Relationship between the corticostriatal terminals from areas 9 and 46, and those from area 8A, dorsal and rostral premotor cortex and area 24c: an anatomical substrate for cognition to action

Our previous data indicate that there are specific features of the corticostriatal pathways from the prefrontal cortex. First, corticostriatal pathways are composed of focal, circumscribed projections and of diffuse, widespread projections. Second, there is some convergence between terminal fields from different functional regions of the prefrontal cortex. Third, anterior cingulate projections from area 24b occupy a large region of the rostral striatum. The goal of this study was to determine whether these features are also common to the corticostriatal projections from area 8A (including the frontal eye field; FEF), the supplementary eye field (SEF), dorsal and rostral premotor cortex (PMdr) and area 24c. Using a new approach of three-dimensional reconstruction of the corticostriatal pathways, along with dual cortical tracer injections, we mapped the corticostriatal terminal fields from areas 9 and 46, 8A-FEF, SEF, PMdr and 24b and c. In addition, we placed injections of retrogradely transported tracers into key striatal regions. The results demonstrated that: (i) a diffuse projection system is a common feature of the corticostriatal projections from different frontal regions; (ii) key striatal regions receive convergent projections from areas 9 and 46 and from areas 8A-FEF, SEF, PMdr and 24c, suggesting a potential pivotal role of these striatal regions in integrating cortical information; (iii) projections from area 24c, like those from area 24b, terminate widely throughout the striatum, interfacing with terminals from several frontal areas. These features of the corticostriatal frontal pathways suggest a potential integrative striatal network for learning.     

Frames of reference for eye–head gaze shifts evoked during frontal eye field stimulation

The frontal eye field (FEF), in the prefrontal cortex, participates in the transformation of visual signals into saccade motor commands and in eye–head gaze control. The FEF is thought to show eye‐fixed visual codes in head‐restrained monkeys, but it is not known how it transforms these inputs into spatial codes for head‐unrestrained gaze commands. Here, we tested if the FEF influences desired gaze commands within a simple eye‐fixed frame, like the superior colliculus (SC), or in more complex egocentric frames like the supplementary eye fields (SEFs). We electrically stimulated 95 FEF sites in two head‐unrestrained monkeys to evoke 3D eye–head gaze shifts and then mathematically rotated these trajectories into various reference frames. In theory, each stimulation site should specify a specific spatial goal when the evoked gaze shifts are plotted in the appropriate frame. We found that these motor output frames varied site by site, mainly within the eye‐to‐head frame continuum. Thus, consistent with the intermediate placement of the FEF within the high‐level circuits for gaze control, its stimulation‐evoked output showed an intermediate trend between the multiple reference frame codes observed in SEF‐evoked gaze shifts and the simpler eye‐fixed reference frame observed in SC‐evoked movements. These results suggest that, although the SC, FEF and SEF carry eye‐fixed information at the level of their unit response fields, this information is transformed differently in their output projections to the eye and head controllers.     

Primate supplementary eye field. II. Comparative aspects of connections with the thalamus, corpus striatum, and related forebrain nuclei

The supplementary eye field (SEF) was defined electrophysiologically in behaving monkeys to study its connections with the diencephalon and corpus striatum. The specificity of SEF pathways was determined with horseradish peroxidase (HRP) histochemistry to compare its connections with those of the arcuate frontal eye field (FEF), contiguous dorsocaudal area 6 (6DC), and primary motor cortex (M1, arm/hand region). Results indicate that patterns of SEF connectivity were similar to the FEF and markedly different from areas 6DC and M1. Primary reciprocal thalamic pathways of the SEF were with the magnocellular ventral anterior (VA) nucleus, medial parvicellular VA, medial area X, and paralaminar medialis dorsalis (multiformis and parvicellularis). FEF showed similar connections but its most robust pathway was with MD rather than VA. In contrast, area 6DC showed the most extensive reciprocal connections with lateral VApc and lateral area X with only sparse connections with paralaminar MD. Area 6DC also exhibited reciprocal connections with the ventral lateral (VL) complex and the ventral posterior lateral nucleus, pars oralis (VPLo). M1 showed dense bidirectional connections with VPLo, and to a lesser extent, with VL. M1 pathways with the medial dorsal nucleus were negligible. All areas exhibited connections with the paracentral and central lateral nuclei and only M1 lacked connections with the central superior lateral nucleus. SEF and FEF exhibited similar efferent projections to the caudate and putamen. In the caudate, terminal fields were restricted to a central longitudinal core while those from area 6DC were more widely distributed. Eye field efferents were restricted to the putamen's face region while 6DC projections were more exuberant. The arm/hand region of M1 projected to the arm/hand region of the putamen. Pathways are discussed with respect to their significance in oculomotor control.     

