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

Date Published: June 18, 2018

Publisher: Public Library of Science

Author(s): Marta Stepien, Andrei Manoliu, Roman Kubli, Karoline Schneider, Philippe N. Tobler, Erich Seifritz, Marcus Herdener, Stefan Kaiser, Matthias Kirschner, Therese van Amelsvoort.


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.

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.

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.

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.

Partial Text

Negative symptoms (NS) are an integral feature of schizophrenia [1]. According to the current consensus, they can be separated into two domains: the apathy domain, consisting of avolition, anhedonia, and asociality and the diminished expression domain, consisting of blunted affect and alogia [2–4]. Moreover, recent studies have shown that this distinction into two subgroups is clearly observable in patients, showing clinically meaningful differences in symptom presentation [5]. Accumulating evidence suggests that both factors are caused by a different neurobiological and behavioral mechanisms [6–8]. However, due to its association with poorer social functioning and strong impact on recovery, understanding the pathophysiology of apathy is highly relevant [5,9].

In this study, we replicated our previous finding of a specific association between reduced ventral striatal activation and apathy in an independent sample of patients with chronic schizophrenia [7]. In addition, we observed, for the first time, that apathy but not diminished expression was associated with dorsal striatal activity in schizophrenia patients. These findings add new evidence for striatal dysfunction as a neural substrate underlying apathy. Critically, the present study suggests that both ventral and dorsal striatal activity during reward anticipation contribute to the pathophysiology of motivational impairments in schizophrenia. In healthy individuals with non-clinical levels of negative symptoms we found that diminished expression but not apathy was related to reduced dorsal striatal activity on the trend level. These results suggest that some of the striatal deficits associated with negative symptoms may also be detectable in healthy individuals and underlies the need for further investigation of apathy and diminished expression in the general population.




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