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 modelDistractibilityNeuropsychological Functioning in Veterans with Posttraumatic Stress Disorder: Associations with Performance Validity, Comorbidities, and Functional Outcomes
Wrocklage KM, Schweinsburg BC, Krystal JH, Trejo M, Roy A, Weisser V, Moore TM, Southwick SM, Scott JC. Neuropsychological Functioning in Veterans with Posttraumatic Stress Disorder: Associations with Performance Validity, Comorbidities, and Functional Outcomes. Journal Of The International Neuropsychological Society 2016, 22: 399-411. PMID: 26892753, DOI: 10.1017/s1355617716000059.Peer-Reviewed Original ResearchConceptsNeuropsychological functioningGroup differencesValidity concernsPhysical health-related qualityDomains of speedPosttraumatic stress disorderInformation processing performanceEpisodic memoryAttention/Executive functionLanguage functioningPerformance validityCognitive functioningDisorder displayNeurocognitive domainsNeurocognitive findingsNeurocognitive functioningComparison participantsPTSD groupNeuropsychological testsStress disorderMost prior researchOccupational functioningNeuropsychological resultsPTSD status
2014
In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5
DeLorenzo C, DellaGioia N, Bloch M, Sanacora G, Nabulsi N, Abdallah C, Yang J, Wen R, Mann JJ, Krystal JH, Parsey RV, Carson RE, Esterlis I. In Vivo Ketamine-Induced Changes in [11C]ABP688 Binding to Metabotropic Glutamate Receptor Subtype 5. Biological Psychiatry 2014, 77: 266-275. PMID: 25156701, PMCID: PMC4277907, DOI: 10.1016/j.biopsych.2014.06.024.Peer-Reviewed Original ResearchConceptsSubtype 5Ketamine administrationPET scansMetabotropic glutamate receptor subtype 5Prefrontal cortexAspartate glutamate receptor antagonistIntravenous ketamine administrationKetamine-induced effectsPositron emission tomography (PET) ligandGlutamate receptor antagonistsVolume of distributionMedial prefrontal cortexNegative allosteric modulatorsKetamine initiationGlutamate releaseDorsal putamenKetamine responseSubanesthetic dosesOrbital prefrontal cortexReceptor antagonistAcute effectsBolus injectionDorsal caudateArterial bloodScan 1
2013
The Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity
Driesen NR, McCarthy G, Bhagwagar Z, Bloch MH, Calhoun VD, D'Souza DC, Gueorguieva R, He G, Leung HC, Ramani R, Anticevic A, Suckow RF, Morgan PT, Krystal JH. The Impact of NMDA Receptor Blockade on Human Working Memory-Related Prefrontal Function and Connectivity. Neuropsychopharmacology 2013, 38: 2613-2622. PMID: 23856634, PMCID: PMC3828532, DOI: 10.1038/npp.2013.170.Peer-Reviewed Original ResearchConceptsNMDA-Rs
2012
A 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 abnormalitiesMild Worry Symptoms Predict Decline in Learning and Memory in Healthy Older Adults: A 2-Year Prospective Cohort Study
Pietrzak RH, Maruff P, Woodward M, Fredrickson J, Fredrickson A, Krystal JH, Southwick SM, Darby D. Mild Worry Symptoms Predict Decline in Learning and Memory in Healthy Older Adults: A 2-Year Prospective Cohort Study. American Journal Of Geriatric Psychiatry 2012, 20: 266-275. PMID: 22354117, PMCID: PMC3285262, DOI: 10.1097/jgp.0b013e3182107e24.Peer-Reviewed Original ResearchConceptsWorry symptomsOlder adultsCommunity-dwelling older adultsCognitive functionAge-related cognitive changesHealthy Older AdultsImportance of anxietyEarly cognitive declineDepressive symptomsAssociate learningCognitive agingVisual learningCognitive changesProspective cohort studyCognitive declineDepression symptomsEarly dementiaCohort studyObservational prospective cohort studyMemoryMild levelsLearningWorryAdultsTheoretical model
2010
Characterization of the Interactive Effects of Glycine and D-Cycloserine in Men: Further Evidence for Enhanced NMDA Receptor Function Associated with Human Alcohol Dependence