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.     

Primate striatonigral projections: A comparison of the sensorimotor-related striatum and the ventral striatum

The striatum receives topographic cortical inputs with the limbic lobe terminating in the ventral striatum and sensorimotor cortical regions terminating in the dorsolateral striatum. The organization of striatonigral projections originating from these different striatal territories was examined in primate by using several anterograde tracers. The ventral striatum innervates a large area of the substantia nigra, including the medial pars reticulata and much of the pars compacta. Moreover, projections from separate areas of the ventral striatum overlap considerably in the substantia nigra. No mediolateral or rostrocaudal topographic order is apparent, and the area of the substantia nigra associated with the ventral striatum is extensive. In contrast, the sensorimotor-related striatum innervates a limited region of the ventrolateral substantia nigra. Similar to ventral striatonigral projections, projections originating from different areas of the sensorimotor-related striatum send converging inputs to the substantia nigra. Sensorimotor-related striatonigral projections avoid the region of the dopaminergic neurons in the dorsal pars compacta. Striatonigral projections from the sensorimotor-related and ventral striatum do not overlap in the substantia nigra. Examination of the outputs of discrete striatal loci indicates that the organization of striatonigral projections is more related to corticostriatal inputs than to a simple rostrocaudal, dorsoventral, or mediolateral tpography of the striatum. Striatal projections that originate from different striatal territories are distinct and nonoverlapping, thus supporting the concept of segregated striatonigral circuits. However, areas of the striatum that receive common cortical inputs send converging inputs to the substantia nigra. This suggests that the substantia nigra is also an important link for integrating information between functionally related (sub)circuits. © 1994 Wiley-Liss, Inc.     

Laminar Origin of Corticostriatal Projections to the Motor Putamen in the Macaque Brain

In the macaque brain, projections from distant, interconnected cortical areas converge in specific zones of the striatum. For example, specific zones of the motor putamen are targets of projections from frontal motor, inferior parietal, and ventrolateral prefrontal hand-related areas and thus are integral part of the so-called “lateral grasping network.” In the present study, we analyzed the laminar distribution of corticostriatal neurons projecting to different parts of the motor putamen. Retrograde neural tracers were injected in different parts of the putamen in 3 Macaca mulatta (one male) and the laminar distribution of the labeled corticostriatal neurons was analyzed quantitatively. In frontal motor areas and frontal operculum, where most labeled cells were located, almost everywhere the proportion of corticostriatal labeled neurons in layers III and/or VI was comparable or even stronger than in layer V. Furthermore, within these regions, the laminar distribution pattern of corticostriatal labeled neurons largely varied independently from their density and from the projecting area/sector, but likely according to the target striatal zone. Accordingly, the present data show that cortical areas may project in different ways to different striatal zones, which can be targets of specific combinations of signals originating from the various cortical layers of the areas of a given network. These observations extend current models of corticostriatal interactions, suggesting more complex modes of information processing in the basal ganglia for different motor and nonmotor functions and opening new questions on the architecture of the corticostriatal circuitry.SIGNIFICANCE STATEMENT Projections from the ipsilateral cerebral cortex are the major source of input to the striatum. Previous studies have provided evidence for distinct zones of the putamen specified by converging projections from specific sets of interconnected cortical areas. The present study shows that the distribution of corticostriatal neurons in the various layers of the primary motor and premotor areas varies depending on the target striatal zone. Accordingly, different striatal zones collect specific combinations of signals from the various cortical layers of their input areas, possibly differing in terms of coding, timing, and direction of information flow (e.g., feed-forward, or feed-back).     

Location of the human frontal eye field as defined by electrical cortical stimulation: anatomical, functional and electrophysiological characteristics

Electrical cortical stimulation of the human frontal gyri and the precentral gyrus has been shown to induce eye movements and it has classically been assumed that these stimulation-induced eye movements result from electrical interference with the human homologue of the monkey frontal eye field (FEF). However, amplitude of electrical current and induced type of eye movement, which are essential for the determination of eye fields in the monkey, have not been investigated systematically in man. We applied electrical cortical stimulation in the lateral frontal cortex in six epileptic patients. Sites whose stimulation resulted in eye movements were determined with respect to gyral and sulcal patterns, Talairach coordinates and neighboring functions as found by electrical cortical stimulation. Based on this approach, a restricted location of the electrically defined FEF is proposed within a larger oculomotor region on the posterior part of the middle frontal gyrus.     

