Old World monkeys (Cercopithecidae) are a group of simians native to Old World regions including Africa, India and Southeast Asia. Old World monkeys are medium to large in size. Some species are arboreal while others are terrestrial. Cercopithecids are almost exclusively diurnal. Most of the anatomical studies on area 8 have been carried out on Cercopithecidae, which includes the diverse genera of the macaques. It is now more than a century since the oculomotor cortical areas in Cercopithecidae were first discovered and described. The cerebral sulcal pattern is very stable across the whole family (Falk, 1978), with an obvious and deep arcuate sulcus and a straight sulcus principalis or rectus. The oculomotor cortex is mainly gyral but also partially sulcal (Brodmann, 1905). Most investigators, including Brodmann, have recognized at least two cytoarchitectonic areas on this gyrus. Walker (1940) distinguished area 8a close to the superior branch of the arcuate sulcus and area 45 (along the inferior part), which is a part of area 8 (Brodmann, 1905; Vogt and Vogt, 1919). Area 8 is characterized by a thin but evident granular layer (Mauss, 1908) with large pyramidal cells in layers III and V (Brodmann, 1905; von Bonin and Bailey, 1947). Briefly, the oculomotor cortex of Cercopithecidae is mainly gyral, partially sulcal, and granular.

The oculomotor effect of cortical stimulation described by Ferrier (1874, 1875), Beevor and Horsley (1888), Mott and Schaefer (1890), and Vogt and Vogt (1907) was found to be the most effective just anterior to the arcuate sulcus (Figure 2). All stimulation studies since agree that the frontal oculomotor cortex has its core in the inferior arcuate sulcus but some (probably depending on stimulation parameters) delineated a wider area. Smith (1936, 1949) described an oculomotor area extending dorsally (to upper 6 and 9). This was reduced by Crosby (1953) and Brucher (1955, 1964), extended by Robinson and Fuchs, even more restricted by Bruce et al. (1985) (to the posterior portion of the arcuate sulcus, and mainly its anterior bank), before being re-extended again by Moschovakis et al. (2004). What is most commonly named today in macaques as the FEF (Huerta et al., 1986) mainly corresponds to cytoarchitectonic area 8 or FDΓ. FEF or area 8 (if they are the same) has been functionally subdivided into two parts (though this distinction was not retained by Huerta et al., 1986): one dealing with pursuit and the other with saccades (Bruce et al., 1985). The saccadic region is located in a restricted area along the anterior wall of the arcuate sulcus, whereas the pursuit part is located deeper in the sulcus close to the fundus (Fukushima et al., 1999, 2008).

The Cebidae family of monkeys are mostly diurnal, but one genus, the Aotus, is primarily active at night. The oculomotor cortex of Cebidae has not been studied as widely or over such a long period of time as that of other monkeys or apes. It will be presented here in more detail. Compared to the gyral pattern of Cercopithecidae, the gyral pattern of Cebidae is variable. Owl monkeys (Aotus trivarigatus) are lissencephalic anterior to the central sulcus (Figure 3), as they only seldom have an inferior arcuate dimple (Huerta et al., 1986, 1987), and the oculomotor cortex is rather frontal. In squirrel monkeys (Saimiri sciureus) gyral variations range from no sulcus at all (Figure 3), to a simple dimple (Emmers and Akert, 1963; Huerta et al., 1987), to a small arcuate sulcus (Akert, 1964). The FEF is close to the dimple with considerable variation between individuals (Huerta et al., 1987). A small dysgranular area close to a particularly large dimple has been reported (Akert, 1964). The gyral pattern (Figure 3) of Cebus (apella or unspecified) is close to that of Cercopithecidae with a more accentuated sulcus arcuatus only (Sanides, 1970) or with a sulcus principalis (Tian and Lynch, 1997). As in the macaque, FEF in Cebus monkeys has been subdivided into two parts, one for smooth movement (FEMsem) and the other for saccadic movements (FEFsacc) (Tian and Lynch, 1996, 1997). In the Cebus, the FEFsacc is located at the apex of the arcuate sulcus on its anterior wall, a position close to that of Old World monkeys (Figure 3).

