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

Stepien, Marta; Manoliu, Andrei; Kubli, Roman; Schneider, Karoline; Tobler, Philippe N.; Seifritz, Erich; Herdener, Marcus; Kaiser, Stefan; Kirschner, Matthias

doi:10.1371/journal.pone.0198215

Cited by 39 publications

(48 citation statements)

References 68 publications

(73 reference statements)

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“…It is well established that striatal dysfunction during reward anticipation plays an important role in the pathophysiology of NS in patients with schizophrenia (SZ) (Heinz and Schlagenhauf, 2010, Nielsen et al , 2018, Radua et al , 2015). Recent studies suggest a specific link between reduced ventral (VS) and dorsal striatal (DS) activity and apathy (Kirschner et al , 2016b, Mucci et al , 2015, Simon et al , 2010, Stepien et al , 2018, Wolf et al , 2014). In contrast, results regarding reward anticipation in euthymic BD patients are conflicting, with studies showing both increased (Mason et al , 2014, Nusslock et al , 2012) and unaltered (Caseras et al , 2013, Dutra et al , 2015) VS activity compared to healthy controls (HC).…”

Section: Introductionmentioning

confidence: 99%

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Kirschner

Cathomas

Manoliu

et al. 2019

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BackgroundBipolar disorder I (BD-I) is defined by episodes of mania, depression, and euthymic states. These episodes are among other symptoms characterized by altered reward processing and negative symptoms (NS), in particular apathy. However, the neural correlates of these deficits are not well understood.MethodsWe first assessed the severity of negative symptoms in 25 euthymic BD-I patients compared to 25 healthy controls (HC) and 27 patients with schizophrenia (SZ). Then, we investigated ventral and dorsal striatal activation during reward anticipation in a Monetary Incentive Delayed Task and its association with NS.ResultsIn BD-I patients NS were clearly present and the severity of apathy was comparable to SZ patients. Apathy scores in the BD-I group but not in the SZ group correlated with sub-syndromal depression scores. At the neural level, we found significant ventral and dorsal striatal activation in BD-I patients and no group differences with HC or SZ patients. In contrast to patients with SZ, apathy did not correlate with striatal activation during reward anticipation. Explorative whole brain analyses revealed reduced extra-striatal activation in BD-I patients compared to HC and an association between reduced activation of the inferior frontal gyrus and apathy.ConclusionThis study found that in BD-I patients apathy is present to an extent comparable to schizophrenia, but is more strongly related to sub-syndromal depressive symptoms. The findings support the view of different pathophysiological mechanisms underlying apathy in the two disorders and suggest that extra-striatal dysfunction may contribute to impaired reward processing and apathy in BD-I.

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Section: Introductionmentioning

confidence: 99%

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Kirschner

Cathomas

Manoliu

et al. 2019

Preprint

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“…The ROI was constructed with the Individual Brain Atlases tool in SPM (IBASPM 71) (Alemán-Gómez et al, 2006) implemented in the Wake Forest University Toolbox (Maldjian et al, 2003) (Fig. 3A).To investigate different effects of VS and DS we selected two additional ROIs, which have been used for the same purpose in a recent fMRI study using a subset of the included sample (Stepien et al, 2018). These ROIs were defined by the striatal subregions based on the atlas of Mai and colleagues (Mai et al, 2015) and used previously from Mawlawi and colleagues (Mawlawi et al, 2001) ( Fig.…”

Section: Vbm Region-of-interestmentioning

confidence: 99%

“…reward anticipation, prediction error coding, receipt of reward), with most evidence for a relationship to blunted reward anticipation ( Fig. 1) (Arrondo et al, 2015;Barch, 2010, 2012;Dowd et al, 2016;Kirschner et al, 2016;Kluge et al, 2018;Moran et al, 2019;Morris et al, 2015;Mucci et al, 2015;Simon et al, 2010;Simon et al, 2015;Stepien et al, 2018;Waltz et al, 2009;Waltz et al, 2010;Waltz et al, 2018;Wolf et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…While most studies in schizophrenia found reduced blood-oxygen-level-dependent (BOLD) activity related to apathy in the ventral striatum (VS), some studies have identified a specific involvement of the dorsal striatum (DS) (Morris et al, 2015;Mucci et al, 2015), or dysfunctions including both VS and DS (Dowd et al, 2016;Moran et al, 2019;Stepien et al, 2018). apathy/diminished motivation and pleasure and striatal activity during processing of reward and salient stimuli (Arrondo et al, 2015;Barch, 2010, 2012;Dowd et al, 2016;Kirschner et al, 2016;Kluge et al, 2018;Moran et al, 2019;Morris et al, 2015;Mucci et al, 2015;Simon et al, 2010;Simon et al, 2015;Stepien et al, 2018;Waltz et al, 2009;Waltz et al, 2010;Waltz et al, 2018;Wolf et al, 2014). (b) 2 studies (n=64) reported an association between apathy/diminished motivation and pleasure and striatal volume (Caravaggio et al, 2018a;Roth et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Apathy is not associated with reduced ventral striatal volume in patients with schizophrenia

