Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey

A comparison of the cytoarchitecture of the human and the macaque monkey ventrolateral prefrontal cortex demonstrated a region in the monkey that exhibits the architectonic characteristic of area 45 in the human brain. This region occupies the dorsal part of the ventrolateral prefrontal convexity just below area 9/46v. Rostroventral to area 45 in the human brain lies a large cortical region labelled as area 47 by Brodmann. The ventrolateral component of this region extending as far as the lateral orbital sulcus has architectonic characteristics similar to those of the ventrolateral prefrontal region labelled by Walker as area 12 in the macaque monkey. We designated this region in both the human and the monkey ventrolateral prefrontal cortex as area 47/12. Thus, area 47/12 designates the specific part of the zone previously labelled as area 47 in the human brain that has the same overall architectonic pattern as that of Walker's area 12 in the macaque monkey brain. The cortical connections of these two areas were examined in the monkey by injecting fluorescent retrograde tracers. Although both area 45 and area 47/12 as defined here had complex multimodal input, they could be differentiated in terms of some of their inputs. Retrograde tracers restricted to area 47/12 resulted in heavy labelling of neurons in the rostral inferotemporal visual association cortex and in temporal limbic areas (i.e. perirhinal and parahippocampal cortex). In contrast, injections of tracers into dorsally adjacent area 45 demonstrated strong labelling in the superior temporal gyrus (i.e. the auditory association cortex) and the multimodal cortex in the upper bank of the superior temporal sulcus.     

Architecture and connections of retrosplenial area 30 in the rhesus monkey (Macaca mulatta).

Because of the sharp curvature of the retrosplenial region around the splenium of the corpus callosum, standard coronal sections are not appropriate for architectonic analysis of its posteroventral part. In the present study, examination of the posteroventral retrosplenial region of the rhesus monkey in sections that were orthogonal to its axis of curvature (and therefore appropriate for architectonic analysis) has permitted definition of its architecture and precise extent. This analysis demonstrated that areas 29 and 30 of the retrosplenial cortex, as well as adjacent area 23 of the posterior cingulate cortex, extend together as an arch around the splenium of the corpus callosum and maintain their topographical relationship with one another throughout their entire course. Injections of anterograde and retrograde tracers confined to retrosplenial area 30 revealed that this area has reciprocal connections with adjacent areas 23, 19 and PGm, with the mid-dorsolateral part of the prefrontal cortex (areas 9, 9/46 and 46), with multimodal area TPO in the superior temporal sulcus, as well as the posterior parahippocampal cortex, the presubiculum and the entorhinal cortex. There are also bidirectional connections with the lateroposterior thalamic nucleus, as well as the laterodorsal and the anteroventral limbic thalamic nuclei. The connectivity of area 30 suggests that it may play a role in working memory processes subserved by the mid-dorsolateral frontal cortex in interaction with the hippocampal system.     

Some observations on the course and composition of the cingulum bundle in the rhesus monkey

The course and composition of the cingulum bundle was examined by using the autoradiographic tracer technique in the rhesus monkey. The cingulum bundle is observed to consist of three major fiber components originating from thalamus, cingulate gyrus, and cortical association areas. Following isotope injections in the anterior and lateral dorsal thalamic nuclei, labelled fibers form an arch in the white matter behind the cingulate sulcus and occupy the ventral sector of the cingulum bundle. The fibers from the anterior thalamic nucleus coursing in the cingulum bundle extended rostrally to the frontal cortex and caudally to area 23 and the retrosplenial cortex. In contrast, the fibers from lateral dorsal nucleus reached the retrosplenial cortex as well as the parahippocampal gyrus and presubiculum. Efferent fibers from the cingulate gyrus occupy a dorsolateral sector of the cingulum bundle. Those fibers from area 24 of the cingulate gyrus are directed to the premotor and prefrontal regions as well as area 23 and retrosplenial cortex. The fibers from area 23 extend rostrally to the prefrontal cortex and caudoventrally to the presubiculum and parahippocampal gyrus. Finally, an association component originates mainly from prefrontal cortex and posterior parietal region. These fibers occupy a more dorsal and lateral periphery in the cingulate white matter. Cingulum bundle fibers from the prefrontal cortex extend up to the retrosplenial cortex while those from the posterior parietal cortex extend caudally to the parahippocampal gyrus and presubiculum, and rostrally up to the prefrontal cortex.     

