Primate Cerebral Cortex Research Articles

Periostin, a neurite outgrowth-promoting factor, is expressed at high levels in the primate cerebral cortex.

Periostin (POSTN or osteoblast specific factor) is an extracellular matrix protein originally identified as a protein highly expressed in osteoblasts. Recently, periostin has been reported to function in axon regeneration and neuroprotection. In the present study, we focused on periostin function in cortical evolution. We performed a comparative gene expression analysis of periostin between rodents (mice) and primates (marmosets and macaques). Periostin was expressed at higher levels in the primate cerebral cortex compared to the mouse cerebral cortex. Furthermore, we performed overexpression experiments of periostin invivo and invitro. Periostin exhibited neurite outgrowth activity in cortical neurons. These results suggested the possibility that prolonged and increased periostin expression in the primate cerebral cortex enhances the cortical plasticity of the mammalian cerebral cortex.

Rediscovering TNAP in the Brain: A Major Role in Regulating the Function and Development of the Cerebral Cortex.

The presence of alkaline phosphatase (AP) activity in the neural tissue has been described decades ago. However, only recent studies clarified the isotype, regional distribution and subcellular localization of the AP expressed in the cerebral cortex of diverse mammalian species including the human. In the primate brain the discovery that the bone AP isotype (TNAP) is expressed provided the opportunity of a deeper understanding of the role of this enzyme in neuronal functions based on the knowledge acquired by studying the role of the enzyme in hypophosphatasia, mostly in bone mineralization. TNAP exhibits widespread substrate specificity and, in the brain, it is potentially involved in the regulation of molecules which play fundamental roles in signal transmission and development. In light of these observations, the localization of TNAP in the human cerebral cortex is of high significance when considering that epilepsy is often diagnosed in hypophosphatasia. Here we overview our results on the identification of TNAP in the primate cerebral cortex: TNAP exhibits a noticeably high activity in the synapses and nodes of Ranvier, is specifically present in layer 4 of the sensory cortices and additionally in layer 5 of prefrontal, temporal and other associational areas in human. Our studies also indicate that bone AP activity depends on the level of sensory input and that its developmental time-course exhibits characteristic regional differences. The relevance of our findings regarding human cortical physiology and brain disorders are discussed.

Neocortical calretinin neurons in primates: increase in proportion and microcircuitry structure.

In this article we first point at the expansion of associative cortical areas in primates, as well as at the intrinsic changes in the structure of the cortical column. There is a huge increase in proportion of glutamatergic cortical projecting neurons located in the upper cortical layers (II/III). Inside this group, a novel class of associative neurons becomes recognized for its growing necessity in both inter-areal and intra-areal columnar integration. Equally important to the changes in glutamatergic population, we found that literature data suggest a 50% increase in the proportion of neocortical GABAergic neurons between primates and rodents. This seems to be a result of increase in proportion of calretinin interneurons in layers II/III, population which in associative areas represents 15% of all neurons forming those layers. Evaluating data about functional properties of their connectivity we hypothesize that such an increase in proportion of calretinin interneurons might lead to supra-linear growth in memory capacity of the associative neocortical network. An open question is whether there are some new calretinin interneuron subtypes, which might substantially change micro-circuitry structure of the primate cerebral cortex.

Postnatal development of dendritic structure of layer III pyramidal neurons in the medial prefrontal cortex of marmoset.

In the primate cerebral cortex, dendritic spines rapidly increase in number after birth up to infancy or mid-childhood, and then decrease towards adulthood. Abnormalities in these processes accompany several psychiatric disorders. In this study, we examined developmental changes of basal dendrites and spines of layer III pyramidal cells in the medial prefrontal cortex (mPFC) of the common marmoset. The mPFC consists of several areas with distinct features in layer organization, histochemistry, connections, and, in humans, vulnerability to psychiatric disorders. We selected three areas for examination: granular dorsomedial prefrontal (area 8B/9), dysgranular ventromedial prefrontal (area 14r), and agranular anterior cingulate (area 24) cortices. Dendritic field areas, lengths, number of branching points, and total spine number reached a peak at 2-3 postnatal months in all three areas. However, the profiles of spine formation and pruning differed across the three areas with different degrees of granularity; the amount of spine loss from the peak to adulthood was less in areas 24 (33%) and 14r (29%) than in area 8B/9 (43%). Disturbance of this modest spine pruning in the less granular cortical areas may lead to an excessive loss of spines reported for areas 24 and 14r of schizophrenic patients.

Spatio-temporal extension in site of origin for cortical calretinin neurons in primates.

