The origin of corticospinal projections from the premotor areas in the frontal lobe.

We determined the origin of corticospinal neurons in the frontal lobe. These neurons were labeled by retrograde transport of tracers after injections into either the dorsolateral funiculus at the second cervical segment or the gray matter of the spinal cord throughout the cervical enlargement. Using retrograde transport of tracer from the arm area of the primary motor cortex, we defined the arm representation in each premotor area in another set of animals. We found that corticospinal projections to cervical segments of the spinal cord originate from the primary motor cortex and from the 6 premotor areas in the frontal lobe. These are the same premotor areas that project directly to the arm area of the primary motor cortex. The premotor areas are located in parts of cytoarchitectonic area 6 on the lateral surface and medial wall of the hemisphere, as well as in subfields of areas 23 and 24 in the cingulate sulcus. The total number of corticospinal neurons in the arm representations of the premotor areas equals or exceeds the total number in the arm representation of the primary motor cortex. The premotor areas collectively comprise more than 60% of the cortical area in the frontal lobe that projects to the spinal cord. Like the primary motor cortex, each of the premotor areas contains local regions that have a high density of corticospinal neurons. These observations indicate that a substantial component of the corticospinal system originates from the premotor areas in the frontal lobe. Each of the premotor areas has direct access to the spinal cord, and as a consequence, each has the potential to influence the generation and control of movement independently of the primary motor cortex. These findings raise serious questions about the utility of viewing the primary motor cortex as the "upper motoneuron" or "final common pathway" for the central control of movement.     

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.     

Organization of prefrontal outflow toward frontal motor-related areas in macaque monkeys

Linkage between the prefrontal cortex and the primary motor cortex is mediated by nonprimary motor-related areas of the frontal lobe. In an attempt to analyse the organization of the prefrontal outflow from area 46 toward the frontal motor-related areas, we investigated the pattern of projections involving the higher-order motor-related areas, such as the presupplementary motor area (pre-SMA) and the rostral cingulate motor area (CMAr). Tracer injections were made into these motor-related areas (their forelimb representation) on the medial wall that had been identified electrophysiologically. The following data were obtained from a series of tract-tracing experiments in Japanese monkeys. (i) Only a few neurons in area 46 were retrogradely labelled from the pre-SMA and CMAr; (ii) terminal labelling from area 46 occurred sparsely in the pre-SMA and CMAr; (iii) a dual labelling technique revealed that the sites of overlap of anterograde labelling from area 46 and retrograde labelling from the pre-SMA and CMAr were evident in the rostral parts of the dorsal and ventral premotor cortices (PMdr and PMvr); (iv) and tracer injections into the PMdr produced neuronal cell labelling in area 46 and terminal labelling in the pre-SMA and CMAr. The present results indicate that a large portion of the prefrontal signals from area 46 is not directly conveyed to the pre-SMA and CMAr, but rather indirectly by way of the PMdr and PMvr. This suggests that area 46 exerts its major influence on the cortical motor system via these premotor areas.     

Ipsilateral cortical connections of motor, premotor, frontal eye, and posterior parietal fields in a prosimian primate, Otolemur garnetti

The ipsilateral connections of motor areas of galagos were determined by injecting tracers into primary motor cortex (M1), dorsal premotor area (PMD), ventral premotor area (PMV), supplementary motor area (SMA), and frontal eye field (FEF). Other injections were placed in frontal cortex and in posterior parietal cortex to define the connections of motor areas further. Intracortical microstimulation was used to identify injection sites and map motor areas in the same cases. The major connections of M1 were with premotor cortex, SMA, cingulate motor cortex, somatosensory areas 3a and 1, and the rostral half of posterior parietal cortex. Less dense connections were with the second (S2) and parietal ventral (PV) somatosensory areas. Injections in PMD labeled neurons across a mediolateral belt of posterior parietal cortex extending from the medial wall to lateral to the intraparietal sulcus. Other inputs came from SMA, M1, PMV, and adjoining frontal cortex. PMV injections labeled neurons across a large zone of posterior parietal cortex, overlapping the region projecting to PMD but centered more laterally. Other connections were with M1, PMD, and frontal cortex and sparsely with somatosensory areas 3a, 1-2, S2, and PV. SMA connections were with medial posterior parietal cortex, cingulate motor cortex, PMD, and PMV. An FEF injection labeled neurons in the intraparietal sulcus. Injections in posterior parietal cortex revealed that the rostral half receives somatosensory inputs, whereas the caudal half receives visual inputs. Thus, posterior parietal cortex links visual and somatosensory areas with motor fields of frontal cortex.     

