Brainnetome: A new -ome to understand the brain and its disorders
Introduction
The human brain is the most complex network system in the world. It comprises about one hundred billion neurons, with thousands of trillions of connections between them. Its complexity is not only reflected in the numbers of neurons and connections, but also in how the brain is wired on different scales and how such patterns of their connections produce cognitive functions, thoughts, feelings, and behaviors. There have long been efforts to make a connection map of the brain, recently called the “Human Connectome” (Sporns et al., 2005). It is of central significance for understanding how the brain works at a detailed level and what happens when something goes wrong (Insel, 2010). A similar opinion can be traced back to an earlier study (Crick and Jones, 1993). Now, both the academic community and government are aware of its importance. This has been demonstrated by a number of programs and projects launched in different countries. The Human Connectome Project was launched by the National Institutes of Health in the USA. A similar project, CONNECT, was launched by the European Community.
Actually, the complex links within the human brain are presented in the physical (static) architecture as well as dynamic activity. Mathematically, a “network” can be used to model a system that contains multiple components interacting with one other. The neuroscience community refers “brain network” to the brain system that consists of relational units at different tempo-spatial scales. We strongly suggest that the unique features of networks (in the structural and dynamic view) are very important for brain science, so we proposed the brainnetome (Brain-net-ome) as a new “ome” in which the brain network is the basic research unit to investigate the hierarchy in human brain from genetics and neuronal circuits to behaviors. Since the two components of the brainnetome, nodes and their connections, can be defined at different scales with different techniques, the brainnetome is as complex as any other –ome, such as the genome and proteome. It includes at least the following five research themes: (1) Identification of Brain Networks. One goal of the brainnetome is to identify brain networks with multimodal neuroimaging techniques, from the finest scale (such as ultramicrotomy, and staining techniques), to the most macroscopic (such as functional MRI, diffusion MRI and electroencephalography); and to explore the relationships among them. In particular, a new human brain atlas beyond Brodmann's will be established by combining connectivity with cytoarchitecture and other information on the microscale. (2) Dynamics and Characteristics of Brain Networks. The brainnetome will investigate the dynamics and characteristics of brain networks during developmental, aging and evolutionary processes and how they are affected by such factors as learning, training, language, culture, diseases, and stimuli. (3) Network Manifestations of Functions and Malfunctions of the Brain. One unique characteristic of the brainnetome is to explore the core brain regions and their connectivity patterns for each cognitive function and to show how they are affected in neurological and psychiatric diseases, and by drugs and other stimuli. A specific goal is to explore how the symptoms of neurological and psychiatric diseases are due to altered brain networks. (4) Genetic Basis of Brain Networks. The brainnetome will investigate the effects of genetic variations on the brain networks associated with behaviors, cognitive functions or cognitive disorders. It will also explore the influence of genetic factors on the developmental processes of specific brain networks through twin and pedigree studies. Moreover, it will investigate the biological mechanisms by which genes modulate the brain networks with gene-modified animal models. (5) Simulating and Modeling for the brainnetome. An essential goal of the brainnetome is to simulate and model brain networks with informatics and simulation technologies to understand the basic organizing principles of the brain. To this end, it is necessary to develop theories and methodologies and to integrate the existing and new supercomputing hardware with software and visualization tools. The concept of the brainnetome has received impetus from a number of programs and projects in China. In 2010, a project with the same name (that is, the Brainnetome Project) was launched in China. Recently, the European Union has just launched the Human Brain Project and the USA is considering launching the “Brain Activity Mapping” Project. These two projects include the studies of neuronal circuits and brain networks. Table 1 lists some worldwide projects related to the brainnetome.
In this paper, we present the methodologies and advances of the brainnetome and focus on the studies in our laboratory. We first give a brief review of the methodologies used in the brainnetome, which include techniques on different scales, the brainnetome atlas, and the methods of brain network analysis. Then we take Alzheimer's disease and schizophrenia as examples to show how the brainnetome can be studied in neurology and psychiatry, called the clinical brainnetome. After that, we review studies of how risk genes for brain diseases affect brain networks. Finally, we give a perspective on the brainnetome.
Section snippets
Methodologies for the brainnetome
The human brain is a massively complex system with a hierarchy of different but tightly integrated levels of organisms: from gene, protein, synapse, neurons, and neuronal circuits, to brain areas, pathways and the whole brain. The brain network, in general, should be investigated at each of these levels. Here, we roughly define the macroscale as the level of brain areas and pathway, and the microscale as the level of genes, neurons and neural circuits. The brainnetome is proposed to
Clinical brainnetome
An increasing number of studies have revealed disturbances of the organized architecture of brain structure/function in various brain disorders (Bullmore, 2012). The malfunctioning of connections and brain networks may underlie many brain disorders. These network studies, especially those using modern imaging techniques in vivo, have revealed that brain disorders can, for the first time, be studied as abnormalities in the connections between brain areas, or as problems in the coordination of
Genetic basis for the brainnetome
Convergent evidence from multimodal imaging studies has demonstrated that brain networks are heritable both structurally and functionally (Meyer-Lindenberg, 2009). Specifically, a twin study based on diffusion MRI found that genetic factors may explain 40% to 80% of the observed variability of integrity in the white matter tracts (Chiang et al., 2011). A pedigree study reported that the heritability of functional connectivity within the default mode network can reach 42% (Glahn et al., 2010).
Perspectives
The human brain can be studied as hierarchical complex networks on different temporal and spatial scales. On the microscale level, recent evidence shows that the human brain functions by the interactions between neurons on different temporal and spatial scales. It is becoming increasingly apparent that such a network structure and dynamic interaction produce the physiological activity of the human brain and finally lead to human cognitive behavior. On the macroscale level, more and more
Acknowledgments
I thank Ming Song, Bing Liu, Yong Liu, Yuan Zhou, Bing Hou, Lingzhong Fan, Xin Zhang, Nianming Zuo, Yue Cui and Yong Fan for their help with manuscript preparation. I also thank Professors Iain Bruce and Sumner MacLean for the proof-reading of the manuscript. This work was partially supported by the National Key Basic Research and Development Program (973) (Grant No. 2011CB707800), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB02030300), and the
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