Abnormal Ventromedial Prefrontal Cortex Function in Children With Psychopathic Traits During Reversal Learning | Attention Deficit/Hyperactivity Disorders | JAMA Psychiatry | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC American Psychiatric Association1994;
Turgay  A Aggression and disruptive behavior disorders in children and adolescents.  Expert Rev Neurother 2004;4 (4) 623- 632PubMedGoogle ScholarCrossref
Frick  PJLilienfeld  SOEllis  MLoney  BSilverthorn  P The association between anxiety and psychopathy dimensions in children.  J Abnorm Child Psychol 1999;27 (5) 383- 392PubMedGoogle ScholarCrossref
Barry  CTFrick  PJDeShazo  TMMcCoy  MGEllis  MLoney  BR The importance of callous-unemotional traits for extending the concept of psychopathy to children.  J Abnorm Psychol 2000;109 (2) 335- 340PubMedGoogle ScholarCrossref
Christian  REFrick  PJHill  NLTyler  LFrazer  DR Psychopathy and conduct problems in children, II.  J Am Acad Child Adolesc Psychiatry 1997;36 (2) 233- 241PubMedGoogle ScholarCrossref
Dadds  MRFraser  JFrost  AHawes  DJ Disentangling the underlying dimensions of psychopathy and conduct problems in childhood: a community study.  J Consult Clin Psychol 2005;73 (3) 400- 410PubMedGoogle ScholarCrossref
Brandt  JRKennedy  WAPatrick  CJCurtin  JJ Assessment of psychopathy in a population of incarcerated adolescent offenders.  Psychol Assess 1997;9 (4) 429- 435Google ScholarCrossref
Forth  AKosson  DSHare  RD Hare Psychopathy Checklist-Youth Version.  Toronto, ON, Canada Multi-Health Systems Inc2004;
Tómasson  KVaglum  P Antisocial addicts: the importance of additional axis I disorders for the 28-month outcome.  Eur Psychiatry 2000;15 (8) 443- 449PubMedGoogle ScholarCrossref
Goodwin  RDHamilton  SP Lifetime comorbidity of antisocial personality disorder and anxiety disorders among adults in the community.  Psychiatry Res 2003;117 (2) 159- 166PubMedGoogle ScholarCrossref
Patrick  CJ Emotion and psychopathy.  Psychophysiology 1994;31 (4) 319- 330PubMedGoogle ScholarCrossref
Dolan  MCRennie  CE Is juvenile psychopathy associated with low anxiety and fear in conduct-disordered male offenders? [published online ahead of print January 10, 2007].  J Anxiety Disord 2007;21 (8) 1028PubMedGoogle ScholarCrossref
Blair  RJMitchell  DGBlair  KS The Psychopath: Emotion and the Brain.  Oxford, England Blackwell Publishing Limited2005;
Dollard  JDoob  CWMiller  NEMowrer  OHSears  RR Frustration and Aggression.  New Haven, CT Yale University Press1939;
Berkowitz  L Frustration-aggression hypothesis: examination and reformulation.  Psychol Bull 1989;106 (1) 59- 73PubMedGoogle ScholarCrossref
Blair  RJ The roles of orbital frontal cortex in the modulation of antisocial behavior.  Brain Cogn 2004;55 (1) 198- 208PubMedGoogle ScholarCrossref
Rolls  ETHornak  JWade  DMcGrath  J Emotion-related learning in patients with social and emotional changes associated with frontal lobe damage.  J Neurol Neurosurg Psychiatry 1994;57 (12) 1518- 1524PubMedGoogle ScholarCrossref
Blair  RJColledge  EMurray  LMitchell  DG A selective impairment in the processing of sad and fearful expressions in children with psychopathic tendencies.  J Abnorm Child Psychol 2001;29 (6) 491- 498PubMedGoogle ScholarCrossref
Budhani  SBlair  RJ Response reversal and children with psychopathic tendencies.   J Child Psychol Psychiatry 2005;46 (9) 972- 981PubMedGoogle ScholarCrossref
Roberts  ACRobbins  TWEveritt  BJMuir  JL A specific form of cognitive rigidity following excitotoxic lesions of the basal forebrain in marmosets.  Neuroscience 1992;47 (2) 251- 264PubMedGoogle ScholarCrossref
Iversen  SDMishkin  M Perseverative interference in monkeys following selective lesions of the inferior prefrontal convexity.  Exp Brain Res 1970;11 (4) 376- 386PubMedGoogle ScholarCrossref
