Perseveration is a core symptom of schizophrenia, the cause, however, is unknown. It has been shown that for people with frontal lobe lesions, perseveration can be explained with a set-maintenance problem. Perseveration in Parkinson's disease can be explained with problems shifting from one set to another without cues (set-shifting). These disorders can be distinguished using a two-choice task and the Wisconsin Card Sorting Test, that is analysed in phases. Analogs of these tests can be used in animal research. By adding an animal part to the human research, more insight can be gained into the role of specific brain areas in set-maintenance and set-shifting.

Research with patients suffering from Parkinson's disease and frontal lobe lesions has shown that disturbances in the fronto-striatal loops in the brain can cause perseveration. Perseveration is a core symptom of schizophrenia, yet the cause is not known. For schizophrenic patients disorders of many parts of the fronto-striatal loops are found, for example disturbances of the prefrontal cortex and the striatum. Perseveration in schizophrenia can be explained with set-maintenance problems, related to dysfunction of the prefrontal cortex, or with set-shifting problems that are related to disorders in the striatum. These set-maintenance and set-shifting problems can be distinguished with neuropsychological tests. Regarding the bloodflow patterns for the different subtypes of schizophrenia three problems are expected as explanations for perseveration: set-maintenance problems concerning abstract information, set-maintenance problems shifting between stimuli and enhanced set-shifting with cues.