Schizophrenia spectrum disorders are frequently associated with motor abnormalities. Aberrant motor function can be observed in patients throughout the course of the disorder, in subjects at high clinical risk and in unaffected first-degree relatives. Schizophrenia is further characterized by white matter abnormalities in multiple fiber tracts and aberrant resting state cerebral perfusion. In a series of studies, we investigated the association of objectively measured motor behavior in terms of activity levels with white matter microstructure and cerebral perfusion at rest. Patients were less active than controls at the behavioral level. In the associations with neuroimaging techniques, we detected that unlike controls, patients’ activity levels were linked to structure and perfusion of cortical motor areas as well as the connecting white matter. In controls instead, motor activity relied on the association of cortico-subcortical motor loops. Thus, some of the motor signs in schizophrenia may result from ineffective coupling between cortical and subcortical motor areas. Finally, preliminary data from functional connectivity analyses support this notion.