Synaptic convergence of motor and somatosensory cortical afferents onto GABAergic interneurons in the rat striatum

Cortical afferents to the basal ganglia, and in particular the corticostriatal projections, are critical in the expression of basal ganglia function in health and disease. The corticostriatal projections are topographically organized but also partially overlap and interdigitate. To determine whether projections from distinct cortical areas converge at the level of single interneurons in the striatum, double anterograde labeling from the primary motor (M1) and primary somatosensory (S1) cortices in the rat, was combined with immunolabeling for parvalbumin (PV), to identify one population of striatal GABAergic interneurons. Cortical afferents from M1 and S1 gave rise to distinct, but partially overlapping, arbors of varicose axons in the striatum. PV-positive neurons were often apposed by cortical terminals and, in many instances, apposed by terminals from both cortical areas. Frequently, individual cortical axons formed multiple varicosities apposed to the same PV-positive neuron. Electron microscopy confirmed that the cortical terminals formed asymmetric synapses with the dendrites and perikarya of PV-positive neurons as well as unlabelled dendritic spines. Correlated light and electron microscopy revealed that individual PV-positive neurons received synaptic input from axon terminals derived from both motor and somatosensory cortices. These results demonstrate that, within areas of overlap of functionally distinct projections, there is synaptic convergence at the single cell level. Sensorimotor integration in the basal ganglia is thus likely to be mediated, at least in part, by striatal GABAergic interneurons. Furthermore, our findings suggest that the pattern of innervation of GABAergic interneurons by cortical afferents is different from the cortical innervation of spiny projection neurons.     

Intraoperative frontal eye field stimulation elicits ocular deviation and saccade suppression

Cortical stimulation is a useful way of elucidating the cortical control of eye movements. The aim of this study was to determine the type of eye movements evoked in response to intraoperative electrical stimulation of the frontal eye field (FEF) region in a fully awake patient during surgery for a frontal lobe glioma. A train of low-intensity electrical pulses within an area in the precentral gyrus evoked contraversive smooth eye movements (SEM) recorded electro-oculographically. Stimulation of an anterior sub-region of this electrically determined FEF disclosed both SEM and suppression of self-paced saccades. However, electrical stimulation of this region evoked no saccades in agreement with pre-operative fMRI using a self-paced saccade paradigm, which did not show activation within the ipsilateral FEF. In humans, intraoperative FEF stimulation may elicit recordable contraversive SEM, and interfere with oculomotor behaviour, suppressing self-paced saccades.     

Mosaic architecture of the somatic sensory-recipient sector of the cat's striatum

The striatum is known to have a compartmental organization in which histochemically defined zones called striosomes form branched 3-dimensional labyrinths embedded within the surrounding matrix. We explored how fiber projections from cortical somatic sensory areas representing cutaneous and deep-receptor inputs are organized in relation to this striatal architecture. Areas SI and 3a were mapped electrophysiologically, and distinguishable anterograde tracers (wheat germ agglutinin-HRP and 35S-methionine) were injected into physiologically identified loci. Primary somatic sensory corticostriatal projections were confined to a small, well-defined sector in the dorsolateral corner of the ipsilateral striatum. The somatic sensory afferents were arranged according to a coherent global body map in which rostral body parts were represented more laterally than caudal body parts. Single cortical loci innervated branched and clustered striatal zones that were reminiscent of the striosomes in their range of sizes and shapes yet lay strictly within the extrastriosomal matrix. In contrast to the global orderliness of the striatal body map, there were clear examples of locally complex patterns in which functionally distinct inputs interdigitated with each other. These patterns were often, but not always, produced when corticostriatal afferents carrying different submodality types were labeled. These findings demonstrate the existence of striosome-like striatal compartments within the seemingly uniform extrastriosomal matrix. The principle of mosaic organization thus holds throughout the tissue of the somatic sensory striatum. The striatal architecture delineated here could provide the anatomical substrate for computations requiring cross-modality comparisons within the framework of an overall somatotopy. If a similar multicompartmental architecture also characterizes other striatal regions, as seems likely, it may set general constraints on the nature of associative processing within the striatum as a whole.     

