[show abstract][hide abstract] ABSTRACT: A visuo-motor sequence can be learned as a series of visuo-spatial cues or as a sequence of effector movements. Earlier imaging studies have revealed that a network of brain areas is activated in the course of motor sequence learning. However, these studies do not address the question of the type of representation being established at various stages of visuo-motor sequence learning. In an earlier behavioral study, we demonstrated that acquisition of visuo-spatial sequence representation enables rapid learning in the early stage and progressive establishment of somato-motor representation helps speedier execution by the late stage. We conducted functional magnetic resonance imaging (fMRI) experiments wherein subjects learned and practiced the same sequence alternately in normal and rotated settings. In one rotated setting (visual), subjects learned a new motor sequence in response to an identical sequence of visual cues as in normal. In another rotated setting (motor), the display sequence was altered as compared to normal, but the same sequence of effector movements was used to perform the sequence. Comparison of different rotated settings revealed analogous transitions both in the cortical and subcortical sites during visuo-motor sequence learning-a transition of activity from parietal to parietal-premotor and then to premotor cortex and a concomitant shift was observed from anterior putamen to a combined activity in both anterior and posterior putamen and finally to posterior putamen. These results suggest a putative role for engagement of different cortical and subcortical networks at various stages of learning in supporting distinct sequence representations.