Neuronal activity in medial frontal cortex during learning of sequential procedures.

To study the role of medial frontal cortex in learning and memory of sequential procedures, we examined neuronal activity of the presupplementary motor area (pre-SMA) and supplementary motor area (SMA) while monkeys (n = 2) performed a sequential button press task, "2 x 5 task." In this paradigm, 2 of 16 (4 x 4 matrix) light-emitting diode buttons (called "set") were illuminated simultaneously and the monkey had to press them in a predetermined order. A total of five sets (called "hyperset") was presented in a fixed order for completion of a trial. We examined the neuronal activity of each cell using two kinds of hypersets: new hypersets that the monkey experienced for the first time for which he had to find the correct orders of button presses by trial-and-error and learned hypersets that the monkey had learned with extensive practice (n = 16 and 10 for each monkey). To investigate whether cells in medial frontal cortex are involved in the acquisition of new sequences or execution of well-learned procedures, we examined three to five new hypersets and three to five learned hypersets for each cell. Among 345 task-related cells, we found 78 cells that were more active during performance of new hypersets than learned hypersets (new-preferring cells) and 18 cells that were more active for learned hypersets (learned-preferring cells). Among new-preferring cells, 33 cells showed a learning-dependent decrease of cell activity: their activity was highest at the beginning of learning and decreased as the animal acquired the correct response for each set with increasing reliability. In contrast, 11 learned-preferring cells showed a learning-dependent increase of neuronal activity. We found a difference in the anatomic distribution of new-preferring cells. The proportion of new-preferring cells was greater in the rostral part of the medial frontal cortex, corresponding to the pre-SMA, than the posterior part, the SMA. There was some trend that learned-preferring cells were more abundant in the SMA. These results suggest that the pre-SMA, rather than SMA, is more involved in the acquisition of new sequential procedures.