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.     

The cortico-basal ganglia integrative network: the role of the thalamus

The thalamus is a critical component of the frontal cortical-basal ganglia-thalamic circuits that mediate motivation and emotional drive, planning and cognition for the development and expression of goal-directed behaviors. Each functional region of the frontal cortex is connected with specific areas of each basal ganglia (BG) structure and of the thalamus. In addition, the thalamus sends a massive, topographically organized projection directly to the striatum. Tract-tracing and physiological experiments have indicated a general topographic organization of the cortical-BG-thalamic loops and supported a model of BG function based on parallel and segregated pathways. However, the learning and execution of appropriate behavioral responses require integration of inputs related to emotional, cognitive, and motor cortical functions. Our recent data indicate that integration may occur via non-reciprocal connections between the striatum and substantia nigra and within "hot spots" of convergence between corticostriatal projections from different functional regions. Similarly, integration may exist in the thalamus. There are non-reciprocal connections between the thalamus and cortex via thalamocortical projections that terminate in the superficial and deep cortical layers. These terminals can influence different functional cortical areas that, in turn, project to the striatum and back to the thalamus. In addition, a non-reciprocal corticothalamic projection terminates in thalamic regions that are parts of other circuits. Finally, 'hot spots' of convergence between terminals from different cortical regions may also occur in the thalamus as is seen in the striatum. Thus, via several different pathways, the thalamus may serve as an important center of integration of networks that underlie the ability to modulate behaviors.     

The corticocortical projections of the physiologically defined eye field in the rat medial frontal cortex

This study investigated in the rat the corticocortical projections of the frontal eye field (FEF), which is located within the medial frontal cortex. The experiments were carried out on Wistar rats. Seven animals received a single iontophoretic injection of Phaseolus vulgaris leucoagglutinin in an FEF site within the medial frontal cortex where intracortical microstimulation elicited eye movements. In these cases, anterogradely labeled fibers and terminal-like elements were found in both hemispheres. The densest labeling was seen in the injected hemisphere, where labeled fibers prevailed in the visual cortex and their laminar distribution differed between the primary and secondary visual cortices. Dense labeled fibers were also seen in the frontal and retrosplenial cortex, whereas a columnar arrangement of terminal-like elements was detected in a restricted part of area 1 of the somatosensory cortex. Contralaterally to the injection site, labeled fibers were distributed mainly in the homotopic region. In two animals, the tracer was injected in a site at the FEF border whose stimulation evoked eye and whisker movements. In these animals, a different distribution of labeling was observed with respect to the other rats in which the tracer was deposited within the FEF, and anterograde labeling was observed in areas 1 and 2 of the parietal cortex of both hemispheres; in addition, no labeling was observed in these cases in the primary visual cortex. These findings suggest that cortical sites confined within the rat FEF are implicated in the control of orienting and exploring behaviors in addition to the control of eye movement.     

The associative striatum: organization of cortical projections to the dorsocentral striatum in rats

The dorsocentral striatum (DCS) is the major site of input from medial agranular cortex (AGm) and has been implicated as an associative striatal area that is part of a cortical-subcortical circuit involved in multimodal spatial functions involving directed attention. Anterograde axonal tracing was used to investigate the spatial organization of corticostriatal projections to DCS. Injections of biotinylated dextran amine were made into several cortical areas known to project to DCS based on retrograde tracing data. These included areas AGm, lateral agranular cortex (AGl), orbital cortex, posterior parietal cortex (PPC), and visual association cortex. We discovered a previously undescribed geometry whereby the projection from AGm is prominent within DCS and the main corticostriatal projections from areas other than AGm are situated around the periphery of DCS: visual association cortex dorsomedially, PPC dorsally, AGl laterally, and orbital cortex ventrally. Each of these cortical projections is also represented by less dense aggregates of terminal labeling within DCS, organized as focal patches and more diffuse labeling. Because these cortical areas are linked by corticocortical connections, the present findings indicate that interconnected cortical areas have convergent terminal fields in the region of DCS. These findings suggest that DCS is a central associative region of the dorsal striatum characterized by a high degree of corticostriatal convergence.     

