Periodic Reporting for period 2 - HESSP (Hippocampus Extracellular Space Simulator Project (HESSP))
Reporting period: 2022-09-01 to 2023-08-31
Understanding the human brain is one of the biggest scientific challenges of the 21st century, and this endeavour has led the European Union to launch the Human Brain Project (HBP) as a FET flagship project. However, even a flagship project such as the HBP cannot study all aspects of the human brain. One aspect that is not covered by the HBP is the extracellular space (ES). The ES of the brain is important in the field of neuropharmacology because it is key to the successful delivery of drugs to the neurons. Also, the importance of the metabolite clearance activity of the ES has led to proposing that a dysfunction of this process plays a role in neurodegenerative diseases. However, no initiative exists to create an ES simulation software that improves the research.
To address this lack of simulation software, the Hippocampus Extracellular Space Simulator Project (HESSP) has been executed. The HESSP’s goal is to develop a simulation software for how substances released by neurons and chemical substances that pass the blood-brain barrier diffuse through the ES. Specifically, the HESSP has developed a software that simulates the diffusion process denominated Hybrid Advanced Particles Simulator (HAPS). The HESSP is an interdisciplinary project that involves computer science, neuroscience and pharmacology, and it addresses the challenge of developing a software architecture to simulate a diffusion process highly complex due to its number of elements formed. The principal researcher had an advisory committee that includes Dr. Herman Moreno, professor Sabina Hrabetova and professor Charle Nicholson. The principal researcher returned to the University of Salamanca for 24 months (part-time employment) and work under the supervision of Dr. Juan M. Corchado and with the support professor Corchado’s research group BISITE.
This project focuses on three main objectives:
• O1. Create a model of the ES of the mouse hippocampus.
• O2. Create simulation software for substances in the mouse hippocampus.
• O3. Make predictions using the simulation software.
During the development of the project, an unexpected result has emerged, the numeric map principle (NMP). The NMP is an hypothesis that explains how the human brain is able to ground arithmetic symbols. It proposes that the human brain uses its navigational system to understand and generate arithmetic knowledge. Its potential impact in resolving the symbol ground problem in numerical cognition and connecting two different areas of cognitive neuroscience, navigation and numerical cognition, has motivated the creation of a fourth objective, O4.
• O4 Formulate, study, and diffuse the numeric map principle.
To address this lack of simulation software, the Hippocampus Extracellular Space Simulator Project (HESSP) has been executed. The HESSP’s goal is to develop a simulation software for how substances released by neurons and chemical substances that pass the blood-brain barrier diffuse through the ES. Specifically, the HESSP has developed a software that simulates the diffusion process denominated Hybrid Advanced Particles Simulator (HAPS). The HESSP is an interdisciplinary project that involves computer science, neuroscience and pharmacology, and it addresses the challenge of developing a software architecture to simulate a diffusion process highly complex due to its number of elements formed. The principal researcher had an advisory committee that includes Dr. Herman Moreno, professor Sabina Hrabetova and professor Charle Nicholson. The principal researcher returned to the University of Salamanca for 24 months (part-time employment) and work under the supervision of Dr. Juan M. Corchado and with the support professor Corchado’s research group BISITE.
This project focuses on three main objectives:
• O1. Create a model of the ES of the mouse hippocampus.
• O2. Create simulation software for substances in the mouse hippocampus.
• O3. Make predictions using the simulation software.
During the development of the project, an unexpected result has emerged, the numeric map principle (NMP). The NMP is an hypothesis that explains how the human brain is able to ground arithmetic symbols. It proposes that the human brain uses its navigational system to understand and generate arithmetic knowledge. Its potential impact in resolving the symbol ground problem in numerical cognition and connecting two different areas of cognitive neuroscience, navigation and numerical cognition, has motivated the creation of a fourth objective, O4.
• O4 Formulate, study, and diffuse the numeric map principle.
The main goal of the HESSP is developing a software to simulate the diffusion of substance through nervous tissue, the Hybrid Advanced Particles Simulator (HAPS). The HESSP project started in September 2020. During the first and second year of the project, Dr Miguel-Tomé worked on creating a model of the ES of the mouse hippocampus by designing data structures so that the simulator can cover different morphological models of nervous tissue and programming algorithms to generate the geometry of it. In addition, a graphical interface to show the geometry of the environment was implemented. Figure 1 shows the graphical interface created to allow the user visualising a geometrical environment where to simulate a diffusion process. The software developed has a graphical interface to configurate a simulation (i.e. Fig 3) and a graphical interface that lets the user observe the diffusion process of substances and visualise the data of the experiments performed with the simulation.The software developed has a graphical interface to configurate a simulation (i.e. Fig 3) and a graphical interface that lets the user observe the diffusion process of substances (i.e. Figure 4) and visualise the data of the experiments performed with the simulation (i.e. Figure 5).
