SIMULATIO Project

Computational simulation of the neurodegenerative mechanisms in Alzheimer's disease: decoding the alterations of the neuronal network

The overall objective of the project is to investigate and computationally simulate alterations in the neural network caused by brain injuries involved in the different stages of dementia due to Alzheimer's disease using magnetoencephalography (MEG) and electroencephalography (EEG) signals

This Project is funded by "Ministerio de Ciencia, Innovación y Universidades, Agencia Estatal de Investigación" and cofunded with Structural Funds of the European Union within the thematic objective "Promote technological development, innovation and quality research"

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Coordination
Partnership - Collaborator Groups

GIB-UVa

The group responsible for this project is the Biomedical Engineering Group of the University of Valladolid (GIB). GIB is a multidisciplinary group, mainly formed by Telecommunication Engineers and Doctors of different specialties (pneumology, neurology, psychiatry, neurophysiology, and ophthalmology). Its members have a wide experience in brain signal processing to help the diagnosis of different neurological diseases.

Jesús Poza Crespo – jesus.poza@tel.uva.es

Hospital Río Hortega

The Río Hortega University Hospital (HURH) is a public center of the Regional Health Management of Castile and Leon. The Department of Neurology and Neurophysiology has an extensive experience in the diagnosis and treatment of Alzheimer's disease.

Grupo de Telemática e Imagen

Telematics and Image Group (GTI) is a multidisciplinary research group of the University of Valladolid. Its objective is to contribute and promote research in the fields of Artificial Vision, e-Health, e-Learning and Intelligent Transportation Systems.

Hokuto Hospital

Hokuto Hospital is located on the island of Hokkaidō (Japan). They have extensive research experience aimed at improving medical care. Since 2004, they use magnetoencephalography (MEG) system for clinical medicine and basic research.

VU University

The Vrije Universitetit (VU) in Amsterdam is a university characterized by a high level of academic research, which encourages free and open communication and ideas. They have a great experience in neuroscience, with pioneer scientists worldwide.

Ottawa University

The Royal’s Institute of Mental Health Research (IMHR), affiliated with the University of Ottawa, is one of Canada’s leading research institutes focused on mental health. They are strongly focused on advancing prevention and early intervention strategies to help stop mental illness before it begins.

Goethe University

Goethe University is one of the leading research universities in Germany, which operates at a leading international level in numerous research fields. His research is supported by both excellent individual projects and excellent collaborative research.

Our Goals

The fundamental objective of the project is to investigate and computationally simulate the alterations in the neural network caused by the brain lesions involved in the different stages of dementia due to AD using MEG and EEG signals.

Specific objectives

Representative sample - SO1

To obtain a representative data set, which allows us to computationally simulate the neurodegeneration mechanisms associated with the progression of dementia due to Alzheimer's disease.

Comprehensive characterization of brain activity - SO2

To generate a new paradigm to build and characterize the functional neural network using MEG and EEG recordings, to reliably represent the inherent properties of functional neural networks: robustness, plasticity and dynamism.

Computational simulation - SO3

To identify the most plausible "in-silico" scenarios to simulate the neurodegeneration mechanisms associated with the progression of Alzheimer's disease.

Dissemination, transfer and exploitation - SO4

To disseminate, transfer and exploit the results of research to promote, increase and improve the scientific-technical, social and economic impact of the research activity.

Internationalization of research

To achieve the ambitious goals of the project, it is essential to join forces with researchers from different disciplines and countries. Therefore, this proposal constitutes a project of Biomedical Engineering and Neuroscience with a clear transnational vocation (researchers from Spain, the Netherlands, Germany, Japan and Canada will participate in this project ) and highly multidisciplinary (involving engineers, neuroscientists, physicists, neurophysiologists, neurologists, psychiatrists and neurosurgeons)

In particular, four foreign leading centers will actively participate in the project

  • Precision Medicine Center at Hokuto Hospital (Japan).
  • The VU University of Amsterdam (The Nederlands).
  • The Royal’s Institute of the University of Ottawa (Canada).
  • The Goethe University of Frankfurt (Germany).

Training capacity

Training plan for new researchers

The training plan for predoctoral researchers is designed to ensure the development of advanced methodological skills and the knowledge necessary to undertake cutting-edge research in advanced methods of neuronal signal processing and computational simulation of biological systems.

