This study is a method comparison of three region-of-interest (ROI) tracing approaches. fMRI images acquired during an event-related frequency discrimination task were used in this study. Three [(1) manual, (2) semi-automated, (3) automated] approaches were applied to generate the ROI in the caudate nucleus and extract fMRI hemodynamic response (HR) from the ROI. Less activation with weak and delayed fMRI HR in the caudate were observed in patients than controls by the 3 approaches, but the manual and automated approaches were more sensitive in detecting such fMRI abnormalities. High correlations of the HR measures were found between the manual and semi-automated ROI approaches, suggesting that the semi-automated approach could be used as an alternative to the manual approach in detecting fMRI experimental effect.