Cortical connections of the inferior arcuate sulcus cortex in the macaque brain

Injections of the retrograde/anterograde tracers Wheat Germ Agglutinin-Horseradish peroxidase (WGA-HRP) into the cortex along the banks of the inferior limb of the arcuate sulcus in the cortex of 4 macaque monkeys (Macaca fascicularis) were used to investigate its cortico-cortical connections. All injections produced transported label within the sulcus principalis, the ventral lateral prefrontal cortex, the anterior cingulate sulcus and the dorsal insular cortex. The distribution of label within each of these areas differed slightly depending on the injection site. Injections along the caudal bank of the inferior arcuate sulcus label premotor, supplementary motor, and precentral motor areas but produce relatively sparse prefrontal labeling. Posteriorly label is transported to the inferior parietal cortex and the dorsal opercular bank of the Sylvian fissure. Injections along the rostral bank of the sulcus do not label motor areas but produce labeling in dorsal, lateral and orbital prefrontal areas, and in cortex along the ventral bank of the superior branch of the arcuate sulcus. Posteriorly label is transported to cortical areas in the superior temporal gyrus including the dorsal bank of the superior temporal sulcus. The more dorsal rostral bank injection produced both superior temporal and some sparse inferior parietal labeling and the more ventral rostral bank injection produced extensive superior temporal labeling but no parietal labeling. No labeling was ever seen in cortex ventral to the fundus of the superior temporal sulcus. Although other auditory recipient prefrontal areas have been reported, this is the first demonstration of a region chiefly devoted to auditory connections within the ventral frontal cortex. Its adjacency to areas associated with vocal muscle movement, and its connections to midline cortical areas associated with vocal functions in both primates and humans may provide important clues to the organization of Broca's language area.     

Inputs from motor and premotor cortex to the superior colliculus of the macaque monkey

In retrograde studies of corticotectal projections in the monkey using horseradish peroxidase (HRP), projections of the frontal lobes were found to originate not only from the frontal eye fields and prefrontal association cortex but also from both motor and premotor cortex. Even small HRP injections into the superficial layers of the superior colliculus yielded labelled cells in the agranular cortex (area 6) of the anterior bank of the arcuate sulcus. After large collicular injections affecting all layers, labelled cells were found in both motor and premotor cortex. This projection appeared to be topographically organized. Injections into the anterolateral parts of the superior colliculus labelled cells that were distributed within the presumed finger-hand--arm-shoulder representation, whereas after more caudal injections labelled cells occurred more in the presumed arm-trunk representation. The supplementary motor cortex was not found to contain labelled cells. The corticotectal cells in the motor cortex differed from those in the premotor cortex in their size distribution; the former being small, the latter both small and large. The functional significance of the motor and premotor input into the superior colliculus for sensory, and particularly visual, guidance of movements is discussed in view of a collicular role in the extrapersonal space representation and of its possible participation in steering arm and hand movements.     

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.     

Distribution of cat-301 immunoreactivity in the frontal and parietal lobes of the macaque monkey