The vast majority of cortical GABAergic neurons can be defined by parvalbumin, somatostatin or calretinin expression. In most mammalians, parvalbumin and somatostatin interneurons have constant proportions, each representing 5–7% of the total neuron number. In contrast, there is a threefold increase in the proportion of calretinin interneurons, which do not exceed 4% in rodents and reach 12% in higher order areas of primate cerebral cortex. In rodents, almost all parvalbumin and somatostatin interneurons originate from the medial part of the subpallial proliferative structure, the ganglionic eminence (GE), while almost all calretinin interneurons originate from its caudal part. The spatial pattern of cortical GABAergic neurons origin from the GE is preserved in the monkey and human brain. However, it could be expected that the evolution is changing developmental rules to enable considerable expansion of calretinin interneuron population. During the early fetal period in primates, cortical GABAergic neurons are almost entirely generated in the subpallium, as in rodents. Already at that time, the primate caudal ganglionic eminence (CGE) shows a relative increase in size and production of calretinin interneurons. During the second trimester of gestation, that is the main neurogenetic stage in primates without clear correlates found in rodents, the pallial production of cortical GABAergic neurons together with the extended persistence of the GE is observed. We propose that the CGE could be the main source of calretinin interneurons for the posterior and lateral cortical regions, but not for the frontal cortex. The associative granular frontal cortex represents around one third of the cortical surface and contains almost half of cortical calretinin interneurons. The majority of calretinin interneurons destined for the frontal cortex could be generated in the pallium, especially in the newly evolved outer subventricular zone that becomes the main pool of cortical progenitors.

Cortical innervation of the hypoglossal nucleus in the non-human primate (Macaca mulatta).

The corticobulbar projection to the hypoglossal nucleus was studied from the frontal, parietal, cingulate, and insular cortices in the rhesus monkey by using high-resolution anterograde tracers and stereology. The hypoglossal nucleus received bilateral input from the face/head region of the primary (M1), ventrolateral pre- (LPMCv), supplementary (M2), rostral cingulate (M3), and caudal cingulate (M4) motor cortices. Additional bilateral corticohypoglossal projections were found from the dorsolateral premotor cortex (LPMCd), ventrolateral proisocortical motor area (ProM), ventrolateral primary somatosensory cortex (S1), rostral insula, and pregenual region of the anterior cingulate gyrus (areas 24/32). Dense terminal projections arose from the ventral region of M1, and moderate projections from LPMCv and rostral part of M2, with considerably fewer hypoglossal projections arising from the other cortical regions. These findings demonstrate that extensive regions of the non-human primate cerebral cortex innervate the hypoglossal nucleus. The widespread and bilateral nature of this corticobulbar connection suggests recovery of tongue movement after cortical injury that compromises a subset of these areas, may occur from spared corticohypoglossal projection areas located on the lateral, as well as medial surfaces of both hemispheres. Since functional imaging studies have shown that homologous cortical areas are activated in humans during tongue movement tasks, these corticobulbar projections may exist in the human brain.

Advances in radiofrequency ablation of the cerebral cortex in primates using the venous system: Improvements for treating epilepsy with catheter ablation technology

Pharmacology frequently fails for the treatment of epilepsy. Although surgical techniques are effective, these procedures are highly invasive. We describe feasibility and efficacy of minimally invasive mapping and ablation for the treatment of epilepsy. Mapping and radiofrequency ablations were performed via the venous system in eleven baboons and three dogs. Mapping in deep cerebral areas was obtained in all animals. High-frequency pacing was able to induce seizure activity of local cerebral tissue in 72% of our attempts. Cerebral activity could be seen during mapping. Ablative lesions were deployed at deep brain sites without steam pops or sudden impedance rise. Histologic analysis showed necrosis at the sites of ablation in all primates. Navigation through the cerebral venous system to map seizure activity is feasible. Radiofrequency energy can be delivered transvenously or transcortically to successfully ablate cortical tissue in this animal model using this innovative approach.

Evolution of the human brain: when bigger is better.

Comparative studies of the brain in mammals suggest that there are general architectural principles governing its growth and evolutionary development. We are beginning to understand the geometric, biophysical and energy constraints that have governed the evolution and functional organization of the brain and its underlying neuronal network. The object of this review is to present current perspectives on primate brain evolution, especially in humans, and to examine some hypothetical organizing principles that underlie the brain's complex organization. Some of the design principles and operational modes that underlie the information processing capacity of the cerebral cortex in primates will be explored. It is shown that the development of the cortex coordinates folding with connectivity in a way that produces smaller and faster brains, then otherwise would have been possible. In view of the central importance placed on brain evolution in explaining the success of our own species, one may wonder whether there are physical limits that constrain its processing power and evolutionary potential. It will be argued that at a brain size of about 3500 cm3, corresponding to a brain volume two to three times that of modern man, the brain seems to reach its maximum processing capacity. The larger the brain grows beyond this critical size, the less efficient it will become, thus limiting any improvement in cognitive power.

