Behavioural Brain Research, 18 (1985) 125-136 125 Elsevier BBR00484 PATTERNS OF CYTOCHROME OXIDASE ACTIVITY IN THE FRONTAL AGRANULAR CORTEX OF THE MACAQUE MONKEY MASSIMO MATELLI, GIUSEPPE LUPPINO and GIACOMO RIZZOLATTI Istituto di Fisiologia Umana dell'Universit~ di Parma, via Gramsci, 14-43100 Parma (Italy) (Received June 3rd, 1985) (Revised version received July 25th, 1985) (Accepted July 29th, 1985) Key words: cytochrome oxidase - area 4-6 complex - macaque monkey The laminar pattern of cytochrome oxidase activity was studied in the agranular frontal cortex (area 4-6 complex) of the macaque monkey. The cortex, stained with this method, showed 6 stripes of different enzymatic activity. On the basis of their characteristics and of the presence of highly active cells, the agranular frontal cortex could be parcellated in 5 areas (F1-F5). F 1 very likely corresponds to area FA ofvon Bonin and Bailey. Rostral to F 1 two large regions could be distinguished, one located medial to the spur of the arcuate sulcus and its imaginary caudal extension, the other laterally. The superior region was formed by areas F2 and F3. The first was located on the dorsomedial cortical surface, the other on the mesial surface. F3 possibly corresponds to the supplementary motor area. The inferior region was formed by areas F4 and F5. The rostral area (F5) showed transition characteristics that rendered it somehow similar to the prefrontal areas. It may correspond to the cytoarchitectonic area FCBm. The cytocrome oxidase technique is a useful means of parcellating the agranular frontal cortex and may greatly help in physiological and behavioral experiments. INTRODUCTION The cortical region lying, in the monkey, between the central and the arcuate sulcus has been classically subdivided into two cytoarchitec- tonic areas: area 4 and area 63. Recent evidence, however, based on the connectivity of this region and the properties of its neurons, has cast serious doubts on the validity of this extremely simple subdivision and suggested that the agranular frontal cortex (area 4-6 complex) is formed by several subareas. The following data point in this direction. First, experiments in which tracers were in- jected in somatotopically discrete regions of pre- central cortex have shown that in area 6 there are two main regions directly connected with area 4. One is located on the mesial surface of the cortex, the other in the posterior bank of the arcuate sulcus and in the adjacent dorsolateral cortical surface7,15,17A 9" Second, studies of connections between the parietal and frontal lobes have made it clear that the partition of the parietal lobe into two lobules has a counterpart in the frontal lobe. The superior parietal lobule (area 5) projects to superior area 6, that is to area 6 lying above the spur of the arcuate sulcus and its imaginary caudal extension; the inferior parietal lobule (area 7b) projects to the inferior area 6, below the arcuate spur 5,7,11,16,20,22. Third, phylogenetic and embryological argu- ments indicate a different genesis of the superior and inferior area 6. The first belongs to cortical areas that originated from the hippocampus, the second one to cortical areas that, like insula, originated from the piriform cortex. Thus the superior and inferior areas 6 represent the motor Correspondence: M. Matelli, Istituto di Fisiologia Umana dell'Universitfi di Parma, via Gramsci, 14-43100 Parma, Italy. 0166-4328/85/$03.30 © 1985 Elsevier Science Publishers B.V. (Biomedical Division)