The brain is the source of human wisdom. Relying on the unique structure of the brain and human body, human beings have become creatures with advanced intelligence, created agricultural civilization, industrial civilization, and are moving towards ecological civilization.
In order to understand the mysteries of the brain, it is necessary to study and clarify the working principles and mechanisms of the brain and nervous system, and develop artificial intelligence based on this. However, human knowledge and understanding of the brain has been very limited. In 2021, the American “Science” magazine published 125 cutting-edge scientific issues in the world, 16 of which are closely related to brain science, such as “where does consciousness exist”, “where does human emotion come from”, “why do people need sleep” wait. So far, nearly one-third of the Nobel Prizes in Physiology or Medicine have been related to brain science, which shows that brain science is not only the key to unraveling the mystery of human innovation and creation, but also the cornerstone of advancing human civilization into an ecological civilization.
There are about 100 billion neurons in the human brain. Only by understanding how they form intricate neural networks and generate creative thinking through synaptic connections, can we combine the achievements of brain science with artificial intelligence, the Internet, big data, cloud computing, etc. Technology is combined to create more material wealth and a higher form of human civilization.
Countries around the world are investing in brain projects
In January 2013, the European Union announced that it would invest 1 billion euros to launch the EU Human Brain Project (HBP), which will involve 135 partner institutions from 26 countries and is expected to last for 10 years. In April 2013, the United States announced that it would invest 3.8 billion U.S. dollars to start the U.S. Brain Research Program (abbreviated as the American Brain Program) – Innovative Neurotechnology Brain Research Program (BRAIN Initiative).
In March 2016, the “13th Five-Year Plan” issued by China listed “Brain Science and Brain-Inspired Research” as a “National Major Scientific and Technological Innovation and Engineering Project”, and officially proposed the “China Brain Project”. In September 2021, the Ministry of Science and Technology of China issued the “Science and Technology Innovation 2030 – 2021 Project Application Guidelines for Major Projects of “Brain Science and Brain-Inspired Research”, officially launching the China Brain Project. The national appropriation budget is nearly 3.2 billion yuan, and the overall scale of the plan is expected to reach 10 billion yuan.
The brain projects of the European Union, the United States and China represent the depth and breadth of today’s brain research. Therefore, from these three brain projects, we can understand the overall picture, important content, substance and progress of today’s cutting-edge human brain projects.
EU’s Brain Project – Simulating Brain Functions
The European Union’s brain plan was put forward earlier and more comprehensive. The original program included 12 sub-programmes:
1. Understanding the mouse brain structure and its electrochemical functions;
2. Understanding the human brain structure and its electrochemical functions;
3. Understanding how the brain performs its system-level and cognitive functions ( Systems and Cognitive Neuroscience);
4. Deriving advanced mathematical models to draw conclusions from research data (Theoretical Neuroscience);
5. Collecting, organizing, and presenting brain data;
6. Building brain simulation platforms;
7. Building brain complexes 8. Research and
understand the distribution of brain diseases and their respective disease characteristics;
9. Develop and apply brain-inspired computing technologies;
10. Develop virtual robots and real robots, and develop brain-simulated test environments;
11. Manage and coordinate the implementation of the Brain Project;
12. Explore the ethical and social implications of the Brain Project.
The EU’s brain project has also been criticized by some EU countries and researchers. On July 7, 2014, 154 European researchers sent an open letter to the European Commission, arguing that the research scope of the plan was too narrow, so the EU made some adjustments to the plan.
In the past 10 years, what achievements has the EU’s brain project achieved?
In the European Union’s Brain Project, the most important research content originated from a brain science research project called “Blue Brain Project”. The project started in 2005 with the aim of artificially simulating the mammalian brain for the treatment of Alzheimer’s and Parkinson’s diseases. Because researchers used IBM’s Blue Gene computer (capable of 22.8 trillion floating-point operations per second) to simulate various mechanisms of the brain, it was named the Blue Brain Project.
In 2013, the European Union expanded on the basis of the Blue Brain Project and proposed a 10-year EU Human Brain Project. The project, led by Henry Markram, uses supercomputers to simulate artificial neural network models and reverse engineer mammalian brains with experimental data. Scientists hope to discover the nature of consciousness through this challenging research project.