Selective prefrontal cortical projections to the region of the locus coeruleus and raphe nuclei in the rhesus monkey

Descending cortical projections to the region of the noradrenergic locus coeruleus (LC) and the serotonergic dorsal and central superior raphe nuclei were analyzed in the rhesus monkey using anterograde labeling techniques. HRP pellets or tritiated leucine were injected into one of 7 cortical areas: the dorsolateral prefrontal cortex, the dorsomedial prefrontal cortex, the orbital prefrontal cortex, the parietal association cortex, somatosensory cortex, the anterior portion of the inferior temporal gyrus, and the posterior portion of the inferior temporal gyrus. Anterogradely labeled fibers were found in and adjacent to the LC and raphe nuclei only following the dorsolateral and dorsomedial prefrontal cortical injections. Terminal labeling was densest at rostral levels of the LC, particularly in the area directly medial to the nucleus. Labeled fibers could not be followed beyond caudal levels of the LC. The projections to the contralateral LC and raphe nuclei were similar to, but less dense than that to the ipsilateral region. Injections into cortical areas other than the dorsal prefrontal cortex resulted in anterograde labeling of the pontine nuclei or pyramids, but not the LC/raphe region. These data, in conjunction with studies in the rat, suggest that the dorsal prefrontal cortex may be the only cortical area to have direct influence on the LC and raphe nuclei and secondary influence on the monoaminergic innervation of large areas of cerebral cortex.     

Frontal granular cortex input to the cingulate (M3), supplementary (M2) and primary (M1) motor cortices in the rhesus monkey

Although frontal lobe interconnections of the primary (area 4 or M1) and supplementary (area 6m or M2) motor cortices are well understood, how frontal granular (or prefrontal) cortex influences these and other motor cortices is not. Using fluorescent dyes in rhesus monkeys, we investigated the distribution of frontal lobe inputs to M1, M2, and the cingulate motor cortex (area 24c or M3, and area 23c). M1 received input from M2, lateral area 6, areas 4C and PrCO, and granular area 12. M2 received input from these same areas as well as M1; granular areas 45, 8, 9, and 46; and the lateral part of the orbitofrontal cortex. Input from the ventral part of lateral area 6, area PrCO, and frontal granular cortex targeted only the ventral portion of M1, and primarily the rostral portion of M2. In contrast, M3 and area 23c received input from M1, M2; lateral area 6 and area 4C; granular areas 8, 12, 9, 46, 10, and 32; as well as orbitofrontal cortex. Only M3 received input from the ventral part of lateral area 6 and areas PrCO, 45, 12vl, and the posterior part of the orbitofrontal cortex. This diversity of frontal lobe inputs, and the heavy component of prefrontal input to the cingulate motor cortex, suggests a hierarchy among the motor cortices studied. M1 receives the least diverse frontal lobe input, and its origin is largely from other agranular motor areas. M2 receives more diverse input, arising primarily from agranular motor and prefrontal association cortices. M3 and area 23c receive both diverse and widespread frontal lobe input, which includes agranular motor, prefrontal association, and frontal limbic cortices. These connectivity patterns suggest that frontal association and frontal limbic areas have direct and preferential access to that part of the corticospinal projection which arises from the cingulate motor cortex. © 1993 Wiley-Liss,Inc.     

