N.G. (Nicky) Klaasen

PhD project: The Neural Substrate of Cognitive and Social-Emotional Apathy in Patients with Schizophrenia

Rationale:  Apathy can be defined as a quantitative reduction of self-generated voluntary and purposeful behavior. It is a common and very debilitating symptom in several neuropathological disorders, like schizophrenia. However, not much is known about the cognitive and neural mechanisms that underlie apathy. Clinically, a distinction has been made between a cognitive form (CA) and a social-emotional form (SEA) of apathy. Both result in reduced behavioral activation. However, CA and SEA might reflect different cognitive deficits with different underlying neural substrates. CA may be due to a lack of self-initiated action and cognitive control, caused by disruptions in a dorsal frontostriatal circuit, including the parietal cortex. Reduced signaling of the salience positive events may lie at the core of SEA. This could be due to disruptions in a ventral frontostriatal reward network.

Objective: The objective of the proposed study is to examine the neural substrate of cognitive and social-emotional apathy in patients with schizophrenia.

Methods: Eighty participants will be included in the study, of which 60 patients with a diagnosis of schizophrenia or schizoaffective disorder and 20 matched healthy controls. The patients will be selected on varying levels of apathy, resulting in a CA group, an SEA group and a group with low levels of apathy. Subjects will be presented with four different fMRI tasks, which we expect to robustly activate underlying circuits for CA or SEA. The tasks intend to measure self-initiated realization of intentions, cognitive control, reward anticipation and affective forecasting. Several interviews will be administered concerning apathy, depression, and other symptoms of schizophrenia. Two questionnaires will be filled out by all participants, in order to assess the experience of pleasure. Neurocognitive tests will be administered to assess cognitive functioning.

Relevance: The outcomes of this study will contribute to the understanding of apathy in patients with schizophrenia. If two distinct types of apathy can indeed be identified, this may inspire the development of more focused and effective treatments for apathy in schizophrenia. Furthermore, understanding apathy in schizophrenia may also increase understanding of apathy in other disorders, such as depression and neurodegenerative disorders.