Limbic frontal cortex in hominoids: A comparative study of area 13

The limbic frontal cortex forms part of the neural substrate responsible for emotional reactions to social stimuli. Area 13 is one of the cortical areas long known to be part of the posterior orbitofrontal cortex in several monkey species, such as the macaque. Its presence nevertheless in the human brain has been unclear, and the cortex of the frontal lobe of the great and lesser apes remains largely unknown. In this study area 13 was identified in human, chimpanzee, bonobo, gorilla, orangutan, and gibbon brains, and cortical maps were generated on the basis of its cytoarchitecture. Imaging techniques were used to characterize and quantify the microstructural organization of the area, and stereological tools were applied for estimates of the volume of area 13 in all species. Area 13 is conservative in its structure, and features such as size of cortical layers, density of neurons, and space available for connections are similar across hominoids with only subtle differences present. In contrast to the homogeneity found in its organization, variation is present in the relative size of this cortical area (as a percentage of total brain volume). The human and the bonobo include a complex orbitofrontal cortex and a relatively smaller area 13. On the contrary the orangutan stands out by having a shorter orbitofrontal region and a more expanded area 13. Differences in the organization and size of individual cortical areas involved in emotional reactions and social behavior can be related to behavioral specializations of each hominoid and to the evolution of emotions in hominids. Am J Phys Anthropol 106:129–155, 1998. © 1998 Wiley-Liss, Inc.     

Organization of the Human Frontal Pole Revealed by Large-Scale DTI-Based Connectivity: Implications for Control of Behavior

The goal of the current study was to examine the pattern of anatomical connectivity of the human frontal pole so as to inform theories of function of the frontal pole, perhaps one of the least understood region of the human brain. Rather than simply parcellating the frontal pole into subregions, we focused on examining the brain regions to which the frontal pole is anatomically and functionally connected. While the current findings provided support for previous work suggesting the frontal pole is connected to higher-order sensory association cortex, we found novel evidence suggesting that the frontal pole in humans is connected to posterior visual cortex. Furthermore, we propose a functional framework that incorporates these anatomical connections with existing cognitive theories of the functional organization of the frontal pole. In addition to a previously discussed medial-lateral distinction, we propose a dorsal-ventral gradient based on the information the frontal pole uses to guide behavior. We propose that dorsal regions are connected to other prefrontal regions that process goals and action plans, medial regions are connected to other brain regions that monitor action outcomes and motivate behaviors, and ventral regions connect to regions that process information about stimuli, values, and emotion. By incorporating information across these different levels of information, the frontal pole can effectively guide goal-directed behavior.     

Human and nonhuman primate brains: Are they allometrically scaled versions of the same design?

Allometric analyses of brain structure sizes across the primate order demonstrate that human, ape, and other anthropoid brains are not simply allometrically scaled versions of the same generalized design. Both human and ape brains exhibit specializations with respect to other anthropoid brains. Ape specializations include elaboration of the cerebellum (all apes) and frontal lobes (great apes only), and probably connectivity between them. Human brain specializations include an overall larger proportion of neocortex, with disproportionate enlargement of prefrontal and temporal association cortices; an apparent increase in cerebellar connections with cerebral cortical association areas involved in cognition; and a probable augmentation of intracortical connectivity in prefrontal cortex.     

Comparative analysis of the neocortex during the ontogenesis of cetaceae and primates

Comparative ontogenetic investigation of cytoarchitectonics of the cerebral neocortex has been performed in Cetacea and Primates using paraffin frontal and sagittal cerebral sections stained after Nissl. Cerebral hemispheres of dolphins, whales, monkeys and human being have been studied at various periods of prenatal development and in mature individuals. The comparison has been made at similar stages of cytoarchitectonical differentiation of the cortical plate. At two first stages of the prenatal ontogenesis (formation of the cortical plate and its differentiation into layers) there is not any principle differences between the Cetacea and Primates. Peculiarities of the cerebral cortical plate differentiation in the Cetacea (absence of the internal granular layer IV) is determined at the stage of stratification. Similar agranular character of the cerebral cortex differentiation is maintained during the whole subsequent ontogenesis in the Cetacea (heterogenetic type of the neocortex after Brodman). Absence of the layer IV in the cerebral neocortex determines some other principles in the spatial organization of the cortical-subcortical and in the intracortical connections in the Cetacea brain. This is confirmed by modern data of morphological and electrophysiological investigations. Perhaps, a comparatively more simple initial architectonics of the Cetacea brain limited the level of their functional possibilities, the latter is comparable only with anthropoid apes.     

