The left primary motor cortex and cerebellar vermis are critical hubs in bimanual sequential learning.

We conducted an fMRI study to investigate the neural basis of bimanual coordination, which is fundamental to upper extremity control. Considering bimanual movement as a combination of bimanual chord formation and sequence control, we hypothesized that the areas with the learning effect of both chord formation and sequence learning are critical in bimanual coordination. We adopted the serial reaction time task (SRTT) to test this hypothesis. Thirty-five healthy right-handed volunteers practiced visually cued bimanual SRTT, including the "mirror" and more complex "parallel" modes of random movements or repeating fixed sequences to separately depict the neural substrates of bimanual posture control for chord formation and those of sequence. Random movements' reaction time (RT) continuously declined, indicating learning of bimanual chord formation. The RT in the sequential condition declined more rapidly than in the random condition, confirming sequence learning. The parallel random conditions evoked a more prominent learning-related decrease of task-related activation in the left M1 and cerebellar vermis than the less difficult mirror random conditions. The left M1 showed learning-related enhancement of functional connectivity with the anterior cingulate cortex during the parallel random conditions compared with the mirror random conditions. Thus, the left M1, anterior cingulate cortex, and cerebellar vermis are related to learning bimanual chord formation. The left M1 and cerebellar vermis also showed sequence-specific learning-related activity increments more prominent in the parallel mode than in the mirror mode. Thus, the left M1 and cerebellar vermis are critical in the bimanual motor learning network.