHealthy subjectsResting-state functional magnetic resonance imagingBlood oxygen level-dependent (BOLD) signalDevelopment of pharmacotherapiesGlobal signal topographyHealthy comparison subjectsFunctional magnetic resonance imagingLevel-dependent signalMagnetic resonance imagingAnti-correlated relationshipExtensive abnormalitiesComparison subjectsAssociation cortexNeural information flowResonance imagingNeuropsychiatric diseasesSensory areasPatientsSchizophreniaSensory regionsProfound alterationsSignal topographyAlterationsReduced global functional connectivity of the medial prefrontal cortex in major depressive disorder
Murrough JW, Abdallah CG, Anticevic A, Collins KA, Geha P, Averill LA, Schwartz J, DeWilde KE, Averill C, Jia-Wei Yang G, Wong E, Tang CY, Krystal JH, Iosifescu DV, Charney DS. Reduced global functional connectivity of the medial prefrontal cortex in major depressive disorder. Human Brain Mapping 2016, 37: 3214-3223. PMID: 27144347, PMCID: PMC4980239, DOI: 10.1002/hbm.23235.Peer-Reviewed Original ResearchConceptsGlobal brain connectivityMedial prefrontal cortexPrefrontal cortexRight subgenual anterior cingulate cortexVentromedial prefrontal cortexCingulate cortexMontgomery-Åsberg Depression Rating ScaleSymptom severityBrain connectivitySubgenual anterior cingulate cortexDepression Rating ScaleMedication-free patientsMajor depressive disorderKey pathological featureDepressive symptom severitySubgenual cingulate cortexHum Brain MappAnterior cingulate cortexHigher symptom severityFunctional connectivity analysisFunctional magnetic resonancePathological featuresHealthy groupAltered connectivityDepressive disorder
2014
N-Methyl-D-Aspartate Receptor Antagonist Effects on Prefrontal Cortical Connectivity Better Model Early Than Chronic Schizophrenia
Anticevic A, Corlett PR, Cole MW, Savic A, Gancsos M, Tang Y, Repovs G, Murray JD, Driesen NR, Morgan PT, Xu K, Wang F, Krystal JH. N-Methyl-D-Aspartate Receptor Antagonist Effects on Prefrontal Cortical Connectivity Better Model Early Than Chronic Schizophrenia. Biological Psychiatry 2014, 77: 569-580. PMID: 25281999, DOI: 10.1016/j.biopsych.2014.07.022.Peer-Reviewed Original ResearchConceptsHealthy volunteersFunctional connectivityKetamine effectsChronic schizophreniaIllness progressionChronic illnessHigh riskRecent pharmacologic studiesReceptor antagonist effectsAspartate glutamate receptorsStages of schizophreniaCourse of schizophreniaGlutamate dysfunctionPharmacologic modelsPrefrontal cortex functionIllness stageNMDAR antagonistsFunctional dysconnectivityGlutamate receptorsPharmacologic studiesHealthy subjectsSchizophrenia onsetFunctional alterationsDevelopment of therapeuticsAntagonist effectsVentral Anterior Cingulate Connectivity Distinguished Nonpsychotic Bipolar Illness From Psychotic Bipolar Disorder and Schizophrenia
Anticevic A, Savic A, Repovs G, Yang G, McKay DR, Sprooten E, Knowles EE, Krystal JH, Pearlson GD, Glahn DC. Ventral Anterior Cingulate Connectivity Distinguished Nonpsychotic Bipolar Illness From Psychotic Bipolar Disorder and Schizophrenia. Schizophrenia Bulletin 2014, 41: 133-143. PMID: 24782562, PMCID: PMC4266289, DOI: 10.1093/schbul/sbu051.Peer-Reviewed Original ResearchConceptsVentral anterior cingulate cortexBipolar illnessPsychosis historyWhole-brain connectivityBipolar patientsConnectivity alterationsBrain connectivityCo-occurring psychosisChronic schizophrenia patientsHealthy comparison subjectsBipolar disorder patientsPsychotic bipolar disorder patientsBipolar disorder groupAnterior cingulate cortexFunctional connectivity studiesPsychotic bipolar disorderLifetime psychosisChronic schizophreniaPsychotic symptomsDisorder patientsPatientsComparison subjectsSchizophrenia patientsBipolar disorderCingulate cortex