Previous experience - Completed PhD Thesis

During the last decade, 14 Doctoral Theses have been defended within the research group that leads the proposal (GIB), all of them related to signal and image processing. They generated a total of 122 articles in JCR journals.

Professional career of graduate PhDs

All the doctors who have developed their Doctoral Thesis at the GIB have continued their career in prestigious institutions or innovative companies, both inside and outside Spain.

Scientific-technical and training context of the team

The researchers involved in the project combine the experience of consolidated scientists and young researchers with enormous potential. The research proposal includes international specialists in Engineering, Neuroscience, Medical Physics, Neurology, Neurophysiology, Psychiatry and Neuroanatomy, who work in various institutions of international prestige.

Expected impact of the results

Scientific-technical impact

  • Application of new techniques to study and simulate the alterations that Alzheimer's disease causes in neural activity.
  • Development of a software tool to simulate the neurodegeneration mechanisms associated with the evolution of Alzheimer's disease, based on MEG and EEG recordings.
  • Investigation of potential biomarkers of the early stages of dementia due to Alzheimer's disease.
  • Knowledge transfer between the various scientific fields involved in the project.
  • Training of new researchers in a promising scientific field.

Social and clinical impact

  • Reduction of the burden on caregivers and the dependence associated with dementia, thanks to the possibility of early and effective planning of therapeutic interventions.
  • Transfer of knowledge to clinical practice to objectify the diagnosis of Alzheimer's disease (and its early stages).
  • Employment: hiring predoctoral researchers.

Economic impact

  • Savings in human, material and economic resources dedicated to diagnosis in the National Health Systems, thanks to the introduction of new biomarkers of Alzheimer's disease in the stage of mild cognitive impairment, based on a technique widely disseminated in the clinical environment and with a reduced cost, as the EEG.
  • Direct and indirect medical cost savings, due to the early application of therapies to delay disabilities associated with Alzheimer's disease and, therefore, to reduce dependence on medical care.

Project stages

Stage 1. Organization of the database.

We will increase the sample size of the three databases that we currently have available to obtain a representative data set, which will be useful for carrying out an appropriate configuration and validation of the plausible "in-silico" scenarios and the identification of potential biomarkers of dementia due to Alzheimer's disease. Currently, these databases are formed by MEG or EEG recordings, sociodemographic variables and clinical data, all acquired according to the same protocol and belonging to cognitively healthy controls of advanced age, patients with mild cognitive impairment and patients with Alzheimer's disease.

Stage 2. Construction and characterization of the functional neural network.

The brain network will be generated independently using the MEG and EEG recordings of each database. For this task, it will be essential to investigate and apply new measures of neuronal coupling, capable of accurately reflecting the dynamic behavior of the brain network. This will provide an accurate representation of the functional neural network as a dynamic graph. Different network parameters will then be calculated to obtain an accurate description of the brain network.

Stage 3. Generation and assessment of computational simulations.

"In-silico" scenarios based on brain lesions previously described in the literature will be proposed, created and evaluated. This ambitious stage can be divided into the following four sub-stages:

  • Identification of neurodegenerative mechanisms associated with the evolution of dementia.
  • Proposal of "in-silico" scenarios to simulate mechanisms of neurodegeneration .
  • Configuration, adjustment and selection of "in-silico" scenarios using MEG data.
  • Replication and generalization of the results.

Related publications


JCR Articles

Computational modeling of the effects of EEG volume conduction on functional connectivity metrics. Application to Alzheimer's disease continuum

Ruiz-Gómez et al. (2019)

Journal of Neural Engineering

Characterizing the fluctuations of dynamic resting-state electrophysiological functional connectivity: Reduced neuronal coupling variability in mild cognitive impairment and dementia due to Alzheimer's disease

Núñez et al. (2019)

Journal of Neural Engineering

EEG Characterization of the Alzheimer’s Disease Continuum by Means of Multiscale Entropies

Maturana-Candelas et al. (2019)

Entropy

Characterization of the dynamic behavior of neural activity in Alzheimer's disease: exploring the non-stationarity and recurrence structure of EEG resting-state activity

Núñez et al. (2020)

Journal of Neural Engineering

Consistency of local activation parameters at sensor- and source-level in neural signals

Rodríguez-González et al. (2020)