In addition to working on the HESSP project goals, Dr Miguel Tomé experienced an unexpected result during the project. Dr. MIguel-Tomé generated a hypothesis about the functioning of the hippocampus for numerical cognition, the numeric map principle.
During the first and second year of the incoming phase the research work has been focused on two tasks: developing HAPS and researching the numerical map principle. The development of HAPS consisted in adding new features dedicated to calculate the volume fraction and tortuosity parameters. It has required studying the simplex algorithm and implementing a version to resolve the equation that determines the diffusion of particles through an empty environment. Also, it has been added a graphical user interface that allows users knowing the values calculated for those parameters. The research carried out on the numerical map principle was focused on review the literature of two research areas within cognitive neuroscience, navigation and numerical cognition, and it was necessary to search for studies that supported the predictions derived from the numerical map principle. During this process, Dr. Miguel-Tomé reviewed 804 articles and books. The results obtained for study about the numeric map principle have been synthesized in an article, which is titled “The Numeric Map Principle: A Navigational-Based Hypothesis to Explain the Human Skills to Perform and Understand Basic Arithmetic.” The final article is 71 pages long.
In addition to working on the HESSP project goals, Dr Miguel Tomé experienced an unexpected result during the project. Dr. MIguel-Tomé generated a hypothesis about the functioning of the hippocampus for numerical cognition, the numeric map principle.
During the first and second year of the incoming phase the research work has been focused on two tasks: developing HAPS and researching the numerical map principle. The development of HAPS consisted in adding new features dedicated to calculate the volume fraction and tortuosity parameters. It has required studying the simplex algorithm and implementing a version to resolve the equation that determines the diffusion of particles through an empty environment. Also, it has been added a graphical user interface that allows users knowing the values calculated for those parameters. The research carried out on the numerical map principle was focused on review the literature of two research areas within cognitive neuroscience, navigation and numerical cognition, and it was necessary to search for studies that supported the predictions derived from the numerical map principle. During this process, Dr. Miguel-Tomé reviewed 804 articles and books. The results obtained for study about the numeric map principle have been synthesized in an article, which is titled “The Numeric Map Principle: A Navigational-Based Hypothesis to Explain the Human Skills to Perform and Understand Basic Arithmetic.” The final article is 71 pages long.
The HAPS will help us to better understand ES and to develop a new tool to examine the role of ES both in the nervous system and in the release of drugs. The software will help to improve our understanding of volume transmission, and the software architecture could be used in other scientific fields for systems that cannot be simulated in a direct way because of memory hardware requirements.
It is hoped that its graphical interface feature will attract the interest of researchers in the software being developed. The tool could help to researchers to make numerical predictions based on hypotheses about the extracelular space and the nervous tissue. It would also provide a proof of concept for the formulated simulation architecture that could be applied to other scientific fields.
The code completed to date for the HAPS will be exploited through collaboration with Professor Nicholson; this work will involve incorporating new features and design experiments in silico to research the extracellular space.
For his secondment, Dr Miguel-Tomé has conceived an hypothesis about the function of the hippocampus and its role in numerical cognition, the numeric map prinicple. The numeric map principle opens a completely new line of research in numerical cognition that involves designing experiments to test it and develop its implications to understand the human brain. If the numeric map principle is confirmed, it will require a campaign of diffusion for the scientific community and the larger society since it will have important implications ranging from cognitive neuroscience research to education.
It is hoped that its graphical interface feature will attract the interest of researchers in the software being developed. The tool could help to researchers to make numerical predictions based on hypotheses about the extracelular space and the nervous tissue. It would also provide a proof of concept for the formulated simulation architecture that could be applied to other scientific fields.
The code completed to date for the HAPS will be exploited through collaboration with Professor Nicholson; this work will involve incorporating new features and design experiments in silico to research the extracellular space.
For his secondment, Dr Miguel-Tomé has conceived an hypothesis about the function of the hippocampus and its role in numerical cognition, the numeric map prinicple. The numeric map principle opens a completely new line of research in numerical cognition that involves designing experiments to test it and develop its implications to understand the human brain. If the numeric map principle is confirmed, it will require a campaign of diffusion for the scientific community and the larger society since it will have important implications ranging from cognitive neuroscience research to education.