Final Report Summary - DRASTIC (Apathy in schizophrenia: time for a DRASTIC (Dual Routes to Apathy in Schizophrenia: Treatment, Imaging, Cognition) study) In this study we investigate the cognitive and neural basis of apathy in schizophrenia and we test an innovative treatment involving brain stimulation. Apathy is an important factor associated with poor outcome in patients with schizophrenia. Apathy refers to a quantitative reduction of goal-directed behavior which typically involves reduced interest and reduced initiative with regard to every-day activities. In our project, we investigate whether apathy can be due to two different mechanisms: a lack of reward anticipation on the one hand (lack of interest) and difficulties with self-initiation of action on the other hand (lack of initiative). The first studies have focused on activation of brain areas involved in planning behavior on the one hand and connectivity of brain areas central to the dopaminergic reward system during resting state on the other. We observed an association of less activation in parietal cortex, precuneus and thalamus with apathy in schizophrenia patients during planning. With regard to connectivity with reward-related brain areas, apathy was negatively correlated with functional connectivity between the substantia nigra/ventral tegmental area and medial- and lateral prefrontal executive control areas, the temporoparietal junction and the striatum. This was independent of depressive symptoms. This finding may have implications for treatment strategies aimed at improving apathy, which may be targeted at improving activation of the reward system. We also investigated the neural basis of apathy in people without a psychiatric of neurological disorder. We found that alterationals in the neural basis of cognitive control, as evidenced during a set-shifting task, may contribute to apathy. This regarded reduced activation of frontal and cerebellar brain areas. Brain activation during a task for self-initiated action was not different between people with low and high levels of apathy, suggesting that motivational and/or cognitive control circuits are more relevant. Our analysis of functional connectivity between brain regions and apathy in patients with schizophrenia yielded interesting results. More specifically, patients with schizophrenia and more severe levels of apathy showed less variability in their physical activity and more rigid functional brain network behavior in the default-mode network (DMN) and salience-reward network (SRN). These networks have been shown relevant for self-reflection, mental simulation, and reward processing, processes that are pivotal for self-initiated goal-directed behavior. Functional rigidity of these networks may therefore contribute to reduced goal-directed behavior, which is characteristic for these patients.The results of the randomized controlled trial of brain stimulation for improving apathy in patients with schizophrenia are expected by September 2018 and will be published over the next year. Analyses of functional neuroimaging data into the putative different forms of apathy, "cognitive apathy" versus "social-emotional apathy" will also be conducted over the next six months and results will be reported next year.