The distribution of the monoclonal antibody Cat-301 was examined in the frontal and parietal cortex of macaque monkeys. In both regions the distribution was uniform within cytoarchitecturally defined areas (or subareas) but varied between them. In all areas, Cat-301 labeled the soma and proximal dendrites of a restricted population of neurons. In the frontal lobe, Cat-301-positive neurons were intensely immunoreactive and present in large numbers in the motor cortex (area 4), premotor cortex (area 6, excluding its lower ventral part), the supplementary motor area (SMA), and the caudal prefrontal cortex (areas 8a, 8b and 45). In the parietal lobe, large numbers of intensely immunoreactive neurons were evident in the post-central gyrus (areas 1 and 2), the superior parietal lobule (PE/5), and the dorsal bank (PEa), fundus (IPd), and deep half of the ventral bank (POa(i] of the intraparietal sulcus (IPS). Two major patterns of laminar distribution were evident. In motor, supplementary motor, premotor (excluding the lower part of its ventral division), and the caudal prefrontal cortex (Walker's areas 8a, 8b and 45), and throughout the parietal cortex (with the exception of area 3), Cat-301-positive neurons were concentrated in the lower part of layer III and in layer V. The laminar positions of labeled cells in these areas were remarkably constant, as were the proportions of labeled neurons that had pyramidal and nonpyramidal morphologies (means of 30.2% and 69.8%, respectively). In contrast, in prefrontal areas 9, 10, 11, 12, 13, 14, and 46, in the cingulate cortex (areas 23, 24 and 25), and in the lower part of the ventral premotor cortex, Cat-301-positive neurons were spread diffusely across layers II to VI and a mean of 3.6% of the labeled neurons were pyramidal while 96.4% were nonpyramidal. Area 3 was unique among frontal and parietal areas, in that the labeled neurons in this area were concentrated in layers IV and VI. The areas in the frontal lobe which were heavily labeled are thought to be involved in the control of somatic (areas 4 and 6) and ocular (areas 8 and 45) movements. Those in parietal cortex may be classified as areas with somatosensory functions (1, 2, PE/5, and PEa) and areas which may participate in the analysis of visual motion (Pandya and Seltzer's IPd and POa(i), which contain Maunsell and Van Essen's VIP). The parietal somatosensory areas are connected to frontal areas with somatic motor functions, while POa(i) is interconnected with the frontal eye fields (8a and 45).(ABSTRACT TRUNCATED AT 250 WORDS)     

Corticocortical projections to representations of the teeth,tongue, and face in somatosensory area 3b of macaques

We placed injections of anatomical tracers into representations of the tongue, teeth, and face in the primary somatosensory cortex (area 3b) of macaque monkeys. Our injections revealed strong projections to representations of the tongue and teeth from other parts of the oral cavity responsive region in 3b. The 3b face also provided input to the representations of the intraoral structures. The primary representation of the face showed a pattern of intrinsic connections similar to that of the mouth. The area 3b hand representation provided little to no input to either the mouth or the face representations. The mouth and face representations of area 3b received projections from the presumptive oral cavity and face regions of other somatosensory areas in the anterior parietal cortex and the lateral sulcus, including areas 3a, 1, 2, the second somatosensory area (S2), the parietal ventral area (PV), and cortex that may include the parietal rostral (PR) and ventral somatosensory (VS) areas. Additional inputs came from primary motor (M1) and ventral premotor (PMv) areas. This areal pattern of projections is similar to the well‐studied pattern revealed by tracer injections in regions of 3b representing the hand. The tongue representation appeared to be unique in area 3b in that it also received inputs from areas in the anterior upper bank of the lateral sulcus and anterior insula that may include the primary gustatory area (area G) and other cortical taste‐processing areas, as well as a region of lateral prefrontal cortex (LPFC) lining the principal sulcus. J. Comp. Neurol. 522:546–572, 2014. © 2013 Wiley Periodicals, Inc.     

The primate mediodorsal (MD) nucleus and its projection to the frontal lobe

The frontal lobe projections of the mediodorsal (MD) nucleus of the thalamus were examined in rhesus monkey by transport of retrograde markers injected into one of nine cytoarchitectonic regions (Walker's areas 6, 8A, 9, 10, 11, 12, 13, 46, and Brodmann's area 4) located in the rostral third of the cerebrum. Each area of prefrontal, premotor, or motor cortex injected was found to receive a topographically unique thalamic input from clusters of cells in specific subdivisions within MD. All of the prefrontal areas examined also receive topographically organized inputs from other thalamic nuclei including, most prominently, the ventral anterior (VA) and medial pulvinar nuclei. Conversely, and in agreement with previous findings, MD projects to areas of the frontal lobe beyond the traditional borders of prefrontal cortex, such as the anterior cingulate and supplementary motor cortex. The topography of thalamocortical neurons revealed in coronal sections through VA, MD, and pulvinar is circumferential. In the medial part of MD, for example, thalamocortical neurons shift from a dorsal to a ventral position for cortical targets lying medial to lateral along the ventral surface of the lobe; neurons in the lateral MD move from a ventral to a dorsal position, for cortical areas situated lateral to medial on the convexity of the hemisphere. The aggregate evidence for topographic specificity is supported further by experiments in which different fluorescent dyes were placed in multiple areas of the frontal lobe in each of three cases. The results show that very few, if any, thalamic neurons project to more than one area of cortex. The widespread cortical targets of MD neurons together with evidence for multiple thalamic inputs to prefrontal areas support a revision of the classical hodological definition of prefrontal cortex as the exclusive cortical recipient of MD projections. Rather, the prefrontal cortex is defined by multiple specific relationships with the thalamus.     

