Effects of olanzapine on cerebellar functional connectivity in schizophrenia measured by fMRI during a simple motor task

Background. According to current theories, schizophrenia results from alter ed connectivity in brain circuits for fundamental cognitive operations. Con sequently, the poorly understood mechanisms of neuroleptic treatment may be explainable by altered functional interactions within such networks. The ' cognitive dysmetria' model hypothesizes that one key structure in these cir cuits is the cerebellum. To investigate the effects of olanzapine on cerebe llar functional connectivity (CFC), a seed-voxel correlation analysis (SVCA ) was used in a functional magnetic resonance imaging (fMRI) study of a sim ple finger-tapping task, Methods. fMRI scans were obtained from six schizophrenic patients under bot h drug-free and olanzapine-treated conditions and from a matched control gr oup of six healthy subjects at corresponding time points. SVCAs were perfor med for anatomically and functionally standardized seed voxels in the anter ior cerebellum. SVCA results were then processed by three different randomi zation analyses. Results. The analyses revealed that olanzapine caused widespread changes of CFC, including prominent changes in prefrontal cortex and mediodorsal thal amus. Significant changes in motor structures were found after subtractions within both groups and may thus indicate repetition effects rather than dr ug effects. Olanzapine 'normalized' the patients' CFC patterns for the righ t, but not for the left cerebellum. Conclusion. Even for a simple motor task, olanzapine affects functional int eractions between the cerebellum and many non-motor brain regions, includin g elements of the 'cognitive dysmetria' circuit. Altogether, our findings s uggest that olanzapine has a stronger differential effect on neural activit y in prefrontal cortex and thalamus than in motor structures.