A computational model for the primate neocortex based on its functional architecture

Experimental evidence has shown that the primate neocortex consists in the main of a set of cortical regions which form a perception hierarchy, an action hierarchy and connections between them. By using a computer science analysis, we develop a computational architecture for the brain in which each cortical region is represented by a computational module with processing and storage abilities. Modules are interconnected according to the connectivity of the corresponding cortical regions. We develop computational principles for designing such a hierarchical and parallel computing system. We demonstrate this approach by proposing a causal functioning model of the brain. We report on results obtained with an implementation of this model. We conclude with a brief discussion of some consequences and predictions of our work.     

On the computational architecture of the neocortex

This paper is a sequel to an earlier paper which proposed an active role for the thalamus, integrating multiple hypotheses formed in the cortex via the thalamo-cortical loop. In this paper, I put forward a hypothesis on the role of the reciprocal, topographic pathways between two cortical areas, one often a higher area dealing with more abstract information about the world, the other lower, dealing with more concrete data. The higher area attempts to fit its abstractions to the data it receives from lower areas by sending back to them from its deep pyramidal cells a template reconstruction best fitting the lower level view. The lower area attempts to reconcile the reconstruction of its view that it receives from higher areas with what it knows, sending back from its superficial pyramidal cells the features in its data which are not predicted by the higher area. The whole calculation is done with all areas working simultaneously, but with order imposed by synchronous activity in the various top-down, bottom-up loops. Evidence for this theory is reviewed and experimental tests are proposed. A third part of this paper will deal with extensions of these ideas to the frontal lobe.     

On the computational architecture of the neocortex

This paper proposes that each area of the cortex carries on its calculations with the active participation of a nucleus in the thalamus with which it is reciprocally and topographically connected. Each cortical area is responsible for maintaining and updating the organism's knowledge of a specific aspect of the world, ranging from low level raw data to high level abstract representations, and involving interpreting stimuli and generating actions. In doing this, it will draw on multiple sources of expertise, learned from experience, creating multiple, often conflicting, hypotheses which are integrated by the action of the thalamic neurons and then sent back to the standard input layer of the cortex. Thus this nucleus plays the role of an 'active blackboard' on which the current best reconstruction of some aspect of the world is always displayed. Evidence for this theory is reviewed and experimental tests are proposed. A sequel to this paper will discuss the cortico-cortical loops and propose quite different computational roles for them.     

Neurogenesis in adult primate neocortex: an evaluation of the evidence

Reports of continuous genesis and turnover of neurons in the adult primate association neocortex--the site of the highest cognitive functions--have generated great excitement. Here, I review the available evidence, and question the scientific basis of this claim.     

Specificity in the functional architecture of primate prefrontal cortex

Multiple lines of evidence indicate that the performance of complex cognitive processes, such as those involving working memory, depend upon the functional properties of the circuitry of the prefrontal cortex (PFC). In primates, working memory has been proposed to be dependent upon the sustained activity of specific populations of PFC pyramidal cells, with this activity regulated by certain types of GABAergic interneurons. Thus, knowledge of the connectivity between PFC pyramidal cells and interneurons is crucial to the understanding the neural mechanisms that subserve working memory. This paper reviews recent findings that reveal specificity in the spatial organization, synaptic targets and postnatal development of pyramidal cells and interneurons in the primate prefrontal cortex, and considers the relevance of these findings for the neural circuitry that subserves working memory.     

Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

1. Download : Download high-res image (204KB)
2. Download : Download full-size image

     

Gene expression profiling of primate neocortex: molecular neuroanatomy of cortical areas

One hundred years have passed since Brodmann's mapping of the mammalian neocortex. Solely on the basis of morphological observations, he envisaged the conservation and differentiation of cortical areal structures across various species. We now know that neurochemical, connectional and functional heterogeneity of the neocortex accompanies the morphological divergence observed in such cytoarchitectonic studies. Nevertheless, we are yet far from fully understanding the biological significance of this cortical heterogeneity. In this article, we review our past works on the gene expression profiling of the postnatal primate cortical areas, by quantitative real-time polymerase chain reaction (PCR), DNA array, differential display PCR and in situ hybridization analyses. These studies revealed both the overall homogeneity of gene expression across different cortical areas and the presence of a small number of genes that show markedly area-specific expression patterns. In situ hybridization showed that, among such genes, occ1 and retinol-binding protein (RBP) mRNAs are selectively expressed in the neuronal populations that seem to be involved in distinct neural processing such as sensory reception (for occ1 ) and associative function (for RBP). Such a molecular neuroanatomical approach has the promise to provide an important link between structure and function of the cerebral cortex.     

The primate neocortex in comparative perspective using magnetic resonance imaging.

