Search

In nonhuman primates, major input to the striatum originates from ipsilateral cortex and thalamus. The striatum is a target also of crossed corticostriatal (CSt) projections from the contralateral hemisphere, which have been so far somewhat neglected. In the present study, based on neural tracer injections in different parts of the striatum in macaques of either sex, we analyzed and compared qualitatively and quantitatively the distribution of labeled CSt cells in the two hemispheres. The results showed that crossed CSt projections to the caudate and the putamen can be relatively robust (up to 30% of total labeled cells). The origin of the direct and the crossed CSt projections was not symmetrical as the crossed ones originated almost exclusively from motor, prefrontal, and cingulate areas and not from parietal and temporal areas. Furthermore, there were several cases in which the contribution of contralateral areas tended to equal that of the ipsilateral ones. The present study is the first detailed description of this anatomic pathway of the macaque brain and provides the substrate for bilateral distribution of motor, motivational, and cognitive signals for reinforcement learning and selection of actions or action sequences, and for learning compensatory motor strategies after cortical stroke. SIGNIFICANCE STATEMENT In nonhuman primates the striatum is a target of projections originating from the contralateral hemisphere (crossed CSt projections), which have been so far poorly investigated. The present study analyzed qualitatively and quantitatively in the macaque brain the origin of the crossed CSt projections compared with those originating from the ipsilateral hemisphere. The results showed that crossed CSt projections originate mostly from frontal and rostral cingulate areas and in some cases their contribution tended to equal that from ipsilateral areas. These projections could provide the substrate for bilateral distribution of motor, motivational, and cognitive signals for reinforcement learning and action selection, and for learning compensatory motor strategies after cortical stroke., (Copyright © 2022 the authors.)

In non-human primates, at the junction of the prefrontal with the premotor cortex, there is a sector designated as frontal eye field (FEF), involved in controlling oculomotor behavior and spatial attention. Evidence for at least two FEFs in humans is at the basis of the still open issue of the possible homologies between the macaque and the human frontal oculomotor system. In this review article we address this issue suggesting a new view solidly grounded on evidence from the last decade showing that, in macaques, the FEF is at the core of an oculomotor domain in which several distinct areas, including areas 45A and 45B, provide the substrate for parallel processing of different aspects of oculomotor behavior. Based on comparative considerations, we will propose a correspondence between some of the macaque and the human oculomotor fields, thus suggesting sharing of neural substrate for oculomotor control, gaze processing, and orienting attention in space. Accordingly, this article could contribute to settle some aspects of the so-called "enigma" of the human FEF anatomy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

We traced the cortical connections of the anterior sector (F5a) of the macaque ventral premotor (PMv) area F5 and compared them with those of the adjacent F5 sectors, F5c and F5p. F5a displays a very dense "intrinsic" connectivity with F5c and F5p, premotor connections limited to F4 and F6/pre-SMA, relatively robust prefrontal connections with areas 46v and 12, and dense connections with rostral opercular frontal areas. Outside the frontal cortex, connections of F5a are dense with the SII region, relatively robust with inferior parietal areas PFG and AIP, weak with the inferior parietal area PF, and moderate with area 24. The comparison with data from injections in F5c and F5p showed that F5a, though sharing some common parietal connections with the other F5 sectors, displays several characterizing features providing robust evidence for its connectional distinctiveness. The present study provides evidence for a general organization of the PMv similar to that of the medial and dorsal premotor cortex, with F5a representing a pre-PMv area. Specifically, the present data suggest that F5a is a privileged site of integration, in the PMv, of parietal sensory-motor signals with higher-order information originating from prefrontal, rostral frontal opercular areas, and F6/pre-SMA. The results of this integration can be then broadcasted to the adjacent F5 sectors for the generation and control of hand actions and cognitive motor functions.

We have found that the 2 architectonic subdivisions of the prefrontal area 45, 45A and 45B, display connectivity patterns that clearly distinguish them from one another and from their neighboring architectonic areas. Area 45A is primarily connected to the frontal areas 45B, 12l, caudal 12r, 12o, 10, rostrodorsal 46, 9/8B, 44, 8/FEF (frontal eye field), and the SEF (supplementary eye field), temporal area IPa, and unique among all the studied areas, to the superior temporal polysensory (STP) area and auditory parabelt areas. Area 45B displayed much stronger frontal connections with the oculomotor areas 8/FEF, 8r, and the SEF than those of area 45A, primary connections with areas 12l, caudal 12r, 12o, and 8B, and unlike area 45A, with areas ventrorostral 46, rostral 12r, 12m, and 13m. Temporal connections were all virtually confined to areas IPa, intermediate TEa/m, and TE. Additional labeling was found in lateral intraparietal area. Our data suggest that 45A and 45B are 2 distinct areas, possibly playing a differential role in nonspatial information processing: area 45A corresponds to the prefrontal sector for which a role in communication behavior and homology with the human area 45 was proposed, whereas area 45B is a distinct prearcuate area, possibly affiliated to the oculomotor frontal system.

