The Fist-Edge-Palm (FEP) task is a motor sequencing task that is widely used in neurological examination. Deficits in this task are believed to reflect impairment in the frontal lobe regions. However, two recent functional brain imaging studies of the FEP task using conventional subtraction analysis failed to demonstrate FEP-induced activation in the prefrontal cortex (PFC), which contradicts existing neuropsychological literature. In this study, psychophysiological interaction (PPI) analysis was used to reanalyze our previous neuroimaging dataset from 10 healthy subjects in order to evaluate the changes of functional connectivity between the sensorimotor cortex and the prefrontal regions during the performances of the FEP task relative to simple motor control tasks. The PPI analysis revealed significantly increased functional connectivity between bilateral sensorimotor cortex and the right inferior and middle frontal cortex during the performance of the FEP task compared with the control tasks. However, regional signal changes showed no significant activation differences in these prefrontal regions. These results provide evidence supporting the involvement of the frontal lobe in the performance of the FEP task, and suggest a role of regulation, rather than direct participation, of the prefrontal cortex in the execution of complex motor sequence tasks such as the FEP task.