Primate supplementary eye field: I. Comparative aspects of mesencephalic and pontine connections

WGA-HRP was used to examine projections to the brainstem from the supplementary eye field (SEF). The SEF was defined electrophysiologically in awake, behaving monkeys and connections were compared to those of the arcuate frontal eye field (FEF), area 6DC, and primary motor cortex. The SEF was found to have either direct or indirect connections with almost every known pre- and paraoculomotor structure of the brainstem. The SEF was found to project bilaterally to layers I and IV of a tangentially widespread region of the superior colliculus. Terminal label was evident in the pretectal olivary nucleus, nucleus of the optic tract, nucleus raphe interpositus (omnipause region), nucleus prepositus hypoglossi, the perioculomotor cap of the central gray, dorsal central gray, nucleus reticularis tegmenti pontis, nucleus reticularis pontis oralis, and to multiple nuclei of the basis pontis (most densely to the dorsomedial nucleus). Bilateral projections were found in the parvicellular red nucleus. Reciprocal connections were present in the nucleus limitans, the mesencephalic reticular formation, locus coeruleus, and the serotonergic nuclei of the raphe complex (dorsalis and central superior). Overall patterns of connectivity were similar to those of the FEF and markedly different from those of the contiguous dorsocaudal area 6 or primary motor cortex. It was concluded that observed patterns of SEF-brainstem connectivity further justifies viewing this region as a distinct eye field that is likely to serve preparatory and trigger functions in the generation of saccadic eye movements.     

Connections between the frontal eye field and pretectum in the monkey: An anterograde/retrograde study using HRP GEL and TMB neurohistochemistry

Horseradish peroxidase (HRP) gel implants in the frontal eye field (FEF) of macaque monkeys, processed with tetramethylbenzidine (TMB) neurohistochemistry and studied with darkfield microscopy, demonstrated bidirectional HRP labeling of the afferents and efferents of this cortical area. It was evident that among the entire scope of its inputs, the FEF received a prominent afferent projection from the nucleus of the optic tract (NOT, nucleus limitans) and the suprageniculate nucleus, and projected to a medial subdivision of NOT, sublentiform nucleus, nucleus of the pretectal area, nucleus of the posterior commissure, and the rostral periaqueductal gray. The directafferent projections to FEF from NOT could provide a route for visual inputto reach FEF via the pretectum without first going to the visual cortex. The efferents probably represent the pathway through which FEF influences pupillary dynamics known to accompany, or occur independently of, eye movements.     

Organization of thalamostriatal terminals from the ventral motor nuclei in the macaque

This study examines the organization of thalamostriatal projections from ventral tier nuclei that relay basal ganglia output to the frontal cortex. Although previous thalamostriatal studies emphasize projections from the intralaminar nuclei, studies in primates show a substantial projection from the ventral anterior (VA) and ventral lateral (VL) nuclei. These nuclei make up the main efferent projection from the basal ganglia to frontal cortical areas, including primary motor, supplementary, premotor, and cingulate motor areas. Functionally related motor areas of the frontal cortex and VA/VL have convergent projections to specific regions of the dorsal striatum. The distribution of VA/VL terminals within the striatum is crucial to understanding their relationship to motor cortical afferents. We placed anterograde tracer injections into discrete VA/VL thalamic areas. VA/VL thalamostriatal projections terminate in broad, rostrocaudal regions of the dorsal striatum, corresponding to regions innervated by functionally related cortical motor areas. The pars oralis division of VL projects primarily to the dorsolateral, postcommissural putamen, whereas the parvicellular VA targets more medial and rostral putamen regions, and the magnocellular division of VA targets the dorsal head of the caudate nucleus. Whereas these results demonstrate a general functional topography, specific VA/VL projections overlap extensively, suggesting that functionally distinct VA/VL projections may also converge in dorsal striatal areas. Within striatal territories, VA/VL projections terminate in a patchy, nonhomogeneous manner, indicating another level of complexity. Moreover, terminal fields contain both terminal clusters and scattered, long, unbranched fibers with many varicosities. These fiber morphologies resemble those from the cortex and raise the possibility that VA/VL thalamostriatal projections neurons have divergent connectional features.     