Cortical projections to the paramedian tegmental and basilar pons in the monkey

The efferent connections of the cerebral cortex to paramedial tegmental and basilar pons were studied in the monkey by using the retrograde and orthograde capabilities of the horseradish peroxidase (HRP) technique. Six capuchin monkeys (Cebus apella) received transcannular pontine HRP gel implants to retrogradely label the cells of origin of corticopontine projections. Four additional capuchin monkeys, one rhesus (Macaca mulatta), and one cynomolgus (Macaca fascicularis) monkey, received HRP gel implants in premotor (area 6), frontal eye field (FEF, area 8), superior (area 5), and inferior (area 7) parietal lobules to orthogradely label the course and termination of corticopontine projections, and thus to confirm the retrograde studies. The brains were processed according to the tetramethylbenzidine (TMB) protocol of Mesulam ('78) and studied with darkfield microscopy. Premotor (area 6) frontal cortex and FEF (area 8) were found to be the main sources of cortical inputs to the ipsilateral paramedian basilar pons, whereas FEF, dorsal prefrontal convexity, and dorsal medial prefrontal (granular frontal association) cortex were the main sources of bilateral projections to the paramedian pontine tegmentum. The medial portion of the nucleus reticularis tegmenti pontis (NRTP), considered to be a tegmental extension of the basilar pontine gray, also received its principal cortical input from the frontal lobe. Parietal cortex, on the other hand, was observed to project to lateral NRTP and lateral basilar pons. Although the possibility exists of convergence of frontal and parietal eye field efferents in the NRTP, the frontal eye field and prefrontal cortex appear to be the principal source of cortical projections to the paramedian pontine tegmentum, which contains the physiologically defined PPRF (paramedian pontine reticular formation), an important preoculomotor center. The results are discussed primarily with regard to their significance for potential cortical influence on the oculomotor system.     

Macaque monkey retrosplenial cortex: II. Cortical afferents

We investigated the cortical afferents of the retrosplenial cortex and the adjacent posterior cingulate cortex (area 23) in the macaque monkey by using the retrograde tracers Fast blue and Diamidino yellow. We quantitatively analyzed the distribution of labeled neurons throughout the cortical mantle. Injections involving the retrosplenial cortex resulted in labeled neurons within the retrosplenial cortex and in areas 23 and 31 (approximately 78% of the total labeled cells). In the remainder of the cortex, the heaviest projections originated in the hippocampal formation, including the entorhinal cortex, subiculum, presubiculum, and parasubiculum. The parahippocampal and perirhinal cortices also contained many labeled neurons, as did the prefrontal cortex, mainly in areas 46, 9, 10, and 11, and the occipital cortex, mainly area V2. Injections in area 23 also resulted in numerous labeled cells in the posterior cingulate and retrosplenial regions (approximately 67% of total labeled cells). As in the retrosplenial cortex, injections of area 23 led to many labeled neurons in the frontal cortex, although most of these cells were in areas 9 and 46. Larger numbers of retrogradely labeled cells were also distributed more widely in the posterior parietal cortex, including areas 7a, 7m, LIP, and DP. There were some labeled cells in the parahippocampal cortex. These connections are consistent with the retrosplenial cortex acting as an interface between the working memory functions in the prefrontal areas and the long-term memory encoding in the medial temporal lobe. The posterior cingulate cortex, in contrast, may be more highly associated with visuospatial functions.     

Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe

We examined interconnections between a portion of the prefrontal cortex and the premotor areas in the frontal lobe to provide insights into the routes by which the prefrontal cortex gains access to the primary motor cortex and the central control of movement. We placed multiple injections of one retrograde tracer in the arm area of the primary motor cortex to define the premotor areas in the frontal lobe. Then, in the same animal, we placed multiple injections of another retrograde tracer in and around the principal sulcus (Walker's area 46). This double labeling strategy enabled us to determine which premotor areas are interconnected with the prefrontal cortex. There are three major results of this study. First, we found that five of the six premotor areas in the frontal lobe are interconnected with the dorsolateral prefrontal cortex. Second, the major site for interactions between the prefrontal cortex and the premotor areas is the ventral premotor area. Third, the prefrontal cortex is interconnected with only a portion of the arm representation in three premotor areas (supplementary motor area, the caudal cingulate motor area on the ventral bank of the cingulate sulcus, and the dorsal premotor area), whereas it is interconnected with the entire arm representation in the ventral premotor area and the rostral cingulate motor area. These observations indicate that the output of the prefrontal cortex targets specific premotor areas and even subregions within individual premotor areas.     