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.     

Cortico-cortical projections of the motorcortical larynx area in the rhesus monkey

The efferent cortico-cortical projections of the motorcortical larynx area were studied in three rhesus monkeys (Macaca mulatta), using biotin dextranamine as anterograde tracer. Identification of the larynx area was made with the help of electrical brain stimulation and indirect laryngoscopy. Heavy projections were found into the surrounding ventral and dorsal premotor cortex (areas 6V and D), primary motor cortex (area 4), the homolog of Broca's area (mainly area 44), fronto- and parieto-opercular cortex (including secondary somatosensory cortex), agranular, dysgranular and granular insula, rostral-most primary somatosensory cortex (area 3a), supplementary motor area (area 6M), anterior cingulate gyrus (area 24c) and dorsal postarcuate cortex (area 8A). Medium projections could be traced to the ventrolateral prefrontal and lateral orbital cortex (areas 47L and O), the primary somatosensory areas 3b and 2, the agranular and dysgranular insula, and the posteroinferior parietal cortex (area 7; PFG, PG). Minor projections ended in the lateral and dorsolateral prefrontal cortex (areas 46V and 8B), primary somatosensory area 1 and cortex within the intraparietal sulcus (PEa) and posterior sulcus temporalis superior (TPO). Due to its close spatial relationship to the insula on the one hand and the premotor cortex on the other, the larynx area shows projections which, in some respects, are not typical for classical primary motor cortex.     

Prefrontal granular cortex of the rhesus monkey. I. Intrahemispheric cortical afferents.

In 6 adolescent rhesus monkeys, unilateral injections of horseradish peroxidase (HRP) were made into 6 regions on the convexity of the prefrontal granular cortex.The afferents to each zone were considered with respect to whether they were local afferents (from adjacent frontal areas) or distal afferents (from outside frontal lobe). The strongest input onto prefrontal granular cortex comes from the temporal lobe and especially areas in and around the superior temporal gyrus. Area 10 in the frontal pole region receives input primarily from area 22 in the superior temporal gyrus and dorsal portion of the superior temporal sulcus. That portion of area 46 above the principal sulcus receives input primarily from area 22 in the upper bank of the superior temporal sulcus while area 46 below the principal sulcus has input from the insula of the superior temporal sulcus and area 21 in the lower bank of the superior temporal sulcus. The cortex within the concavity of the acurate sulcus differs in that the dorsal half (including areas 46 and 8a) receives input primarily from the dorsal bank and to a lesser degree the insula of the superior temporal sulcus while the ventral portion of this region including areas 45 and 46 receives input primarily from the lower bank of the superior temporal sulcus, inferior temporal gyrus and insula of the superior temporal sulcus. Input was noted from cingulate areas 23 and 24 to all 6 injected regions while retrosplenial cortex was noted to project to all but one of the injected regions, i.e. area 10. In addition, some labeled neurons were seen in area 7 after injections into area 46 and some were also seen in the inferior temporal gyrus and parahippocampal region after injections into the arcuate region. Finally, labeled neurons were noted in area 19 after injections into the ventral portion of the prefrontal granular cortex bounded by the arcuate sulcus.The HRP-positive neurons that comprised the intrahemispheric cortical afferents to prefrontal granular cortex were located primarily in layer iii. They were pyramidal in shape and ranged in size from small to medium. These neurons were found to be distributed in a horizontal band in which the number of labeled neurons waxed and waned, or they were distributed in a patchy or clumped manner. The possibility that both patterns of distribution represent a vertical or columnar organization to these afferent neurons is discussed.     

