Multi-modal characterization of the subcortical involvement in focal epilepsy

Project Information

SUCCEED

Grant agreement ID: 101061988

DOI

10.3030/101061988

Project closed

EC signature date 6 July 2022

Start date 1 January 2023

End date 31 December 2024

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 211 754,88

Coordinated by

UNIVERSITE D'AIX MARSEILLE
France

Periodic Reporting for period 1 - SUCCEED (Multi-modal characterization of the subcortical involvement in focal epilepsy)

Reporting period: 2023-01-01 to 2024-12-31

Summary of the context and overall objectives of the project

Focal epilepsy is a chronic brain disorder that causes repeated, spontaneous seizures that start in specific parts of the brain. These seizures often spread to other areas, affecting overall brain function and cognition. Although some evidence suggests that deeper brain regions play a role in the spread of these seizures, we do not fully understand how this happens.

In this project (‘SUCCEED’), I will study focal epilepsy by using 7 Tesla MRI to get a detailed look at the deeper parts of the brain. By doing this, I hope to uncover important connections between these areas and epilepsy, which could explain the variety in symptoms and treatment success among patients. Specifically, I will:

Objective 1: Use MRI scans to map the connections between deep brain regions in both epilepsy patients and healthy individuals. This will help us understand how these connections differ in patients.
Objective 2: Measure various properties of these deep brain regions using MRI, to see what changes occur in the brains of epilepsy patients compared to healthy controls.
Objective 3: Explore how these MRI findings relate to the patient’s symptoms and treatment outcomes. By doing this, we aim to identify specific patterns in the deep brain regions that could serve as biomarkers for epilepsy.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the SUCCEED project, we have achieved significant progress in understanding the complex mechanisms of focal epilepsy.

By processing high-resolution anatomical data, we have parcellated the thalamus and basal ganglia in both healthy controls and focal epilepsy patients using our in-house developed subcortical atlas, '7TAMIBrain'. This parcellation has enabled us to quantify microstructural and morphometric properties of these subcortical brain structures based on voxel-based T1, deformation, as well as volume and shape analyses.

Additionally, we have characterized tissue sodium homeostasis using 7 Tesla sodium MRI, which has provided new insights into the ionic imbalance in focal epilepsy, and how these can be used to assess the involvement of a brain structure in seizure organization.

Our assessment of structural and functional connectivity using diffusion and functional MRI has yielded comprehensive data on brain network topology, utilizing graph theory to measure global and local connectivity, as well as functional integrity through metrics like regional homogeneity and amplitude of low-frequency fluctuations.

We are also performing partial least squares analyses to link these MRI findings to patient characteristics, including the type of epilepsy. These efforts are collectively advancing our understanding of how deep brain regions contribute to epilepsy and helping us identify potential biomarkers for diagnosis and treatment outcomes.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our work has demonstrated notable changes in the thalamus and basal ganglia characteristics due to focal epilepsy. Uniquely, we highlighted the added value of evaluating multiple features to understand the heterogeneity among focal epilepsy patients. Specifically, we found that changes in the structures' volumes are effective in distinguishing between patients and controls, while alterations in T1 properties are useful in differentiating between various epilepsy types. Importantly, these results were consistent across different subcortical parcellation schemes, reaffirming their reliability.

Moreover, our preprint that integrates sodium MRI with structural connectivity has identified a particular sodium metric, termed 'f', which is especially sensitive to the epileptogenicity of brain structures. On a global scale, we observed that sodium homeostasis differs in hub regions, showing higher sodium levels compared to non-hub regions. This finding underscores the sensitivity of sodium MRI to the degree of connectivity of brain regions.

Additionally, in another preprint, we proposed a framework based on structural connectivity pattern analysis that has the potential to optimize deep brain stimulation targeting. This framework could have significant implications for personalizing thalamic stimulation in focal epilepsy patients, offering a tailored approach to treatment that could enhance therapeutic outcomes.