Description

PhD: Impacts of Meditation Training on the Organisation of Resting State Intrinsic Connectivity Networks in the Brain: Implications for the Study of Cognition, Well-being and Ageing

The 3-year-funded position can be filled as soon as September 1st 2024 and up to September 2025 . The fellowship will involve working on several large brain imaging dataset on meditation including the ERC consolidator Brain& Mindfulness, and EC-funded Silver Santé Study –research project investigating the impacts of mental training techniques, such as meditation and language-learning, on mental health and well-being in Europe's ageing population (or watch the project's 3-minute film at ).

The PhD student will have opportunity to collaborate with a postdoctoral fellow also funded by this grant. A. Lutz's group will collaborate during this research with Dr. Sofie Louise Valk and her group at the Max Planck Institute for Human Cognitive and Brain Sciences for the methodological aspect of this project and with Gaël Chételat and her group at the laboratory Inserm U1237, PhIND, in Caen for research questions related to the Silver Santé study. The protocols of the study are described in the manuscripts listed below.

The candidate should possess a Master of psychology, or cognitive and/or affective neurosciences or engineering applied to neuroimaging. The candidates should ideally have previous experiences in analyzing functional neuroimaging in particular resting-state functional connectivity. Theoretical and practical experiences with the following software will be relevant: Matlab, Python, statistical software (R), standard neuroimaging software (e.g. SPM, freesurfer). Proficiency in written and oral English is required. The candidates should also have some interest in meditation practices or contemplative sciences.

This 3-year position follows standard French salaries at INSERM. To apply for this position, please send a curriculum vita with references, cover letter describing research interest and experience to Antoine Lutz ( ). Please write in the title ("Application to the ANR doctoral fellowship").

ANR project's objectives and research hypotheses:

The overall aim of the project is to characterize the plasticity of the aging brain following meditation training as measured by the reorganisation of the brain intrinsic functional connectivity and changes in cognitive, and affective skills important for healthy aging and well-being. This project is a follow-up from the Medit-Ageing research project1, an European consortium previously funded by the Horizon 2020 program (public name Silver Santé Study , ). To this end, we will investigate four specific aims organized in two work packages (WP). WP1 led by Gaël Chételat (INSERM, U1237) will be focusing on the neurophysiology of aging. WP2 led by Antoine Lutz (INSERM, U1028) will be focusing on the neurophysiology of meditation and attention and emotion regulations (WP2, Antoine Lutz). The PhD candidate in this position will primarily work on the objective of WP2, but could be invite to participate in some research questions from WP1.

More specifically:

Aim 1 (WP1) will assess age-related effects on the hierarchical functional organisation of the cortex in resting state functional MRI data in a sample of healthy older adults (N=137) from the Silver Santé Study1 and the associations between these markers and brain structure and function, and between these markers and measures of cognition, affects, and lifestyles. To this end, we will use state-of-the-art gradient mapping techniques2,3 to characterize the segregation and integration of functional brain networks, which are known to be impacted by ageing. We hypothesize that the frontoparietal, attention and default mode networks will exhibit more dissimilar functional connectivity profiles within each of these networks as a function of age. We also hypothesize that the dispersion within these networks will be influenced by cortical morphology and will predict decreased cognition and increased Alzheimer risks factors. Finally, we will explore how the dispersion within limbic regions, in particular the salience network, will be associated with low score in affect regulation.

Aim 2 (WP1) will assess longitudinally the measures described in Aim 1. After Visit 1 (V1, pre-intervention), participants were randomized into either a meditation training program, an non-native language (English) program or a passive control group (no intervention), and the same data collected at V1 were collected at the end of the 18-month intervention (V2, post intervention) and 42 months later (V3, long-term follow-up). We hypothesize that age-related changes from V1 to V2, and to V3, will be associated with enhanced dispersion in the frontoparietal, attention, and default mode networks, and that the magnitude of these changes i) will be correlated to the magnitude of the changes in cognition, and ii) will be sensitive to participants' lifestyles (Aim 2.a). We also predict, that the meditation and English training groups will have a protective effect on frontoparietal, and attention networks compared to the no-intervention group and that meditation will have a specific effect on the salience and default-mode networks4 (Aim 2.b).

Aim 3 (WP2) will assess the effects of meditation expertise and states on the hierarchical functional organisation of the cortex in functional MRI data from a sample of 27 older expert meditators from the Silver Santé Study during rest, mindfulness meditation or loving-kindness and compassion meditation. In this pre-proposition, we will only present the prediction regarding the expertise/ trait effects. On the based on a previous study (see Figure 1), we predict that expert meditators compared to aged-matched controls from Aim 1 will have a lower dispersion in the frontoparietal, attention, and default mode networks suggesting a connectivity profile in these communities less impacted by aging. In addition, as we detected a shift of the visual network toward a more central position in the 3D gradient space in young novices compared to young age-matched expert meditators (Figure 1), and as Bethlehen et al. reported similarly strong shift of the visual network but as a function age in adult lifespan3, we predict that older expert meditators will exhibit a similar pattern compared to old novices, suggesting again a reduced impact of age. Finally, we observed a reduction in between networks dispersions, and more broadly a reduced voxel-wise eccentricity in expert meditators compared to young novices (Figure 1). We will explore whether this enhanced integration in meditators endow their brain with more resilient to the damage occurring during aging, as previously reported5. We aim to replicate this finding with the older experts from the Silver Santé study, and to explore its association with the measures of cognitive reserve collected in the project.

Aim 4 (WP2) will assess longitudinally the meditation-related effects on the intrinsic connectivity networks identified in Aim 3 in the longitudinal trial described in Aim 2. We predict that the meditation training will specifically impact at V2 the network dispersions in the same direction as experts. We will explore whether these effects remain at V3. Finally, we will replicate the same approach in a published dataset of resting state fMRI collected pre and post an 8 week Mindfulness-Based-Stress-Reduction (MBSR) program in young adults6. We will explore whether this intervention is sufficient to detect

physiological effect on the network dispersions and compare our framework to standard approaches of network connectivity. This exploratory analysis will inform the feasibility to impact the aging brain with short intervention.

1. Poisnel, G. et al. The Age-Well randomized controlled trial of the Medit-Ageing European project: Effect of meditation or foreign language training on brain and mental health in older adults. Alzheimers Dement (N Y) 4 , 714–

2. Margulies, D. S. et al. Situating the default-mode network along a principal gradient of macroscale cortical organization. Proc Natl Acad Sci U S A 113 , 12574–

3. Bethlehem, R. A. I. et al. Dispersion of functional gradients across the adult lifespan. NeuroImage 222 ,

4. Lutz, A. et al. The protective effect of mindfulness and compassion meditation practices on ageing: Hypotheses, models and experimental implementation. Ageing Research Reviews 72 ,

5. Gard, T. et al. Fluid intelligence and brain functional organization in aging yoga and meditation practitioners. Frontiers in Aging Neuroscience 6 ,

6. Kral, T. R. A. et al. Mindfulness-Based Stress Reduction-related changes in posterior cingulate resting brain connectivity. Social Cognitive and Affective Neuroscience 14 , 777–

7. Livingston, G. et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet 396 , 413–