Journal of Neural Engineering

Relationship between the presence of the ApoE ε4 Allele and EEG Complexity along the Alzheimer's Disease Continuum

Gutiérrez-de-Pablo et al. (2020)

Sensors

Inter-band Bispectral Analysis of EEG Background Activity to Characterize Alzheimer's Disease Continuum

Maturana-Candelas et al. (2020)

Frontiers in Computational Neuroscience

Predicting the outcome of non-pharmacological treatment for patients with dementia-related mild cognitive impairment

Shigihara et al. (2020)

Aging

Abnormal meta-state activation of dynamic brain networks across the Alzheimer spectrum

Núñez et al. (2021)

NeuroImage

Exploring the Alterations in the Distribution of Neural Network Weights in Dementia Due to Alzheimer’s Disease

Revilla-Vallejo et al. (2021)

Entropy

Influence of PICALM and CLU risk variants on beta EEG activity in Alzheimer’s disease patients

Maturana-Candelas et al. (2021)

Scientific Reports

A new method to build multiplex networks based on neural data using Canonical Correlation Analysis. Application to Alzheimer’s disease continuum

Ruiz-Gómez et al. (2020)

Journal of Neural Engineering

Genome-wide scan for five brain oscillatory phenotypes identifies a new QTL associated with theta EEG band

Rebelo et al. (2020)

Brain Sciences

Main symptomatic treatment targets in suspected and early psychosis: new insights from network analysis

Jimeno et al. (2020)

Schizophrenia Bulletin

Exploring the interactions between neurophysiology and cognitive and behavioral changes induced by a non-pharmacological treatment: a network approach

Rodríguez-González et al. (2021)

Frontiers in Aging Neuroscience

The menstrual cycle alters resting-state cortical activity: A magnetoencephalography study

Haraguchi et al. (2021)

Frontiers in Human Neuroscience

Spectral and temporal characterization of sleep spindles – Methodological implications

Gomez-Pilar et al. (2021)

Journal of Neural Engineering

Risk variants in three Alzheimer’s disease genes show association with EEG endophenotypes

Macedo et al. (2021)

Journal of Alzheimers Disease

The association between carotid blood flow and resting-state brain activity in patients with cerebrovascular diseases

Matsumoto et al. (2021)

Scientific Reports

Pediatric Sleep Apnea: The Overnight Electroencephalogram as a Phenotypic Biomarker

Gutiérrez-Tobal et al. (2021)

Frontiers in Neuroscience

Schizophrenia induces abnormal frequency-dependent patterns of dynamic brain network reconfiguration during an auditory oddball task

Nuñez et al. (2022)

Journal of Neural Engineering

Distinctive effects of executive dysfunction and loss of learning/memory abilities on resting- state brain activity

Hoshi et al. (2022)

Scientific Reports

”(Attenuated) hallucinations join basic symptoms in a transdiagnostic network cluster analysis

Jimeno et al. (2022)

Schizophrenia Research

Editorial: Complexity and Connectivity: Functional Signatures of Neurodegenerative Disorders

Gómez et al. (2020)

Frontiers in Neuroscience

Editorial: Entropy in Brain Networks

Poza et al. (2021)

Entropy

Conference reports

Influencia de la reserva cognitiva en los patrones neurofisiológicos asociados a la evolución de la enfermedad de Alzheimer

Rodríguez-González et al. (2019)

XXXVII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2019)

Assessing the influence of cognitive reserve in EEG signals through Alzheimer’s Disease progression

Rodríguez-González et al. (2019)

XXXIV Simposium Nacional de la Unión Científica Internacional de Radio (URSI 2019)

Volume Conduction Effects on Connectivity Metrics: Application of Network Parameters to Characterize Alzheimer's Disease Continuum

Ruiz-Gómez et al. (2020)

42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society

Evaluación de la robustez de la red neuronal funcional en la demencia por enfermedad de Alzheimer

Revilla-Vallejo et al. (2020)

XXXVIII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2020)

Estudio de la relación entre el gen MAPT y la conectividad cerebral en la demencia por enfermedad de Alzheimer

Maturana-Candelas et al. (2020)

XXXVIII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2020)

Redes de asociación: una nueva forma de explorar la huella fisiopatológica de la enfermedad de Azlheimer

Gutiérrez-de-Pablo et al. (2020)

XXXVIII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2020)