In this project, the scientists focused their research on the cerebral cortex unit. The cortical unit is a structure unique to the mammalian brain, also called the neocortex, which is involved in all cognitive and emotional functions. Initially, the researchers simulated the neocortical column of the rat brain and believed that this is the smallest functional unit of the neocortex, which is responsible for higher functions such as consciousness and thinking. A rat neocortical column contains about 10,000 neurons and 10 synapses . Although similar to the rat brain, the neocortex of the human brain is larger and more complex, with each cylinder about 2 millimeters long and 0.5 millimeters in diameter, containing about 60,000 neurons.
In November 2007, during the Blue Brain Project phase, researchers established a data-driven process for creating, validating, and studying neocortical columns. In 2008, researchers built the first neocortical column of artificial cells composed of 10,000 nerve cells. In July 2011, the program already had a central circuit of cells consisting of 100 neocortical columns containing 1 million nerve cells.
In 2014, after the launch of the European Union’s Human Brain Project, researchers built a mouse brain model that contained 100 central circuits, totaling 100 million nerve cells. At that time, researchers predicted that a similar human brain model could be built in 2023, and the total number of cells would reach 100 billion, equivalent to the total number of cells in 1,000 mouse brains. In fact, that’s the size of the average human brain.
On the other hand, in 2015, scientists from the Swiss Federal Institute of Technology in Lausanne, participating in the European Union’s Human Brain Project, built a quantitative model that revealed a previously unknown relationship between glial cells, astrocytes, and neurons in the brain. This model describes the energy management of the brain through the function of the glial vascular unit (NGV).
In 2017, researchers from the European Union’s Human Brain Project discovered that there are as many as 11 levels of connections between clusters of neurons. As a result, Mark Ram, the project leader, believes that part of the reason why we are currently struggling to understand the brain’s “network mechanism” is that the mathematical methods usually used to study networks cannot detect enough layers. Therefore, the next step for the researchers is to model the neural network using algebraic topology.
In 2018, the EU Human Brain Project released the first digital 3D brain cell atlas. This progress is like going from hand-drawn maps to “Google Earth”, providing information on the main cell types, numbers and locations of 737 regions of the brain. In 2019, the researchers of the project have completed all the rat cerebral cortex maps, and the virtual EEG experiment is about to begin. However, using supercomputers to establish and simulate human brain functions and understand the operating mechanism of the brain still faces great challenges.
The results of the European Union’s Human Brain Project do not stop there, and progress has also been made in other areas. The EU Human Brain Project has established six informatics and communication technology platforms including neuroinformatics, brain simulation, neurocomputing, neuromorphic computing, artificial intelligence robots and medical big data, allowing scientists from various countries to share, edit and simulate brain research data.
In the past 10 years, some European countries have successively released a lot of research results in brain science. For example, the Dutch Depression and Anxiety Research (NESDA) has collected more than 3,000 depression and anxiety patients’ data, which is helpful for understanding and preventing depression, Anxiety Disorders provides information on psychology, sociology, biology and genetics. At the same time, the UK Biobank established by the UK is by far the largest human health resource bank in the world, containing the data of 500,000 volunteers aged 40 to 69 in the UK, not only involving genetics, environment and other major human diseases. There is also a large amount of information about the brain for scientists to analyze and study.
American Brain Project—Open Brain Project 2.0
The American Brain Project is led by the National Institutes of Health (NIH), and the participants include not only American research institutions such as the Salk Institute for Biological Studies, Duke University, Massachusetts Institute of Technology, and Harvard University, but also representatives from many countries and regions around the world. Area universities and research institutes.
The American Brain Project is currently divided into two phases, and it is expected that the third and fourth phases will be developed as the research progresses. The first phase of the project is called the “Brain Plan Cell Census Consortium” (BICCC), which was officially launched in 2014. It mainly develops high-throughput, high-precision research tools to characterize the brain and classify brain cells. The main tasks of the American Brain Project focus on seven aspects: discover the diversity of neurons and glial cell types; draw multi-scale maps from synapses to the whole brain; develop and apply methods for large-scale monitoring of neuronal activity; Prove the causal relationship between brain activity and behavior; confirm the basic working principles of the brain; promote the development of human neuroscience; explore how neural activity patterns are translated into emotional cognitive mechanisms.
