Dynamic cortical and subcortical networks in learning and delayed recall of timed motor sequences

We used positron emission tomography to examine learning and retention of timed motor sequences. Subjects were scanned during learning (LRN) and baseline (ISO) on 3 d: day 1, after 5 d of practice (day 5) and after a 4 week delay (recall). Blood flow was compared across days of learning and between the LRN and ISO conditions. Overall, significant changes in activity were seen across days for the LRN condition, but not the ISO baseline. Day 1 results revealed extensive activation in the cerebellar cortex, particularly lobules III/IV and VI. Day 5 results showed increased activity in the basal ganglia (BG) and frontal lobe, with no significant cerebellar activity. At recall, significantly greater activity was seen in M1, premotor, and parietal cortex. Blood flow in the cerebellum decreased significantly between day 1 and recall. These results reveal a dynamic network of motor structures that are differentially active during different phases of learning and delayed recall. For the first time our findings show that recall of motor sequences in humans is mediated by a predominantly cortical network. Based on these results, we suggest that during early learning cerebellar mechanisms are involved in adjusting movement kinematics according to sensory input to produce accurate motor output. Thereafter, the cerebellar mechanisms required for early learning are no longer called into play. During late learning, the BG may be involved in automatization. At delayed recall, movement parameters appear to be encoded in a distributed representation mediated by M1, premotor, and parietal cortex.