Topographical organization of the cortical afferent connections of the prefrontal cortex in the cat

The topographical distribution of the cortical afferent connections of the prefrontal cortex (PFC) in adult cats was studied by using the retrograde axonal transport of horseradish peroxidase technique. Small single injections of the enzyme were made in different locations of the PFC, and the areal location and density of the subsequent neuronal labeling in neocortex and allocortex were evaluated in each case. The comparison of the results obtained in the various cases revealed that four prefrontal sectors (rostral, dorsolateral, ventral, and dorsomedial) can be distinguished, each exhibiting a particular pattern of cortical afferents. All PFC sectors receive projections from the ipsilateral insular (agranular and granular subdivisions) and limbic (infralimbic, prelimbic, anterior limbic, cingular, and retrosplenial areas) cortices. These cortices provide the most abundant cortical projections to the PFC, and their various subdivisions have different preferential targets within the PFC. The premotor cortex and the following neocortical sensory association areas project differentially upon the various ipsilateral PFC sectors: the portion of the somatosensory area SIV in the upper bank of the anterior ectosylvian sulcus, the visual area in the lower bank of the same sulcus, the auditory area AII, the temporal area, the perirhinal cortex, the posterior suprasylvian area, area 20, the posterior ectosylvian area, the suprasylvian fringe, the lateral suprasylvian area (anterolateral and posterolateral subdivisions), area 5, and area 7. The olfactory peduncle, the prepiriform cortex, the cortico-amygdaloid transition area, the entorhinal cortex, the subiculum (ventral, posteroventral, and posterodorsal sectors), the caudomedial band of the hippocampal formation and the postsubiculum are the allocortical sources of afferents to the PFC. The dorsolateral PFC sector is the target of the largest insular, limbic, and neocortical sensory association projections. The dorsomedial and rostral sectors receive notably less abundant cortical afferents than the dorsolateral sector. Those to the dorsomedial sector arise from the same areas that project to the dorsolateral sector and are more abundant to the dorsal part, where the medial frontal eye field cortex is located. The rostral sector receives projections principally from all other PFC sectors, and from the limbic and insular cortices. The projections from the allocortex reach preferentially the ventral PFC sector. Intraprefrontal connections are most abundant within each PFC sector. Commissural interprefrontal connections are largest from the site homotopic to the HRP injection.(ABSTRACT TRUNCATED AT 400 WORDS)     

Forebrain connectivity of the prefrontal cortex in the marmoset monkey (Callithrix jacchus): an anterograde and retrograde tract-tracing study

The cortical and subcortical forebrain connections of the marmoset prefrontal cortex (PFC) were examined by injecting the retrograde tracer, choleratoxin, and the anterograde tracer, biotin dextran amine, into four sites within the PFC. Two of the sites, the lateral and orbital regions, had previously been shown to provide functionally dissociable contributions to distinct forms of behavioral flexibility, attentional set-shifting and discrimination reversal learning, respectively. The dysgranular and agranular regions lying on the orbital and medial surfaces of the frontal lobes were most closely connected with limbic structures including cingulate cortex, amygdala, parahippocampal cortex, subiculum, hippocampus, hypothalamus, medial caudate nucleus, and nucleus accumbens as well as the magnocellular division of the mediodorsal nucleus of the thalamus and midline thalamic nuclei, consistent with findings in the rhesus monkey. In contrast, the granular region on the dorsal surface closely resembled area 8Ad in macaques and had connections restricted to posterior parietal cortex primarily associated with visuospatial functions. However, it also had connections with limbic cortex, including retrosplenial and caudal cingulate cortex as well as auditory processing regions in the superior temporal cortex. The granular region on the lateral convexity had the most extensive connections. Based on its architectonics and functionality, it resembled areas 12/45 in macaques. It had connections with high-order visual processing regions in the inferotemporal cortex and posterior parietal cortex, higher-order auditory and polymodal processing regions in the superior temporal cortex. In addition it had extensive connections with limbic regions including the amygdala, parahippocampal cortex, cingulate, and retrosplenial cortex.     