In 2017, the BICCC project expanded into the “Brain Plan Cell Census Network” (BICCN). On the basis of integrating the molecular, morphological, physiological and anatomical characteristics of brain cells, the project further optimizes the classification of brain cells, and identifies and numbers different types of cells in the mammalian brain.
No matter what kind of organ, its basic unit is cells. Only by understanding the composition of brain cells can we better understand the working mechanism of the brain and further explore the pathogenesis of related diseases. The brain cell census is to understand and understand all brain cells, record their shape, characteristics, quantity, location, bioelectrical signals and other comprehensive information, and finally compile the obtained information into maps and catalogs. So the job is sort of like a census.
Now, the work on the first phase of the American Brain Project has come to fruition. Researchers have completed mapping the primary motor cortex in humans and some other mammalian brains, with the main results published in the October 6, 2021, issue of the journal Nature. This atlas is a molecular-level map of the cell type characteristics of the mammalian primary motor cortex, and it is also the most comprehensive and detailed map of the mammalian brain to date.
According to the researchers, through large-scale analysis of single-cell transcriptome, chromatin accessibility, DNA methylome, spatially resolved single-cell transcriptome, morphological and electrophysiological properties, and through cross-modal computational analysis Integration, completes the primary product of BICCN.
This achievement can improve the overall knowledge and understanding of the organization of brain cell types. For example, it can reveal the unified molecular genetic background of cerebral cortex cell types; provide a spatially resolved cell type map of motor cortex; prove the biological validity and genomic basis of neurons; find that intracerebral (IT) cells are primary motor cortex The largest neuron branch.
The researchers also found that clusters of cells in the brain that secrete GABA also showed a lamellar distribution. Among nonneuronal cell clusters, vascular leptomeningeal cells (VLMCs) form the outermost layer of cells in the cerebral cortex. Mature oligodendrocytes and some astrocytes are enriched in white matter (in the deep part of the cerebral cortex, also known as the medulla). Other subtypes of non-neuronal cells are basically scattered throughout the layers of the brain. In conclusion, neuronal and non-neuronal cell populations in the primary motor cortex form complex spatial distributions. The complex spatial organization formed by the primary motor cortex completes the traditionally defined cortical layers. Furthermore, the projections of primary motor cortex neurons did not follow a simple “one cell type to one target area” pattern, but formed a complex many-to-many projection network.
The first phase of the American Brain Project not only achieved the above-mentioned achievements, but also promoted some researches on brain diseases. Data such as neuropsychology provide a research platform for studying long-term changes in adolescent cognitive function and childhood brain diseases such as autism. The ENIGMA project in the United States collected the brain imaging scan data and genetic data of more than 30,000 people. It is the world’s largest brain map project and a part of the American Brain Project. With this data, medical institutions can better screen patients with autism, depression or Alzheimer’s disease and provide early diagnosis.
In 2022, the second phase of the American Brain Project will be officially launched. The main research work is to describe the “Brain Project Whole Cell Atlas Network” (BICAN), with the goal of drawing a complete map of human brain cell types within the next five years. The task at this stage is also known as “Brain Project 2.0”, including three major research topics: drawing a comprehensive human brain whole-cell map; constructing a mammalian brain micro-connectivity map; developing tools and methods for precisely targeting various types of cells in the brain. technology.
Specifically, the Brain Project 2.0 is to draw a whole-cell map of the human brain from birth, development to maturity, aging and other stages, and at the same time describe the influence of different races, different living habits and other factors on the whole-cell map of the human brain. Therefore, the completion of the human brain whole-cell atlas can provide more and better clues for the study of brain-related diseases, and provide help for the study of the pathogenesis and prevention of neurodegenerative diseases, dementia, mental diseases, and addiction diseases.
The National Institutes of Health of the United States will invest more than US$500 million in the Brain Project 2.0. In addition to drawing the whole cell map of the human brain, it will also develop tools and technologies that accurately target various types of cells in the brain, and develop viral vectors and lipid nanoparticles. , to target and tune specific types of brain cells. In addition, scientists will study hundreds of human brains.
As a result, America’s Brain Project 2.0 is likely to see more breakthroughs in the next few years (to 2027).
