"Apathy is a prominent and severely debilitating aspect of several psychiatric disorders, most notably schizophrenia. Little is known regarding the neuroscientific basis of apathy, however. Clinically, it has been suggested that two forms of apathy can be distinguished: cognitive apathy (CA) which concerns reduced initiative to start daily activities and social-emotional apathy (SEA) which concerns reduced interest in otherwise gratifying activities. I hypothesize that CA is primarily a dysfunction of cognitive control and self-initiated action, whereas SEA is primarily a failure to signal the salience of positive events. The present project, for the first time, tests the hypothesis that two neuroanatomically distinct routes underlie these two forms of apathy: a dorsal frontostriatal circuit including also the right parietal cortex for CA (associated with abnormalities of glutamate neurotransmission), and a more ventral frontostriatal circuit including the reward system for SEA (involving abnormal dopamine transmission). The objective of this project is threefold. First, to investigate the two neural circuits in relation to the two forms of apathy using functional MRI and positron emission tomography. Second, I will test the hypothesis that CA is associated with poorer long-term functioning using longitudinal data. Third, we will conduct a controlled treatment study of a novel intervention to improve CA: transcranial magnetic stimulation over the right prefrontal cortex to target the relevant network.Thus, the present proposal aims to elucidate fundamental cognitive and emotional processes underlying apathy by unravelling the neural basis of two pathways that may lead to apathy. Last but not least, the treatment study may contribute to novel strategies that will ultimately improve patients’ lives. The results will also have implications for understanding apathy in patients with depression, brain damage and neurodegenerative diseases."