Cingulate cortex of the rhesus monkey: II. Cortical afferents

Cortical projections to subdivisions of the cingulate cortex in the rhesus monkey were analyzed with horseradish peroxidase and tritiated amino acid tracers. These projections were evaluated in terms of an expanded cytoarchitectural scheme in which areas 24 and 23 were divided into three ventrodorsal parts, i.e., areas 24a-c and 23a-c. Most cortical input to area 25 originated in the frontal lobe in lateral areas 46 and 9 and orbitofrontal areas 11 and 14. Area 25 also received afferents from cingulate areas 24b, 24c, and 23b, from rostral auditory association areas TS2 and TS3, from the subiculum and CA1 sector of the hippocampus, and from the lateral and accessory basal nuclei of the amygdala (LB and AB, respectively). Areas 24a and 24b received afferents from areas 25 and 23b of cingulate cortex, but most were from frontal and temporal cortices. These included the following areas: frontal areas 9, 11, 12, 13, and 46; temporal polar area TG as well as LB and AB; superior temporal sulcus area TPO; agranular insular cortex; posterior parahippocampal cortex including areas TF, TL, and TH and the subiculum. Autoradiographic cases indicated that area 24c received input from the insula, parietal areas PG and PGm, area TG of the temporal pole, and frontal areas 12 and 46. Additionally, caudal area 24 was the recipient of area PG input but not amygdalar afferents. It was also the primary site of areas TF, TL, and TH projections. The following projections were observed both to and within posterior cingulate cortex. Area 29a-c received inputs from area 46 of the frontal lobe and the subiculum and in turn it projected to area 30. Area 30 had afferents from the posterior parietal cortex (area Opt) and temporal area TF. Areas 23a and 23b received inputs mainly from frontal areas 46, 9, 11, and 14, parietal areas Opt and PGm, area TPO of superior temporal cortex, and areas TH, TL, and TF. Anterior cingulate areas 24a and 24b and posterior areas 29d and 30 projected to area 23. Finally, a rostromedial part of visual association area 19 also projected to area 23. The origin and termination of these connections were expressed in a number of different laminar patterns. Most corticocortical connections arose in layer III and to a lesser extent layer V, while others, e.g., those from the cortex of the superior temporal sulcus, had an equal density of cells in both layers III and V.(ABSTRACT TRUNCATED AT 400 WORDS)     

Macaque monkey retrosplenial cortex: III. Cortical efferents

We have investigated the cortical efferent projections of the macaque monkey retrosplenial and posterior cingulate cortices by using (3)H-amino acids as anterograde tracers. All the injections produced extensive local connections to other portions of this region. There were also a number of extrinsic efferent cortical connections, many of which have not hitherto been reported. Major projections from the retrosplenial cortex were directed to the frontal lobe, with heaviest terminations in areas 46, 9, 10, and 11. There were also very substantial projections to the entorhinal cortex, presubiculum, and parasubiculum of the hippocampal formation, as well as to areas TH and TF of the parahippocampal cortex. Some injections led to labeling of area V4, the dorsal bank of the superior temporal sulcus, and area 7a of the parietal cortex. Projections from the posterior cingulate cortex innervated all these same regions, although the density of termination was different from the retrosplenial projections. The posterior cingulate cortex gave rise to additional projections to parietal area DP and to the cortex along the convexity of the superior temporal gyrus. The ventral portion of the posterior cingulate cortex (area 23v) gave rise to much denser efferent projections to the hippocampal formation than the dorsal portions (areas 23e and i). These connections are discussed in relation to the clinical syndromes of retrosplenial amnesia and topographic disorientation in humans commonly caused by lesions in the caudoventral portions of the retrosplenial and posterior cingulate cortices.     

Intrahemispheric cortico-cortical afferent connections of the prefrontal cortex in the cat

Ipsilateral cortical projections to the prefrontal cortex of the cat were investigated by means of the retrograde axonal transport of horseradish peroxidase technique. Labeled neurons were identified in frontal, insular, parietal and temporal regions, as well as in cingular, retrosplenial and perirhinal areas. These intrahemispheric cortical connections can be compared to those described in the rhesus monkey.     

