## Section: Partnerships and Cooperations

### Regional Initiatives

#### Digiteo/DIM

##### HIDINIM Digiteo project

Participants : Bertrand Thirion [Correspondant] , Virgile Fritsch.

High-dimensional Neuroimaging– Statistical Models of Brain Variability observed in Neuroimaging

This is a joint project with Select project team and with SUPELEC Sciences des Systèmes (E3S), Département Signaux & Systèmes Électroniques (A. Tennenhaus), 2010-2013.

Statistical inference in a group of subjects is fundamental to draw valid neuroscientific conclusions that generalize to the whole population, based on a finite number of experimental observations. Crucially, this generalization holds under the hypothesis that the population-level distribution of effects is estimated accurately. However, there is growing evidence that standard models, based on Gaussian distributions, do not fit well empirical data in neuroimaging studies.

In particular, Hidinim is motivated by the analysis of new databases
hosted and analyzed at Neurospin that contain neuroimaging data from
hundreds of subjects, in addition to genetic and behavioral data. We
propose to investigate the statistical structure of large populations
observed in neuroimaging. In particular, we investigate the use of
region-level averages of brain activity, that we plan to co-analyse
with genetic and behavioral information, in order to understand the
sources of the observed variability. This entails a series of modeling
problems that we address in this project: *i)* Distribution
normality assessment and variables covariance estimation, *ii)*
model selection for mixture models and *iii)* setting of
classification models for heterogeneous data, in particular for mixed
continuous/discrete distributions.

##### ICOGEN Digiteo project

Participants : Bertrand Thirion [Correspondant] , Benoit Da Mota.

**ICOGEN : Intensive COmputing for GEnetic-Neuroimaging studies**

Project supported by a Digiteo grant in collaboration with Inria’s KerData Team, MSR-Inria joint centre, Supélec Engineer School, Imagen project and CEA/Neurospin, 2012-2014.

In this project, we design and deploy some computational tools to perform neuroimaging-genetics association studies at a large scale.

Unveiling the relationships between genetic variability and brain structure and function is one of the main challenges in neuroscience, which can be partly addressed through the information conveyed by high-throughput genotyping on the one hand, and neuroimaging data on the other hand. Finding statistical associations between these different variables is important in order to find relevant biomarkers for various brain diseases and improve patient handling. Due to the huge size of the datasets involved and the requirement for tight bounds on statistical significance, such statistical analysis are particularly demanding and cannot be performed easily at a large scale with standard software and computational tools. In ICOGEN, we design and deploy some computational tools to perform neuroimaging-genetics association studies at a large scale. We implement and assess on real data the use of novel statistical methodologies and run the statistical analysis on various architectures (grids, clouds), in a unified environment.

##### SUBSAMPLE Digiteo chair

Participants : Bertrand Thirion [Correspondant] , Gaël Varoquaux, Alexandre Abraham.

Parietal is associated with this Digiteo Chair by Dimitris Samaras, in which we will address the probabilistic structure learning of salient brain states (PhD thesis of Alexandre Abraham, 2012-2015).

Cognitive tasks systematically involve several brain regions, and exploratory approaches are generally necessary given the lack of knowledge of the complex mechanisms that are observed. The goal of the project is to understand the neurobiological mechanisms that are involved in complex neuro-psychological disorders. A crucial and poorly understood component in this regard refers to the interaction patterns between different regions in the brain. In this project we will develop machine learning methods to capture and study complex functional network characteristics. We hypothesize that these characteristics not only offer insights into brain function but also can be used as concise features that can be used instead of the full dataset for tasks like classification of healthy versus diseased populations or for clustering subjects that might exhibit similarities in brain function. In general, the amount of correlation between distant brain regions may be a more reliable feature than the region-based signals to discriminate between two populations e.g. in schizophrenia. For such exploratory methods to be successful, close interaction with neuroscientists is necessary, as the salience of the features depends on the population and the observed effects of psychopathology. For this aim we propose to develop a number of important methodological advances in the context of prediction of treatment outcomes for drug addicted populations, i.e. for relapse prediction.

##### MMoVNI Digiteo project

Participants : Bertrand Thirion [Correspondant] , Pierre Fillard, Viviana Siless, Stéphanie Allassonnière, Hao Xu.

This is a joint project with CMAP http://www.cmapx.polytechnique.fr/~allassonniere/ , 2010-2013.

Modeling and understanding brain structure is a great challenge, given the anatomical and functional complexity of the brain. In addition to this, there is a large variability of these characteristics among the population. To give a possible answer to these issues, medical imaging researchers proposed to construct a template image. Most of the time, these analysis only focus on one category of signals (called modality), in particular, the anatomical one was the main focus of research these past years. Moreover, these techniques are often dedicated to a particular problem and raise the question of their mathematical foundations. The MMoVNI project aims at building atlases based on multi-modal images (anatomy, diffusion and functional) data bases for given populations. An atlas is not only a template image but also a set of admissible deformations which characterize the observed population of images. The estimation of these atlases will be based on a new generation of deformation and template estimation procedures that build an explicit statistical generative model of the observed data. Moreover, they make it possible to infer all the relevant variables (parameters of the atlases) thanks to stochastic algorithms. Lastly, this modeling allows also to prove the convergence of both the estimator and the algorithms which provides a theoretical guarantee to the results. The models will first be proposed independently for each modality and then merged together to take into account, in a correlated way, the anatomy, the local connectivity through the cortical fibers and the functional response to a given cognitive task. This model will then be generalized to enable the non-supervised clustering of a population. This leads therefore to a finer representation of the population and a better comparison for classification purposes for example. The Neurospin center, partner of this project, will allow us to have access to databases of images of high-quality and high-resolution for the three modalities: anatomical, diffusion and functional imaging. This project is expected to contribute to making neuroimaging a more reliable tool for understanding inter-subject differences, which will eventually benefit to the understanding and diagnosis of various brain diseases like Alzheimer's disease, autism or schizophrenia.