Computational analysis of functional connectivity between areas of primate cerebral cortex

Recent analyses of association fibre networks in the primate cerebral cortex have revealed a small number of densely intra-connected and hierarchically organized structural systems. Corresponding analyses of data on functional connectivity are required to establish the significance of these structural systems. We therefore built up a relational database by systematically collating published data on the spread of activity after strychnine-induced disinhibition in the macaque cerebral cortex in vivo. After mapping these data to two different parcellation schemes, we used three independent methods of analysis which demonstrate that the cortical network of functional interactions is not homogeneous, but shows a clear segregation into functional assemblies of mutually interacting areas. The assemblies suggest a principal division of the cortex into visual, somatomotor and orbito-temporo-insular systems, while motor and somatosensory areas are inseparably interrelated. These results are largely compatible with corresponding analyses of structural data of mammalian cerebral cortex, and deliver the first functional evidence for 'small-world' architecture of primate cerebral cortex.     

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 in vivo and in vitro. 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.     

Dispersion of the neurons expressing layer specific markers in the reeler brain

Neurons with similar functions including neuronal connectivity and gene expression form discrete condensed structures within the vertebrate brain. This is exemplified within the circuitry formed by the cortical layers and the neuronal nuclei. It is well known that the Reelin protein is required for development of these neuronal structures in rodents and human, but the function of Reelin remains controversial. In this report, we used “layer‐specific markers” of the cerebral cortex to carry out detailed observations of spatial distribution of the neuronal subpopulations in the brain of the Reelin deficient mouse, reeler. We observed a spatially dispersed expression of the markers in the reeler cerebral cortex. These markers are expressed also in other laminated and non‐laminated structures of brain, in which we observed similar abnormal gene expression. Our observations suggest that neurons within the brain structures (such as the layers and the nuclei), which normally exhibit condensed distribution of marker expressions, loosen their segregation or scatter by a lack of Reelin.     

Genetic mechanisms specifying cortical connectivity: let's make some projections together

Great neuroanatomists of the twentieth century recognized that the cerebral cortex of mammals is the single most complex structure of the central nervous system both in terms of neuronal diversity and connectivity. Understanding the cellular and molecular mechanisms specifying the afferent and efferent connectivity in the neocortex may seem like a daunting task. However, recent technical advances have greatly improved our ability to (1) profile gene expression of neuronal populations isolated based on their connectional properties, (2) manipulate gene expression in specific neuronal populations, and (3) visualize their axonal projections in vivo. These new tools are revolutionizing our ability to identify the molecular mechanisms patterning afferent and efferent cortical projections.     

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.     

Cortical Folding of the Primate Brain: An Interdisciplinary Examination of the Genetic Architecture,Modularity, and Evolvability of a Significant Neurological Trait in Pedigreed Baboons (Genus Papio)

Folding of the primate brain cortex allows for improved neural processing power by increasing cortical surface area for the allocation of neurons. The arrangement of folds (sulci) and ridges (gyri) across the cerebral cortex is thought to reflect the underlying neural network. Gyrification, an adaptive trait with a unique evolutionary history, is affected by genetic factors different from those affecting brain volume. Using a large pedigreed population of ∼1000 Papio baboons, we address critical questions about the genetic architecture of primate brain folding, the interplay between genetics, brain anatomy, development, patterns of cortical–cortical connectivity, and gyrification’s potential for future evolution. Through Mantel testing and cluster analyses, we find that the baboon cortex is quite evolvable, with high integration between the genotype and phenotype. We further find significantly similar partitioning of variation between cortical development, anatomy, and connectivity, supporting the predictions of tension-based models for sulcal development. We identify a significant, moderate degree of genetic control over variation in sulcal length, with gyrus-shape features being more susceptible to environmental effects. Finally, through QTL mapping, we identify novel chromosomal regions affecting variation in brain folding. The most significant QTL contain compelling candidate genes, including gene clusters associated with Williams and Down syndromes. The QTL distribution suggests a complex genetic architecture for gyrification with both polygeny and pleiotropy. Our results provide a solid preliminary characterization of the genetic basis of primate brain folding, a unique and biomedically relevant phenotype with significant implications in primate brain evolution.     

Rich Club Organization of Macaque Cerebral Cortex and Its Role in Network Communication

Graph-theoretical analysis of brain connectivity data has revealed significant features of brain network organization across a range of species. Consistently, large-scale anatomical networks exhibit highly nonrandom attributes including an efficient small world modular architecture, with distinct network communities that are interlinked by hub regions. The functional importance of hubs motivates a closer examination of their mutual interconnections, specifically to examine the hypothesis that hub regions are more densely linked than expected based on their degree alone, i.e. forming a central rich club. Extending recent findings of rich club topology in the cat and human brain, this report presents evidence for the existence of rich club organization in the cerebral cortex of a non-human primate, the macaque monkey, based on a connectivity data set representing a collation of numerous tract tracing studies. Rich club regions comprise portions of prefrontal, parietal, temporal and insular cortex and are widely distributed across network communities. An analysis of network motifs reveals that rich club regions tend to form star-like configurations, indicative of their central embedding within sets of nodes. In addition, rich club nodes and edges participate in a large number of short paths across the network, and thus contribute disproportionately to global communication. As rich club regions tend to attract and disperse communication paths, many of the paths follow a characteristic pattern of first increasing and then decreasing node degree. Finally, the existence of non-reciprocal projections imposes a net directional flow of paths into and out of the rich club, with some regions preferentially attracting and others dispersing signals. Overall, the demonstration of rich club organization in a non-human primate contributes to our understanding of the network principles underlying neural connectivity in the mammalian brain, and further supports the hypothesis that rich club regions and connections have a central role in global brain communication.     