Heterotopic Cortical Afferents to the Medial Prefrontal Cortex in the Rat. A Combined Retrograde and Anterograde Tracer Study

Cortical afferent projections towards the medial prefrontal cortex (mPFC) were investigated with retrograde and anterograde tracer techniques. Heterotopical afferent projections to the medial prefrontal cortex arise in secondary, or higher order, sensory areas, motor areas and paralimbic cortices. On the basis of these projections three subfields can be discriminated within the mPFC. (1) The ventromedial part of mPFC, comprising the pre- and infralimbic areas, receives mainly projections from the perirhinal cortex. (2) The caudal two-thirds of the dorsomedial PFC, comprising frontal area 2 and the dorsal anterior cingulate area, receives projections from the secondary visual areas, the posterior agranular insular area and the retrosplenial areas. (3) The rostral one-third of the dorsomedial PFC is the main recipient of projections from the somatosensory and motor areas and the posterior agranular insular area. The laminar distribution of cells projecting to the mPFC varies considerably in the different cortical areas, just as the laminar distribution of termination of their fibres within the mPFC does. It is concluded that the corticocortical connections corroborate with subcortical connectivity in attributing to the mediodorsal projection cortex of the rat functions which are comparable to those of certain prefrontal, premotor and anterior cingulate areas in the monkey.     

Cortical connections of the frontoparietal opercular areas in the Rhesus monkey

The connections of the frontoparietal opercular areas were studied in rhesus monkeys by using antero- and retrograde tracer techniques. The rostral opercular cortex including the gustatory and proisocortical motor (ProM) areas is connected with precentral areas 3, 1, and 2 as well as with the rostral portion of the opercular area which resembles the second somatosensory type of cortex (area SII) and the ventral portion of area 6. Its distant connections are with the ventral portion of prefrontal areas 46, 11, 12, and 13 as well as with the rostral insula and cingulate motor area (CMAr). The mid opercular region (areas 1 and 2) is connected with pre- and postcentral areas 3, 1, and 2 as well as SII. Additionally, it is connected with the ventral portion of area 6, area 44, area ProM, the gustatory area, and the rostral insula. Its distant connections are with area 4, the ventral portion of area 46, area 7b, and area POa in the intraparietal sulcus (IPS). The rostral parietal opercular region is connected with the postcentral portions of areas 3, 1, and 2; areas 5, 7, and SII; the gustatory area; and the vestibular area. Its other connections are with area 4, area 44, the ventral portion of area 46, area ProM, CMAr, and the supplementary motor area (SMA). The caudal opercular region is connected with the dorsal portion of area 3; areas 2, 5, and 7a; and areas PEa as well as IPd of IPS. It is also connected with area SII, insula, and the superior temporal sulcus. Its distant connections are with area 44; the dorsal portion of area 8 and the ventral portion of area 46; as well as CMAr, SMA, and the supplementary sensory area. This connectivity suggests that the ventral somatosensory areas are involved in sensorimotor activities mainly related to head, neck, and face structures as well as to taste. Additionally, these areas may have a role in frontal (working) and temporal (tactile) memory systems. J. Comp. Neurol. 403:431–458, 1999. © 1999 Wiley-Liss, Inc.     

Ipsilateral cortical connections of dorsal and ventral premotor areas in New World owl monkeys

In order to compare connections of premotor cortical areas of New World monkeys with those of Old World macaque monkeys and prosimian galagos, we placed injections of fluorescent tracers and wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in dorsal (PMD) and ventral (PMV) premotor areas of owl monkeys. Motor areas and injection sites were defined by patterns of movements electrically evoked from the cortex with microelectrodes. Labeled neurons and axon terminals were located in brain sections cut either in the coronal plane or parallel to the surface of flattened cortex, and they related to architectonically and electrophysiologically defined cortical areas. Both the PMV and PMD had connections with the primary motor cortex (M1), the supplementary motor area (SMA), cingulate motor areas, somatosensory areas S2 and PV, and the posterior parietal cortex. Only the PMV had connections with somatosensory areas 3a, 1, 2, PR, and PV. The PMD received inputs from more caudal portions of the cortex of the lateral sulcus and more medial portions of the posterior parietal cortex than the PMV. The PMD and PMV were only weakly interconnected. New World owl monkeys, Old World macaque monkeys, and galagos share a number of PMV and PMD connections, suggesting preservation of a common sensorimotor network from early primates. Comparisons of PMD and PMV connectivity with the cortex of the lateral sulcus and posterior parietal cortex of owl monkeys, galagos, and macaques help identify areas that could be homologous.     

