Organization of prefrontal outflow toward frontal motor-related areas in macaque monkeys

Linkage between the prefrontal cortex and the primary motor cortex is mediated by nonprimary motor-related areas of the frontal lobe. In an attempt to analyse the organization of the prefrontal outflow from area 46 toward the frontal motor-related areas, we investigated the pattern of projections involving the higher-order motor-related areas, such as the presupplementary motor area (pre-SMA) and the rostral cingulate motor area (CMAr). Tracer injections were made into these motor-related areas (their forelimb representation) on the medial wall that had been identified electrophysiologically. The following data were obtained from a series of tract-tracing experiments in Japanese monkeys. (i) Only a few neurons in area 46 were retrogradely labelled from the pre-SMA and CMAr; (ii) terminal labelling from area 46 occurred sparsely in the pre-SMA and CMAr; (iii) a dual labelling technique revealed that the sites of overlap of anterograde labelling from area 46 and retrograde labelling from the pre-SMA and CMAr were evident in the rostral parts of the dorsal and ventral premotor cortices (PMdr and PMvr); (iv) and tracer injections into the PMdr produced neuronal cell labelling in area 46 and terminal labelling in the pre-SMA and CMAr. The present results indicate that a large portion of the prefrontal signals from area 46 is not directly conveyed to the pre-SMA and CMAr, but rather indirectly by way of the PMdr and PMvr. This suggests that area 46 exerts its major influence on the cortical motor system via these premotor areas.