| Summary: | Abstract Introduction High reproducibility is critical for ensuring the confidence needed to use functional magnetic resonance imaging (fMRI) activation maps for presurgical planning. Methods In this study, the comparison of different motion correction methods, spatial smoothing methods, regression methods, and thresholding methods was performed to see whether specific data processing methods can be employed to improve the reproducibility of single‐subject fMRI activation. Three test–retest metrics were used: the percent difference in activation volume (PDAV), the difference in the center of mass (DCM), and the Dice Similarity Coefficient (DSC). Results The PDAV was minimized when using little or no spatial smoothing and AMPLE thresholding. The DCM was minimized when using affine motion correction and little or no spatial smoothing. The DSC was improved when using affine motion correction and generous spatial smoothing. However, it is believed that the overlap metric may be unsuitable for testing fMRI reproducibility. Conclusion Processing methods to improve fMRI reproducibility were determined. Importantly, the processing methods needed to improve reproducibility were dependent on the fMRI activation metric of interest.
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