Burrer

Caravaggio

Manoliu

et al. 2020

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Background: A growing body of neuroimaging research has revealed a relationship between blunted activation of the ventral striatum (VS) and apathy in schizophrenia. In contrast, the association between reduced striatal volume and apathy is less well established, while the relationship between VS function and structure in patients with schizophrenia remains an open question. Here, we aimed to replicate previous structural findings in a larger independent sample and to investigate the relationship between VS hypoactivation and VS volume. Methods: We included brain structural magnetic resonance imaging (MRI) data from 60 patients with schizophrenia (SZ) that had shown an association of VS hypoactivation with apathy during reward anticipation and 58 healthy controls (HC). To improve replicability, we applied analytical methods developed in two previously published studies: Voxel-based morphometry and the Multiple Automatically Generated Templates (MAGeT) algorithm. VS and dorsal striatum (DS) volume were correlated with apathy correcting for age, gender and total brain volume. Additionally, left VS activity was correlated with left VS volume. Results: We failed to replicate the association between apathy and reduced VS volume and did not find a correlation with DS volume. Functional and structural left VS measures exhibited a trend-level correlation (rs=0.248, p=0.067, r2=0.06). Conclusions: Our present data suggests that functional and structural striatal neuroimaging correlates of apathy can occur independently. Replication of previous findings may have been limited by other factors (medication, illness duration, age) potentially related to striatal volume changes in SZ. Finally, associations between reward-related VS function and structure should be further explored.

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“…[12][13][14] One of the most consistent findings from functional magnetic resonance imaging (fMRI) in schizophrenia is the association between negative symptoms and blunted ventral striatum (VS) activation. 15,16 More specifically, apathy has been related to blunted striatal activation during: reward anticipation [17][18][19][20][21][22] , reward feedback processing 23 and prediction error coding. 24,25 These associations extend across a continuum from the general population to individuals in at-risk stages and early psychosis 26,27 , although negative 28,29 and contradictory findings have been reported.…”

Section: Introductionmentioning

confidence: 99%

Orbitofrontal-striatal structural alterations linked to negative symptoms at different stages of the schizophrenia spectrum

Kirschner

Schmidt

Hodzic-Santor

et al. 2020

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Among the most debilitating manifestations of schizophrenia are negative symptoms such as anhedonia and apathy. Imaging studies have linked these symptoms to morphometric abnormalities in two brain regions implicated in reward and motivation: the orbitofrontal cortex (OFC) and ventral striatum. Negative symptoms generally are associated with reduced OFC thickness, while apathy specifically maps to reduced striatal volume. However, it remains unclear whether these tissue losses are a consequence of chronic illness and its treatment, or an underlying phenotypic trait. Here we use multicentre MRI data to investigate orbitofrontal-striatal abnormalities across the schizophrenia-spectrum from healthy populations with schizotypy, to unmedicated and medicated first-episode psychosis patients, and patients with chronic schizophrenia. Striatal volumes and OFC thickness were estimated from T1-weighted images acquired in all three diagnostic groups and controls from four sites (n=337). Results were first established in one test cohort (‘Zurich sample’) and replicated in three independent samples. There was a correlation between apathy and striatal volume only in healthy individuals with schizotypy; however, medicated patients exhibited larger striatal volumes, which appears to be a consequence of antipsychotic medications. The association between reduced OFC thickness and negative symptoms generally also appeared to vary along the disease course, being significant only in first-episode psychosis patients. In schizotypy there was increased OFC relative to controls. Our findings suggest that negative symptoms associate with a temporal continuum of orbitofrontal-striatal abnormalities that may predate the occurrence of schizophrenia. Thicker OFC in schizotypy may represent either compensatory or pathological mechanisms prior to disease-onset.

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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

Cited by 39 publications

References 68 publications

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Shared and dissociable features of apathy and reward system dysfunction in bipolar I disorder and schizophrenia

Apathy is not associated with reduced ventral striatal volume in patients with schizophrenia

Orbitofrontal-striatal structural alterations linked to negative symptoms at different stages of the schizophrenia spectrum

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