The human brain: rewired and running hot

The past two decades have witnessed tremendous advances in noninvasive and postmortem neuroscientific techniques, advances that have made it possible, for the first time, to compare in detail the organization of the human brain to that of other primates. Studies comparing humans to chimpanzees and other great apes reveal that human brain evolution was not merely a matter of enlargement, but involved changes at all levels of organization that have been examined. These include the cellular and laminar organization of cortical areas; the higher order organization of the cortex, as reflected in the expansion of association cortex (in absolute terms, as well as relative to primary areas); the distribution of long-distance cortical connections; and hemispheric asymmetry. Additionally, genetic differences between humans and other primates have proven to be more extensive than previously thought, raising the possibility that human brain evolution involved significant modifications of neurophysiology and cerebral energy metabolism.     

Cortico-cortical projections from the prefrontal cortex to the superior temporal sulcal area (STs) in the monkey studied by means of HRP method.

Cortico-cortical connections from the prefrontal cortex to the superior temporal sulcal cortex (STs area) were studied in the monkey by means of retrograde axonal transport of horseradish peroxidase (HRP). After injections of 0.15-0.6 microliter of 50% HRP into the STs area, labeled cells were found in various cortical regions. In the prefrontal-STs projections, main features of topographic correlation were revealed; the posterior part of the STs area receives fibers from the superior frontal convexity (areas dorsal to the principal sulcus) and areas 8 and 6, whereas the anterior part of the STs area receives fibers from the inferior frontal convexity (areas ventral to the principal sulcus) and the frontal pole (area FD). The principal sulcus sends fibers to the entire STs area except for its ventral wall of the posterior part. A small cortical area adjacent to the inferior ramus of the arcuate sulcus (area 45 of ref. 41) sends fibers to the entire STs area. In addition, the orbitofrontal cortex projects mainly to the rostral part of the STs area, and the parahippocampal gyrus (areas TF and TH) projects to the deeper part of the entire STs area.     

The organization of somatosensory cortex in the short-tailed opossum ( Monodelphis domestica )

The organization of neocortex in the short-tailed opossum ( Monodelphis domestica ) was explored with multiunit microelectrode recordings from middle layers of cortex. Microelectrode maps were subsequently related to the chemoarchitecture of flattened cortical preparations, sectioned parallel to the cortical surface and processed for either cytochrome oxidase (CO) or NADPH-diaphorase (NADPHd) histochemistry. The recordings revealed the presence of at least two systematic representations of the contralateral body surface located in a continuous strip of cortex running from the rhinal sulcus to the medial wall. The primary somatosensory area (S1) was located medially while secondary somatosensory cortex (S2) formed a laterally located mirror image of S1. Auditory cortex was located in lateral cortex at the caudal border of S2, and some electrode penetrations in this area responded to both auditory and somatosensory stimulation. Auditory cortex was outlined by a dark oval visible in flattened brain sections. A large primary visual cortex (V1) was located at the caudal pole of cortex, and also consistently corresponded to a large chemoarchitecturally visible oval. Cortex just rostral and lateral to V1 responded to visual stimulation, while bimodal auditory/visual responses were obtained in an area between V1 and somatosensory cortex. The results are compared with brain organization in other marsupials and with placentals and the evolution of cortical areas in mammals is discussed.     

