Neural mechanisms of sequence learning

A large number of brain areas are involved in learning complex motor behaviors. The supplementary motor area (SMA) and pre-supplementary motor area (pre-SMA) is known to be involved in motor sequence learning, and the primary motor cortex (M1) has recently been found to exhibit sequence-specific activity during the production of motor sequences. However, the roles of these areas in sequence learning are still in question. We suggest that three areas in primates, the presupplementary motor area (pre-SMA), the supplementary motor area (SMA), and the primary motor area (M1), play prominent and specific roles in motor learning that have only begun to be elucidated.;To examine the role of these areas in the learning and memory of new motor sequences, we recorded neural activity in M1, SMA and pre-SMA as monkeys learned novel motor sequences. Each sequence was composed of six movements to six different targets that were evenly spaced and distributed evenly on a circle around a central starting position. The order of targets in each new sequence was chosen randomly and was determined before the start of each recording session. The monkey learned the sequence by trial and error during the session. We found that neural activity during sequence learning heavily represented target, and that the representation of target changed in a dynamic and complex manner with learning. Direction, serial order, reaction time and error rate related activity was common, though activity relating to relationships between the targets was less so. In general, representation shifted from the supplementary motor areas to M1 with learning. We suggest that the pre-SMA, SMA and M1 have integrated roles in learning new sequences by trial and error under over-learned, well-structured conditions, with the pre-SMA and SMA especially important in early learning and SO representation and M1 developing and maintaining a directional representation of the sequence over time.