Cytoarchitecture and cortical connections of the anterior cingulate and adjacent somatomotor fields in the rhesus monkey

The cytoarchitecture and cortical connections of the anterior cingulate, medial and dorsal premotor, and precentral region are investigated using the Nissl and NeuN staining methods and the fluorescent retrograde tract tracing technique. There is a gradual stepwise laminar change in the cytoarchitectonic organization from the proisocortical anterior cingulate region, through the lower and upper banks of the cingulate sulcus, to the dorsolateral isocortical premotor and precentral motor regions of the frontal lobe. These changes are characterized by a gradational emphasis on the lower stratum layers (V and VI) in the proisocortical cingulate region to the upper stratum layers (II and III) in the premotor and precentral motor region. This is accompanied by a progressive widening of layers III and VI, a poorly delineated border between layers III and V and a sequential increase in the size of layer V neurons culminating in the presence of giant Betz cells in the precentral motor region. The overall patterns of corticocortical connections paralleled the sequential changes in cytoarchitectonic organization. The proisocortical areas have connections with cingulate motor, supplementary motor, premotor and precentral motor areas on the one hand and have widespread connections with the frontal, parietal, temporal and multimodal association cortex and limbic regions on the other. The dorsal premotor areas have connections with the proisocortical areas including cingulate motor areas and supplementary motor area on the one hand, and premotor and precentral motor cortex on the other. Additionally, this region has significant connections with posterior parietal cortex and limited connections with prefrontal, limbic and multimodal regions. The precentral motor cortex also has connections with the proisocortical areas and premotor areas. Its other connections are limited to the somatosensory regions of the parietal lobe. Since the isocortical motor areas on the dorsal convexity mediate voluntary motor function, their close connectional relationship with the cingulate areas form a pivotal limbic-motor interface that could provide critical sources of cognitive, emotional and motivational influence on complex motor function.     

Connections of the ventral granular frontal cortex of macaques with perisylvian premotor and somatosensory areas: anatomical evidence for somatic representation in primate frontal association cortex

In macaque monkeys with injections of tritiated amino acids or horseradish peroxidase in the ventrolateral granular frontal cortex, we observed extensive anterograde and retrograde labeling of the premotor and somatosensory cortex in and around the lateral sulcus. Comparable labeling was not present with large and small control injections of the dorsal granular cortex. Cytoarchitectonic evaluation of the perisylvian cortex in the three cases examined in detail indicated that labeled areas included the ventral premotor cortex (area 6V); the precentral opercular and orbitofrontal opercular areas (PrCO and OFO); the second somatosensory area (S-II); the opercular cortex immediately anterior to S-II, possibly corresponding to area 2 of the S-I complex; and the central part of the insular cortex, including portions of the granular and dysgranular insular fields (Ig, Idg). Labeling was particularly dense and extensive in areas 6V, S-II, and OFO. Lighter labeling was also present in the rostral inferior parietal lobule (areas 7b and POa). The distribution of label within perisylvian areas was not uniform: certain parts were heavily labeled, while other parts were lightly labeled or unlabeled. Comparison of label distribution with published accounts of the somatotopy of these areas indicates that forelimb and orofacial representations were selectively labeled. Further, our results, taken together with other recent anatomical findings (e.g., Matelli et al.: Journal of Comparative Neurology 251:281-298, 1987; Barbas and Pandya: Journal of Comparative Neurology 256:211-228, 1987) suggest strongly that there is a network of interconnected forelimb and orofacial representations in macaque cortex, involving the ventral granular frontal cortex, area 6V, OFO, opercular area 2, S-II, the central insula, and area 7b. Each injection of frontal cortex which labeled the perisylvian somatic cortex involved the cortex of the ventral rim of the principal sulcus (PSvr). The cortex surrounding the PSvr does not stand out as a distinct area in Nissl-stained material. However, examination of myelin-stained sections prepared from uninjected hemispheres with the Gallyas technique revealed the existence of a distinct zone centered on the PSvr. This myeloarchitectonic area, which we term area 46vr, is more heavily myelinated than the ventral bank and fundus of the principal sulcus (area 46v) but is less heavily myelinated than the ventral (inferior) convexity (area 12). Involvement of area 46vr in our injections was probably responsible for the strong labeling observed in perisylvian somatic areas.(ABSTRACT TRUNCATED AT 400 WORDS)     