We used a cyto-, myelo-, and chemoarchitectonic (distribution of SMI-32 and calbindin immunoreactivity) approach to assess whether the rostral histochemical area F5 of the ventral premotor cortex (PMv) comprises architectonically distinct areas, possibly corresponding to functionally different fields. Three areas were identified, occupying different parts of F5. One area, designated as "convexity" F5 (F5c), extends on the postarcuate convexity cortex adjacent to the inferior arcuate sulcus and is characterized, cytoarchitectonically, by a poorly laminated appearance, resulting from an overall cell population rather homogeneous in size and density. The other two areas, designated as "posterior" and "anterior" F5 (F5p and F5a, respectively), lie within the postarcuate bank at different anteroposterior levels. Major cytoarchitectonic features of F5p are a layer III relatively homogeneous in cell size and density, a cell-dense layer Va, and the presence of relatively large pyramids in layer Vb. Major cytoarchitectonic features of F5a are the presence of relatively large pyramids in lowest layer III and a prominent, homogenous layer V. Furthermore, our results showed that F5c and F5p border caudally with a caudal PMv area corresponding to histochemical area F4, providing additional evidence for a general subdivision of the macaque PMv into a caudal and a rostral part, corresponding to F4 and to the F5 complex, respectively. The present data, together with other functional and connectional data, suggest that the three rostral PMv areas F5p, F5a, and F5c correspond to distinct cortical entities, possibly involved in different aspects of motor control and cognitive motor functions.

Over the last century, anatomical studies have shown that the cerebral cortex can be subdivided into structurally distinct regions, giving rise to a new branch of neuroanatomy: 'architectonics'. Since then, architectonics has been often accused of being overly subjective, and its validity for the definition of functionally different cortical fields has been seriously questioned. Since the late 1980s, however, the problem of localization has become particularly important in functional studies of the primate motor cortex, because of evidence that (1) the primate motor cortex is made up of a mosaic of functionally specialized areas and (2) the human motor cortex shares several general organizational principles with the monkey motor cortex. Studies of the macaque agranular frontal cortex that used a multimodal cyto-, myelo- and immuno-architectonic approach have shown that architectonic borders can be reliably and consistently defined across different individuals, even at a qualitative level of analysis. The validity of this approach has been confirmed by its ability to localize functionally distinct areas precisely and to predict the existence of new functional areas. After more than a century, architectonics as a discipline goes far beyond its original aim of generating cortical maps.

We traced the cortical connections of the 4 cytoarchitectonic fields--Opt, PG, PFG, PF--forming the cortical convexity of the macaque inferior parietal lobule (IPL). Each of these fields displayed markedly distinct sets of connections. Although Opt and PG are both targets of dorsal visual stream and temporal visual areas, PG is also target of somatosensory and auditory areas. Primary parietal and frontal connections of Opt include area PGm and eye-related areas. In contrast, major parietal and frontal connections of PG include IPL, caudal superior parietal lobule (SPL), and agranular frontal arm-related areas. PFG is target of somatosensory areas and also of the medial superior temporal area (MST) and temporal visual areas and is connected with IPL, rostral SPL, and ventral premotor arm- and face-related areas. Finally, PF is primarily connected with somatosensory areas and with parietal and frontal face- and arm-related areas. The present data challenge the bipartite subdivision of the IPL convexity into a caudal and a rostral area (7a and 7b, respectively) and provide a new anatomical frame of reference of the macaque IPL convexity that advances our present knowledge on the functional organization of this cortical sector, giving new insight into its possible role in space perception and motor control.

The human and macaque sensorimotor cortex was subdivided into numerous areas by a correlative analysis based on cytoarchitectonics, myeloarchitecture and the distribution of transmitter receptors. Receptor densities and laminar distribution patterns differ not only between motor and somatosensory regions, but also between different areas within these regions of the cortex. Changes in receptor distribution often match architectonically defined borders. Receptor findings provide new criteria for a more detailed mapping in the human brain which cannot be achieved by cytoarchitectonic analysis alone. Morphological data on these areas were integrated with functional data from positron emission tomography (PET) on the basis of a recently developed computerised brain atlas. The central sulcus marks the border between (1) the agranular motor cortex with a generally low density of glutamatergic, muscarinic, GABAergic and serotoninergic receptors, and (2) the granular somatosensory cortex with higher densities of these receptors. Rostral to the primary motor cortex, 2 isocortical areas are found on the mesial cortex which probably represent the functionally defined supplementary motor areas (SMA) SMA-proper (caudally) and pre-SMA (rostrally). Below SMA-proper the areas 24d (macaque) and the caudal cingulate motor area cmc (human) are located in the cingulate sulcus. Both regions correspond to the 'posterior cingulate motor areas' of recent PET studies and to the posterior part of the agranular cingulate cortex of architectonic studies. Below pre-SMA the area 24c (macaque) and the rostral cingulate motor area cmr (human) are located in the cingulate sulcus; they correspond to the 'anterior cingulate motor areas' of recent PET observations and to the anterior part of the agranular cingulate cortex of architectonic studies. Homologous sensorimotor areas can be defined in both species on the basis of common architectonic features.