The organization of somatosensory cortex in the short-tailed opossum (Monodelphis domestica)

The organization of neocortex in the short-tailed opossum (Monodelphis domestica) was explored with multiunit microelectrode recordings from middle layers of cortex. Microelectrode maps were subsequently related to the chemoarchitecture of flattened cortical preparations, sectioned parallel to the cortical surface and processed for either cytochrome oxidase (CO) or NADPH-diaphorase (NADPHd) histochemistry. The recordings revealed the presence of at least two systematic representations of the contralateral body surface located in a continuous strip of cortex running from the rhinal sulcus to the medial wall. The primary somatosensory area (S1) was located medially while secondary somatosensory cortex (S2) formed a laterally located mirror image of S1. Auditory cortex was located in lateral cortex at the caudal border of S2, and some electrode penetrations in this area responded to both auditory and somatosensory stimulation. Auditory cortex was outlined by a dark oval visible in flattened brain sections. A large primary visual cortex (V1) was located at the caudal pole of cortex, and also consistently corresponded to a large chemoarchitecturally visible oval. Cortex just rostral and lateral to V1 responded to visual stimulation, while bimodal auditory/visual responses were obtained in an area between V1 and somatosensory cortex. The results are compared with brain organization in other marsupials and with placentals and the evolution of cortical areas in mammals is discussed.     

An Evaluation of the Left-Brain vs. Right-Brain Hypothesis with Resting State Functional Connectivity Magnetic Resonance Imaging

Lateralized brain regions subserve functions such as language and visuospatial processing. It has been conjectured that individuals may be left-brain dominant or right-brain dominant based on personality and cognitive style, but neuroimaging data has not provided clear evidence whether such phenotypic differences in the strength of left-dominant or right-dominant networks exist. We evaluated whether strongly lateralized connections covaried within the same individuals. Data were analyzed from publicly available resting state scans for 1011 individuals between the ages of 7 and 29. For each subject, functional lateralization was measured for each pair of 7266 regions covering the gray matter at 5-mm resolution as a difference in correlation before and after inverting images across the midsagittal plane. The difference in gray matter density between homotopic coordinates was used as a regressor to reduce the effect of structural asymmetries on functional lateralization. Nine left- and 11 right-lateralized hubs were identified as peaks in the degree map from the graph of significantly lateralized connections. The left-lateralized hubs included regions from the default mode network (medial prefrontal cortex, posterior cingulate cortex, and temporoparietal junction) and language regions (e.g., Broca Area and Wernicke Area), whereas the right-lateralized hubs included regions from the attention control network (e.g., lateral intraparietal sulcus, anterior insula, area MT, and frontal eye fields). Left- and right-lateralized hubs formed two separable networks of mutually lateralized regions. Connections involving only left- or only right-lateralized hubs showed positive correlation across subjects, but only for connections sharing a node. Lateralization of brain connections appears to be a local rather than global property of brain networks, and our data are not consistent with a whole-brain phenotype of greater “left-brained” or greater “right-brained” network strength across individuals. Small increases in lateralization with age were seen, but no differences in gender were observed.     

Neuroanatomical basis of behavioral disturbances in patients with prefrontal lesions

The role of the frontal lobe in control of behavioral and cognitive abilities is explored in a group of 34 patients with brain lesions restricted to the prefrontal cortex. The scores in both structured behavioral questionnaires and standard neuropsychological tests were analyzed using the injured area of the frontal lobe as the independent variable. Our results show that patients with simultaneous lesions in supero- and inferomedial areas of the prefrontal cortex exhibit higher behavioral disturbances. Bilateral lesions also are associated with greater behavioral troubles. On the contrary, cognitive abilities are globally impaired in prefrontal patients. Results are discussed in relation to current models of the organization of the prefrontal cortex and its role on behavior control.     

The connectional organization of neural systems in the cat cerebral cortex

BACKGROUND: The mammalian brain consists of the cerebral cortical sheet, which is composed of many distinct areas, the cerebellar cortex, and many non-cortical nuclei. Powerful neuroanatomical techniques have revealed a large number of connections between these structures. The large number of brain structures and the very many connections between them form a strikingly complex network. The complexity of this network has made it difficult to understand how the central nervous system is organized. Recently, however, optimization analysis of an important subset of central nervous connections that occur between the different areas of the cerebral cortex has produced understandable and quantitative representations of the organization of cortical systems of the primate brain. RESULTS: Here we briefly report the extension of this approach to the cortical systems of the cat. There were four connectional clusters of cortical areas in the cat. These clusters of areas corresponded to the visual, auditory, and somato-motor systems, and to the frontal and limbic areas, which we call the fronto-limbic complex. All the major sensory systems were hierarchically organized, and their 'higher' stations were more closely associated with the fronto-limbic complex than were their 'lower' stations. CONCLUSIONS: Features of the organization of the cat brain, together with earlier primate results, suggest that there may be a common cortical plan in mammals. We suggest that this common plan may involve relatively discrete, hierarchically organized, cortical sensory systems and a topologically central fronto-limbic complex. Specific variations on this wiring plan may relate to evolutionary history and selection for particular ecological niches.     

A specialized area in limbic cortex for fast analysis of peripheral vision

In primates, prostriata is a small area located between the primary visual cortex (V1) and the hippocampal formation. Prostriata sends connections to multisensory and high-order association areas in the temporal, parietal, cingulate, orbitofrontal, and frontopolar cortices. It is characterized by a relatively simple histological organization, alluding to an early origin in mammalian evolution. Here we show that prostriata neurons in marmoset monkeys exhibit a unique combination of response properties, suggesting a new pathway for rapid distribution of visual information in parallel with the traditionally recognized dorsal and ventral streams. Whereas the location and known connections of prostriata suggest a high-level association area, its response properties are unexpectedly simple, resembling those found in early stages of the visual processing: neurons have robust, nonadapting responses to simple stimuli, with latencies comparable to those found in V1, and are broadly tuned to stimulus orientation and spatiotemporal frequency. However, their receptive fields are enormous and form a unique topographic map that emphasizes the far periphery of the visual field. These results suggest a specialized circuit through which stimuli in peripheral vision can bypass the elaborate hierarchy of extrastriate visual areas and rapidly elicit coordinated motor and cognitive responses across multiple brain systems.     

Connections between the frontal and parietal areas of the cerebral cortex and the caudate nucleus in the cat]

In 10 cats with aseptically extirpated frontal and parietal areas of the brain cortex, efferent connections of the areas in question with the nucleus caudatus were experimentally studied by means of morphological methods. The preparations were stained according the methods of Nauta, Knuck, Finck-Haimer, and Kawamura-Niimi. The results of the investigations performed demonstrate a perfect topically organized caudal projection of the "associative" cortical areas. The frontal area is projected on the oral ventro-medial parts of the nucleus caudatus head, while the parietal area--on the central and lateral parts at the medial and more caudal levels.     

Dissimilar Aluminum and Gallium Permeation of the Blood-Brain Barrier Demonstrated by In Vivo Microdialysis

Aluminum (Al) and gallium (Ga) permeations of the blood-brain barrier (BBB) were assessed in rats. Unbound extracellular Al and Ga concentrations were ascertained at the two potential sites of BBB permeation, cerebral capillaries and choroid plexuses, by implantation of microdialysis probes in the frontal cortex and lateral ventricle, respectively. A microdialysis probe implanted in the jugular vein revealed unbound blood Al or Ga concentrations. Al or 67Ga citrate was administered via the femoral vein. Peak Al and Ga concentrations were seen within the first 10 min at all three sites. Area under the curve (concentration vs. time to final sample) values were calculated using RSTRIP. Within-rat overall frontal cortical/blood and lateral ventricular/blood ratios [brain/blood ratios (oBBRs)] were calculated from area under the curve values. Aluminum frontal cortical oBBRs were significantly higher than those for the lateral ventricle. Ga oBBRs were not significantly different between the two sites. Al and Ga oBBRs were significantly different in the lateral ventricle. These results suggest that the primary site of A1 permeation across the BBB is at cerebral capillaries, whereas Ga permeation across the BBB does not significantly differ between cerebral capillaries and choroid plexuses. The use of Ga as a model to study Al pharmacokinetics may not be appropriate in the elucidation of the site or mechanism of Al entry into the brain.     

