Impact of cognitive performance on the reproducibility of fMRI activation in schizophrenia.

Background: Longitudinal functional magnetic resonance imaging (fMRI) studies in patients with schizophrenia allow exploration of the course of the illness and brain activity after therapy. A crucial question, however, is whether fMRI findings are reliable, because they can be affected by performance deficits in patients with schizophrenia. Our aim was to evaluate the reproducibility of fMRI activations in highly integrated language areas in patients with schizophrenia, taking into account task performance.

Methods: Ten patients with schizophrenia and 10 matched healthy controls were scanned twice, 21 months apart, while performing a story comprehension task. The reproducibility of the activations in each participant was evaluated globally by the percentage of spatial overlap between the 2 sessions and locally by a voxel-wise computation of the between-session relative standard deviation. We performed between-group comparisons both with and without the inclusion of comprehension scores (measuring task performance) as a covariate.

Results: On average, patients with schizophrenia had significantly lower comprehension scores than controls (4.5/12 v. 7.8/12, p = 0.002). The mean spatial overlap between fMRI sessions was 30.6% in the patient group and 47.0% in the control group (p = 0.017). Locally, the lower reproducibility in patients was most prominent in the left posterior middle temporal gyrus, inferior frontal gyrus and medial prefrontal cortex (p < 0.001 uncorrected for multiple comparisons). Comprehension scores were positively correlated with both reproducibility measures in patients (overlap: r = 0.82, p = 0.004; relative standard deviation: several significant clusters at p < 0.001). When we included the comprehension scores as a covariate, most of the local between-group differences in reproducibility were removed, and the difference in overlap was not significant.

Limitations: Owing to the small sample size, we could not investigate the impact of clinical subtypes and different types of medications on reproducibility.

Conclusion: Our findings suggest that the greater variability in activation in patients with schizophrenia compared with controls concerns high-level areas and is mainly attributable to deficient task performance. Consequently, cognitive performance must be carefully controlled when longitudinal fMRI studies are undertaken.