Studies of schizophrenia with functional MRI showed hyper- and hypoactivations in various brain regions including the prefrontal cortex. Functional abnormalities have also been reported in first-degree relatives of schizophrenic patients. The aim of this study was to examine working memory related brain functions in healthy subjects, schizophrenic patients and unaffected relatives and to determine the influence of psychopathology on these processes.A parametric n-back working memory task and functional MRI were used to examine 61 schizophrenic patients on antipsychotic medication, 11 nonpsychotic relatives of schizophrenic patients and a comparison group of 61 healthy subjects. The task difficulty was incrementally increased using a parametric task (0-back, 1-back, 2-back, and 3-back) to examine the relationship between working memory load, performance, and brain activity.The results indicated that during the attention task (0-back) behavioral responses of patients and healthy subjects hardly differed but BOLD responses were considerably enhanced in schizophrenic patients. With increasing task difficulty differences between groups in BOLD responses diminished whereas behavioral deficits of patients increased. The examination of attention-independent working memory-functions (2- vs. 0-back) produced hypoactivations in patients, especially in frontal, temporal and subcortical brain regions. Behavioral performance and neural responses of unaffected relatives of schizophrenic patients were intermediate between schizophrenic patients and controls indicating slight brain dysfunctions. In addition, compensatory strategies were demonstrated.These findings suggest that the genetic risk for schizophrenia is accompanied by neural inefficiency which is associated with cognitive deficits, especially in difficult tasks.

Studies of schizophrenia with functional MRI have shown hyper- and hypoactivations in various brain regions including the prefrontal cortex. Functional anomalies have also been reported in first-degree relatives of schizophrenic patients. The aim of this study was to examine working memory related brain functions in healthy subjects, schizophrenic patients and unaffected relatives and to determine the influence of psychopathology on these processes. A parametric n-back working memory task and functional MRI were used to examine 61 patients with schizophrenia, 11 nonpsychotic relatives of schizophrenic patients and a comparison group of 61 healthy subjects. The results indicated increased as well as decreased brain functions in schizophrenic patients compared to the control group depending on the task difficulty and the performance: during the attention task (0-back), which served as control condition, behavioral responses of patients and healthy subjects hardly differed but BOLD responses were considerably enhanced in schizophrenic patients. With increasing task difficulty differences between groups in BOLD responses diminished whereas behavioral deficits of patients increased. The examination of attention-independent working memory-functions (2- vs. 0-back) produced hypoactivations in patients, especially in frontal, temporal and subcortical brain regions. Furthermore, positive symptoms were associated with parietal dysfunctions. Behavioral performance and neural responses of unaffected relatives of schizophrenic patients were intermediate between schizophrenic patients and controls indicating slight brain dysfunctions. In addition, compensatory strategies were demonstrated. These findings suggest that the genetic risk for schizophrenia is accompanied by neural inefficiency which is associated with cognitive deficits, especially in difficult tasks.

Das Arbeitsgedächtnis umfasst die Fähigkeit,bei der Bearbeitung kognitiver Aufgaben Informationen gleichzeitig zu verarbeiten und zu speichern. Defizite im Bereich des Arbeitsgedächtnisses werden häufig bei Patienten mit Schizophrenie beschrieben (z.B. Callicott et al. (2003) Am J Psychiatry;160(12):2209–15).

FMRT-Untersuchungen mit einem parametrischen n-back-Paradigma an Patienten Schizophrenie erhärten die Annahme einer leistungsabhängigen Hyper- bzw. Hypofrontalität (1, 2) als neuronales Korrelat kognitiver Defizite bei schizophrener Erkrankung. In unserer Studie wurden neben Patienten mit Schizophrenie und gesunden Kontrollen zusätzlich gesunde Angehörige von Schizophrenie-Patienten mit dem Ziel untersucht, einen möglichen genetischen Einfluss auf frontale Aktivitätsänderungen zu bestimmen.