Frontal projections to the region of the oculomotor complex in the rat: a retrograde and anterograde HRP study

The retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique were employed to study frontal projections to the perioculomotor region in the rat. Following HRP microinjections or transcannular HRP gel implants into the oculomotor complex (OMC), the majority of retrogradely labeled pyramidal cells were located in lamina V of the dorsomedial frontal shoulder cortex, i.e., medial precentral and anterior cingulate (PrCm/AC) cortices, the proposed frontal eye field (FEF) in the rat. A smaller number of labeled cells were present in the frontal polar cortex, agranular insular (AI), and lateral precentral (PrCl) cortices. Following HRP gel implants into the PrCM/Ac, anterogradely labeled projections were observed to the dorsal medial subthalamic region (nucleus campi Foreli, NCF) and medial accessory nucleus of Bechterew (MAB), and to other subcortical nuclei known to receive inputs from cortical area 8 in the monkey. These results, taken together with previous anatomical and physiological studies, support the conclusion that the PrCm/AC cortex contains the rat FEF. Its homology with the primate FEF is discussed.     

Cortical projections to nuclei adjacent to the oculomotor complex in the medial dien-mesencephalic tegmentum in the monkey

Cortical projections to cell groups surrounding the oculomotor complex were studied by using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique in old and new world monkeys. Fluid HRP injections or transcannular solid polyacrylamide HRP gel implants were made into the oculomotor nucleus (OMN) and adjacent nuclei to label retrogradely corticofugal neurons that project to this region, and cortical HRP gel implants were made in various areas of the frontal lobe to label anterogradely the trajectories and terminations of cortico-paraoculomotor projections and thus to confirm the retrograde findings. Projections to the paraoculomotor cell groups in the medial dien-mesencephalic tegmentum originate almost exclusively from the frontal lobe. Both retrograde and anterograde studies confirmed that the prearcuate cortex in the concavity of the arcuate sulcus, including the frontal eye field, and, to a lesser extent, suprarcuate rostral dorsal area 6 cortex and the dorsomedial convexity (area 9), project to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in the dorsal region of the prerubral field, nucleus of Darkschewitsch (ND), medial accessory nucleus of Bechterew (NB) and dorsomedial parvocellular red nucleus (dmPRN). The premotor area 6 and motor area 4 cortex, on the other hand, give rise to projections that target a larger portion of the parvocellular red nucleus, extending rostrally into the ventral region of the prerubral field, and a rather intense projection to the ND. The interstitial nucleus of Cajal (IC) was distinguished more by its light, or lack of, projections from the frontal cortex. The inferior parietal lobule (IPL, area 7) which has certain common physiological properties with the frontal eye field (FEF area 8) related to the oculomotor system, lacked retrogradely labeled neurons in all cases where transcannular gel implants into the OMN eliminated the possibility of HRP uptake in the corpus callosum or other structures traversed in needle injections, suggesting that the IPL affects eye movement primarily through its rostrally directed corticocortical associational connections with the FEF. In additional cases, the ND-NB-dmPRN configuration of cells that receives FEF input is shown to project to the inferior olivary complex (i.e., is pre-olivo-cerebellar), whereas riMLF and IC give rise to descending projections in the MLF, which target extraocular muscle motor nuclei, vestibular complex, and spinal cord. The results are discussed in terms of the potential role of the cerebral cortex in eye movement mechanisms.     

Cerebral ocular motor signs

Eye movement disturbances resulting from cerebral lesions are reviewed and the specific roles of the different ocular motor areas are summarized. Three cortical areas may trigger saccades: the frontal eye field (FEF), the supplementary eye field (SEF) and the parietal eye field (PEF). The FEF could be involved mainly in intentional visual exploration (intentional saccades), the PEF mainly in reflexive visual exploration (reflexive saccades) and the SEF in the preparation of motor programs (sequences of saccades). Only bilateral lesions affecting these areas result in visible saccade disturbances (at bedside examination), as manifested in Balint’s syndrome after parietal lesions, and ocular motor apraxia after fronto-parietal lesions. Other cortical areas prepare saccades: the posterior parietal cortex (near the PEF) controls visuomotor integration; the prefrontal cortex (i.e. area 46 of Brodmann) is involved in inhibition of unwanted reflexive saccades, prediction (predictive saccades) and spatial memory. Smooth pursuit is controlled by the FEF and the medial superior temporal area, located in the posterior part of the cerebral hemisphere. Eye movement disorders resulting from basal ganglia lesions are also reviewed. Lastly, the contribution of eye movement recordings in early diagnosis of some cerebral degenerative diseases (such as progressive supranuclear palsy or cortico-basal degeneration) is emphasized. Received: 15 August 1996 Accepted: 1 October 1996