Cortical connections of the lateral mediodorsal thalamus in cynomolgus monkeys

The prefrontal cortex has been defined as that cortical territory that has "essential or sustaining" connections with the mediodorsal (MD) nucleus of the thalamus. However, recent studies in the monkey have documented projections from MD to the more caudal, agranular regions of the frontal cortex, suggesting that the connections of MD may be characterized by a breadth of distribution and diversity of functional roles too great to be useful as a unifying and defining feature for a specific cortical territory. In this study, we placed tracer injections in the lateral divisions of MD in cynomolgus monkeys (Macaca fascicularis) to assess the relative proportions of connections devoted to diverse regions of the frontal cortex (FC). Three different patterns of label were observed in the cortex, associated with different locations within lateral MD. We have designated these as the ventrolateral MD-arcuate FC circuit, having most label in areas 8 and 6; the caudoventral MD-dorsomedial FC circuit, having most label in areas 24 and presupplementary motor area (SMA); and the anterodorsal MD-anterior FC circuit, with the most label in areas 9, 46, 12, and 10. Only two of the nine cases injected in lateral MD were predominantly connected with the anterior FC. Thus, particular locales within lateral MD are connected with multiple, functionally diverse cortical regions, including several not classically recognized as "prefrontal" areas. This divergence may distinguish MD-frontocortical and reciprocal corticothalamic pathways from the largely segregated pathways arising from the other thalamic nuclei that are interconnected with the frontal cortex, such as those from the ventrolateral nuclear group.     

Posterior parietal cortex in rhesus monkey: II. Evidence for segregated corticocortical networks linking sensory and limbic areas with the frontal lobe

We have examined the circuitry connecting the posterior parietal cortex with the frontal lobe of rhesus monkeys. HRP-WGA and tritiated amino acids were injected into subdivisions 7m, 7a, 7b, and 7ip of the posterior parietal cortex, and anterograde and retrograde label was recorded within the frontal motor and association cortices. Our main finding is that each subdivision of parietal cortex is connected with a unique set of frontal areas. Thus, area 7m, on the medial parietal surface, is interconnected with the dorsal premotor cortex and the supplementary motor area, including the supplementary eye field. Within the prefrontal cortex, area 7m's connections are with the rostral sector of the frontal eye field (FEF), the dorsal bank of the principal sulcus, and the anterior bank of the inferior arcuate sulcus (Walker's area 45). In contrast, area 7a, on the posterior parietal convexity, is not linked with premotor regions but is heavily interconnected with the rostral FEF in the anterior bank of the superior arcuate sulcus, the dorsolateral prefrontal convexity, the rostral orbitofrontal cortex, area 45, and the fundus and adjacent cortex of the dorsal and ventral banks of the principal sulcus. Area 7b, in the anterior part of the posterior parietal lobule, is interconnected with still a different set of frontal areas, which include the ventral premotor cortex and supplementary motor area, area 45, and the external part of the ventral bank of the principal sulcus. The prominent connections of area 7ip, in the posterior bank of the intraparietal sulcus, are with the supplementary eye field and restricted portions of the ventral premotor cortex, with a wide area of the FEF that includes both its rostral and caudal sectors, and with area 45. All frontoparietal connections are reciprocal, and although they are most prominent within a hemisphere, notable interhemispheric connections are also present. These findings provide a basis for a parcellation of the classically considered association cortex of the frontal lobe, particularly the cortex of the principal sulcus, into sectors defined by their specific connections with the posterior parietal subdivisions. Moreover, the present findings, together with those of a companion study (Cavada and Goldman-Rakic: J. Comp. Neurol. this issue) have allowed us to establish multiple linkages between frontal areas and specific limbic and sensory cortices through the posterior parietal cortex. The networks thus defined may form part of the neural substrate of parallel distributed processing in the cerebral cortex.     

