In macaques, the frontal eye field and the recently defined supplementary eye field play a role in the production of eye movements. Whereas the structure and function of the frontal eye field are well understood, little is known about the supplementary eye field. The goal of this study was to determine the connections of the physiologically defined supplementary eye field. In each case, the location of the supplementary eye field was determined by using intracortical microstimulation, the borders were marked with small electrolytic lesions, and horseradish peroxidase conjugated to wheat germ agglutinin was injected into the supplementary eye field. After the tissue was incubated with tetramethyl benzidine, it was determined that in three cases the injection site was confined to the physiologically defined supplementary eye field. The present results indicate that the supplementary eye field is reciprocally connected with the claustrum, ventral anterior nucleus, including pars magnocellularis, nucleus X, posterior subdivision of the ventral lateral nucleus, multiform, parvocellular, magnocellular, and densocellular subdivisions of the medial dorsal nucleus, central lateral nucleus, parafascicular nucleus, and suprageniculate-limitans complex. The supplementary eye field projects to the putamen, caudate, reticular nucleus of the thalamus, central densocellular nucleus, zona incerta, subthalamic nucleus, rostral interstitial nucleus of the medial longitudinal fasciculus, parvocellular part of the red nucleus, intermediate and deep layers of the superior colliculus, central gray, cuneiform nucleus, mesencephalic reticular formation, pontine gray, nucleus reticularis tegmenti pontis, and nucleus reticularis pontis oralis. The supplementary eye field is reciprocally and bilaterally connected with periprincipal and inferior prefrontal cortex, with periarcuate cortex, including the frontal eye field, the frontal ventral region, and with postarcuate premotor cortex, and cortex surrounding the supplementary eye field, including the supplementary motor area. The supplementary eye field is also reciprocally connected ipsilaterally with cortex in and around the cingulate sulcus and the intraparietal sulcus, whereas cortex within the superior temporal sulcus projects to the supplementary eye field. The connections of the physiologically defined supplementary eye field are compared to previously demonstrated connections of the supplementary motor region and of the physiologically defined frontal eye field. Comparisons between the connections of the frontal and supplementary eye fields reveal that both regions are connected with structures related to visuomotor functions, but the frontal eye field has more extensive connections with vision-related structures, and the supplementary eye field has more extensive connections with structures related to prefrontal and skeletomotor functions. Such connectional differences suggest functional differences between these two sensorimotor regions of the frontal lobe.

Physiological (intracortical microstimulation) and anatomical (transport of horseradish peroxidase conjugated to wheat germ agglutinin as shown by tetramethyl benzidine) approaches were combined in the same animals to reveal the locations, extents, and cortical connections of the frontal eye fields (FEF) in squirrel, owl, and macaque monkeys. In some of the same owl and macaque monkeys, intracortical microstimulation was also used to evoke eye movements from dorsomedial frontal cortex (the supplementary motor area). In addition, in all of the owl and squirrel monkeys, intracortical microstimulation was also used to evoke body movements from the premotor and motor cortex situated between the central dimple and the FEF. These microstimulation data were directly compared to the distribution of anterogradely and retrogradely transported label resulting from injections of tracer into the FEF in each monkey. Since the injection sites were limited to the physiologically defined FEF, the demonstrated connections were solely those of the FEF. To aid in the interpretation of areal patterns of connections, the relatively smooth cortex of owl and squirrel monkeys was unfolded, flattened, and cut parallel to the flattened surface. Cortex of macaque monkeys, which has numerous deep sulci, was cut coronally. Reciprocal connections with the ipsilateral frontal lobe were similar in all three species: dorsomedial cortex (supplementary motor area), cortex just rostral (periprincipal prefrontal cortex) to the FEF, and cortex just caudal (premotor cortex) to the FEF. In squirrel and owl monkeys, extensive reciprocal connections were made with cortex throughout the caudal half of the lateral fissure and, to a much lesser extent, cortex around the superior temporal sulcus. In macaque monkeys, only sparse connections were present with cortex of the lateral fissure, but extensive and dense connections were made with cortex throughout the caudal one-third to one-half of the superior temporal sulcus. In addition, very dense reciprocal connections were made with the cortex of the lateral, or inferior, bank of the intraparietal sulcus. Contralateral reciprocal connections in all three species were virtually limited to regions that correspond in location to the FEF and the supplementary motor area. The results of this study reveal connections between the physiologically defined frontal eye field and cortical regions known to participate in higher order visual processing, short-term memory, multimodal, visuomotor, and skeletomotor functions.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracortical microstimulation was used to define the borders of the frontal eye fields in squirrel, owl, and macaque monkeys. The borders were marked with electrolytic lesions, and horseradish peroxidase conjugated to wheat germ agglutinin was injected within the field. Following tetramethyl benzidine histochemistry, afferent and efferent connections of the frontal eye field with subcortical structures were studied. Most connections were ipsilateral and were similar in all primates studied. These include reciprocal connections with the following nuclei: medial dorsal (lateral parts), ventral anterior (especially with pars magnocellularis), central lateral, paracentral, ventral lateral, parafascicular, medial pulvinar, limitans, and suprageniculate. The frontal eye field also projects to the ipsilateral pretectal nuclei, subthalamic nucleus, nucleus of the posterior commissure, superior colliculus (especially layer four), zona incerta, rostral interstitial nucleus of the medial longitudinal fasciculus, nucleus Darkschewitsch, dorsomedial parvocellular red nucleus, interstitial nucleus of Cajal, basilar pontine nuclei, and bilaterally to the paramedian pontine reticular formation and the nucleus reticularis tegmenti pontis. Many of these structures also receive input from deeper layers of the superior colliculus and are known to participate in visuomotor function. These results reveal connections that account for the parallel influence of the superior colliculus and the frontal eye field on visuomotor function; suggest that there has been little evolutionary change in subcortical connections, and therefore function, of the frontal eye fields since the time that these lines of primates diverged; and support the conclusion that the frontal eye fields are homologous in New and Old World monkeys.