Fellows  LKFarah  MJ Ventromedial frontal cortex mediates affective shifting in humans,   Brain 2003;126 (pt 8) 1830- 1837PubMedGoogle ScholarCrossref
Blair  RJPeschardt  KSBudhani  SMitchell  DGPine  DS The development of psychopathy.  J Child Psychol Psychiatry 2006;47 (3-4) 262- 276PubMedGoogle ScholarCrossref
O'Doherty  JCritchley  HDeichmann  RDolan  RJ Dissociating valence of outcome from behavioral control in human orbital and ventral prefrontal cortices.  J Neurosci 2003;23 (21) 7931- 7939PubMedGoogle Scholar
Remijnse  PLNielen  MMUylings  HBVeltman  DJ Neural correlates of a reversal learning task with an affectively neutral baseline: an event-related fMRI study.  Neuroimage 2005;26 (2) 609- 618PubMedGoogle ScholarCrossref
Kringelbach  MLRolls  ET Neural correlates of rapid reversal learning in a simple model of human social interaction.  Neuroimage 2003;20 (2) 1371- 1383PubMedGoogle ScholarCrossref
Budhani  SMarsh  AAPine  DSBlair  RJ Neural correlates of response reversal: considering acquisition.  Neuroimage 2007;34 (4) 1754- 1765PubMedGoogle ScholarCrossref
Cools  RClark  LOwen  AMRobbins  TW Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging.  J Neurosci 2002;22 (11) 4563- 4567PubMedGoogle Scholar
Botvinick  MMCohen  JDCarter  CS Conflict monitoring and anterior cingulate cortex: an update.  Trends Cogn Sci 2004;8 (12) 539- 546PubMedGoogle ScholarCrossref
Carter  CSBraver  TSBarch  DMBotvinick  MMNoll  DCohen  JD Anterior cingulate cortex, error detection, and the online monitoring of performance.  Science 1998;280 (5364) 747- 749PubMedGoogle ScholarCrossref
Tremblay  LSchultz  W Modifications of reward expectation-related neuronal activity during learning in primate orbitofrontal cortex.  J Neurophysiol 2000;83 (4) 1877- 1885PubMedGoogle Scholar
Rogers  RDRamnani  NMackay  CWilson  JLJezzard  PCarter  CSSmith  SM Distinct portions of anterior cingulate cortex and medial prefrontal cortex are activated by reward processing in separable phases of decision-making cognition.  Biol Psychiatry 2004;55 (6) 594- 602PubMedGoogle ScholarCrossref
Jensen  JSmith  AJWilleit  MCrawley  APMikulis  DJVitcu  IKapur  S Separate brain regions code for salience vs valence during reward prediction in humans.  Hum Brain Mapp 2007;28 (4) 294- 302PubMedGoogle ScholarCrossref
Yacubian  JGlascher  JSchroeder  KSommer  TBraus  DFBuchel  C Dissociable systems for gain- and loss-related value predictions and errors of prediction in the human brain.  J Neurosci 2006;26 (37) 9530- 9537PubMedGoogle ScholarCrossref
Knutson  BFong  GWAdams  CMVarner  JLHommer  D Dissociation of reward anticipation and outcome with event-related fMRI.  Neuroreport 2001;12 (17) 3683- 3687PubMedGoogle ScholarCrossref
O'Doherty  JPDayan  PFriston  KCritchley  HDolan  RJ Temporal difference models and reward-related learning in the human brain.  Neuron 2003;38 (2) 329- 337PubMedGoogle ScholarCrossref
McClure  SMBerns  GSMontague  PR Temporal prediction errors in a passive learning task activate human striatum.  Neuron 2003;38 (2) 339- 346PubMedGoogle ScholarCrossref
Ramnani  NElliott  RAthwal  BSPassingham  RE Prediction error for free monetary reward in the human prefrontal cortex.  Neuroimage 2004;23 (3) 777- 786PubMedGoogle ScholarCrossref
Kosson  DSSuchy  YMayer  ARLibby  J Facial affect recognition in criminal psychopaths.  Emotion 2002;2 (4) 398- 411PubMedGoogle ScholarCrossref
Durston  STottenham  NTThomas  KMDavidson  MCEigsti  IMYang  YUlug  AMCasey  BJ Differential patterns of striatal activation in young children with and without ADHD.  Biol Psychiatry 2003;53 (10) 871- 878PubMedGoogle ScholarCrossref
Dickstein  SGBannon  KXavier Castellanos  FMilham  MP The neural correlates of attention deficit hyperactivity disorder: an ALE meta-analysis.  J Child Psychol Psychiatry 2006;47 (10) 1051- 1062PubMedGoogle ScholarCrossref
Bush  GFrazier  JARauch  SLSeidman  LJWhalen  PJJenike  MARosen  BRBiederman  J Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop.  Biol Psychiatry 1999;45 (12) 1542- 1552PubMedGoogle ScholarCrossref
Booth  JRBurman  DDMeyer  JRLei  ZTrommer  BLDavenport  NDLi  WParrish  TBGitelman  DRMesulam  MM Larger deficits in brain networks for response inhibition than for visual selective attention in attention deficit hyperactivity disorder (ADHD).  J Child Psychol Psychiatry 2005;46 (1) 94- 111PubMedGoogle ScholarCrossref
Vaidya  CJBunge  SADudukovic  NMZalecki  CAElliott  GRGabrieli  JD Altered neural substrates of cognitive control in childhood ADHD: evidence from functional magnetic resonance imaging.  Am J Psychiatry 2005;162 (9) 1605- 1613PubMedGoogle ScholarCrossref
Itami  SUno  H Orbitofrontal cortex dysfunction in attention-deficit hyperactivity disorder revealed by reversal and extinction tasks.  Neuroreport 2002;13 (18) 2453- 2457PubMedGoogle ScholarCrossref
Forth  AEKosson  DSHare  RD The Hare Psychopathy Checklist: Youth Version.  Toronto, ON, Canada Multi-Health Systems2003;
Kates  WRAbrams  MTKaufmann  WEBreiter  SNReiss  AL Reliability and validity of MRI measurement of the amygdala and hippocampus in children with fragile X syndrome.  Psychiatry Res 1997;75 (1) 31- 48PubMedGoogle ScholarCrossref
Frick  PJBodin  SDBarry  CT Psychopathic traits and conduct problems in community and clinic-referred samples of children: further development of the psychopathy screening device.  Psychol Assess 2000;12 (4) 382- 393PubMedGoogle ScholarCrossref
Edens  JFSkeem  JLCruise  KRCauffman  E Assessment of “juvenile psychopathy” and its association with violence.   Behav Sci Law 2001;19 (1) 53- 80PubMedGoogle ScholarCrossref
Murrie  DCCornell  DG Psychopathy screening of incarcerated juveniles: a comparison of measures.  Psychol Assess 2002;14 (4) 390- 396PubMedGoogle ScholarCrossref
Frick  PJHare  RD Antisocial Process Screening Device.  Toronto, ON, Canada Multi-Health Systems Inc2001;
Vitale  JENewman  JPBates  JEGoodnight  JDodge  KAPettit  GS Deficient behavioral inhibition and anomalous selective attention in a community sample of adolescents with psychopathic traits and low-anxiety traits.  J Abnorm Child Psychol 2005;33 (4) 461- 470PubMedGoogle ScholarCrossref
Snodgrass  JGVanderwart  M A standardized set of 260 pictures: norms for name agreement, image agreement, familiarity, and visual complexity.  J Exp Psychol [Hum Learn] 1980;6 (2) 174- 215PubMedGoogle ScholarCrossref
Cox  RWHyde  JS Software tools for analysis and visualization of fMRI data.  NMR Biomed 1997;10 (4-5) 171- 178PubMedGoogle ScholarCrossref
Talairach  JTournoux  P Co-planar Stereotaxic Atlas of the Human Brain.  Stuttgart, Germany Thieme1988;
Kang  HCBurgund  EDLugar  HMPetersen  SESchlaggar  BL Comparison of functional activation foci in children and adults using a common stereotactic space.  Neuroimage 2003;19 (1) 16- 28PubMedGoogle ScholarCrossref
Burgund  EDKang  HCKelly  JEBuckner  RLSnyder  AZPetersen  SESchlaggar  BL The feasibility of a common stereotactic space for children and adults in fMRI studies of development.  Neuroimage 2002;17 (1) 184- 200PubMedGoogle ScholarCrossref
Swainson  RRogers  RDSahakian  BJSummers  BAPolkey  CERobbins  TW Probabilistic learning and reversal deficits in patients with Parkinson's disease or frontal or temporal lobe lesions.  Neuropsychologia 2000;38 (5) 596- 612PubMedGoogle ScholarCrossref
Lapierre  DBraun  CMHodgins  S Ventral frontal deficits in psychopathy: neuropsychological test findings.  Neuropsychologia 1995;33 (2) 139- 151PubMedGoogle ScholarCrossref