China Brain Project—Strive for International Leading Achievements
The China Brain Project focuses on the analysis of the principles of brain cognition, major brain diseases related to cognitive impairment, brain-inspired computing chips and brain-computer intelligent robots, research on the brain intelligence development of children and adolescents, and the construction of technology platforms.
According to the “Science and Technology Innovation 2030-“Guidelines for the 2021 Annual Project Application of Major Projects of “Brain Science and Brain-Inspired Research”” published by the Ministry of Science and Technology in 2021, relevant institutions in my country have deployed 59 research projects, such as the origin, differentiation and aging process of nerve cells ; new non-invasive brain-computer interface technology; brain mechanism of infant social emotion and communication ability development; new technology of multi-modal and multi-scale brain map research, etc. The China Brain Project will achieve world-leading results in the three frontier fields of brain science, early diagnosis and intervention of brain diseases, and brain-inspired smart devices.
At present, the China Brain Project has proposed a specific task goal in the early stage:
through the establishment of a large multi-dimensional database of Chinese brain health, combined with multi-modal data such as genetics, imaging, and symptomology, and using a shared computing and analysis platform, to establish several recognition methods. Accurate early diagnosis standards and intervention methods for cognitive impairment-related severe brain diseases, and strive to make Chinese research evidence more than 1/3 of the international clinical guidelines for autism, depression, dementia and other diseases; by drawing the phenotype spectrum of severe brain diseases
, Developed internationally leading new technologies for early diagnosis, effective treatment and disease recurrence early warning system to achieve early prevention, early diagnosis and early treatment of brain diseases; relying on clinical cohort studies and databases, with the help of molecular biology, bioinformatics
and The rapid development of imaging and other disciplines has comprehensively analyzed the pathogenesis of brain diseases at multiple levels such as molecules, neural circuits, neural networks, and disease populations.
Since the China Brain Project focuses on the prevention and treatment of brain diseases, three sub-tasks have been set up in the direction of diagnosis and treatment of brain diseases: research on childhood diseases such as autism, adult diseases such as depression, and geriatric diseases such as dementia. Each subtask has a specific research goal: increase the diagnosis rate and effective treatment rate of autism by 40%; The disability rate is reduced by 20%; early warning of dementia is realized, the occurrence of the disease is delayed, and the quality of life is improved. At the same time, in the first 5-year mission period of the China Brain Project, strive to build a large multi-dimensional database of Chinese brain health; develop a brain health risk prediction model suitable for the Chinese population, as well as individualized early diagnosis, treatment plans and comprehensive intervention models.
At present, brain diseases related to cognitive impairment have surpassed tumors and cardiovascular diseases in the “burden ranking”. About 970 million people worldwide suffer from brain diseases, accounting for more than 13% of the world’s total population. In China, there are about 240 million people with mental disorders, and the prevalence rate is as high as 17.5%, among which the prevalence rate of autism is 0.7%, and the prevalence rate of depression is 3% to 5%. The prevalence of Parkinson’s disease is 0.7% to 22%; among the elderly over 65 years old, the prevalence of Parkinson’s disease is 1.7%.
In addition, brain disease is also the disease with the highest disability rate and fatality rate in my country. 90% of suicide victims suffer from brain diseases related to cognitive impairment. In recent years, Alzheimer’s disease has shown a younger trend in my country. However, there is still a lack of effective means of preventing, diagnosing and treating brain diseases. Therefore, preventing, diagnosing and treating various brain diseases is an extremely important task in the China Brain Project.
The EU’s Brain Project focuses on simulating brain functions through supercomputer technology to achieve artificial intelligence. The American Brain Project focuses on exploring the working mechanism of the human brain and developing treatments for incurable diseases of the brain. The goal of the China Brain Project is to achieve internationally leading results in the three frontier fields of brain science, early diagnosis and intervention of brain diseases, and brain-like smart devices within 15 years (2016-2030) after the plan is proposed.
Although the goals are different, it can be seen from the brain projects of the European Union, the United States and China that brain science is the key field of future biomedicine and artificial intelligence research. I believe that in the near future, with the joint efforts of scientists from all over the world, breakthroughs will be made in brain science-related disciplines, and more patients with brain damage and brain diseases and their families will benefit from it.