2013
Amygdala Connectivity Differs Among Chronic, Early Course, and Individuals at Risk for Developing Schizophrenia
Anticevic A, Tang Y, Cho YT, Repovs G, Cole MW, Savic A, Wang F, Krystal JH, Xu K. Amygdala Connectivity Differs Among Chronic, Early Course, and Individuals at Risk for Developing Schizophrenia. Schizophrenia Bulletin 2013, 40: 1105-1116. PMID: 24366718, PMCID: PMC4133672, DOI: 10.1093/schbul/sbt165.Peer-Reviewed Original ResearchConceptsHealthy comparison subjectsAmygdala connectivityHigh riskSymptom severityOrbitofrontal cortexWhole-brain functional connectivityHR individualsResting-state connectivitySchizophrenia symptom severityFunctional magnetic resonanceAmygdala seedArousal nucleiInitial episodeSchizophrenia neuropathologyChronic schizophreniaBrainstem regionsIllness phasePsychosis onsetElevated riskAmygdala circuitsEarly courseComparison subjectsFunctional alterationsClinical groupsFunctional connectivityGlobal Resting-State Functional Magnetic Resonance Imaging Analysis Identifies Frontal Cortex, Striatal, and Cerebellar Dysconnectivity in Obsessive-Compulsive Disorder
Anticevic A, Hu S, Zhang S, Savic A, Billingslea E, Wasylink S, Repovs G, Cole MW, Bednarski S, Krystal JH, Bloch MH, Li CS, Pittenger C. Global Resting-State Functional Magnetic Resonance Imaging Analysis Identifies Frontal Cortex, Striatal, and Cerebellar Dysconnectivity in Obsessive-Compulsive Disorder. Biological Psychiatry 2013, 75: 595-605. PMID: 24314349, PMCID: PMC3969771, DOI: 10.1016/j.biopsych.2013.10.021.Peer-Reviewed Original ResearchConceptsObsessive-compulsive disorderPrefrontal cortexResting-state functional connectivity dataStriatum/nucleus accumbensVentral striatum/nucleus accumbensResting-state functional connectivity studiesVentral anterior cingulate cortexCortico-striatal circuitsMagnetic Resonance Imaging AnalysisAnterior cingulate cortexFunctional connectivity studiesBasal gangliaControl subjectsFunctional connectivity dataAnterior thalamusRight putamenFrontal cortexNucleus accumbensDorsal striatumCerebellar cortexAbnormal neural connectivityCerebellar dysconnectivityCingulate cortexWhole brainFunctional magnetic resonance imaging (fMRI) analysisCharacterizing 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 cortexSchizophreniaIllness
2012
Global Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History
Anticevic A, Brumbaugh MS, Winkler AM, Lombardo LE, Barrett J, Corlett PR, Kober H, Gruber J, Repovs G, Cole MW, Krystal JH, Pearlson GD, Glahn DC. Global Prefrontal and Fronto-Amygdala Dysconnectivity in Bipolar I Disorder with Psychosis History. Biological Psychiatry 2012, 73: 565-573. PMID: 22980587, PMCID: PMC3549314, DOI: 10.1016/j.biopsych.2012.07.031.Peer-Reviewed Original ResearchConceptsPsychosis historyRisk factorsBipolar patientsSymptom severityResting-state functional magnetic resonanceAmygdala-mPFC connectivityFronto-limbic dysfunctionSevere clinical courseBipolar I patientsEmotion regulation regionsPsychotic symptom severityFunctional magnetic resonanceClinical courseI patientsLimbic structuresBipolar illnessConnectivity deficitsAmygdala findingsConnectivity abnormalitiesPathophysiological modelBipolar IPatientsBipolar disorderDysconnectivityAbnormal inhibitionA broken filter: Prefrontal functional connectivity abnormalities in schizophrenia during working memory interference
