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Clinical Trial
. 2018 Jun 18;13(6):e0198215.
doi: 10.1371/journal.pone.0198215. eCollection 2018.

Investigating the association of ventral and dorsal striatal dysfunction during reward anticipation with negative symptoms in patients with schizophrenia and healthy individuals

Marta Stepien  1 , Andrei Manoliu  1 , Roman Kubli  1 , Karoline Schneider  1 , Philippe N Tobler  2   3   4 , Erich Seifritz  1   3   4 , Marcus Herdener  1   5 , Stefan Kaiser  6 , Matthias Kirschner  1   5
Affiliations
Clinical Trial

Investigating the association of ventral and dorsal striatal dysfunction during reward anticipation with negative symptoms in patients with schizophrenia and healthy individuals

Marta Stepien et al. PLoS One. .

Abstract

Background: Negative symptoms are a core feature of schizophrenia and also found in healthy individuals in subclinical forms. According to the current literature the two negative symptom domains, apathy and diminished expression may have different underlying neural mechanisms. Previous observations suggest that striatal dysfunction is associated with apathy in schizophrenia. However, it is unclear whether apathy is specifically related to ventral or dorsal striatal alterations. Here, we investigated striatal dysfunction during reward anticipation in patients with schizophrenia and a non-clinical population, to determine whether it is associated with apathy.

Methods: Chronic schizophrenia patients (n = 16) and healthy controls (n = 23) underwent an event- related functional MRI, while performing a variant of the Monetary Incentive Delay Task. The two negative symptom domains were assessed in both groups using the Brief Negative Symptoms Scale.

Results: In schizophrenia patients, we saw a strong negative correlation between apathy and ventral and dorsal striatal activation during reward anticipation. In contrast, there was no correlation with diminished expression. In healthy controls, apathy was not correlated with ventral or dorsal striatal activation during reward anticipation.

Conclusion: This study replicates our previous findings of a correlation between ventral striatal activity and apathy but not diminished expression in chronic schizophrenia patients. The association between apathy and reduced dorsal striatal activity during reward anticipation suggests that impaired action-outcome selection is involved in the pathophysiology of motivational deficits in schizophrenia.

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Conflict of interest statement

We have read the journal’s policy and the authors of this manuscript have the following competing interests: ES has received grant support from H. Lundbeck and has served as a consultant and/or speaker for AstraZeneca, Otsuka, Takeda, Eli Lilly, Janssen, Lundbeck, Novartis, Pfizer, Roche, and Servier. PNT has received grant money from Pfizer. S. Kaiser has received speaker’s fees from Janssen, Otsuka, Takeda, Lundbeck and Sandoz. None of these activities is related to the present study. None declared by any other authors. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Schematic illustration of the variant of Monetary Incentive Delay Task (MID) (adapted from Kirschner et al. [6]).
In each trial, participants saw 1 of 3 cues, indicating the amount of money to be won. After a delay period, participants had to identify an outlier from an array of 3 circles by pressing a correct button (either left or right). Immediately after a correct button press, participants were informed via visual feedback about the amount of money they had won during the current trial. A red horizontal line on the column ranging from the minimal amount (0 CHF) to the maximal win amount (2.0 CHF) indicated the precise amount of money won in each trial.
Fig 2
Fig 2. Whole brain within-group activation during reward anticipation.
Whole brain within-group activation maps of the contrast anticipation of high reward versus no reward (p < 0.001, uncorrected). The within group t-maps are shown together with outlines of the ventral striatum (VS) and dorsal striatum (DS) our predefined regions of interest. (A), (E) Coronal and (B), (F) axial contrast images of healthy controls. (C), (G) Coronal and (D), (H) axial contrast images of patients with schizophrenia.
Fig 3
Fig 3. Correlations of the two negative symptom dimensions with VS activation during reward anticipation.
Bivariate Spearman correlation of (A) apathy (rs = -.59, p = .02) and (B) diminished expression (rs = .30 p = .26) with percent signal change in the ventral striatum in patients with schizophrenia. Bivariate Spearman correlation of (C) apathy (rs = -.06, p = .79) and (D) diminished expression (rs = -.20, p = .35) with percent signal change in the ventral striatum in healthy controls. BNSS = Brief Negative Symptom Scale.
Fig 4
Fig 4. Correlations of the two negative symptom dimensions with DS activation during reward anticipation.
Bivariate Spearman correlation of (A) apathy (rs = -.56, p = .02) and (B) diminished expression (rs = .30, p = .26) with percent signal change in the dorsal striatum in patients with schizophrenia. Bivariate Spearman correlation of (C) apathy (rs = -.01, p = .96) and (D) diminished expression (rs = -.39, p = .07) with percent signal change in the dorsal striatum in healthy controls. BNSS = Brief Negative Symptom Scale.
Fig 5
Fig 5. Summary of the main findings.
Correlations between the striatal signal during reward anticipation and dimensions of negative symptoms in patients with chronic schizophrenia and healthy participants.
See this image and copyright information in PMC

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