Estudio de la asociación entre los patrones de activación local y de sincronización global en el EEG en la enfermedad de Alzheimer

Rodriguez-González et al. (2020)

XXXVIII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2020)

Evaluación de la robustez de la red neuronal funcional en la enfermedad de Alzheimer

Revilla-Vallejo et al. (2021)

XXXIX Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2021)

Análisis de las alteraciones en la organización jerárquica de la actividad neuronal debidas a la enfermedad de Alzheimer

Gutiérrez-de-Pablo et al. (2021)

XXXIX Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2021)

La importancia dinámica como indicador de comportamiento de hub en la región parietal de la red neuronal por defecto

Maturana-Candelas et al. (2021)

XXXIX Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2021)

Functional connectivity metrics and volume conduction effects in Alzheimer's disease

Revilla-Vallejo et al. (2021)

Basic and Clinical Multimodal Imaging (BaCI) Virtual Conference

Effect of segment length, sampling frequency, and imaging modality on the estimation of measures of brain meta-state activation: an MEG/EEG study

Nuñez et al. (2021)

43nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2021)

High Frequential Resolution Networks: Considerations on a New Functional Brain Connectivity Framework

Rodríguez-González et al. (2021)

43nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2021)

Exploring the robustness of the MEG functional neural network in patients with dementia due to Alzheimer’s disease

Revilla-Vallejo et al. (2022)

The 22nd International Conference on Biomagnetism (BIOMAG 2022)

Characterization of dynamic resting-state electrophysiological functional connectivity fluctuations: application to clinical populations

Nunez et al. (2022)

The 22nd International Conference on Biomagnetism (BIOMAG 2022)

Modelado computacional de la conducción de volumen en el EEG. Caracterización del deterioro cognitivo leve y su progresión a la enfermedad de Alzheimer

Ruiz-Gómez et al. (2019)

XXXVII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2019)

Estudio del comportamiento dinámico del EEG durante la progresión de deterioro cognitivo leve a demencia por enfermedad de Alzheimer

Nuñez et al. (2019)

XXXVII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2019)

Intraindividual Characterization of the Sleep Spindle Variability in Healthy Subjects

Gomez-Pilar et al. (2020)

42nd Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC 2020)

Estudio de la arquitectura temporal de la actividad neuronal en la demencia por enfermedad de Alzheimer mediante técnicas de conectividad funcional dinámica

Bautista-Salinero et al. (2021)

XXXIX Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2021)

Assessing the influence of power line interference In connectivity analyses

Rodríguez-González et al. (2022)

IUPESM World Congress on Medical Physics and Biomedical Engineering 2022

Acoplamiento cruzado amplitud-amplitud: un nuevo método para caracterizar la actividad neuronal y las alteraciones provocadas por la enfermedad de Alzheimer

Revilla-Vallejo et al. (2022)

XL Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2022)

Estudio de las alteraciones en la arquitectura temporal de la actividad neuronal provocadas por la enfermedad de Alzheimer

Carretero-Calvo et al. (2022)

XL Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2022)

Análisis espectral de la electroencefalográfica basal a nivel de fuente para la diferenciación de subtipos de migraña

Gomez-Pilar et al. (2022)

XL Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2022)

Impacto de la expresión del gen MAPT en las relaciones inter-banda de la actividad eléctrica cerebral

Maturana-Candelas et al. (2022)

XL Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2022)

Alteraciones patológicas de la estructura neurofisiológica en los diferentes subtipos de migraña en mujeres

Gutiérrez-de-Pablo et al. (2022)

XL Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2022)

Aplicación de Deep Learning para el procesado automático de componentes ICA de registros de magnetoencefalografía

Gutiérrez-de-Pablo, Laura et al. (2022)

XL Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2022)

Estructura temporal de la actividad neuronal: de la dinámica de la activación local a la cronectómica

Poza, Jesús (2022)

I International Congress ‘Brain Dynamics and Consciousness

Diffusion

Video to illustrate the dynamic brain state switching between dominant states in resting-state EEG activity and the alterations in dynamic network configuration behavior associated with dementia due to AD in the theta band

Pablo Núñez y Jesús Poza (2020)

--VIDEO--

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Address

  • Jesús Poza Crespo, PhD
  • Grupo de Ingeniería Biomédica
  • Paseo Belén 15 | 47011 - Valladolid, España
  • +34 983 18 5569
  • jesus.poza@tel.uva.es