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

PLOS ONE, Nov 2019

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

June Investigating the association of ventral and dorsal striatal dysfunction during reward anticipation with negative symptoms in patients with schizophrenia and healthy individuals Marta Stepien 0 1 2 Andrei Manoliu 0 1 2 Roman Kubli 0 1 2 Karoline Schneider 0 1 2 Philippe N. Tobler 0 2 Erich Seifritz 0 1 2 Marcus Herdener 0 1 2 3 Stefan Kaiser 0 2 Matthias Kirschner 0 1 2 3 0 Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Additional data queries may be directed to Dr Matthias Kirschner 1 Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich , Zurich , Switzerland , 2 Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich , Zurich , Switzerland , 3 Neuroscience Center Zurich, University of Zurich , Zurich , Switzerland , 4 Zurich Center for Integrative Human Physiology, University of Zurich , Zurich , Switzerland 2 Editor: Therese van Amelsvoort, Maastricht University , NETHERLANDS 3 Center for Addictive Disorders, Psychiatric Hospital, University of Zurich , Zurich , Switzerland , 6 Division of Adult Psychiatry, Department of Mental Health and Psychiatry, Geneva University Hospitals , Chemin du Petit- Bel-Air, Chêne-Bourg , Switzerland Symptoms Scale. - Funding: This study was supported by the EMDO Stiftung (SK) and Hartmann MuÈller Stiftung (MH). The funders had no role in study design, data 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 Results Chronic schizophrenia patients (n = 16) and healthy controls (n = 23) underwent an eventrelated 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 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. collection and analysis, decision to publish, or preparation of the manuscript. 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. Introduction 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 ]. Apathy can be defined as a quantitative reduction in goal-directed behavior due to diminished motivation [10±13]. According to the extensive evidence coming from animal and human research, dopamine (DA) mediates anticipation of rewards, as well as motivation to obtain them, and is therefore considered essential for goal-directed behavior [ 14,15 ]. In particular, mesolimbic dopaminergic projections from the ventral tegmental area (VTA) to the ventral striatum (VS) are thought to have a critical role in reward processing, especially reward ªwantingº that generates motivation [ 8,15,16 ]. In addition, nigrostriatal dopaminergic projections from the substantia nigra to the dorsal part of the striatum are implicated in action outcome selection and are closely related to goal-directed behavior [ 15,17 ]. Current literature provides compelling evidence, that dysfunctions in reward processing play a crucial role for global negative symptoms, which ar (...truncated)


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Marta Stepien, Andrei Manoliu, Roman Kubli, Karoline Schneider, Philippe N. Tobler, Erich Seifritz, Marcus Herdener, Stefan Kaiser, Matthias Kirschner. Investigating the association of ventral and dorsal striatal dysfunction during reward anticipation with negative symptoms in patients with schizophrenia and healthy individuals, PLOS ONE, 2018, Volume 13, Issue 6, DOI: 10.1371/journal.pone.0198215