Birbaumer  NVeit  RLotze  MErb  MHermann  CGrodd  WFlor  H Deficient fear conditioning in psychopathy.  Arch Gen Psychiatry 2005;62 (7) 799- 805PubMedGoogle ScholarCrossref
Rilling  JKGlenn  ALJairam  MRPagnoni  GGoldsmith  DRElfenbein  HALilienfeld  SO Neural correlates of social cooperation and non-cooperation as a function of psychopathy.  Biol Psychiatry 2007;61 (11) 1260- 1271PubMedGoogle ScholarCrossref
Rogers  RDEveritt  BJBaldacchino  ABlackshaw  AJSwainson  RWynne  KBaker  NBHunter  JCarthy  TBooker  ELondon  MDeakin  JFSahakian  BJRobbins  TW Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms.  Neuropsychopharmacology 1999;20 (4) 322- 339PubMedGoogle ScholarCrossref
Gottfried  JAO'Doherty  JDolan  RJ Encoding predictive reward value in human amygdala and orbitofrontal cortex.  Science 2003;301 (5636) 1104- 1107PubMedGoogle ScholarCrossref
Schoenbaum  GNugent  SLSaddoris  MPSetlow  B Orbitofrontal lesions in rats impair reversal but not acquisition of go, no-go odor discriminations.  Neuroreport 2002;13 (6) 885- 890PubMedGoogle ScholarCrossref
Jentsch  JDOlausson  PDe La Garza  R  IITaylor  JR Impairments of reversal learning and response perseveration after repeated, intermittent cocaine administrations to monkeys.  Neuropsychopharmacology 2002;26 (2) 183- 190PubMedGoogle ScholarCrossref
Hampton  ANAdolphs  RTyszka  MJO'Doherty  JP Contributions of the amygdala to reward expectancy and choice signals in human prefrontal cortex.  Neuron 2007;55 (4) 545- 555PubMedGoogle ScholarCrossref
Haruno  MKawato  M Different neural correlates of reward expectation and reward expectation error in the putamen and caudate nucleus during stimulus-action-reward association learning.  J Neurophysiol 2006;95 (2) 948- 959PubMedGoogle ScholarCrossref
Haruno  MKawato  M Heterarchical reinforcement-learning model for integration of multiple cortico-striatal loops.  Neural Netw 2006;19 (8) 1242- 1254PubMedGoogle ScholarCrossref
Satterfield  JHFaller  KJCrinella  FMSchell  AMSwanson  JMHomer  LD A 30-year prospective follow-up study of hyperactive boys with conduct problems: adult criminality.  J Am Acad Child Adolesc Psychiatry 2007;46 (5) 601- 610PubMedGoogle ScholarCrossref
Frick  PJCornell  AHBarry  CTBodin  SDDane  HE Callous-unemotional traits and conduct problems in the prediction of conduct problem severity, aggression, and self-report of delinquency.  J Abnorm Child Psychol 2003;31 (4) 457- 470PubMedGoogle ScholarCrossref
Flor  HBirbaumer  NHermann  CZiegler  SPatrick  CJ Aversive Pavlovian conditioning in psychopaths: peripheral and central correlates.  Psychophysiology 2002;39 (4) 505- 518PubMedGoogle ScholarCrossref
Blair  RJMorris  JSFrith  CDPerrett  DIDolan  RJ Dissociable neural responses to facial expressions of sadness and anger.  Brain 1999;122 (pt 5) 883- 893PubMedGoogle ScholarCrossref
Raine  ALencz  TBihrle  SLaCasse  LColletti  P Reduced prefrontal gray matter volume and reduced autonomic activity in antisocial personality disorder.  Arch Gen Psychiatry 2000;57 (2) 119- 127, discussion 128-119PubMedGoogle ScholarCrossref
Kiehl  KA A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.  Psychiatry Res 2006;142 (2-3) 107- 128PubMedGoogle ScholarCrossref
Price  JLCarmichael  STDrevets  WC Networks related to the orbital and medial prefrontal cortex.   Prog Brain Res 1996;107523- 536PubMedGoogle Scholar
Schoenbaum  GChiba  AAGallagher  M Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning.  Nat Neurosci 1998;1 (2) 155- 159PubMedGoogle ScholarCrossref
Baxter  MGMurray  EA The amygdala and reward.  Nat Rev Neurosci 2002;3 (7) 563- 573PubMedGoogle ScholarCrossref
Izquierdo  AMurray  EA Selective bilateral amygdala lesions in rhesus monkeys fail to disrupt object reversal learning.  J Neurosci 2007;27 (5) 1054- 1062PubMedGoogle ScholarCrossref
Original Article
May 2008