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Autoradiographic tracing procedures have been used to study the organization of retinogeniculate axons in seven primates, i.e., four species of New World monkeys, one species of Old World monkeys and two species of prosimians. These data suggest that the basic primate pattern of geniculate lamination consists of two parvocellular layers, two magnocellular layers, and two poorly developed and highly variable superficial (S) layers which are ventrally located. Ocular input to each member of each of the three pairs differs. In the macaque, the squirrel, and the saki monkey, the parvocellular layers subdivide and interdigitate into four leaflets so as to give the appearance of four parvocellular "layers." These leaflets are much less extensive in the owl and marmoset monkeys. In some individual macaque monkeys, there is further splitting of the parvocellular leaflets into subleaflets, giving the appearance of six parvocellular "layers." The prosimians (galago and slow loris) have two additional layers that are not found in pithecoid primates, and only one superficial layer is apparent. The two additional layers are termed "koniocellular" since they consist of very small cells. Finally, New and Old World monkeys have both ipsilateral and contralateral retinal input to the interlaminar zones. We conclude that the basic pattern of lateral geniculate organization is six layers, but not the traditional six. Prosimians have evolved two additional layers, the koniocellular layers, and have possibly lost one superficial layer. Both New World and Old World monkeys have elaborated the parvocellular layers by forming leaflets to varying extents. With the possible exception of the single S layer in prosimians, layers form pairs that are similar in cell types, but different in ocular input.

Biomedical research has and will continue to generate large amounts of data (termed ‘big data’) in many formats and at all levels. Consequently, there is an increasing need to better understand and mine the data to further knowledge and foster new discovery. The National Institutes of Health (NIH) has initiated a Big Data to Knowledge (BD2K) initiative to maximize the use of biomedical big data. BD2K seeks to better define how to extract value from the data, both for the individual investigator and the overall research community, create the analytic tools needed to enhance utility of the data, provide the next generation of trained personnel, and develop data science concepts and tools that can be made available to all stakeholders.

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Anterograde and retrograde transport methods have been used to analyze the projection of the superior colliculus upon the dorsal lateral geniculate nucleus in 19 mammalian species. Our retrograde findings reveal that tectogeniculate neurons are relatively small, and lie dorsally within the superficial gray. These small tectogeniculate neurons are spatially related to a dense tier of W-cell retinal input. Our anterograde tracing results show that tectogeniculate axons are visuotopically distributed to small-celled regions of the lateral geniculate in all nineteen species. In the majority of these species, the small-celled, tectally innervated regions of the lateral geniculate lie adjacent to the optic tract and contain W-cell-like neurons. Our findings suggest that neuroanatomical demonstration of the tectogeniculate projection is a relatively simple and straightforward way of revealing regions of the lateral geniculate which contain W-cells. This is true even in species in which the lateral geniculate lacks obvious cellular laminae, and in regions of the lateral geniculate where W-cells are few in number. The present data are especially interesting in light of the cortical projections of tectally innervated, small-celled regions of the lateral geniculate to the patches or puffs within layer III of area 17. Since these regions of small-celled geniculocortical axons are co-extensive with zones ("blobs") rich in cytochrome oxidase, it might be that information carried over the tectogeniculate circuitry plays an important role in the functions of the blob system.