Representation of Naturalistic Image Structure in the Primate Visual Cortex.

The perception of complex visual patterns emerges from neuronal activity in a cascade of areas in the primate cerebral cortex. We have probed the early stages of this cascade with "naturalistic" texture stimuli designed to capture key statistical features of natural images. Humans can recognize and classify these synthetic images and are insensitive to distortions that do not alter the local values of these statistics. The responses of neurons in the primary visual cortex, V1, are relatively insensitive to the statistical information in these textures. However, in the area immediately downstream, V2, cells respond more vigorously to these stimuli than to matched control stimuli. Humans show blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI responses in V1 and V2) that are consistent with the neuronal measurements in macaque. These fMRI measurements, as well as neurophysiological work by others, show that true natural scenes become a more prominent driving feature of cortex downstream from V2. These results suggest a framework for thinking about how information about elementary visual features is transformed into the specific representations of scenes and objects found in areas higher in the visual pathway.

Metabolic energy per synapse is approximately conserved during development in mammalian brains.

Event Abstract Back to Event Metabolic energy per synapse is approximately conserved during development in mammalian brains. Jan Karbowski1* 1 Polish Academy of Sciences, Poland During mammalian development the cerebral metabolic rate correlates qualitatively with synaptogenesis, and both often exhibit bimodal temporal profiles. Despite these non-monotonic dependencies, it is found based on empirical data for different mammals that regional metabolic rate per synapse is approximately conserved from birth to adulthood for a given species (with a slight deviation from this constancy for human visual and temporal cortices during adolescence). A typical synapse uses about 7000 glucose molecules per second in primate cerebral cortex, and about 5 times of that amount in cat and rat visual cortices. A theoretical model for brain metabolic expenditure is used to estimate synaptic signaling and neural spiking activity during development. It is found that synaptic efficacy is generally inversely correlated with average firing rate, and additionally, synapses consume a bulk of metabolic energy, roughly 50-90% during most of the developmental process (except human temporal cortex < 50%). Overall, these results suggest a tight regulation of brain electrical and chemical activities during the formation and consolidation of neural connections. This presumably reflects strong energetic constraints on brain development.

Controlling working memory with learned instructions

Many neural network models of cognition rely heavily on the modeler for control over aspects of model behavior, such as when to learn and whether an item is judged to be present in memory. Developing neurocomputational methods that allow these cognitive control mechanisms to be performed autonomously has proven to be surprisingly difficult. Here we present a general purpose framework called GALIS that we believe is amenable to developing a broad range of cognitive control models. Models built using GALIS consist of a network of interacting “regions” inspired by the organization of primate cerebral cortex. Each region is an attractor network capable of learning temporal sequences, and the individual regions not only exchange task-specific information with each other, but also gate the others’ functions and interactions. As a result, GALIS models can learn both task-specific content and also the necessary cognitive control procedures (instructions) needed to perform a task in the first place. As an initial test of this approach, we use GALIS to implement a model that is trained simultaneously to perform five versions of the n-Back task. Not only does the resulting n-Back model function correctly, determining when to learn or remove items in working memory, but its accuracy and response times correlate strongly with those of human subjects performing the same task. The n-Back model also makes testable predictions about how human accuracy would be affected by intra-trial changes in n’s value. We conclude that GALIS opens a potentially effective pathway toward developing a range of cognitive control models with improved autonomy.

Journal-related Activities and Other Special Activities at the 2012 American Society of Anesthesiologists Annual Meeting

Journal-related Activities and Other Special Activities at the 2012 American Society of Anesthesiologists Annual Meeting

Reduced Variability of Ongoing and Evoked Cortical Activity Leads to Improved Behavioral Performance

Sensory responses of the brain are known to be highly variable, but the origin and functional relevance of this variability have long remained enigmatic. Using the variable foreperiod of a visual discrimination task to assess variability in the primate cerebral cortex, we report that visual evoked response variability is not only tied to variability in ongoing cortical activity, but also predicts mean response time. We used cortical local field potentials, simultaneously recorded from widespread cortical areas, to gauge both ongoing and visually evoked activity. Trial-to-trial variability of sensory evoked responses was strongly modulated by foreperiod duration and correlated both with the cortical variability before stimulus onset as well as with response times. In a separate set of experiments we probed the relation between small saccadic eye movements, foreperiod duration and manual response times. The rate of eye movements was modulated by foreperiod duration and eye position variability was positively correlated with response times. Our results indicate that when the time of a sensory stimulus is predictable, reduction in cortical variability before the stimulus can improve normal behavioral function that depends on the stimulus.