In this study we use neuroanatomic data from living anthropoid primate subjects to test the following three hypotheses: (1) that the human neocortex is significantly larger than expected for a primate of our brain size, (2) that the human prefrontal cortex is significantly more convoluted than expected for our brain size, and (3) that increases in cerebral white matter volume outpace increases in neocortical gray matter volume among anthropoid primates. Whole brain MRI scans were obtained from 44 living primate subjects from 11 different species. Image analysis software was used to calculate total brain volume, neocortical gray matter volume, cerebral white matter volume, and the cross sectional area of the spinal cord in each scan. Allometric regression analyses were used to compare the relative size of these brain structures across species, with an emphasis on determining whether human brain proportions correspond with predictions based on nonhuman primate allometric trajectories. All three hypotheses were supported by our analysis. The results of this study provide additional insights into human brain evolution beyond the important observation that brain volume approximately tripled in the hominid lineage by demonstrating that the neocortex was uniquely modified throughout hominid evolution. These modifications may constitute part of the neurobiological substrate that supports some of our species most distinctive cognitive abilities.     

Transcriptional and anatomical diversity of medium spiny neurons in the primate striatum

1. Download : Download high-res image (270KB)
2. Download : Download full-size image

     

The early postnatal nonhuman primate neocortex contains self-renewing multipotent neural progenitor cells

The postnatal neocortex has traditionally been considered a non-neurogenic region, under non-pathological conditions. A few studies suggest, however, that a small subpopulation of neural cells born during postnatal life can differentiate into neurons that take up residence within the neocortex, implying that postnatal neurogenesis could occur in this region, albeit at a low level. Evidence to support this hypothesis remains controversial while the source of putative neural progenitors responsible for generating new neurons in the postnatal neocortex is unknown. Here we report the identification of self-renewing multipotent neural progenitor cells (NPCs) derived from the postnatal day 14 (PD14) marmoset monkey primary visual cortex (V1, striate cortex). While neuronal maturation within V1 is well advanced by PD14, we observed cells throughout this region that co-expressed Sox2 and Ki67, defining a population of resident proliferating progenitor cells. When cultured at low density in the presence of epidermal growth factor (EGF) and/or fibroblast growth factor 2 (FGF-2), dissociated V1 tissue gave rise to multipotent neurospheres that exhibited the ability to differentiate into neurons, oligodendrocytes and astrocytes. While the capacity to generate neurones and oligodendrocytes was not observed beyond the third passage, astrocyte-restricted neurospheres could be maintained for up to 6 passages. This study provides the first direct evidence for the existence of multipotent NPCs within the postnatal neocortex of the nonhuman primate. The potential contribution of neocortical NPCs to neural repair following injury raises exciting new possibilities for the field of regenerative medicine.     

Three-dimensional analysis of nonhuman primate trabecular architecture using micro-computed tomography

Until recently, detailed analyses of the architecture of nonhuman primate cancellous bone have not been possible due to a combination of methodological constraints, including poor resolution imaging or destructive protocols. The development of micro-computed tomography (microCT) and morphometric methods associated with this imaging modality offers anthropologists a new means to study the comparative architecture of cancellous bone. Specifically, microCT will allow anthropologists to investigate the relationship between locomotor behavior and trabecular structure. We conducted a preliminary study on the trabecular patterns in the proximal humerus and femur of Hylobates lar, Ateles paniscus, Macaca mulatta, and Papio anubis to investigate the quantitative differences in their trabecular architecture and evaluate the potential of microCT in anthropological inquiry. MicroCT allows the researcher to evaluate variables beyond simple two-dimensional orientations and radiographic densities. For example, this methodology facilitates the study of trabecular thickness and bone volume fraction using three-dimensional data. Results suggest that density-related parameters do not reliably differentiate suspensory-climbing species from quadrupedal species. However, preliminary results indicate that measurements of the degree of anisotropy, a measure of trabecular orientation uniformity, do distinguish suspensory-climbing taxa from more quadrupedal species. The microCT method is an advance over conventional radiography and medical CT because it can accurately resolve micron-sized struts that make up cancellous bone, and from these images a wide array of parameters that have been demonstrated to be related to cancellous bone mechanical properties can be measured. Methodological problems pertinent to any comparative microCT study of primate trabecular architecture are discussed.     

Transcriptional regulation of human eosinophil RNases by an evolutionary- conserved sequence motif in primate genome

Background  

Human eosinophil-derived neurotoxin (edn) and eosinophil cationic protein (ecp) are members of a subfamily of primate ribonuclease (rnase) genes. Although they are generated by gene duplication event, distinct edn and ecp expression profile in various tissues have been reported.