Abstract. Primates are unique among mammals in possessing a region
of dorsolateral prefrontal cortex with a well-developed internal granular
layer. This region is commonly associated with higher cognitive functions.
Despite the histological distinctiveness of primate dorsolateral prefrontal
cortex, the work of Rose, Woolsey, and Akert produced a broad consensus among
neuroscientists that homologues of primate granular frontal cortex exist
in nonprimates, and can be recognized by their dense innervation from the
mediodorsal thalamic nucleus (MD). Additional characteristics have come to
be identified with dorsolateral prefrontal cortex, including rich dopaminergic
innervation and involvement in spatial delayed-reaction tasks. However, recent
studies reveal that these characteristics are not distinctive of the dorsolateral
prefrontal region in primates: MD and dopaminergic projections are widespread
in the frontal lobe, and medial and orbital frontal areas may play a role
in delay tasks. A re-evaluation of rat frontal cortex suggests that the medial
frontal cortex, usually considered to homologous to the dorsolateral prefrontal
cortex of primates, actually consists of cortex homologous to primate premotor
and anterior cingulate cortex. The lateral MD-projection cortex of rats resembles
portions of primate orbital cortex. If prefrontal cortex is construed broadly
enough to include orbital and cingulate cortex, rats can be said to have
prefrontal cortex. However, they evidently lack homologues of the dorsolateral
prefrontal areas of primates. This assessment suggests that rats probably
do not provide useful models of human dorsolateral frontal lobe function
and dysfunction, although they might prove valuable for understanding other
regions of frontal cortex.
On the uniqueness of primate prefrontal cortex My dissertation research, carried out in the laboratory of Dr. Patricia Goldman-Rakic at Yale, concerned the evolution of primate prefrontal cortex, a region of cortex implicated in higher-order cognitive functions. Primates are unusual among mammals in having a region of dorsolateral prefrontal cortex with a reasonably well-developed internal granular layer (granular frontal cortex). Nevertheless, since the work of Rose & Woolsey (1948) and Akert (1964), neuroscientists have generally accepted that most or all mammals possess cortex homologous to primate prefrontal cortex, although the region lacks a dense granular layer in nonprimates. Thus, it was argued that homologues of prefrontal cortex could be distinguished from other regions by (1) their afferents from the mediodorsal thalamic nucleus (MD), (2) dense dopaminergic inputs, and (3) involvement in delayed-response and delayed-alternation tasks. Furthermore, it has been argued the the same basic subdivisions of prefrontal cortex present in primates could be identified in nonprimate mammals such as rats and cats, including specifically the frontal eyefield and principalis cortex (the latter being named for its location along the banks of the principal sulcus of macaque monkeys).
My dissertation research compared the histology and connectivity of the
prefrontal region in two different primates, macaques and galagos (Preuss
& Goldman-Rakic, 1991a,b,c). Galagos are prosimian primates with
relatively small brains and very small frontal lobes. We found that
galagos, like monkeys, possess a discrete region of frontal cortex with a
well-developed internal granular layer. This region was tiny however,
and while it contained cortex that resembled the frontal eyefield, we could
find no region of galago cortex that had the distinctive connectional and
architectonic characteristics of principalis cortex.
These results raised questions about the generality of prefrontal cortex among mammals, and upon reviewing the modern evidence regarding the structure and function of frontal cortex in primates and other mammals, I came to the conclusion that Rose & Woolsey and Akert were wrong, and that at least the dorsolateral portion of primate prefrontal cortex is unique to primates. The crux of the argument, as developed in Preuss (1995) is as follows. First, MD projections in primates are not restricted to the dorsolateral prefrontal cortex; they reach virtually the entire frontal lobe with the exception of primary motor cortex (in cats they reach primary motor cortex as well). Of course, the dorsolateral PFC receives a particularly strong MD projection, but so does cingulate and orbital cortex. Thus, MD projections are not diagnostic of dorsolateral prefrontal cortex. Similarly, dense dopamine afferents are also not diagnostic of dorsolateral prefrontal cortex: In macaques and humans, the motor and premotor cortex are the targets of the strongest dopaminergic projections to the frontal lobe; dense projections also reach the cingulate and orbital cortex. Finally, in macaques, dorsolateral prefrontal cortex is not uniquely associated with performance on delayed-response and delayed-alternation tasks: substantial deficits on such tasks can be produced with lesions of the medial wall of the frontal lobe.
These considerations prompted the new interpretation of the frontal-lobe
homologies of macaques and rats articulated in Preuss (1995) and summarized
in the figure above. The region of rat frontal cortex usually
considered homologous to the dorsolateral PFC of primates is located along
the dorsomedial edge ("shoulder") of the hemisphere and the medial wall, anterior
to the corpus callosum. This region receives dense inputs from MD and
from the dopamine-containing nuclei of the brainstem. The shoulder
cortex is considered to be the rat's frontal eyefield, because stimulation
of this zone yields head and eye movements. The medial cortex is considered
to be homologous to macaque principalis cortex, because lesions of this zone
produce deficits (albeit rather short-lived) on delayed-alternation tasks.
Nevertheless, the data just cited are consistent with an alternative interpretation
of homology, namely, that the shoulder cortex is homologous to some portion
of the non-primary motor cortex of primates and that the medial cortex is
homologous to the medial frontal cortex of primates (areas 32 and 25, a.k.a.
the prelimbic and infralimbic areas). This scheme makes much better
sense of the comparative anatomical, neurochemical, and behavioral data for
rats and macaques than does the traditional interpretation. The
new interpretation, however, leaves rats without cortex homologous to the
dorsolateral PFC of primates.
by Dr. Todd M. Preuss.
Document last revised 04-October-2002.
© Copyright 2002.