Fetal Gyrification in Cynomolgus Monkeys: A Concept of Developmental Stages of Gyrification

Our article summarizes a series of studies about fetal gyrification and its relation to cerebral growth in cynomolgus monkeys. Based on the cerebral growth (i.e., brain weight, cerebral volume, and frontooccipital length of the cerebral hemisphere) and the developmental pattern of gyrification in each sulcus of cynomolgus monkeys, we divided the gyrification process into four stages: Stage 1. Demarcation of cerebral lobes and limbic gyri; Stage 2. Demarcation of neocortical gyri; Stage 3. Emergence of secondary and tertiary sulci; and Stage 4. Growth of sulcal length and depth. Each stage of those gyrification processes was influenced by different developmental events, such as the emergence of corticocortical long-associative fiber tracts, cortical maturations, and subcortical white-matter development. This is the first report to systematically propose gyrification processes closely related to the order of phyologenetical development of the cerebral cortex in primates.

Approximate Invariance of Metabolic Energy per Synapse during Development in Mammalian Brains

During mammalian development the cerebral metabolic rate correlates qualitatively with synaptogenesis, and both often exhibit bimodal temporal profiles. Despite these non-monotonic dependencies, it is found based on empirical data for different mammals that regional metabolic rate per synapse is approximately conserved from birth to adulthood for a given species (with a slight deviation from this constancy for human visual and temporal cortices during adolescence). A typical synapse uses about glucose molecules per second in primate cerebral cortex, and about five times of that amount in cat and rat visual cortices. A theoretical model for brain metabolic expenditure is used to estimate synaptic signaling and neural spiking activity during development. It is found that synaptic efficacy is generally inversely correlated with average firing rate, and, additionally, synapses consume a bulk of metabolic energy, roughly during most of the developmental process (except human temporal cortex ). Overall, these results suggest a tight regulation of brain electrical and chemical activities during the formation and consolidation of neural connections. This presumably reflects strong energetic constraints on brain development.

Transcriptional Profiling of Layers of the Primate Cerebral Cortex

In this issue of Neuron, Bernard etal. (2012) report microarray-based transcriptional profiling of individually isolated layers from several cortical areas in adult Rhesus monkeys (Macaca mulatta). The resulting molecular signatures of neocortical organization are compared with human and mouse.

Spectral fingerprints of large-scale neuronal interactions

Cognition results from interactions among functionally specialized but widely distributed brain regions; however, neuroscience has so far largely focused on characterizing the function of individual brain regions and neurons therein. Here we discuss recent studies that have instead investigated the interactions between brain regions during cognitive processes by assessing correlations between neuronal oscillations in different regions of the primate cerebral cortex. These studies have opened a new window onto the large-scale circuit mechanisms underlying sensorimotor decision-making and top-down attention. We propose that frequency-specific neuronal correlations in large-scale cortical networks may be 'fingerprints' of canonical neuronal computations underlying cognitive processes.

What’s the hype about CDK5RAP2?

Cyclin dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) has gained attention in the last years following the discovery, in 2005, that recessive mutations cause primary autosomal recessive microcephaly. This disease is seen as an isolated developmental defect of the brain, particularly of the cerebral cortex, and was thus historically also referred to as microcephalia vera. Unraveling the pathomechanisms leading to this human disease is fascinating scientists because it can convey insight into basic mechanisms of physiologic brain development (particularly of cortex formation). It also finds itself in the spotlight because of its implication in trends in mammalian evolution with a massive increase in the size of the cerebral cortex in primates. Here, we provide a timely overview of the current knowledge on the function of CDK5RAP2 and mechanisms that might lead to disease in humans when the function of this protein is disturbed.

