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Further evidence for aberrant prefrontal salience coding in schizophrenia.

Walter H, Heckers S, Kassubek J, Erk S, Frasch K, Abler B - Front Behav Neurosci (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Division of Medical Psychology, University of Bonn Bonn, Germany.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Salience in outcome (reward probability). Brain activation and beta weights in the right VLPFC/anterior insula as found for the contrast modelling salience scanned during the probability paradigm. Study 3 was performed in healthy controls (HC), study 4 in patients with RLS off and on their regular medication. The beta values were extracted from the maximum voxel of the demonstrated activation. The map was thresholded at p < 0.005 FWE corrected for healthy controls and at p < 0.001 at the voxel-level and at an extent threshold of p < 0.05 at the cluster-level in patients. The coefficient “a” taken as a measure of the shape of a U-shaped regression curve indicates a more shallow curve the lower the levels in healthy controls. In RLS patients on regular medication, the coefficient “a” taken as a measure of the shape of a U-shaped regression curve indicates a trend (p = 0.06) towards a more shallow curve. r/25%, r/50%, r/75%, 0%, 100%, o/25%, o/50%, o75%: receipt (r) or omission (o) of reward expected at 0%, 25%, 50%, 75% or 100%.
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Figure 3: Salience in outcome (reward probability). Brain activation and beta weights in the right VLPFC/anterior insula as found for the contrast modelling salience scanned during the probability paradigm. Study 3 was performed in healthy controls (HC), study 4 in patients with RLS off and on their regular medication. The beta values were extracted from the maximum voxel of the demonstrated activation. The map was thresholded at p < 0.005 FWE corrected for healthy controls and at p < 0.001 at the voxel-level and at an extent threshold of p < 0.05 at the cluster-level in patients. The coefficient “a” taken as a measure of the shape of a U-shaped regression curve indicates a more shallow curve the lower the levels in healthy controls. In RLS patients on regular medication, the coefficient “a” taken as a measure of the shape of a U-shaped regression curve indicates a trend (p = 0.06) towards a more shallow curve. r/25%, r/50%, r/75%, 0%, 100%, o/25%, o/50%, o75%: receipt (r) or omission (o) of reward expected at 0%, 25%, 50%, 75% or 100%.

Mentions: In the replication study 2, we found a significant negative correlation (r = −0.43, p = 0.03) of the Physical Anhedonia scores in all subjects, patients and controls and the coefficient “a” characterizing the regression curves, that is, lower anhedonia scores predicted a pattern with more U-shaped curves more similar to the controls (Figure 2). The correlation was driven by the significant correlation in the patients (r = -0.75, p = 0.02). In controls alone, the correlation was not significant (r = -0.23, p > 0.05 [0.24]). Likewise, in the index study 1, we found a significant negative correlation (r = −0.34, p = 0.036) of the Social, but not Physical Anhedonia scores in all subjects, patients and controls and the coefficient “a” characterizing the regression curves. However, this correlation was partly driven by the group differences in both, fMRI signal and anhedonia scores as can be seen in Figure 3.


Further evidence for aberrant prefrontal salience coding in schizophrenia.

Walter H, Heckers S, Kassubek J, Erk S, Frasch K, Abler B - Front Behav Neurosci (2010)

Salience in outcome (reward probability). Brain activation and beta weights in the right VLPFC/anterior insula as found for the contrast modelling salience scanned during the probability paradigm. Study 3 was performed in healthy controls (HC), study 4 in patients with RLS off and on their regular medication. The beta values were extracted from the maximum voxel of the demonstrated activation. The map was thresholded at p < 0.005 FWE corrected for healthy controls and at p < 0.001 at the voxel-level and at an extent threshold of p < 0.05 at the cluster-level in patients. The coefficient “a” taken as a measure of the shape of a U-shaped regression curve indicates a more shallow curve the lower the levels in healthy controls. In RLS patients on regular medication, the coefficient “a” taken as a measure of the shape of a U-shaped regression curve indicates a trend (p = 0.06) towards a more shallow curve. r/25%, r/50%, r/75%, 0%, 100%, o/25%, o/50%, o75%: receipt (r) or omission (o) of reward expected at 0%, 25%, 50%, 75% or 100%.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2821181&req=5

Figure 3: Salience in outcome (reward probability). Brain activation and beta weights in the right VLPFC/anterior insula as found for the contrast modelling salience scanned during the probability paradigm. Study 3 was performed in healthy controls (HC), study 4 in patients with RLS off and on their regular medication. The beta values were extracted from the maximum voxel of the demonstrated activation. The map was thresholded at p < 0.005 FWE corrected for healthy controls and at p < 0.001 at the voxel-level and at an extent threshold of p < 0.05 at the cluster-level in patients. The coefficient “a” taken as a measure of the shape of a U-shaped regression curve indicates a more shallow curve the lower the levels in healthy controls. In RLS patients on regular medication, the coefficient “a” taken as a measure of the shape of a U-shaped regression curve indicates a trend (p = 0.06) towards a more shallow curve. r/25%, r/50%, r/75%, 0%, 100%, o/25%, o/50%, o75%: receipt (r) or omission (o) of reward expected at 0%, 25%, 50%, 75% or 100%.
Mentions: In the replication study 2, we found a significant negative correlation (r = −0.43, p = 0.03) of the Physical Anhedonia scores in all subjects, patients and controls and the coefficient “a” characterizing the regression curves, that is, lower anhedonia scores predicted a pattern with more U-shaped curves more similar to the controls (Figure 2). The correlation was driven by the significant correlation in the patients (r = -0.75, p = 0.02). In controls alone, the correlation was not significant (r = -0.23, p > 0.05 [0.24]). Likewise, in the index study 1, we found a significant negative correlation (r = −0.34, p = 0.036) of the Social, but not Physical Anhedonia scores in all subjects, patients and controls and the coefficient “a” characterizing the regression curves. However, this correlation was partly driven by the group differences in both, fMRI signal and anhedonia scores as can be seen in Figure 3.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Division of Medical Psychology, University of Bonn Bonn, Germany.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus