Primate Cerebral Cortex Research Articles

In vivo visualization of single-unit recording sites using MRI-detectable elgiloy deposit marking

Precise localization of single-neuron activity has elucidated functional architectures of the primate cerebral cortex, related to vertically stacked layers and horizontally aligned columns. The traditional "gold standard" method for localizing recorded neuron is histological examination of electrolytic lesion marks at recording sites. Although this method can localize recorded neurons with fine neuroanatomy, the necessity for postmortem analysis prohibits its use in long-term chronic experiments. To localize recorded single-neuron positions in vivo, we introduced MRI-detectable elgiloy deposit marks, which can be created by electrolysis of an elgiloy microelectrode tip and visualized on highly contrasted magnetic resonance (MR) images. Histological analysis validated that the deposit mark centers could be localized relative to neuroanatomy in vivo with single-voxel accuracy, at an in-plane resolution of 200 μm. To demonstrate practical applications of the technique, we recorded single-neuron activity from a monkey performing a cognitive task and localized it in vivo using deposit marks (deposition: 2 μA for 3 min; scanning: fast-spin-echo sequence with 0.15 × 0.15 × 0.8 mm(3) resolution, 120/4,500 ms of echo-time/repetition-time and 8 echo-train-length), as is usually performed with conventional postmortem methods using electrolytic lesion marks. Two localization procedures were demonstrated: 1) deposit marks within a microelectrode track were used to reconstruct a dozen recorded neuron positions along the track directly on MR images; 2) combination with X-ray imaging allowed estimation of hundreds of neuron positions on MR images. This new in vivo method is feasible for chronic experiments with nonhuman primates, enabling analysis of the functional architecture of the cerebral cortex underlying cognitive processes.

Connectivity-driven white matter scaling and folding in primate cerebral cortex

Larger brains have an increasingly folded cerebral cortex whose white matter scales up faster than the gray matter. Here we analyze the cellular composition of the subcortical white matter in 11 primate species, including humans, and one Scandentia, and show that the mass of the white matter scales linearly across species with its number of nonneuronal cells, which is expected to be proportional to the total length of myelinated axons in the white matter. This result implies that the average axonal cross-section area in the white matter, a, does not scale significantly with the number of neurons in the gray matter, N. The surface area of the white matter increases with N(0.87), not N(1.0). Because this surface can be defined as the product of N, a, and the fraction n of cortical neurons connected through the white matter, we deduce that connectivity decreases in larger cerebral cortices as a slowly diminishing fraction of neurons, which varies with N(-0.16), sends myelinated axons into the white matter. Decreased connectivity is compatible with previous suggestions that neurons in the cerebral cortex are connected as a small-world network and should slow down the increase in global conduction delay in cortices with larger numbers of neurons. Further, a simple model shows that connectivity and cortical folding are directly related across species. We offer a white matter-based mechanism to account for increased cortical folding across species, which we propose to be driven by connectivity-related tension in the white matter, pulling down on the gray matter.

Cerebral Blood Flow Modeling in Primate Cortex

We report new results on blood flow modeling over large volumes of cortical gray matter of primate brain. We propose a network method for computing the blood flow, which handles realistic boundary conditions, complex vessel shapes, and complex nonlinear blood rheology. From a detailed comparison of the available models for the blood flow rheology and the phase separation effect, we are able to derive important new results on the impact of network structure on blood pressure, hematocrit, and flow distributions. Our findings show that the network geometry (vessel shapes and diameters), the boundary conditions associated with the arterial inputs and venous outputs, and the effective viscosity of the blood are essential components in the flow distribution. In contrast, we show that the phase separation effect has a minor function in the global microvascular hemodynamic behavior. The behavior of the pressure, hematocrit, and blood flow distributions within the network are described through the depth of the primate cerebral cortex and are discussed.

Neuronal and Axonal Loss Are Selectively Linked to Fibrillar Amyloid-β within Plaques of the Aged Primate Cerebral Cortex

The amyloid-beta peptide (Abeta) deposited in plaques in Alzheimer's disease has been shown to cause degeneration of neurons in experimental paradigms in vivo and in vitro. However, it has been difficult to convincingly demonstrate toxicity of native amyloid deposits in the aged and Alzheimer brains. Here we provide evidence that the fibrillar conformation of Abeta (fAbeta) deposited in compact plaques is associated with the pathologies observed in Alzheimer brains. fAbeta containing compact but not diffuse plaques in the aged rhesus cortex contained activated microglia and clusters of phosphorylated tau-positive swollen neurites. Scholl's quantitative analysis revealed that the area adjacent to fAbeta, containing compact but not diffuse plaques in aged rhesus, aged human, and Alzheimer's disease cortex, displays significant loss of neurons and small but statistically significant reduction in the density of cholinergic axons. These observations suggest that fAbeta toxicity may not be restricted to cultured cells and animal injection models. Rather, fAbeta deposited in native compact plaques in aged and AD brains may exert selective toxic effects on its surrounding neural environment.

Optimizing automated preprocessing streams for brain morphometric comparisons across multiple primate species

Optimizing automated preprocessing streams for brain morphometric comparisons across multiple primate species

Retinotopy versus category specificity throughout primate cerebral cortex

Retinotopy versus category specificity throughout primate cerebral cortex

Cytoarchitectural differences are a key determinant of laminar projection origins in the visual cortex

Regularity of laminar origin and termination of projections appears to be a common feature of corticocortical connections. We tested three models of this regularity, originally formulated for primate cerebral cortex, using quantitative data on the relative supragranular layer origins (SGN%) of 151 projections from 19 areas (∼145,000 neurons) to four areas of cat extrastriate cortex. Predictive variables in the models were: hierarchical level differences (Barone et al., 2000), structural type differences (Barbas, 1986), and distances (Salin and Bullier, 1995) between areas. Global and local hierarchies of cat visual cortex were used to evaluate the hierarchical model. Ranking of areas by their cytoarchitectural differentiation (e.g., relative prominence of layer IV) allowed testing of the structural model, while the distance model was tested for the number of borders separating areas. Laminar projection origins correlated moderately with hierarchical differences, and poorly with border distances, but were strongly and consistently correlated with area differences in cytoarchitectural rank. Moreover, projection densities were moderately and negatively correlated with area distances and structural differences. Our findings suggest that the relative cytoarchitectural differentiation of cortical areas is the main determinant of laminar projection origins in cat visual cortex, and may underlie a general laminar regularity of mammalian cortical connections.

Mapping primary gyrogenesis during fetal development in primate brains: high-resolution in utero structural MRI of fetal brain development in pregnant baboons.

The global and regional changes in the fetal cerebral cortex in primates were mapped during primary gyrification (PG; weeks 17–25 of 26 weeks total gestation). Studying pregnant baboons using high-resolution MRI in utero, measurements included cerebral volume, cortical surface area, gyrification index and length and depth of 10 primary cortical sulci. Seven normally developing fetuses were imaged in two animals longitudinally and sequentially. We compared these results to those on PG that from the ferret studies and analyzed them in the context of our recent studies of phylogenetics of cerebral gyrification. We observed that in both primates and non-primates, the cerebrum undergoes a very rapid transformation into the gyrencephalic state, subsequently accompanied by an accelerated growth in brain volume and cortical surface area. However, PG trends in baboons exhibited some critical differences from those observed in ferrets. For example, in baboons, the growth along the long (length) axis of cortical sulci was unrelated to the growth along the short (depth) axis and far outpaced it. Additionally, the correlation between the rate of growth along the short sulcal axis and heritability of sulcal depth was negative and approached significance (r = −0.60; p < 0.10), while the same trend for long axis was positive and not significant (p = 0.3; p = 0.40). These findings, in an animal that shares a highly orchestrated pattern of PG with humans, suggest that ontogenic processes that influence changes in sulcal length and depth are diverse and possibly driven by different factors in primates than in non-primates.

Populations of auditory cortical neurons can accurately encode acoustic space across stimulus intensity

The auditory cortex is critical for perceiving a sound's location. However, there is no topographic representation of acoustic space, and individual auditory cortical neurons are often broadly tuned to stimulus location. It thus remains unclear how acoustic space is represented in the mammalian cerebral cortex and how it could contribute to sound localization. This report tests whether the firing rates of populations of neurons in different auditory cortical fields in the macaque monkey carry sufficient information to account for horizontal sound localization ability. We applied an optimal neural decoding technique, based on maximum likelihood estimation, to populations of neurons from 6 different cortical fields encompassing core and belt areas. We found that the firing rate of neurons in the caudolateral area contain enough information to account for sound localization ability, but neurons in other tested core and belt cortical areas do not. These results provide a detailed and plausible population model of how acoustic space could be represented in the primate cerebral cortex and support a dual stream processing model of auditory cortical processing.

Doublecortin expression in adult cat and primate cerebral cortex relates to immature neurons that develop into GABAergic subgroups

DCX-immunoreactive (DCX+) cells occur in the piriform cortex in adult mice and rats, but also in the neocortex in adult guinea pigs and rabbits. Here we describe these cells in adult domestic cats and primates. In cats and rhesus monkeys, DCX+ cells existed across the allo- and neocortex, with an overall ventrodorsal high to low gradient at a given frontal plane. Labeled cells formed a cellular band in layers II and upper III, exhibiting dramatic differences in somal size (5–20 μm), shape (unipolar, bipolar, multipolar and irregular), neuritic complexity and labeling intensity. Cell clusters were also seen in this band, and those in the entorhinal cortex extended into deeper layers as chain-like structures. Densitometry revealed a parallel decline of the cells across regions with age in cats. Besides the cellular band, medium-sized cells with weak DCX reactivity resided sparsely in other layers. Throughout the cortex, virtually all DCX+ cells co-expressed polysialylated neural cell adhesion molecule. Medium to large mature-looking DCX+ cells frequently colocalized with neuron-specific nuclear protein and γ-aminobutyric acid (GABA), and those with a reduced DCX expression also partially co-labeled for glutamic acid decarboxylase, parvalbumin, calbindin, β-nicotinamide adenine dinucleotide phosphate diaphorase and neuronal nitric oxide synthase. Similar to cats and monkeys, small and larger DCX+ cells were detected in surgically removed human frontal and temporal cortices. These data suggest that immature neurons persist into adulthood in many cortical areas in cats and primates, and that these cells appear to undergo development and differentiation to become functional subgroups of GABAergic interneurons.

Action without perception in human vision

In 1992, David Milner and I (Goodale & Milner, 1992) proposed a division of labour in the visual pathways of the primate cerebral cortex between a dorsal stream specialized for the visual control of action and a ventral stream dedicated to constructing our percepts of the visual world. Support for the perception–action distinction has come from neuroimaging experiments, human neuropsychology, and monkey neurophysiology. Differences in the timing and spatial metrics of vision-for-perception and vision-for-action have been studied in human psychophysical experiments, particularly in those that have looked at the way in which each system deals with pictorial illusions. Although the literature is not free from controversy, a large number of studies have found that actions such as grasping and reaching are often unaffected by high-level pictorial illusions, which by definition affect perception. Recent experiments have shown that for actions to escape the effects of such illusions, however, they must be highly practised actions, preferably with the right hand, and must be directed in real time at visible targets. But even though the behavioural evidence suggests that the dorsal and ventral streams make use of different timing, different metrics, and different frames of reference in carrying out their computations, there is a seamless interaction between the two streams in the production of adaptive behaviour. A full understanding of the integrated nature of visually guided behaviour will require that we specify the nature of the interactions and information exchange that occur between these two streams of visual processing.

A 3D-investigation shows that angiogenesis in primate cerebral cortex mainly occurs at capillary level

This paper describes the use of a new 3D high-resolution imaging technique dedicated to functional vessels for a systematic quantitative study of angiogenesis in the primate cortex. We present a new method which permits, using synchrotron X-ray micro-tomography imaging, the identification of micro-vascular components as well as their automatic numerical digitalization and extraction from very large 3D image analysis and post-treatments. This method is used to analyze various levels of micro-vascular organization and their postnatal modifications. Comparing newborn- and adult marmosets, we found an increase in vascular volume (270%), exchange surface (260%) and vessel length (290%) associated to a decrease in distances between vessel and tissue (32%). The increase in relative vascular volumes between the two ages, examined through the whole cortical depth, has been found to be mainly sustained by events occurring at the capillary level, and only marginally at the perforating vessel level. This work shows that the postnatal cortical maturation classically described in terms of synaptogenesis, gliogenesis and connectivity plasticity is accompanied by an intensive remodeling of micro-vascular patterns.

Making bigger brains–the evolution of neural-progenitor-cell division

Relative brain size differs markedly between species. This variation might ultimately result from differences in the cell biology of neural progenitors, which might underlie their different proliferative potential. On the basis of the cell-biological properties of neural progenitors of animals of varying brain size and complexity (namely, Drosophila melanogaster, rodents and primates), we hypothesize that the evolution of four related cell-biological features has contributed to increases in neuron number. Three of these features-the pseudostratification of the progenitor layer, the loss of (Inscuteable-mediated) mitotic-spindle rotation and the evolution of proteins (such as Aspm) that maintain the precision of symmetric progenitor division-affect the mode of cell division in the apically dividing progenitors of the ventricular zone. The fourth feature, however, concerns the evolution of the basally dividing progenitors of the subventricular zone. In rodents, these basal (or intermediate) progenitors lack cell polarity, whereas in primates a subpopulation of radial, presumably polarized, progenitors has evolved (outer-subventricular-zone progenitors). These cells undergo basal mitoses and are thought to retain epithelial characteristics. We propose the epithelial-progenitor hypothesis, which argues that evolutionary changes that promote the maintenance of epithelial features in neural progenitors, including outer-subventricular-zone progenitors, have been instrumental in the expansion of the cerebral cortex in primates.

D1 Receptors Physically Interact with N-Type Calcium Channels to Regulate Channel Distribution and Dendritic Calcium Entry

Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling. Here, we show that D1 receptors potently inhibit N-type channels in dendrites of rat PFC neurons. Using coimmunoprecipitation, we demonstrate the existence of a D1 receptor-N-type channel signaling complex in this region, and we provide evidence for a direct receptor-channel interaction. Finally, we demonstrate the importance of this complex to receptor-channel colocalization in heterologous systems and in PFC neurons. Our data indicate that the N-type calcium channel is an important physiological target of D1 receptors and reveal a mechanism for D1 receptor-mediated regulation of cognitive function in the PFC.

Capillary hydrophilic interaction chromatography/mass spectrometry for simultaneous determination of multiple neurotransmitters in primate cerebral cortex

A diverse array of neurotransmitters and neuromodulators control and affect brain function. A profound understanding of the signaling pathways and the neural circuits underlying behavior is therefore likely to require the tracking of concentration changes of active neurochemicals. In the present study, we demonstrate the feasibility of a method allowing the simultaneous determination of the concentrations of six neurotransmitters: acetylcholine, serotonin, dopamine, gamma-aminobutyric acid (GABA), glutamate and aspartate, in the extracellular brain fluid (EBF). We used hydrophilic interaction chromatography (HILIC) coupled to tandem mass spectrometry (MS/MS) to analyze the EBF from the monkey brain. A push-pull sampling method was used to collect EBF from the prefrontal cortex (PFC) of conscious monkeys at flow rates in the range of low nL/min. The detection limits of acetylcholine, serotonin, dopamine, GABA, glutamate and aspartate were 0.015, 0.15, 0.3, 1.2, 6 and 15 femtomoles, respectively, allowing us to quantitatively determine the concentrations of these six neurotransmitters simultaneously from 500 nL in vivo samples. We conclude that HILIC/MS/MS combined with the push-pull sampling method represents a sensitive technique for simultaneous monitoring of neurotransmitters from EBF samples.

Vision for perception and vision for action in the primate brain.

Visual systems first evolved not to enable animals to see, but to provide distal sensory control of their movements. Vision as 'sight' is a relative newcomer to the evolutionary landscape, but its emergence has enabled animals to carry out complex cognitive operations on perceptual representations of the world. The two streams of visual processing that have been identified in the primate cerebral cortex are a reflection of these two functions of vision. The dorsal 'action' stream projecting from primary visual cortex to the posterior parietal cortex provides flexible control of more ancient subcortical visuomotor modules for the production of motor acts. The ventral 'perceptual' stream projecting from the primary visual cortex to the temporal lobe provides the rich and detailed representation of the world required for cognitive operations. Both streams process information about the structure of objects and about their spatial locations--and both are subject to the modulatory influences of attention. Each stream, however, uses visual information in different ways. Transformations carried out in the ventral stream permit the formation of perceptual representations that embody the enduring characteristics of objects and their relations; those carried out in the dorsal stream which utilize moment-to-moment information about objects within egocentric frames of reference, mediate the control of skilled actions. Both streams work together in the production of goal-directed behaviour.

Difference in sensory dependence of occ1/ Follistatin-related protein expression between macaques and mice

occ1/ Follistatin-related protein ( Frp) is strongly expressed in the primary visual cortex (V1) of macaque monkeys, and its expression is strongly down-regulated by intraocular tetrodotoxin (TTX) injection. The pronounced area selectivity of occ1/ Frp mRNA expression occurs in macaques and marmosets, but not in mice, rabbits and ferrets, suggesting that occ1/ Frp is an important clue to the evolution of the primate cerebral cortex. To further determine species differences, we examined the sensory-input dependency of occ1/ Frp mRNA expression in mice in comparison with macaque V1. In macaque V1, occ1/ Frp mRNA expression level significantly decreased with even 1-day monocular deprivation (MD) by TTX injection. In contrast to that in macaques, however, the occ1/ Frp mRNA expression in the visual cortex in mice was not down-regulated by 1- to 7-day MD by TTX injection. Similarly, MD had no effect on occ1/ Frp mRNA expression level in the dorsal lateral geniculate nucleus of mice. In addition, the extirpation of the cochlear or olfactory epithelium had no effect on occ1/ Frp mRNA expression in either the cochlear nucleus or the olfactory bulb in mice. Thus, occ1/ Frp mRNA expression is independent of sensory-input in mice. The results suggest that activity-dependent occ1/ Frp mRNA expression is not common between mice and monkeys, and that primate V1 has acquired a unique gene regulatory mechanism that enables a rapid response to environmental changes. The characteristic feature of the activity dependency of occ1/ Frp mRNA expression is discussed, in comparison with that of the expression of the immediate-early genes, c-fos and zif268.

Compact Movable Microwire Array for Long-Term Chronic Unit Recording in Cerebral Cortex of Primates

We describe a small, chronically implantable microwire array for obtaining long-term unit recordings from the cortex of unrestrained nonhuman primates. After implantation, the depth of microwires can be individually adjusted to maintain large-amplitude action potential recordings from single neurons over many months. We present data recorded from the primary motor cortex of two monkeys by autonomous on-board electronic circuitry. Waveforms of individual neurons remained stable for recording periods of several weeks during unrestrained behavior. Signal-to-noise ratios, waveform stability, and rates of cell loss indicate that this method may be particularly suited to experiments investigating the neural correlates of processes extending over multiple days, such as learning and plasticity.

Predicting the connectivity of primate cortical networks from topological and spatial node properties

BackgroundThe organization of the connectivity between mammalian cortical areas has become a major subject of study, because of its important role in scaffolding the macroscopic aspects of animal behavior and intelligence. In this study we present a computational reconstruction approach to the problem of network organization, by considering the topological and spatial features of each area in the primate cerebral cortex as subsidy for the reconstruction of the global cortical network connectivity. Starting with all areas being disconnected, pairs of areas with similar sets of features are linked together, in an attempt to recover the original network structure.ResultsInferring primate cortical connectivity from the properties of the nodes, remarkably good reconstructions of the global network organization could be obtained, with the topological features allowing slightly superior accuracy to the spatial ones. Analogous reconstruction attempts for the C. elegans neuronal network resulted in substantially poorer recovery, indicating that cortical area interconnections are relatively stronger related to the considered topological and spatial properties than neuronal projections in the nematode.ConclusionThe close relationship between area-based features and global connectivity may hint on developmental rules and constraints for cortical networks. Particularly, differences between the predictions from topological and spatial properties, together with the poorer recovery resulting from spatial properties, indicate that the organization of cortical networks is not entirely determined by spatial constraints.

MRI-based localization of electrophysiological recording sites within the cerebral cortex at single-voxel accuracy

The localization of microelectrode recording sites in the layers of primate cerebral cortex permits the analysis of relationships between recorded neuronal activities and underlying anatomical connections. We present a magnetic resonance imaging method for precise in vivo localization of cortical recording sites. In this method, the susceptibility-induced effect thickens the appearance of the microelectrode and enhances the detectability of the microelectrode tip, which usually occupies less than a few percent of the volume of an image voxel. In a phantom study, the optimized susceptibility-induced effect allowed tip detection with single-voxel accuracy (in-plane resolution, 50 mum). We applied this method to recording microelectrodes inserted into the brains of macaque monkeys, and localized the microelectrode tip at an in-plane resolution of 150 mum within the cortex of 2-3 mm in thickness. Subsequent histological analyses validated the single-voxel accuracy of the in vivo tip localization. This method opens up a way to investigate information flow during cognitive processes in the brain.