Two series of experiments are reported in this paper. The first concerns the movement representation in the macaque inferior area 6, the second the functional properties of neurons located in the caudal part of this area (histochemical area F4). By combining single neuron recording and intracortical microstimulation, we found that inferior area 6 is somatotopically organized. The axio-proximal movements are represented caudally, the distal movements are represented near the arcuate sulcus. The mouth field is located laterally, the hand field medially. There is no leg field. A comparison between neuron properties and histochemical characteristics of inferior area 6 showed that the proximal movements representation includes most of area F4, whereas the distal movements representation corresponds to area F5 and to the rostral part of F4. Neurons located in that part of F4 where proximal movements are represented respond very well to tactile stimuli. They have large receptive fields mostly located on the face and on the upper part of the body. A large number of these neurons respond to visual stimuli. Objects approaching the animal are particularly effective. The tactile and the visual receptive fields are in register. The most represented movements are reaching movements, movements bringing the hand to the mouth or to the body and facial movements. There is a congruence between location of visual fields and preferred arm movements. It is argued that the receptive field arrangement and the response properties are more complex in area F4 than in the primary motor cortex and that area F4 neurons are involved in the control of arm movements towards different space sectors.

Recent cytoarchitectonic, histochemical, and hodological studies in primates have shown that area 6 is formed by three main sectors: the supplementary motor area, superior area 6, which lies medial to the spur of the arcuate sulcus, and inferior area 6, which is located lateral to it. Inferior area 6 has been further subdivided into two histochemical areas: area F5, located along the inferior limb of the arcuate sulcus, and area F4, located between area F5 and area 4 (area F1). The present study traced the thalamocortical projections of inferior area 6 and the adjacent part of area 4 by injecting small amounts of WGA-HRP in specific sectors of the agranular frontal cortex. Our data showed that each histochemical area receives a large projection from one nucleus of the ventrolateral thalamus (motor thalamus) and additional projections from other nuclei of this thalamic sector. Area F5 receives a large projection from area X of Olszewski ('52) and additional projections from the caudal part of the nucleus ventralis posterior lateralis, pars oralis (VPLo), and the nucleus ventralis lateralis, pars caudalis (VLc) (VPLo-VLc complex). Area F4 receives a large projection from the nucleus ventralis lateralis, pars oralis (VLo), and additional projections from area X and the VPLo-VLc complex. The rostral part of area F1 is innervated chiefly by VLo, plus smaller contributions from rostral VPLo and the VPLo-VLc complex. The caudal part of F1 receives its greatest input from VPLo, with a small contribution from VLo. In addition, each histochemical area receives projections originating from the intralaminar thalamic nuclei, the posterior thalamus, and--for area F4 and area F5--also from the nucleus medialis dorsalis (MD). Analysis of the physiological properties of the various histochemical areas in relation to their main thalamic input showed that those cortical fields in which distal movements are predominant (area F5, caudal part of area F1) are innervated chiefly by area X and VPLo, whereas those cortical fields in which proximal movements are predominant receive their main input from VLo. Because VPLo and area X are targets of cerebellothalamic pathways, whereas VLo receives a pallidal input, we propose that the cortical fields in which distal movements are most heavily represented are mainly under the influence of the cerebellum, whereas the cortical fields in which proximal movements are most heavily represented are mainly under the influence of the basal ganglia.

The functional properties of neurons located in the rostral part of inferior area 6 were studied in awake, partially restrained macaque monkeys. The most interesting property of these neurons was that their firing correlated with specific goal-related motor acts rather than with single movements made by the animal. Using the motor acts as the classification criterion we subdivided the neurons into six classes, four related to distal motor acts and two related to proximal motor acts. The distal classes are: "Grasping-with-the-hand-and-the-mouth neurons", "Grasping-with-the-hand neurons", "Holding neurons" and "Tearing neurons". The proximal classes are: "Reaching neurons" and "Bringing-to-the-mouth-or-to-the-body neurons". The vast majority of the cells belonged to the distal classes. A particularly interesting aspect of distal class neurons was that the discharge of many of them depended on the way in which the hand was shaped during the motor act. Three main groups of neurons were distinguished: "Precision grip neurons", "Finger prehension neurons", "Whole hand prehension neurons". Almost the totality of neurons fired during motor acts performed with either hand. About 50% of the recorded neurons responded to somatosensory stimuli and about 20% to visual stimuli. Visual neurons were more difficult to trigger than the corresponding neurons located in the caudal part of inferior area 6 (area F4). They required motivationally meaningful stimuli and for some of them the size of the stimulus was also critical. In the case of distal neurons there was a relationship between the type of prehension coded by the cells and the size of the stimulus effective in triggering the neurons. It is proposed that the different classes of neurons form a vocabulary of motor acts and that this vocabulary can be assessed by somatosensory and visual stimuli.