Organization of the nigrothalamocortical system in the rhesus monkey

The nigrothalamocortical connections and their topography were analyzed by autoradiography and double or triple retrograde labeling with the fluorescent dyes Fast Blue, Diamidino Yellow, and Propidium Iodide. Injections of tritiated leucine into different parts of the substantia nigra (SN) revealed that the medial SN projects to the medial magnocellular subdivisions of the ventral anterior (VAmc) and mediodorsal (MDmc) nuclei of the thalamus while the lateral SN projects to the more lateral and more posterior part of the VAmc, and the paralaminar, parvicellular, and densocellular subdivisions of the mediodorsal nucleus (MDmf, MDpc, and MDdc). With the exception of the MDmf, terminal areas observed in the mediodorsal nucleus were in the form of scattered clusters of grains. Analysis of the thalamus in cases with fluorescent dye injections into the lateral orbital gyrus (Walker's area 11), principal sulcus (area 46), anterior bank of the arcuate gyrus (areas 8 and 45), supplementary motor area (area 6), and motor cortex (area 4) revealed topographic organization of the nigrothalamocortical projection system. The parts of the VAmc and MDmc which receive afferents from the medial part of the SN in turn project to the most anterior regions of the frontal lobe including principal sulcus and orbital cortex. The lateral posterior VAmc, MDmf, MDpc, and MDdc, all of which receive afferents from the lateral part of the SN; project to more posterior regions of the frontal lobe including, in addition to the principal sulcus, the frontal eye field and also areas of the premotor cortex. These findings indicate that the SN has preferential targets in the thalamus and cerebral cortex which are segregated from those of the globus pallidus and cerebellum. Whereas the motor cortex is the primary target of cerebellar output (Asanuma et al., '83b), and the premotor cortex is the target of pallidal output (Schell and Strick, '84), the SN output appears to be directed more anteriorally--to the prefrontal cortex.     

Frontal eye field in prosimian galagos: Intracortical microstimulation and tracing studies

The frontal eye field (FEF) in prosimian primates was identified as a small cortical region, above and anterior to the anterior frontal sulcus, from which saccadic eye movements were evoked with electrical stimulation. Tracer injections revealed FEF connections with cortical and subcortical structures participating in higher order visual processing. Ipsilateral cortical connections were the densest with adjoining parts of the dorsal premotor and prefrontal cortex (PFC). Label in a region corresponding to supplementary eye field (SEF) of other primates, suggests the existence of SEF in galagos. Other connections were with ventral premotor cortex (PMV), the caudal half of posterior parietal cortex, cingulate cortex, visual areas within the superior temporal sulcus, and inferotemporal cortex. Callosal connections were mostly with the region of the FEF of another hemisphere, SEF, PFC, and PMV. Most subcortical connections were ipsilateral, but some were bilateral. Dense bilateral connections were to caudate nuclei. Densest reciprocal ipsilateral connections were with the paralamellar portion of mediodorsal nucleus, intralaminar nuclei and magnocellular portion of ventral anterior nucleus. Other FEF connections were with the claustrum, reticular nucleus, zona incerta, lateral posterior and medial pulvinar nuclei, nucleus limitans, pretectal area, nucleus of Darkschewitsch, mesencephalic and pontine reticular formation and pontine nuclei. Surprisingly, the superior colliculus (SC) contained only sparse anterograde label. Although most FEF connections in galagos are similar to those in monkeys, the FEF‐SC connections appear to be much less. This suggests that a major contribution of the FEF to visuomotor functions of SC emerged with the evolution of anthropoid primates.