Abstract
Background
Recent studies have pointed at the ventral striatum as one of the main candidates underlying motivational dysfunctions in schizophrenia. Patients with negative symptoms show decreased BOLD activity in the ventral striatum and this activity strongly correlates with apathy scores during reward anticipation.
While in patients with schizophrenia blunted ventral striatal activation during reward anticipation has been widely reported, little is known about abnormal striatal functional connectivity during reward anticipation. In this study, we performed generalized whole-brain psychophysiological interaction (gPPI) analyses using the right and left ventral striatum as seeds in schizophrenia patients with apathy and reduced ventral striatal activation from two published fMRI studies (Kirschner et al., 2016; Stepien et al., 2018).
Methods
Forty-four healthy controls (18 females, mean age = 31.1) and 40 patients with schizophrenia (10 females, mean age = 32.5) performed a variant of the Monetary Incentive Delay task within an fMRI design. Negative symptoms were assessed with the Brief Negative Symptoms Scale (BNSS). GPPI analyses were done using the PPPI toolbox on SPM 8. To examine potential difference in striatal functional connectivity, we performed two sample t-tests between patients with schizophrenia and healthy controls using the contrast [High Reward Anticipation – No Reward Anticipation].
Results
Patients with schizophrenia showed increased functional connectivity between the right ventral striatum and the anterior cingulate cortex, posterior cingulate cortex, cerebellum, motor cortex, parietal cortex, temporo-parietal junction and thalamus compared to controls (cluster-level FDR p<0.05). No higher connectivity was found in controls compared to patients.
For the regions with increased functional connectivity, we performed correlations between the patients’ gPPI signal and apathy. We found significant correlations between apathy and functional connectivity between the right ventral striatum and the right posterior cingulate cortex (r=0.40, p<.05) and right parietal cortex (r=0.39, p<.05).
Discussion
Our preliminary results indicate that physiological changes in the ventral striatum lead to dysfunctional connectivity with a cortex-wide network, affecting both cortico-striatal-thalamic-cortical and cortico-striatal-thalamic-cerebellar pathways. In addition, we show that some of these changes are related to apathy levels. This work provides novel insights in cortico-striatal network dysfunction during reward processing in patients with schizophrenia.
Chronic methylphenidate preferentially alters catecholamine protein targets in the parietal cortex and ventral striatum