Hominoidea are a branch of Old World tailless anthropoid primates native to Africa and Southeast Asia. In comparison to the Cercopithecidae, major changes have occurred in the cortex of apes, especially in the areas anterior to the central sulcus. There is no sulcus resembling the arcuate sulcus of Cercipithecidae in apes. Differential studies carried out on a large number of chimpanzee brains showed considerable individual variation, particularly in the inferior precentral region (Sherwood et al., 2003). These authors insisted on the variability of the Broca’s area homologue in great apes in area 44 and had some difficulty in accurately identifying the inferior part of the precentral sulcus. They concluded that the inferior part of the precentral sulcus is not a reliable criterion for delimiting area 44. The location of the oculomotor area in chimpanzees has mainly been mapped using electrical stimulation (Grünbaum and Sherrington, 1903; Hines, 1940; Dusser de Barenne et al., 1941; Bailey et al., 1950). Despite these differences in cerebral sulcal patterns in chimpanzees, the position of the oculomotor area in the gorilla (Sherwood et al., 2003, 2004) and the orangutan (Beevor and Horsley, 1890) is about the same as that of the chimpanzee (Figure 7). Sherwood et al. (2004) suggested that this uniformity might reflect a common Bauplan¹ to great ape brain macrostructural organization.

The individual variability of cerebral sulcal patterns makes it difficult to examine this idea closely. For, chimpanzees, gorillas and orangutans, the sulcus containing the oculomotor FD is always distant from the motor cortex, is agranular (von Bonin and Bailey, 1947), and has been functionally defined using microstimulation as homologous to the FD of macaques.

There are major differences between apes and humans. However, even today, the location of the FEF in humans still raises intriguing problems. The human cerebral sulcal pattern is discernibly different from that of apes. The significant individual gyral variation, sometimes even between one hemisphere and the other, may partly explain the evident discrepancies in historical interpretations, which is particularly noticeable when comparing maps. Histologic studies have shown that the human FEF is not linked to any major sulcus (Pandya and Yeterian, 1996; Amiez et al., 2006) and that FEF is not located in Brodmann area 8 (Brodmann, 1909) (part of the granular cortex) but within the agranular cortex (Figure 4). Both PET and fMRI studies suggest that the activity of Brodmann area 8 is more associated with working memory, handling uncertainty, and analyzing coherent movements in the visual field, than eye movement per se (Cheng et al., 1995; Hyder et al., 1997; du Boisgueheneuc et al., 2006; Janata, 2009). Finally, some imaging studies have localized the human FEF in the precentral sulcus, abutting or within the primary motor strip.

These imaging studies have tended to characterize the human FEF as mainly precentral, premotor, and agranular (Figure 5). According to these properties, the human FEF might have been associated with the premotor cortex in Cercopithecidae (area 6 of Brodmann, 1909), area FB of von Economo and Koskinas (1925), area 4 s of von Bonin (1949), between FA and FB for Bailey and von Bonin (1951), and in area 6 for Sarkissov et al. (1955). However, it is important to question the assumption that the measured neuronal activity is only related to moving the eyes (Kawashima et al., 1996). Images derived from control scans performed while subjects fixate are compared with images gathered during saccadic test scans. However, as Kawashima et al. (1996) mention, unless subjects are specifically instructed to inhibit blinking, it is common for blinking to occur when saccades are made. In contrast, subjects blink less frequently during steady fixation or at rest. It is therefore possible that imaging studies may have located the FEF too far caudally, toward a motor strip containing a region that mediates blinking responses. An imaging study designed to examine saccade generation failed to find the FEF near the expected precentral sulcus location. Instead insignificant precentral sulcus activation, with marked activation in the middle frontal gyrus was observed (Kawashima et al., 1996; Sugiura et al., 2004). An active region located in the middle frontal gyrus suggests anatomy homologous to monkey FEF. However, when Guipponi and colleagues tackled this question again recently, they showed that the identification of the neural correlates of spontaneous blinks in macaque monkeys does not map to the anterior bank of the arcuate sulcus (Guipponi et al., 2014). The measured fMRI activation has been identified as belonging to area 3b and not to motor primary cortex or to premotor area 6, calling into question the possible confounding factors revealed by previous studies. Evidence gathered using transcranial magnetic stimulation combined with structural MRI (Müri et al., 1991; Wessel and Kömpf, 1991) or imaging methods (Paus et al., 1996; Luna et al., 1998; Tehovnik et al., 2000) lends support to the location of the human FEF in the middle frontal gyrus.

