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 ResearchConceptsCortical 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 paradigmDopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia
Abi-Dargham A, Javitch JA, Slifstein M, Anticevic A, Calkins ME, Cho YT, Fonteneau C, Gil R, Girgis R, Gur RE, Gur RC, Grinband J, Kantrowitz J, Kohler C, Krystal J, Murray J, Ranganathan M, Santamauro N, Van Snellenberg J, Tamayo Z, Wolf D, D’Souza D, Srihari V, Gueorguieva R, Patel P, Forselius-Bielen K, Lu J, Butler A, Fram G, Afriyie-Agyemang Y, Selloni A, Cadavid L, Gomez-Luna S, Gupta A, Radhakrishnan R, Rashid A, Aker R, Abrahim P, Nia A, Surti T, Kegeles L, Carlson M, Goldberg T, Gangwisch J, Benedict E, Govil P, Brazis S, Mayer M, de la Garrigue N, Fallon N, Baumvoll T, Abeykoon S, Perlman G, Bobchin K, Elliott M, Schmidt L, Rush S, Port A, Heffernan Z, Laney N, Kantor J, Hohing T, Gray D, Lieberman J. Dopamine D1R Receptor Stimulation as a Mechanistic Pro-cognitive Target for Schizophrenia. Schizophrenia Bulletin 2021, 48: 199-210. PMID: 34423843, PMCID: PMC8781338, DOI: 10.1093/schbul/sbab095.Peer-Reviewed Original ResearchConceptsCortical dopamine neurotransmissionPositive allosteric modulationImportant therapeutic targetPF-06412562Dopaminergic receptorsD1R stimulationDA levelsTolerable dosesLevel of stimulationDopamine neurotransmissionReceptor stimulationTherapeutic targetPartial agonistCognitive deficitsBiased agonismFull agonismTarget engagementAllosteric modulationNew drugsStimulationPoor bioavailabilitySchizophreniaOptimal stimulationDrugsExpression levels
2017
389 In Vivo Evidence of Lower Synaptic Density in Depression and Associated Mood and Cognitive Deficits: A [11C]UCB-J PET Imaging Study
Esterlis I, Pietrzak R, DellaGioia N, Matuskey D, Huang H, Krystal J, Duman R, Carson R, Finnema S. 389 In Vivo Evidence of Lower Synaptic Density in Depression and Associated Mood and Cognitive Deficits: A [11C]UCB-J PET Imaging Study. Biological Psychiatry 2017, 81: s159. DOI: 10.1016/j.biopsych.2017.02.406.Peer-Reviewed Original Research
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
2015
A Quantitative Meta-Analysis of Neurocognitive Functioning in Posttraumatic Stress Disorder
Scott JC, Matt GE, Wrocklage KM, Crnich C, Jordan J, Southwick SM, Krystal JH, Schweinsburg BC. A Quantitative Meta-Analysis of Neurocognitive Functioning in Posttraumatic Stress Disorder. Psychological Bulletin 2015, 141: 105-140. PMID: 25365762, PMCID: PMC4293317, DOI: 10.1037/a0038039.Peer-Reviewed Original ResearchConceptsPosttraumatic stress disorderVerbal memoryInformation processingVerbal learningAttention/Cognitive domainsComparison participantsStress disorderCognitive deficitsAttention-deficit/hyperactivity disorderEffect size estimatesHealthy comparison participantsQuantitative Meta-AnalysisEffect sizeLarge effect sizesVisual memoryCognitive modelExecutive functionVisual learningVisuospatial abilitiesNeuropsychological functioningTrauma exposureNeurocognitive functioningHyperactivity disorderPTSD group
2014
Going up in smoke? A review of nAChRs-based treatment strategies for improving cognition in schizophrenia.
