Further Evidence for Aberrant Prefrontal Salience Coding in Schizophrenia

The revised dopamine hypothesis of schizophrenia postulates that dopamine metabolism is impacted differently with increased dopamine in the subcortical mesolimbic system and decreased dopamine in prefrontal cortical regions. Recently, we described findings supporting this hypothesis using a financial reward task in patients with schizophrenia (Walter et al., 2009). In addition to analysing prediction and prediction error coding, we found in this study evidence for aberrant cortical representation of salience in the right ventrolateral prefrontal cortex (VLPFC) in patients. Here, we reanalysed data of four other published reward studies of our group in order to investigate (i) whether we could replicate this finding in an independent cohort of patients with schizophrenia and (ii) how dopaminergic modulation impacts on cortical salience representation. Our main result was that we could replicate the finding of aberrant salience coding in the right VLPFC in patients with schizophrenia. Furthermore, we found evidence that the degree of salience coding in this region was correlated inversely with negative symptoms (anhedonia). Results of dopaminergic modulation showed tentative evidence for an influence of dopaminergic stimulation, but were not conclusive. In summary, we conclude that the right VLPFC might play a crucial role in salience coding and is impaired in schizophrenia.

[1]  Henrik Walter,et al.  Neural correlates of frustration , 2005, Neuroreport.

[2]  Oshin Vartanian,et al.  Dissociating the roles of right ventral lateral and dorsal lateral prefrontal cortex in generation and maintenance of hypotheses in set-shift problems. , 2005, Cerebral cortex.

[3]  H. Wetzel,et al.  [Evaluation of standardized training for the "Positive and Negative Syndrome Scale" (PANSS)]. , 2000, Der Nervenarzt.

[4]  J. Gläscher,et al.  Dissociable Systems for Gain- and Loss-Related Value Predictions and Errors of Prediction in the Human Brain , 2006, The Journal of Neuroscience.

[5]  L. J. Chapman,et al.  Scales for physical and social anhedonia. , 1976, Journal of abnormal psychology.

[6]  James A. Waltz,et al.  Probabilistic reversal learning impairments in schizophrenia: Further evidence of orbitofrontal dysfunction , 2007, Schizophrenia Research.

[7]  M. Hautzinger,et al.  Zur psychometrischen Erfassung von Schizotypie: Methodische Überprüfung und erste Validierung von zwei Skalen zur Erfassung von Risikomerkmalen , 1991 .

[8]  S. Kapur,et al.  How antipsychotics work—From receptors to reality , 2011, NeuroRX.

[9]  A. Carlsson,et al.  EFFECT OF CHLORPROMAZINE OR HALOPERIDOL ON FORMATION OF 3METHOXYTYRAMINE AND NORMETANEPHRINE IN MOUSE BRAIN. , 2009, Acta pharmacologica et toxicologica.

[10]  M. Vogt The neurobiology of dopamine, A.S. Horn, J. Korf, B.H.C. Westerink (Eds.). Academic Press, London (1979), 723, £39.60 , 1982 .

[11]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[12]  Brian Knutson,et al.  Valence and salience contribute to nucleus accumbens activation , 2008, NeuroImage.

[13]  S. Kapur Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. , 2003, The American journal of psychiatry.

[14]  B. Abler,et al.  Altered reward functions in patients on atypical antipsychotic medication in line with the revised dopamine hypothesis of schizophrenia , 2009, Psychopharmacology.

[15]  E T Bullmore,et al.  Substantia nigra/ventral tegmental reward prediction error disruption in psychosis , 2008, Molecular Psychiatry.

[16]  M. Spitzer,et al.  A cognitive neuroscience view of schizophrenic thought disorder. , 1997, Schizophrenia bulletin.

[17]  Brian Knutson,et al.  Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics , 2006, Psychopharmacology.

[18]  K. Berridge,et al.  Parsing reward , 2003, Trends in Neurosciences.

[19]  A. Heinz,et al.  Dopaminergic dysfunction in alcoholism and schizophrenia – psychopathological and behavioral correlates , 2002, European Psychiatry.

[20]  S. Heckers,et al.  Abnormal Reward System Activation in Mania , 2008, Neuropsychopharmacology.

[21]  S. Kapur,et al.  The Formation of Abnormal Associations in Schizophrenia: Neural and Behavioral Evidence , 2008, Neuropsychopharmacology.

[22]  Brian Knutson,et al.  Dissociation of reward anticipation and outcome with event-related fMRI , 2001, Neuroreport.

[23]  Henrik Walter,et al.  Prediction error as a linear function of reward probability is coded in human nucleus accumbens , 2006, NeuroImage.

[24]  Arno Villringer,et al.  Dysfunction of ventral striatal reward prediction in schizophrenia , 2006, NeuroImage.

[25]  R. Wise,et al.  Neuroleptic-induced "anhedonia" in rats: pimozide blocks reward quality of food. , 1978, Science.

[26]  G. Juckel,et al.  Reward Feedback Alterations in Unmedicated Schizophrenia Patients: Relevance for Delusions , 2009, Biological Psychiatry.

[27]  Jeffrey C. Cooper,et al.  Functional magnetic resonance imaging of reward prediction , 2005, Current opinion in neurology.

[28]  J. Meador-Woodruff,et al.  Neurocognitive measures of prefrontal cortical dysfunction in schizophrenia , 2004, Schizophrenia Research.

[29]  A. Carlsson,et al.  Network interactions in schizophrenia — therapeutic implications , 2000, Brain Research Reviews.

[30]  S. Kapur,et al.  Separate brain regions code for salience vs. valence during reward prediction in humans , 2007, Human brain mapping.

[31]  B. Abler,et al.  At-risk for pathological gambling: imaging neural reward processing under chronic dopamine agonists. , 2009, Brain : a journal of neurology.

[32]  J. Parkinson,et al.  Dissociable Contributions of the Human Amygdala and Orbitofrontal Cortex to Incentive Motivation and Goal Selection , 2003, The Journal of Neuroscience.

[33]  D. Barch,et al.  Imaging genetic liability to schizophrenia: systematic review of FMRI studies of patients' nonpsychotic relatives. , 2009, Schizophrenia bulletin.

[34]  B. Abler,et al.  Human reward system activation is modulated by a single dose of olanzapine in healthy subjects in an event-related, double-blind, placebo-controlled fMRI study , 2007, Psychopharmacology.

[35]  A. Dickinson,et al.  Disrupted prediction-error signal in psychosis: evidence for an associative account of delusions. , 2007, Brain : a journal of neurology.