Krystal JH, Petrakis IL, Limoncelli D, Nappi SK, Trevisan L, Pittman B, D'Souza DC. Characterization of the Interactive Effects of Glycine and D-Cycloserine in Men: Further Evidence for Enhanced NMDA Receptor Function Associated with Human Alcohol Dependence. Neuropsychopharmacology 2010, 36: 701-710. PMID: 21124304, PMCID: PMC3055693, DOI: 10.1038/npp.2010.203.Peer-Reviewed Original ResearchConceptsNMDA receptor functionAlcohol-dependent patientsHuman alcohol dependenceAntagonist-like effectsReceptor functionReceptor antagonistDCS effectsD-cycloserineAlcohol-like effectsAlcohol dependenceNMDA glutamate receptor functionN-methyl-D-aspartate (NMDA) glutamate receptor antagonistStandard alcohol drinksGlutamate receptor antagonistsChronic alcohol consumptionDouble-blind conditionsNMDA receptor antagonistAlcohol-dependent menGlutamate receptor functionAlcohol-dependent animalsPlasma levelsGlycine administrationGlycine levelsNMDA receptorsCoagonist siteClinical significance of neurological soft signs in schizophrenia: Factor analysis of the Neurological Evaluation Scale
Sewell RA, Perry EB, Karper LP, Bell MD, Lysaker P, Goulet JL, Brenner L, Erdos J, d'Souza DC, Seibyl JP, Krystal JH. Clinical significance of neurological soft signs in schizophrenia: Factor analysis of the Neurological Evaluation Scale. Schizophrenia Research 2010, 124: 1-12. PMID: 20855185, DOI: 10.1016/j.schres.2010.08.036.Peer-Reviewed Original ResearchConceptsNeurological Evaluation ScaleAbnormal Involuntary Movement ScaleDigit Symbol Substitution TaskWisconsin Card Sorting TestNeurologic deficitsClinical significanceExtrapyramidal Symptom Rating ScaleMore extrapyramidal symptomsBarnes Akathisia ScaleDetailed clinical assessmentNeurological soft signsSymptom Rating ScaleNegative Syndrome ScaleHigher AIMS scoresEvaluation ScaleNeurological deficitsExtrapyramidal symptomsClinical correlatesDeficit syndrome schizophreniaClinical evaluationClinical assessmentAIMS scoresLower PANSSMovement ScaleSoft signsSex-related differences in amygdala activity influences immediate memory
Aikins DE, Anticevic A, Kiehl KA, Krystal JH. Sex-related differences in amygdala activity influences immediate memory. Neuroreport 2010, 21: 273-276. PMID: 20093991, DOI: 10.1097/wnr.0b013e328335b3f9.Peer-Reviewed Original ResearchMeSH KeywordsAdultAmygdalaEmotionsFemaleFunctional LateralityHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedNeuropsychological TestsPattern Recognition, VisualPhotic StimulationPsychomotor PerformanceRecognition, PsychologyRegression AnalysisSex CharacteristicsSex FactorsConceptsAmygdala activationImmediate memoryUnpleasant picturesImmediate recognition memoryRecognition memory testRight amygdala activationLong-term memoryFunctional magnetic resonanceUnpleasant picture viewingEmotional picturesRecognition memoryMemory testAmygdala responsePicture viewingMemoryFalse positive error rateSex differencesSex-related differencesAmygdalaError ratePictureViewingLearningMagnetic resonanceDifferencesWorking 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
2008
Impairment of Working Memory Maintenance and Response in Schizophrenia: Functional Magnetic Resonance Imaging Evidence
Driesen NR, Leung HC, Calhoun VD, Constable RT, Gueorguieva R, Hoffman R, Skudlarski P, Goldman-Rakic PS, Krystal JH. Impairment of Working Memory Maintenance and Response in Schizophrenia: Functional Magnetic Resonance Imaging Evidence. Biological Psychiatry 2008, 64: 1026-1034. PMID: 18823880, PMCID: PMC2650279, DOI: 10.1016/j.biopsych.2008.07.029.Peer-Reviewed Original ResearchConceptsMemory taskPrefrontal activityMemory maintenanceBrain activationFunctional Magnetic Resonance Imaging EvidenceWorking Memory MaintenanceCognitive impairmentHealthy comparison participantsPrefrontal cortical activityFunctional magnetic resonanceMemory loadComparison participantsTask accuracyDistinct neurobiologyCortical activityHealthy participantsBasic research insightsImaging EvidenceMemoryCortical deficitsCortical functionPoor performanceTaskSchizophreniaResponse phaseIdentifying Cognitive Mechanisms Targeted for Treatment Development in Schizophrenia: An Overview of the First Meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative
Carter CS, Barch DM, Buchanan RW, Bullmore E, Krystal JH, Cohen J, Geyer M, Green M, Nuechterlein KH, Robbins T, Silverstein S, Smith EE, Strauss M, Wykes T, Heinssen R. Identifying Cognitive Mechanisms Targeted for Treatment Development in Schizophrenia: An Overview of the First Meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative. Biological Psychiatry 2008, 64: 4-10. PMID: 18466880, PMCID: PMC2577821, DOI: 10.1016/j.biopsych.2008.03.020.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntipsychotic AgentsBiomedical ResearchBrainCognition DisordersCooperative BehaviorDrug IndustryHumansNational Institute of Mental Health (U.S.)Neuropsychological TestsResearch Support as TopicSchizophreniaSchizophrenic PsychologyUnited StatesUnited States Food and Drug AdministrationConceptsCognitive Neuroscience Treatment ResearchSchizophrenia (MATRICS) initiativeTreatment researchCognitive neuroscience fieldCNTRICS initiativeCognitive mechanismsCognitive constructsTreatment developmentNeuroscience fieldCognitive impairmentCognitionBasic animalSchizophreniaResearchFirst meetingImpairmentConstructsParadigmTranslational researchTranslation effortsNovel treatmentsOrganization
2007
Luteal-Phase Accentuation of Acoustic Startle Response in Women with Premenstrual Dysphoric Disorder
Epperson CN, Pittman B, Czarkowski KA, Stiklus S, Krystal JH, Grillon C. Luteal-Phase Accentuation of Acoustic Startle Response in Women with Premenstrual Dysphoric Disorder. Neuropsychopharmacology 2007, 32: 2190-2198. PMID: 17314917, PMCID: PMC2713599, DOI: 10.1038/sj.npp.1301351.Peer-Reviewed Original ResearchConceptsPremenstrual dysphoric disorderMenstrual cycle phaseMenstrual cycleHealthy womenFollicular phaseDysphoric disorderLuteal phasePhysiologic responsesMenstrual cycle-related fluctuationsStartle magnitudeCentral nervous system responseHealthy menstruating womenAcoustic startle responseAcoustic startle paradigmNervous system responsesPowerful modulatory effectsStartle response magnitudeVisual affective stimuliNeuroactive steroidsMenstruating womenASR magnitudeModulatory effectsCycle phaseNeuroendocrine milieuAcoustic startle response magnitudes
2006
Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects
Neumeister A, Carson R, Henry S, Planeta-Wilson B, Binneman B, Maguire RP, Luckenbaugh DA, D'Souza C, Krystal JH, Frost JJ. Cerebral Metabolic Effects of Intravenous Glycine in Healthy Human Subjects. Journal Of Clinical Psychopharmacology 2006, 26: 595-599. PMID: 17110816, DOI: 10.1097/01.jcp.0000245558.14284.aa.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntipsychotic AgentsBehaviorBrainBrain MappingCluster AnalysisCross-Over StudiesDouble-Blind MethodFemaleFluorodeoxyglucose F18GlycineHumansInfusions, IntravenousMagnetic Resonance ImagingMaleNeuropsychological TestsPositron-Emission TomographyRadiopharmaceuticalsReference ValuesSerineConceptsN-methyl-D-aspartate receptor functionReceptor functionRegional cerebral metabolic rateAdministration of glycineCerebral metabolic effectsMagnetic resonance imaging studyPositron emission tomography studyHealthy control subjectsNMDA receptor functionCerebral metabolic rateEmission tomography studiesTest dayHealthy human subjectsResonance imaging studySignificant reductionPositron emission tomographyDorsolateral prefrontal cortexIntravenous glycinePlacebo infusionCerebral metabolismPatient populationControl subjectsGlycine administrationGlycine infusionIntravenous administrationEnhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia
D'Souza DC, Gil RB, Madonick S, Perry EB, Forselius-Bielen K, Braley G, Donahue L, Tellioglu T, Zimolo Z, Gueorguieva R, Krystal JH. Enhanced Sensitivity to the Euphoric Effects of Alcohol in Schizophrenia. Neuropsychopharmacology 2006, 31: 2767-2775. PMID: 16985503, DOI: 10.1038/sj.npp.1301207.Peer-Reviewed Original ResearchConceptsEffects of alcoholHealthy subjectsBlood alcohol levelsPositive psychotic symptomsSmall transient increaseSelf-medication hypothesisPerceptual alterationsAlcohol administrationMotor functionAlcohol dosesElevated riskPsychotic symptomsLifetime exposureSchizophrenia patientsSchizophrenia symptomsEuphoric effectsNegative symptomsAlcohol levelsAlcohol useStimulatory effectSubjective effectsTransient increaseSchizophreniaStimulatory responseAlcohol responses
2005
Abnormal hemodynamics in schizophrenia during an auditory oddball task
Kiehl KA, Stevens MC, Celone K, Kurtz M, Krystal JH. Abnormal hemodynamics in schizophrenia during an auditory oddball task. Biological Psychiatry 2005, 57: 1029-1040. PMID: 15860344, PMCID: PMC2771438, DOI: 10.1016/j.biopsych.2005.01.035.Peer-Reviewed Original ResearchConceptsAuditory oddball taskHealthy participantsOddball taskThree-stimulus auditory oddball taskDiffuse brain abnormalitiesHealthy control subjectsNovelty processingWidespread pathologic processCerebral areasControl subjectsBrain abnormalitiesMagnetic resonance imaging dataAbnormal hemodynamicsPathologic processesSchizophrenia patientsParietal cortexCognitive functionHeterogeneous disorderCerebellar circuitsSchizophreniaAbnormalitiesSignificant activationSubcortical systemsFunctional magnetic resonance imaging (fMRI) dataPatientsDelta-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 alterationsDeficitsCannabisSubjectsAkathisiaExacerbationEffects of smoking and smoking abstinence on cognition in adolescent tobacco smokers
Jacobsen LK, Krystal JH, Mencl WE, Westerveld M, Frost SJ, Pugh KR. Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers. Biological Psychiatry 2005, 57: 56-66. PMID: 15607301, DOI: 10.1016/j.biopsych.2004.10.022.Peer-Reviewed Original ResearchConceptsAdolescent smokersVerbal memoryTobacco cravingAdolescent daily smokersNicotine withdrawalAdolescent tobacco smokersDaily tobacco smokersDivided attentionVerbal learningCognitive enhancementMemory performanceSustained attentionCognitive performanceGeneral intelligenceAdolescent nonsmokersPerformance decrementsParental educational attainmentFemale smokersDepressed moodMemoryAffective symptomsDaily smokersRecency of smokingTobacco smokersEarly age
2004
Nicotine effects on brain function and functional connectivity in schizophrenia
Jacobsen LK, D'Souza DC, Mencl WE, Pugh KR, Skudlarski P, Krystal JH. Nicotine effects on brain function and functional connectivity in schizophrenia. Biological Psychiatry 2004, 55: 850-858. PMID: 15050867, DOI: 10.1016/j.biopsych.2003.12.023.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnalysis of VarianceAttentionBrainBrain MappingBrief Psychiatric Rating ScaleCase-Control StudiesFemaleHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMemory, Short-TermMiddle AgedNeuropsychological TestsNicotineNicotinic AgonistsReaction TimeRegression AnalysisSchizophreniaSmokeTask Performance and AnalysisVerbal LearningConceptsTask performanceFunctional connectivityFunctional magnetic resonance imaging (fMRI) scanningBrain regionsN-back taskMultiple cognitive domainsNetwork of regionsDifficult task conditionsAnterior cingulate cortexAttention loadMemory loadSelective attentionCognitive domainsTask conditionsCognitive functionCingulate cortexThalamocortical functional connectivityNicotine effectsCognitive dysfunctionBrain functionSchizophrenia patientsControl subjectsSchizophrenic subjectsMagnetic resonance imaging (MRI) scanningMental illness
2003
Frontostriatal 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 ResearchMeSH KeywordsAdolescentAge FactorsBasal GangliaBipolar DisorderChildFemaleHumansMagnetic Resonance ImagingMaleNeural PathwaysNeuropsychological TestsPrefrontal CortexConceptsBipolar 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