Anticevic A, Repovs G, Krystal JH, Barch DM. A broken filter: Prefrontal functional connectivity abnormalities in schizophrenia during working memory interference. Schizophrenia Research 2012, 141: 8-14. PMID: 22863548, PMCID: PMC3879404, DOI: 10.1016/j.schres.2012.07.007.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceBrain MappingFemaleFunctional LateralityHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMemory DisordersMemory, Short-TermMiddle AgedNerve NetNeural PathwaysNeuropsychological TestsOxygenPrefrontal CortexSchizophreniaSchizophrenic PsychologyConceptsFunctional connectivity abnormalitiesConnectivity abnormalitiesMedio-dorsal thalamusTask-based functional connectivityFinal common pathwayMaintenance phasePrefrontal cortical regionsDorsolateral prefrontal cortex activationPrefrontal cortex activationFunctional deficitsHealthy controlsSub-cortical regionsExtended amygdalaPatientsCortex activationCognitive deficitsCortical regionsFunctional connectivityLife outcomesAbnormalitiesDLPFC networkCommon pathwaySchizophrenia researchSchizophreniaMemory abnormalities
2010
Working Memory Overload: Fronto-Limbic Interactions and Effects on Subsequent Working Memory Function
Yun RJ, Krystal JH, Mathalon DH. Working Memory Overload: Fronto-Limbic Interactions and Effects on Subsequent Working Memory Function. Brain Imaging And Behavior 2010, 4: 96-108. PMID: 20503117, PMCID: PMC2854358, DOI: 10.1007/s11682-010-9089-9.Peer-Reviewed Original ResearchConceptsMemory systemAmygdala-prefrontal interactionsSubsequent cognitive performanceWorking Memory FunctionFunctional magnetic resonanceDorsolateral prefrontal cortexMemory taskCognitive functioningNegative affectAmygdala activationCognitive performanceTask performanceCognitive overloadNeural effectsPrefrontal cortexMemory functionPerformance accuracySubsequent functioningSeparate factorsBrain regionsPerformance declineReduced activationFunctioningInverse couplingOverload effect
2005
Untangling depression and anxiety: clinical challenges.
Keller MB, Krystal JH, Hen R, Neumeister A, Simon NM. Untangling depression and anxiety: clinical challenges. The Journal Of Clinical Psychiatry 2005, 66: 1477-84. PMID: 16420087, DOI: 10.4088/jcp.v66n1119.Peer-Reviewed Original Research
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 insightsAntagonistFrontostriatal Abnormalities in Adolescents With Bipolar Disorder: Preliminary Observations From Functional MRI
Blumberg HP, Martin A, Kaufman J, Leung HC, Skudlarski P, Lacadie C, Fulbright RK, Gore JC, Charney DS, Krystal JH, Peterson BS. Frontostriatal Abnormalities in Adolescents With Bipolar Disorder: Preliminary Observations From Functional MRI. American Journal Of Psychiatry 2003, 160: 1345-1347. PMID: 12832254, DOI: 10.1176/appi.ajp.160.7.1345.Peer-Reviewed Original ResearchConceptsBipolar disorder groupBipolar disorderHealthy groupComparison subjectsDisorder groupNormal comparison subjectsAdult bipolar disorderHealthy comparison subjectsPresence of dysfunctionFunctional magnetic resonance imagingMagnetic resonance imagingBipolar disorder subjectsAge-related increaseEvent-related functional magnetic resonance imagingFrontostriatal abnormalitiesLeft putamenFunctional abnormalitiesPrefrontal abnormalitiesDepressive symptomsResonance imagingVentral striatumFrontostriatal circuitsDisorder subjectsFunctional MRIDevelopmental disturbances