Clarification of the confusion in the definition of area 45
Most modern architectonic studies of the prefrontal cortex in the monkey were largely based on the map by Walker 1. Walker designated as “area 45" a part of the frontal cortex that lies along the rostral bank of the inferior arcuate sulcus and tentatively suggested that it may correspond to area 45 of the human brain. He was, however, uncertain about this correspondence because he had not explicitly compared monkey with human architecture (see Walker 1, p. 67). Walker characterized the region he labelled “area 45" as having large pyramidal cells both in layers III and V (p. 68, l. 1-2). However, in the human brain 2, area 45 is characterized by large neurons in layer III, but medium size neurons in layer V. Thus, Walker’s definition of the key characteristic of monkey area 45 is not that of area 45 in the human brain, namely the asymmetry in the size of the largest neurons of layers III and V. We wish to emphasize the fact that, in the present study, area 45 in the monkey was defined by architectonic characteristics comparable to those of area 45 in the human brain.
The term “area 45” in the monkey has sometimes been used to refer to a ventral part of the frontal eye field 3, from which small amplitude saccades can be evoked with electrical microstimulation, in order to contrast it to the more dorsal part of the frontal eye field where large amplitude saccades can be evoked and which is referred to as being in caudal area 8A. This use of the term “area 45” by some oculomotor neurophysiologists to refer to the ventral part of the frontal eye field is confusing for a number of reasons. First, in the monkey, the ventral part of the frontal eye field from which small amplitude saccades can be evoked, and which has sometimes been referred to as “area 45”, is characterized by large neurons in layer V and, therefore, falls outside the limits of area 45 when defined by the characteristics of area 45 of the human brain (i.e. medium neurons in layer V). Stanton et al 4 have shown that, in the microstimulation-defined ventral frontal eye field region, the cortex exhibits large and dense pyramidal neurons in layer V. These large layer V neurons diminish sharply as one proceeds into the lower part of the rostral bank of the inferior arcuate sulcus, i.e. as one moves away from the region where eye movements can be evoked 4. Note that it is precisely this lower part of the rostral bank of the inferior arcuate sulcus where there are no large pyramidal neurons in layer V that is comparable to area 45 of the human brain. The results of the present study were consistent with those of Stanton et al 4 with regards to the location of the frontal eye field. We found that all sites from which eye movements were evoked were located in a part of the arcuate cortex having large neurons in layer V, i.e. they were located in architectonic area 8Av. No eye movements could be evoked from stimulation more ventrally in the region that has architectonic characteristics similar to those of area 45 of the human brain, namely large pyramids in layer III but medium pyramids in layer V. Thus, in our cytoarchitectonic studies, the upper part of the inferior arcuate sulcus that exhibits large neurons in layer V and where eye movements are recorded (both large and small amplitude saccades) is considered to be part of caudal area 8, in agreement with other investigators (e.g. Brodmann 5, Barbas and Pandya 6).
Second, in an anatomical study 2 in which we injected retrograde fluorescent tracers into the part of the monkey prefrontal cortex that we identified as comparable to area 45 of the human brain, we observed that cortical inputs originate from the superior temporal gyrus (i.e. the auditory system) and the multimodal areas of the superior temporal sulcus and not from areas that are known to be connected with the frontal eye field. Thirdly, there is no evidence that, in the human brain, area 45 is involved in any way with eye movement control. In terms of function, area 45 in the human brain is involved in active memory retrieval, nonverbal in the right hemisphere 7 and verbal including semantic memory in the left hemisphere 8, 9. Finally, in a recent single neuron recording study in behaving monkeys 10, we showed that monkey area 45, defined by the same criteria as in the human brain, is involved in active memory retrieval (as in the human brain) and not with oculomotor function. In conclusion, area 45 in the monkey ventrolateral prefrontal cortex, when defined by criteria comparable to those of human area 45, is not identical with Walker’s area 45 and does not include any part of the frontal-eye field.
1. Walker, A. E. A cytoarchitectonic study of the prefrontal area of the macaque monkey. J. Comp. Neurol. 73, 59-86 (1940).
2. Petrides, M. & Pandya, D.N. Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey. Eur. J. Neurosci. 16, 291-310 (2002).
3. Schall, J.D., Morel, A., King, D. J. & Bullier, J. Topography of visual cortex connections with frontal eye field in macaque: Convergence and segregation of processing streams. J. Neurosci. 15, 4464-4487 (1995).
4. Stanton, G.B., Deng, S.-Y., Goldberg, M.E. & McMullen, N.T. Cytoarchitectural characteristic of the frontal eye fields in macaque monkeys. J. Comp. Neurol. 282, 415-427 (1989).
5. Brodmann, K. Beitraege zur histologischen Lokalisation der Grosshirnrinde. III. Mitteilung: Die Rindenfelder der niederen Affen. J. Psychol. Neurol. (Lzp) 4, 177-226 (1905).
6. Barbas, H. & Pandya, D.N. Architecture and intrinsic connections of the prefrontal cortex in the rhesus monkey. J. Comp. Neurol. 286, 353-375 (1989).
7. Cadoret, G., Pike, G.B. & M. Petrides, M. Selective activation of the ventrolateral prefrontal cortex in the human brain during active retrieval processing. Eur. J. Neurosci. 14, 1164-1170 (2001)
8. Petrides, M., Alivisatos, B, Meyer, E. & Evans, A.C. Functional activation of the human ventrolateral frontal cortex during mnemonic retrieval of verbal information. Proc. Natl. Acad. Sci. USA 92, 5803-5807 (1993).
9. Amunts, K. et al. Analysis of neural mechanisms underlying verbal fluency in cytoarchitectonically defined stereotaxic space-The roles of Brodmann areas 44 and 45. NeuroImage 22, 42-56 (2004).
10. Cadoret, G. & Petrides, M. Neuronal mechanisms underlying active retrieval processing in the monkey. Abstract Viewer/Itinerary Planner. Soc. Neurosci. Prog. No. 324.3 (2004).