Quantitative demonstration of comparable architectonic areas within the ventromedial and lateral orbital frontal cortex in the human and the macaque monkey brains

The orbital and ventromedial frontal cortical regions of the human and the macaque monkey brains include several spatially discrete areas which are defined histologically by their distinctive laminar architecture. Although considerable information has been collected on the function and anatomical connections of specific architectonic areas within the orbital and ventromedial frontal cortex of the macaque monkey, the location of comparable areas in the human brain remains controversial. We re-examined the comparability of orbital and ventromedial frontal areas across these two species and provide the first quantitative demonstration of architectonically comparable cortical areas in the human and the macaque brains. Images of Nissl-stained sections of the cortex were obtained at low magnification. Differences in the typical size of neurons in alternating pyramidal and granule cell layers were exploited to segregate the cortical layers before sampling. Profiles of areal neuronal density were sampled across the width of the cortex. The location of individual cortical layers was identified on each profile by sampling a set of equally sized images on which the cortical layers had been manually traced. The rank order of sampled architectonic features in comparable architectonic areas in the two species was significantly correlated. The differences in measured features between gyral and sulcal parts of the same architectonic area are at a minimum 3-4 times smaller than the differences between architectonic areas for the areas examined. Furthermore, the quantified architectonic features arrange areas within the orbital and ventromedial frontal cortex along two dimensions: an anterior-to-posterior and a medial-to-lateral dimension. On the basis of these findings, and in light of known anatomical connections in the macaque, this region of the human cortex appears to comprise at least two hierarchically structured networks of areas.     

Development of non-phosphorylated neurofilament protein expression in neurones of the New World monkey dorsolateral frontal cortex

We studied developmental changes in the expression of non-phosphorylated neurofilament protein (NNF) (a marker of the structural maturation of pyramidal neurones) in the dorsolateral frontal cortex of marmoset monkeys, between embryonic day 130 and adulthood. Our focus was on cortical fields that send strong projections to extrastriate cortex, including the dorsal and ventral subdivisions of area 8A, area 46 and area 6d. For comparison, we also investigated the maturation of prefrontal area 9, which has few or no connections with visual areas. The timing of expression of NNF immunostaining in early life can be described as the result of the interaction of two developmental gradients. First, there is an anteroposterior gradient of maturation in the frontal lobe, whereby neurones in caudal areas express NNF earlier than those in rostral areas. Second, there is a laminar gradient, whereby the first NNF-immunoreactive neurones emerge in layer V, followed by those in progressively more superficial parts of layer III. Following a peak in density of NNF-immunopositive cell numbers in layer V at 2-3 months of age, there is a gradual decline towards adulthood. In contrast, the density of immunopositive cells in layer III continues to increase throughout the first postnatal year in area 6d and until late adolescence (> 1.5 years of age) in prefrontal areas. The present results support the view that the maturation of visual cognitive functions involves relatively late processes linked to structural changes in frontal cortical areas.     

Cytoarchitecture and intrafrontal connections of the frontal cortex of the brain of the hamadryas baboon (Papio hamadryas).

A study was made of the cytoarchitecture of the lateral and medial frontal cortex in the hamadryas baboon (Papio hamadryas). The frontal corticocortical connections of areas 46, 8, 6, and 4 were investigated by injection of wheat-germ agglutinine conjugated to horseradish peroxiase (WGA-HRP) into different regions of areas 46, 8, and 6. The lateral region of the frontal lobe of the baboon consists of broad areas of motor (area 4), premotor (area 6), and the dorsolateral prefrontal cortex, each of which is further divided into subdivisions with distinct cytoarchitectural features: areas 4a, 4b, 4c; 6aα, 6aβ, 6aγ, 6bα, and 6β; 8A and 8B; 45; 46 and 46ps; 9; 10; and 12. Although the frontal cortex of the baboon brain exhibits the same basic cytoarchitectural features as the frontal corticies of the cercopithecus (campbelli?) (Vogt and Vogt, '19) or the macaque (Walker, '40; Barbas and Pandya, '87, '89), the baboon frontal cortex is very different from that of the macaque and cercopithecus in terms of cytoarchitecture: (1) the baboon frontal cortex has an additional area, termed here “6aγ”, within area 6, which has cytoarchitectural characteristics that are intermediate between those of areas 6 and 8; (2) the aggregation of giant pyramidal cells (> 50 μm. in diameter) is found only in area 4a in the baboon, whereas such aggregates are found in areas 4a and 4b and, occasionally, in area 4c in the macaque; and (3) area 46 of the prefrontal cortex of the baboon can be subdivided into the cortex that surrounds the principal sulcus (area 46) and the upper and lower banks of the principal sulcus (area 46ps). Retrogradely WGA-HRP labeled cells and anterogradely WGA-HRP labeled terminals coexisted in the frontal cortex in a columnar fashion, indicative of a reciprocity among the connections. The frontal cortico-cortical connections of areas 46, 8, 6, and 4 in the hamadryas baboon were organized as follows: (1) areas 46, 8, and 6 were connected to one another, (2) area 4 was connected only to area 6, and (3) these connections showed a gross ventrodorsal topography: the ventral regions of each of areas 46, 8, and 6 were connected more strongly to the ventral than the dorsal regions of the other areas; the dorsal regions of each of areas 46, 8, and 6 were connected more strongly to the dorsal than the ventral regions of the other areas. Moreover, the ventral region of area 6 was more strongly connected to the ventral than to the dorsal region of area 4, whereas the dorsal region of area 6 was more strongly connected to the dorsal than to the ventral region of area 4.     

Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update

Frontal-subcortical circuits form the principal network, which mediate motor activity and behavior in humans. Five parallel frontal-subcortical circuits link the specific areas of the frontal cortex to the striatum, basal ganglia and thalamus. These frontal-subcortical circuits originate from the supplementary motor area, frontal eye field, dorsolateral prefrontal region, lateral orbitofrontal region and anterior cingulate portion of the frontal cortex. The open afferent and efferent connections to the frontal-subcortical circuits mediate coordination between functionally similar areas of the brain. Specific chemoarchitecture and multiple neurotransmitter interactions modulate the functional activity of each circuit. Dorsolateral prefrontal circuit lesions cause executive dysfunction, orbitofrontal circuit lesions lead to personality changes characterized by disinhibition and anterior cingulate circuit lesions present with apathy. The neurobiological correlates of neuropsychiatric disorders including depression, obsessive-compulsive disorder, schizophrenia and substance abuse, imply involvement of frontal-subcortical circuits.     

Pathways for motion analysis: cortical connections of the medial superior temporal and fundus of the superior temporal visual areas in the macaque

To identify the cortical connections of the medial superior temporal (MST) and fundus of the superior temporal (FST) visual areas in the extrastriate cortex of the macaque, we injected multiple tracers, both anterograde and retrograde, in each of seven macaques under physiological control. We found that, in addition to connections with each other, both MST and FST have widespread connections with visual and polysensory areas in posterior prestriate, parietal, temporal, and frontal cortex. In prestriate cortex, both areas have connections with area V3A. MST alone has connections with the far peripheral field representations of V1 and V2, the parieto-occipital (PO) visual area, and the dorsal prelunate area (DP), whereas FST alone has connections with area V4 and the dorsal portion of area V3. Within the caudal superior temporal sulcus, both areas have extensive connections with the middle temporal area (MT), MST alone has connections with area PP, and FST alone has connections with area V4t. In the rostral superior temporal sulcus, both areas have extensive connections with the superior temporal polysensory area (STP) in the upper bank of the sulcus and with area IPa in the sulcal floor. FST also has connections with the cortex in the lower bank of the sulcus, involving area TEa. In the parietal cortex, both the central field representation of MST and FST have connections with the ventral intraparietal (VIP) and lateral intraparietal (LIP) areas, whereas MST alone has connections with the inferior parietal gyrus. In the temporal cortex, the central field representation of MST as well as FST has connections with visual area TEO and cytoarchitectonic area TF. In the frontal cortex, both MST and FST have connections with the frontal eye field. On the basis of the laminar pattern of anterograde and retrograde label, it was possible to classify connections as forward, backward, or intermediate and thereby place visual areas into a cortical hierarchy. In general, MST and FST receive forward inputs from prestriate visual areas, have intermediate connections with parietal areas, and project forward to the frontal eye field and areas in the rostral superior temporal sulcus. Because of the strong inputs to MST and FST from area MT, an area known to play a role in the analysis of visual motion, and because MST and FST themselves have high proportions of directionally selective cells, they appear to be important stations in a cortical motion processing system.