Doublecortin‐positive cells in the adult primate cerebral cortex and possible role in brain plasticity and development

We have demonstrated that cortical cell autografts might be a useful therapy in two monkey models of neurological disease: motor cortex lesion and Parkinson's disease. However, the origin of the useful transplanted cells obtained from cortical biopsies is not clear. In this report we describe the expression of doublecortin (DCX) in these cells based on reverse-transcription polymerase chain reaction (RT-PCR) and immunodetection in the adult primate cortex and cell cultures. The results showed that DCX-positive cells were present in the whole primate cerebral cortex and also expressed glial and/or neuronal markers such as glial fibrillary protein (GFAP) or neuronal nuclei (NeuN). We also demonstrated that only DCX/GFAP positive cells were able to proliferate and originate progenitor cells in vitro. We hypothesize that these DCX-positive cells in vivo have a role in cortical plasticity and brain reaction to injury. Moreover, in vitro these DCX-positive cells have the potential to reacquire progenitor characteristics that confirm their potential for brain repair.

Constrain your data: relating detailed animal studies to spatial templates in neuroimaging

Event Abstract Back to Event Constrain your data: relating detailed animal studies to spatial templates in neuroimaging Gleb Bezgin1* and Rembrandt Bakker2 1 Baycrest, Rotman Research Institute, Canada 2 Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behavior, Netherlands Techniques such as EEG, fMRI, PET and DTI are widely utilized to extract information on functional and anatomical connectivity in the human brain. For each analyzed brain, these methods provide a complete picture of the measured quantity at a limited resolution. This is in sharp contrast with invasive animal studies, carried out primarily in non-human primates. In particular, the most unambiguous information on long-range interareal connectivity is provided by axonal fibre tract tracing studies. Obtained data are precise up to axonal level, albeit typically apply only to a particular part of the analyzed brain. Hence, linking these two kinds of resources is mutually beneficial. We describe an approach for spatially registering all cortical brain regions from the textual database CoCoMac (K?tter, 2004). Currently, it contains 458 studies, mainly tract tracing experiments, many of which define their own cortical (sub)parcellation. Direct registration to a surface-based Macaque cortex is applied to 9 core parcellations using the tool Caret (Van Essen and Dierker, 2007). The rest of the database is semantically linked to these core parcellations using previously developed algebraic and machine learning techniques (Stephan et al., 2000; Bezgin et al., 2008; Bakker et al., ongoing work). For the translation to the human cortex we rely on Van Essen's landmark-based macaque to human warpings. As a result, one can query CoCoMac for a given spatial coordinate in any of the Caret-supported macaque and human cortical templates. Connectivity was analyzed using multiple graph-theoretical measures to capture global properties of the derived network using the new brain network visualization and analysis tool ConJUNGtion developed on the basis of JUNG software (Madadhain et al., 2005). As a next step, the spatial connectivity maps can be used either as a direct validation of neuroimaging data, or indirectly by constraining generative models of brain activity with a plausible anatomical connectivity assignment. References Bezgin G., Wanke E., Krumnack A., Kötter R. (2008) Deducing logical relationships between spatially registered cortical parcellations under conditions of uncertainty. Neural Networks 21(8): 1132-1145. K?tter R. (2004) Online retrieval, processing, and visualization of primate connectivity data from the CoCoMac database. Neuroinformatics 2(2), 127-44. Madadhain J., Fisher D., Smyth P., White S., Boey Y.B. (2005) Analysis and visualization of network data using JUNG. Journal of Statistical Software, Vol. 10, p. 1--35. Paxinos G., Huang X.-F., Petrides M. and Toga A.W. (2009) The Rhesus Monkey Brain in Stereotaxic Coordinates, 2nd Edition. Amsterdam: Elsevier Science. Stephan K.E., Zilles K., Kötter R. (2000) Coordinate-independent mapping of structural and functional data by objective relational transformation (ORT). Phil. Trans. R. Soc. Lond. B 355, 37-54. Van Essen D. C., Dierker D. L. (2007) Surface-based and probabilistic atlases of primate cerebral cortex. Neuron 56, 209–225. Figure 1 Keywords: digital atlasing Conference: 4th INCF Congress of Neuroinformatics, Boston, United States, 4 Sep - 6 Sep, 2011. Presentation Type: Poster Presentation Topic: Digital atlasing Citation: Bezgin G and Bakker R (2011). Constrain your data: relating detailed animal studies to spatial templates in neuroimaging. Front. Neuroinform. Conference Abstract: 4th INCF Congress of Neuroinformatics. doi: 10.3389/conf.fninf.2011.08.00070 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Oct 2011; Published Online: 19 Oct 2011. * Correspondence: Dr. Gleb Bezgin, Baycrest, Rotman Research Institute, Toronto, Canada, gbezgin@rotman-baycrest.on.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gleb Bezgin Rembrandt Bakker Google Gleb Bezgin Rembrandt Bakker Google Scholar Gleb Bezgin Rembrandt Bakker PubMed Gleb Bezgin Rembrandt Bakker Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.