Mapping behavioral repertoire onto the cortex

A traditional view of the motor cortex in the primate brain is that it contains a map of the body arranged across the cortical surface. This traditional topographic scheme, however, does not capture the actual pattern of overlaps, fractures, re-representations, and multiple areas separated by fuzzy borders. Here, we suggest that the organization of the motor cortex, premotor cortex, supplementary motor cortex, frontal eye field, and supplementary eye field can in principle be understood as a best-fit rendering of the motor repertoire onto the two-dimensional cortical sheet in a manner that optimizes local continuity.     

Interhemispheric asymmetry of the spatial-temporal potentials of the human cerebral cortex under various conditions of the formation of verbal conditioning

It was shown on the basis of electrophysiological data in 60 healthy subjects that the interhemispheric brain asymmetry in the course of formation and actualization of the verbal set depends on the context of the cognitive activity. More complex cognitive activity results in a development of regional interhemispheric differences in the studied characteristics of the spatiotemporal organization of cortical potentials. These differences are most spectacular in the frontal areas of the cortex.     

Distinct Parietal and Temporal Pathways to the Homologues of Broca's Area in the Monkey

The homologues of the two distinct architectonic areas 44 and 45 that constitute the anterior language zone (Broca's region) in the human ventrolateral frontal lobe were recently established in the macaque monkey. Although we know that the inferior parietal lobule and the lateral temporal cortical region project to the ventrolateral frontal cortex, we do not know which of the several cortical areas found in those regions project to the homologues of Broca's region in the macaque monkey and by means of which white matter pathways. We have used the autoradiographic method, which permits the establishment of the cortical area from which axons originate (i.e., the site of injection), the precise course of the axons in the white matter, and their termination within particular cortical areas, to examine the parietal and temporal connections to area 44 and the two subdivisions of area 45 (i.e., areas 45A and 45B). The results demonstrated a ventral temporo-frontal stream of fibers that originate from various auditory, multisensory, and visual association cortical areas in the intermediate superolateral temporal region. These axons course via the extreme capsule and target most strongly area 45 with a more modest termination in area 44. By contrast, a dorsal stream of axons that originate from various cortical areas in the inferior parietal lobule and the adjacent caudal superior temporal sulcus was found to target both areas 44 and 45. These axons course in the superior longitudinal fasciculus, with some axons originating from the ventral inferior parietal lobule and the adjacent superior temporal sulcus arching and forming a simple arcuate fasciculus. The cortex of the most rostral part of the inferior parietal lobule is preferentially linked with the ventral premotor cortex (ventral area 6) that controls the orofacial musculature. The cortex of the intermediate part of the inferior parietal lobule is linked with both areas 44 and 45. These findings demonstrate the posterior parietal and temporal connections of the ventrolateral frontal areas, which, in the left hemisphere of the human brain, were adapted for various aspects of language production. These precursor circuits that are found in the nonlinguistic, nonhuman, primate brain also exist in the human brain. The possible reasons why these areas were adapted for language use in the human brain are discussed. The results throw new light on the prelinguistic precursor circuitry of Broca's region and help understand functional interactions between Broca's ventrolateral frontal region and posterior parietal and temporal association areas.     

Lateral prefrontal cortex: architectonic and functional organization

A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral-caudal axis and a dorsal-ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal-ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information.     

Intracortical connections between neuron groups in the somatosensory cortex studied by the retrograde horseradish peroxidase transport method in rats

Short corticocortical connections between specialized groups of neurons (so-called barrels) were studied in the somatosensory cortex. After microinjections of horseradish peroxidase into a definite "barrel" labeled neurons were found in nearby groups within a radius of up to 400 µ. Labeled neurons were located chiefly in cortical layers V and III; 90% of them were pyramidal cells. Intracortical connection of labeled neurons were 1.6 times more numerous than thalamocortical connections. It is postulated that connections between neighboring cortical neuron groups are effected through their output cells, i.e., through pyramidal neurons of layers V and III.