Abnormal Ventromedial Prefrontal Cortex Function in Children With Psychopathic Traits During Reversal Learning

Author Affiliations

Author Affiliations: National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland (Drs Finger, Marsh, Budhani, Chen, Towbin, Leibenluft, Pine, and Blair and Mss Reid and Sims); Departments of Clinical Neurological Sciences (Dr Finger) and Psychiatry and Anatomy and Cell Biology (Dr Mitchell), University of Western Ontario, London, Ontario, Canada; and Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois (Dr Kosson).

Arch Gen Psychiatry. 2008;65(5):586-594. doi:10.1001/archpsyc.65.5.586

Context  Children and adults with psychopathic traits and conduct or oppositional defiant disorder demonstrate poor decision making and are impaired in reversal learning. However, the neural basis of this impairment has not previously been investigated. Furthermore, despite high comorbidity of psychopathic traits and attention-deficit/hyperactivity disorder, to our knowledge, no research has attempted to distinguish neural correlates of childhood psychopathic traits and attention-deficit/hyperactivity disorder.

Objective  To determine the neural regions that underlie the reversal learning impairments in children with psychopathic traits plus conduct or oppositional defiant disorder.

Design  Case-control study.

Setting  Government clinical research institute.

Participants  Forty-two adolescents aged 10 to 17 years: 14 with psychopathic traits and oppositional defiant disorder or conduct disorder, 14 with attention-deficit/hyperactivity disorder only, and 14 healthy controls.

Main Outcome Measure  Blood oxygenation level–dependent signal as measured via functional magnetic resonance imaging during a probabilistic reversal task.

Results  Children with psychopathic traits showed abnormal responses within the ventromedial prefrontal cortex (Brodmann area 10) during punished reversal errors compared with children with attention-deficit/hyperactivity disorder and healthy children (P < .05 corrected for multiple comparisons).

Conclusions  To our knowledge, this study provides the first evidence of abnormal ventromedial prefrontal cortex responsiveness in children with psychopathic traits and demonstrates this dysfunction was not attributable to comorbid attention-deficit/hyperactivity disorder. These findings suggest that reversal learning impairments in patients with developmental psychopathic traits relate to abnormal processing of reinforcement information.