A systematic review and ALE meta-analysis of cognitive control, motivation and effort-based decision-making in schizophrenia and mood disorders: Implications for multidimensional apathy

Background Apathy is present in about 50% of patients suffering from schizophrenia (SZ) and mood disorders (MD). Even though these two disorders are different, in psychiatry, apathy refers typically to the same unidimensional clinical entity, sharing the same pathophysiological processes and symptoms regardless of the underlying diagnosis. Neurology proposes another perspective: three forms of apathy —emotional, executive, and initiative— are related to a disturbance in motivational processing, cognitive control, and effort-based decision-making, respectively. We explored whether this latter model can be applied in psychiatry by identifying differences between SZ and MD through a PRISMA meta-analysis of imaging studies on motivational, cognitive control, and effort-based decision-making networks. Methods We searched the Sleuth BrainMap database for studies on SZ, MD, and/or healthy controls using tasks that explore motivation, cognitive control, and effort-based decision-making. Twenty-eight functional MRI studies were identified and included for a coordinate-based activation likelihood estimation analysis. Results In SZ, hypoactivity in the motivational structures, a specific hyperactivity in the right cerebellar vermis that has previously been linked to emotional blunting and apathy, and a lack of activation during effort-based decision-making that could imply an impaired reward processing, suggest a dominant form of emotional apathy. In MD, hypoactivity in both cognitive control and motivational structures, which has previously been linked to the co-occurrence of executive difficulty and amotivation, suggests a dominant mix of emotional/executive apathy. Conclusions Despite a small number of studies, our results could help target new individualized treatment strategies in precision psychiatry based on a multidimensional approach to apathy. Graphical abstract The results of this meta-analysis highlight different activation profiles in SZ and in MD during motivational, cognitive control, and effort-based decision-making tasks, suggesting a dominant form of emotional apathy in SZ and a dominant coexistence of emotional and executive apathy in MD.