综述: 大脑新皮层和神经发育疾病

哺乳动物进化过程中,大脑皮层逐渐增大增厚和脑容量增大,从而构成了脑神经环路复杂性的细胞生物学基础.皮层出现皱褶是非人类灵长类演化的重要特征.成体人脑大约由近860多亿个神经细胞组成,其中,在人脑神经发生高峰,每小时有近400多万个兴奋性神经细胞产生.如此高速的神经生成过程需要精确的细胞与分子调控机制.本文主要讨论调控大脑皮层增大增厚的细胞与分子机制和相关的脑发育疾病.     

The case for primate V3

The visual system in primates is represented by a remarkably large expanse of the cerebral cortex. While more precise investigative studies that can be performed in non-human primates contribute towards understanding the organization of the human brain, there are several issues of visual cortex organization in monkey species that remain unresolved. In all, more than 20 areas comprise the primate visual cortex, yet there is little agreement as to the exact number, size and visual field representation of all but three. A case in point is the third visual area, V3. It is found relatively early in the visual system hierarchy, yet over the last 40 years its organization and even its very existence have been a matter of debate among prominent neuroscientists. In this review, we discuss a large body of recent work that provides straightforward evidence for the existence of V3. In light of this, we then re-examine results from several seminal reports and provide parsimonious re-interpretations in favour of V3. We conclude with analysis of human and monkey functional magnetic resonance imaging literature to make the case that a complete V3 is an organizational feature of all primate species and may play a greater role in the dorsal stream of visual processing.     

Decreased Thalamocortical Functional Connectivity after 36 Hours of Total Sleep Deprivation: Evidence from Resting State fMRI

Objectives

The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections, which hold a key function in segregating internally and externally directed awareness information. Previous task-related studies have revealed altered activities of the thalamus after total sleep deprivation (TSD). However, it is still unclear how TSD impacts on the communication between the thalamus and cerebral cortex. In this study, we examined changes of thalamocortical functional connectivity after 36 hours of total sleep deprivation by using resting state function MRI (fMRI).

Materials and Methods

Fourteen healthy volunteers were recruited and performed fMRI scans before and after 36 hours of TSD. Seed-based functional connectivity analysis was employed and differences of thalamocortical functional connectivity were tested between the rested wakefulness (RW) and TSD conditions.

Results

We found that the right thalamus showed decreased functional connectivity with the right parahippocampal gyrus, right middle temporal gyrus and right superior frontal gyrus in the resting brain after TSD when compared with that after normal sleep. As to the left thalamus, decreased connectivity was found with the right medial frontal gyrus, bilateral middle temporal gyri and left superior frontal gyrus.

Conclusion

These findings suggest disruptive changes of the thalamocortical functional connectivity after TSD, which may lead to the decline of the arousal level and information integration, and subsequently, influence the human cognitive functions.     

Analysis of Nonlinear Gene Expression Progression Reveals Extensive Pathway and Age-Specific Transitions in Aging Human Brains

Several recent gene expression studies identified hundreds of genes that are correlated with age in brain and other tissues in human. However, these studies used linear models of age correlation, which are not well equipped to model abrupt changes associated with particular ages. We developed a computational algorithm for age estimation in which the expression of each gene is treated as a dichotomized biomarker for whether the subject is older or younger than a particular age. In addition, for each age-informative gene our algorithm identifies the age threshold with the most drastic change in expression level, which allows us to associate genes with particular age periods. Analysis of human aging brain expression datasets from three frontal cortex regions showed that different pathways undergo transitions at different ages, and the distribution of pathways and age thresholds varies across brain regions. Our study reveals age-correlated expression changes at particular age points and allows one to estimate the age of an individual with better accuracy than previously published methods.     

灵长类比较基因组学的研究进展

随着人类和黑猩猩全基因组测序工作宣布完成,以及其他灵长类基因组测序工作的逐步开展,目前已经积累了大量的灵长类基因组数据,一个崭新的研究领域——灵长类比较基因组学应运而生。该文主要通过对人类和其他非人灵长类系统关系和基因组结构的比较,从系统进化、基因组结构和基因表达调控等方面评述该领域的研究进展,阐述人类、黑猩猩与其他非人灵长类之间的主要生物学差异,揭示人类进化的生物学机制。     

Positive selection in ASPM is correlated with cerebral cortex evolution across primates but not with whole-brain size

The rapid increase of brain size is a key event in human evolution. Abnormal spindle-like microcephaly associated (ASPM) is discussed as a major candidate gene for explaining the exceptionally large brain in humans but ASPM's role remains controversial. Here we use codon-specific models and a comparative approach to test this candidate gene that was initially identified in Homo-chimp comparisons. We demonstrate that accelerated evolution of ASPM (omega = 4.7) at 16 amino acid sites occurred in 9 primate lineages with major changes in relative cerebral cortex size. However, ASPM's evolution is not correlated with major changes in relative whole-brain or cerebellum sizes. Our results suggest that a single candidate gene such as ASPM can influence a specific component of the brain across large clades through changes in a few amino acid sites. We furthermore illustrate the power of using continuous phenotypic variability across primates to rigorously test candidate genes that have been implicated in the evolution of key human traits.     

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

Background  

The 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.     

Focusing on comparative ape population genetics in the post-genomic age

The initial human and chimpanzee genome sequences have been published, and additional primate genomes, including those of gorilla and orang-utan, are in progress. With these new resources, we can now address what makes our species unique, by focusing on the underlying genetic differences associated with phenotypes. Comparative primate population genomics, including studies of structural changes, mobile elements, gene expression and functional analyses, will shed light on how natural selection and population demography are involved in the processes that lead to differences among great apes. Historically, this research has focused on the human perspective; however, we will learn much about ourselves with a focus on genomic diversity in hominoids as a group.