In animal models, there is a major discrepancy between two major classical anatomical works. For Bailey and von Bonin (1951), macaque FDΓ is almost entirely buried in the inferior frontal sulcus, and is thus much smaller than von Economo’s area (Figure 6). None of the three areas—Brodmann’s area 8, von Economo’s area FdΓ, nor Bailey and von Bonin’s FdΓ—has a topographical relation with human FEF. Bailey and von Bonin (1951) noted that Brodmann’s work on the human brain was not extensive, and followed lengthy study of lemurs and monkeys. He published only a few figures of the human structures. Today, it is agreed that Brodmann’s human area 8 is not functionally homologous to simian area 8. Bailey et al. (1950) had already expressed doubt as to whether this area (in macaques) was homologous to FDΓ in the human brain. Foerster published on two occasions Foerster (1931, 1936) two maps drawn after direct stimulations in man. In his 1931 work, reproduced by Tehovnik et al. (2000) and redrawn by Brucher (1964), the FEF area is shown just in front of the precentral sulcus, close to the inferior frontal sulcus. This is approximately the position of area D that Dejerine (Dejerine and Roussy, 1906; Dejerine, 1914), claimed dealt with conjugate deviation of the head and eyes. The 2000 redrawing of Foerster’s (1936) map by Blanke and colleagues, places the eye field more medially, even crossing the superior frontal sulcus. Penfield and Rasmussen (1957) later showed that the sites that effectively stimulate eyelid movements or eye rotations were located more posteriorly just in front of the central sulcus or, more precisely, just in front of the motor cortex where movement of the arms, face, and mouth could be elicited (Figure 5). The only area of controversy was the evoked head movement that was sometimes located more anteriorly, close to, and around, the precentral sulcus. Penfield and Rasmussen’s (1957) localizations appear more posteriorly in comparison to recent maps (Chica et al., 2014). Blanke et al. (2000) also applied direct electrical stimulation to localize the FEF. They placed it in front of the precentral sulcus on both sides of the superior frontal sulcus, extending to the middle frontal gyrus. More recently, imaging methods have placed the human FEF in the precentral sulcus (Paus et al., 1996; Luna et al., 1998; Tehovnik et al., 2000).

Returning to histoanatomical data, the human FEF, as located by the recent histologic studies, is not located in Brodmann area 8 nor in von Economo FDΓ (Brodmann, 1909; von Economo, 1929; Huerta et al., 1987; Tehovnik et al., 2000; Amiez and Petrides, 2009). Surprisingly, the FEF of humans, in contrast to that of monkeys and apes, is no longer in the granular part of the cortex. Reviewing the data published on classical maps, FEF appears to be located within the agranular cortex—not in the giganto-pyramidal part of the motor cortex, but in the isocortex agranularis simplex of Bailey and von Bonin (1951). This region may be associated with the premotor cortex in Cercopithecidae: Brodmann’s (1909) area 6, von Economo and Koskinas’s (1925) area FB, von Bonin’s (1949) area 4 s, between FA and FB for Bailey and von Bonin (1951), and in area 6 for Sarkissov et al. (1955). This observation has also been made by Tehovnik et al. (2000). In all these species there are connections with the frontal cortex just anterior to, and within, the premotor cortex, just caudal to the FEF, though the connections to the supplementary motor area are controversial in macaques (Stanton et al., 1995) and differences in cortico-cortical connections have been reported between Cebidae and macaques (Huerta et al., 1987).

In addition, within the striatum, it is also known that in macaques the FEF sends axons to the dorsal part of the caudate nucleus (Künzle and Akert, 1977; Huerta et al., 1986; Stanton et al., 1988; Pouget et al., 2009) interspaced with the frontal granular islands, which are in the associative part of the striatum not the sensorimotor part. There is no indication that this would be the case in humans. In fact the thalamic territories where the largest differences between macaques and humans were observed, were those involved in oculomotor function. A recent review confirmed these observations by comparing diffusion tractography imaging of FEF-striatal motor pathways in humans and macaques (Neggers et al., 2015). The authors confirmed that in macaques FEF is connected with the head of the caudate and anterior putamen, and M1 is connected with more posterior sections of caudate and putamen, corroborating neuroanatomical tract tracing findings. In humans FEF and M1 are connected to largely overlapping portions of posterior putamen and only a small portion of the caudate. In that respect, some of the hypothetical differences between the cortico-subcortical connections with the FEF might explain some of the functional differences between the FEF in humans and macaques. This different position and histology of FEF in humans and macaques should discourage making of assumptions about its connections to other cortical and subcortical regions. Most of these connections in apes are unknown.