Individual brain lateralisation, simulation of lesions, and stroke recovery – How the two halves of the brain interact: New insights from neuroimaging

Project Information

PERSONALISED

Grant agreement ID: 101028551

DOI

10.3030/101028551

Project terminated on 3 June 2022

EC signature date 9 April 2021

Start date 1 May 2021

End date 30 April 2023

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 184 707,84

EU contribution

€ 184 707,84

Coordinated by

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 1 - PERSONALISED (Individual brain lateralisation, simulation of lesions, and stroke recovery – How the two halves of the brain interact: New insights from neuroimaging)

Reporting period: 2021-05-01 to 2023-04-30

Summary of the context and overall objectives of the project

Neurosciences have long been working under the assumption that each half of the brain (hemisphere) is dominant for a different set of functions. For example, language is considered a left hemisphere function while visuospatial functions are attributed to the right hemisphere. However, clinical data has repeatedly challenged our assumptions on brain lateralisation and a fundamental challenge in neuroscience is to reconcile neuroimaging findings with clinical evidence.

PERSONALISED tackled these questions by measuring the dynamic interaction between the hemispheres. Using a large dataset of healthy volunteers (Human Connectome Project), the lateralisation was unravelled using the functional activation in each hemisphere during movie watching. This analysis allows us to identify when the brain responds to motion (e.g. an actor running), language (e.g. conversation), or auditory stimulation (e.g. bird chirping). Measuring these activations throughout the movies and for every part of the brain, we were able to measure where and when the brain responds to each type of movie snippet. We were able to demonstrate that overall, the brain is not functionally lateralised but dynamically adapts and shifts activation depending on the input.

As such, PERSONALISED has led to theoretical and anatomical innovations that will be of interest to neurosciences and the clinical arena. The results of this project will enable us to build novel models of dynamic lateralisation in the largest population investigated thus far. In the future, validation in a stroke population would identify the impact of brain dynamics on the recovery of language and potentially offer novel treatment avenues.
Further, neuroimaging methods are often ignoring anatomical and functional individual differences in the brain as they often rely on average templates. With the results from PERSONALISED, interindividual differences can be further studied in a dynamic functional framework to stratify different phenotypes.
Overall, after one year into the project, we have mapped a comprehensive model of brain lateralisation across functions (e.g. language, visuospatial, motor) and its dynamic course across time. These findings advance our fundamental understanding of how the brain functions but also has far-reaching clinical implications (e.g recovery from a stroke). Beyond stroke, the output of this project can be extended to other datasets, diseases or clinical questions.

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

The human brain has been considered to have strong functional lateralisation where language is dominant in the left hemisphere and visuospatial functions in the right hemisphere (REfs). This strict dichotomy has been challenged repeatedly by clinical data and individual patients (REfs). In addition, studies looking at language recovery after stroke indicated a dynamic shift in functional activation during recovery (Saur et al. 2006).
We, therefore, used structural and functional data from the Human Connectome Project (www.humanconnectomeproject.com) to study functional activation in both hemispheres using a naturalistic viewing task that showed Hollywood movie snippets to the participants.

In a first step, we parcellated the left and right hemispheres using the Atlas of Intrinsic Connectivity of Homotopic Areas (AICHA), a functional brain ROIs atlas developed by the host, Group d’imagerie neurofunctional (GIN) at the University of Bordeaux (https://www.gin.cnrs.fr/en/tools/aicha/).

Second, a time point of the fMRI was taken and for each voxel, a t-test was conducted across the whole study cohort. This analysis resulted in a t-map of the brain for that specific time point. This process was repeated for all time points in the fMRI resulting in a fine-grained 1-sec segmentation of the data. The result is a 4D volume (i.e. 3D plus time dimension) of the t-values across all healthy participants. From this 4D volume, the activation and deactivation that are common across the volunteers at a given time point can be extracted. Building on this innovative approach, we projected the functional activations on the cortical surface and matched the activation with each second of the movie. The results can be viewed as a movie and as individual sequences (see Figure 1). Adjusting the hemodynamic delay, we mapped the functional activations to the movie sequences that elicited them.
Putting these results together, we have mapped a comprehensive model of brain lateralisation across functions (e.g. language, visuospatial, motor), brain regions, and its dynamic course across time (WP1).

The statistical analysis of the functional time series and across brain areas has revealed that activation variability is linked with lateralisation. The results have shown that functional activation dynamically shifts to each hemisphere depending on the movie input (WP1). This is a groundbreaking finding that will have far-reaching implications.

In preparation for WP2 and 3, I summarised the literature on white matter connection variability and cognitive-clinical variability (Forkel et al., 2022). The conceptual shift from single cases to studying the white matter disconnection studies was published as a book chapter (Forkel, 2022). My integration into the host department has led to several co-publications .

During the first year of PERSONALISED, I disseminated the project and its results as MSCA ambassador for the European Research Night (24/09/2021) and 12 invited talks at international laboratories or conferences. In line with the project proposal, I organised an international workshop on ‘Brain anatomy - theories, methods, applications' that is freely available online through my Clinical Neuroanatomy Seminar YouTube channel (https://www.youtube.com/c/ClinicalNeuroanatomySeminars). On this channel, we also made several tutorials available to foster a mutual transfer of skills between the host and the awardee and have a wider impact on the community.

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)

For the first time, we mapped the functional dynamics between the two hemispheres across 1h of movie material (4 times 15 minutes) and localise the laterality index for each brain area. With that achievement, WP1 is completed and will be ready for publication in the very near future. As this project has to be terminated early, WP2 and WP3 will not be completed within the MSCA framework. In the future, the data analysed for WP1 can be used for secondary analysis and clinical impact analysis (WP2, WP3).

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