Boggs DL, Carlson J, Cortes-Briones J, Krystal JH, D'Souza DC. Going up in smoke? A review of nAChRs-based treatment strategies for improving cognition in schizophrenia. Current Pharmaceutical Design 2014, 20: 5077-92. PMID: 24345265, PMCID: PMC4442779, DOI: 10.2174/1381612819666131216121019.Peer-Reviewed Original ResearchConceptsCognitive impairmentStandardized cognitive test batteryCognitive test batteryInformation processing impairmentsNicotinic medicationsProcessing impairmentsCore deficitAttentional deficitsTest batteryCognitive deficitsProximal measuresBrain functionCognitionSchizophreniaDeficitsImpairmentNumber of medicationsNicotinic acetylcholine receptorsCertain symptomsConsistent improvementClinical evidenceTreatment strategiesClinical studiesNicotinic receptorsClinical utility
2013
Translational cognitive neuroscience of schizophrenia: bridging neurocognitive and computational approaches toward understanding cognitive deficits
Anticevic A, Krystal J, Barch D. Translational cognitive neuroscience of schizophrenia: bridging neurocognitive and computational approaches toward understanding cognitive deficits. 2013, 193-230. DOI: 10.1017/cbo9781139003872.013.Peer-Reviewed Original ResearchCognitive deficitsCognitive neuroscienceCourse of impairmentSevere mental illnessDeficitsSchizophreniaMental illnessPharmacological techniquesBiological contributionPrecise mechanismNeuroscienceIllnessLittle disputeRelated featuresStyleFunctional implicationsImpairmentManagement optionsImplicationsDisabilityPatientsSymptomsCliniciansDisease
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 deficitsDeficitsA 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
2005
Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction
D’Souza D, Abi-Saab WM, Madonick S, Forselius-Bielen K, Doersch A, Braley G, Gueorguieva R, Cooper TB, Krystal JH. Delta-9-tetrahydrocannabinol effects in schizophrenia: Implications for cognition, psychosis, and addiction. Biological Psychiatry 2005, 57: 594-608. PMID: 15780846, DOI: 10.1016/j.biopsych.2004.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAdultAkathisia, Drug-InducedArousalCognitionDose-Response Relationship, DrugDouble-Blind MethodDronabinolEndocrine SystemFemaleHumansInjections, IntravenousMaleMental RecallMiddle AgedMotor ActivityNeuropsychological TestsPerceptionPsychiatric Status Rating ScalesPsychotic DisordersPsychotropic DrugsSchizophreniaVerbal LearningConceptsSchizophrenia patientsAntipsychotic-treated schizophrenia patientsDelta-9-tetrahydrocannabinol effectsLong-term adverse eventsCognitive deficitsPlacebo-controlled studyDelta-9-THCTransient exacerbationAdverse eventsReceptor dysfunctionEndocrine effectsHealthy subjectsStudy participationPsychotic disordersPlasma prolactinSchizophrenia symptomsPatientsSchizophreniaCognitive effectsPerceptual alterationsDeficitsCannabisSubjectsAkathisiaExacerbation
2004
The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis
D'Souza DC, Perry E, MacDougall L, Ammerman Y, Cooper T, Wu YT, Braley G, Gueorguieva R, Krystal JH. The Psychotomimetic Effects of Intravenous Delta-9-Tetrahydrocannabinol in Healthy Individuals: Implications for Psychosis. Neuropsychopharmacology 2004, 29: 1558-1572. PMID: 15173844, DOI: 10.1038/sj.npp.1300496.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnxietyArousalAttentionBehaviorCognitionDose-Response Relationship, DrugDouble-Blind MethodDronabinolFemaleHallucinogensHemodynamicsHumansHydrocortisoneInjections, IntravenousMaleMemory, Short-TermMental RecallPanicProlactinPsychiatric Status Rating ScalesPsychometricsPsychoses, Substance-InducedSpeechVerbal LearningConceptsCannabinoid receptor functionWord recallRecognition recallVerbal fluencyCognitive deficitsProspective safety dataNegative symptomsAbuse disordersHealthy individualsCounterbalanced studyMonths poststudyRecallPsychotomimetic effectsPsychotic disordersReceptor functionPsychosisEndogenous psychosesIndividualsDistractibilityFluencyTransient symptomsDisordersEndocrine effectsSafety dataAnxiety
2003
Preliminary evidence of hippocampal dysfunction in adolescent MDMA (“ecstasy”) users: possible relationship to neurotoxic effects
Jacobsen LK, Mencl WE, Pugh KR, Skudlarski P, Krystal JH. Preliminary evidence of hippocampal dysfunction in adolescent MDMA (“ecstasy”) users: possible relationship to neurotoxic effects. Psychopharmacology 2003, 173: 383-390. PMID: 14647960, DOI: 10.1007/s00213-003-1679-4.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingMDMA usersCognitive deficitsMDMA useBrain functionDivided attentionMemory taskMemory loadResultsMDMA usersLeft hippocampusHippocampal dysfunctionSubstance useCognitive impairmentAdolescencePreliminary evidenceReaction timeDevelopmental impactPilot sampleDeficitsMDMAMagnetic resonance imagingIQAttentionMemoryHippocampus
1994
Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans: Psychotomimetic, Perceptual, Cognitive, and Neuroendocrine Responses
Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB, Charney DS. Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans: Psychotomimetic, Perceptual, Cognitive, and Neuroendocrine Responses. JAMA Psychiatry 1994, 51: 199-214. PMID: 8122957, DOI: 10.1001/archpsyc.1994.03950030035004.Peer-Reviewed Original ResearchMeSH KeywordsAdultBlood PressureCognitionDissociative DisordersDose-Response Relationship, DrugDouble-Blind MethodFemaleFrontal LobeHomovanillic AcidHumansHydrocortisoneKetamineMaleMethoxyhydroxyphenylglycolNeuropsychological TestsPerceptionProlactinPsychiatric Status Rating ScalesPsychoses, Substance-InducedPulseReceptors, N-Methyl-D-AspartateSchizophreniaSchizophrenic PsychologyConceptsWisconsin Card Sorting TestCard Sorting TestMini-Mental State ExaminationSorting TestNegative symptomsTests of vigilanceVerbal fluency taskDissociative statesState ExaminationFrontal cortical dysfunctionPsychosis Proneness ScalesClinician-Administered Dissociative States ScaleWord recallImmediate recallVerbal fluencyFluency taskVigilance taskCognitive deficitsCognitive functionRecallState scaleBrief Psychiatric Rating ScaleCortical dysfunctionTest dayPsychiatric Rating Scale