Luca Passamonti

Giovanna Maria Dimitri, Simeon Spasov, Andrea Duggento et al.

Recently, it has become progressively more evident that classic diagnostic labels are unable to reliably describe the complexity and variability of several clinical phenotypes. This is particularly true for a broad range of neuropsychiatric illnesses (e.g., depression, anxiety disorders, behavioral phenotypes). Patient heterogeneity can be better described by grouping individuals into novel categories based on empirically derived sections of intersecting continua that span across and beyond traditional categorical borders. In this context, neuroimaging data carry a wealth of spatiotemporally resolved information about each patient's brain. However, they are usually heavily collapsed a priori through procedures which are not learned as part of model training, and consequently not optimized for the downstream prediction task. This is because every individual participant usually comes with multiple whole-brain 3D imaging modalities often accompanied by a deep genotypic and phenotypic characterization, hence posing formidable computational challenges. In this paper we design a deep learning architecture based on generative models rooted in a modular approach and separable convolutional blocks to a) fuse multiple 3D neuroimaging modalities on a voxel-wise level, b) convert them into informative latent embeddings through heavy dimensionality reduction, c) maintain good generalizability and minimal information loss. As proof of concept, we test our architecture on the well characterized Human Connectome Project database demonstrating that our latent embeddings can be clustered into easily separable subject strata which, in turn, map to different phenotypical information which was not included in the embedding creation process. This may be of aid in predicting disease evolution as well as drug response, hence supporting mechanistic disease understanding and empowering clinical trials.

Alexander Campbell, Antonio Giuliano Zippo, Luca Passamonti et al.

Graph neural networks (GNNs) have demonstrated success in learning representations of brain graphs derived from functional magnetic resonance imaging (fMRI) data. However, existing GNN methods assume brain graphs are static over time and the graph adjacency matrix is known prior to model training. These assumptions contradict evidence that brain graphs are time-varying with a connectivity structure that depends on the choice of functional connectivity measure. Incorrectly representing fMRI data with noisy brain graphs can adversely affect GNN performance. To address this, we propose DynDepNet, a novel method for learning the optimal time-varying dependency structure of fMRI data induced by downstream prediction tasks. Experiments on real-world fMRI datasets, for the task of sex classification, demonstrate that DynDepNet achieves state-of-the-art results, outperforming the best baseline in terms of accuracy by approximately 8 and 6 percentage points, respectively. Furthermore, analysis of the learned dynamic graphs reveals prediction-related brain regions consistent with existing neuroscience literature.

Tiago Azevedo, Luca Passamonti, Pietro Liò et al.

The characterisation of the brain as a "connectome", in which the connections are represented by correlational values across timeseries and as summary measures derived from graph theory analyses, has been very popular in the last years. However, although this representation has advanced our understanding of the brain function, it may represent an oversimplified model. This is because the typical fMRI datasets are constituted by complex and highly heterogeneous timeseries that vary across space (i.e., location of brain regions). We compare various modelling techniques from deep learning and geometric deep learning to pave the way for future research in effectively leveraging the rich spatial and temporal domains of typical fMRI datasets, as well as of other similar datasets. As a proof-of-concept, we compare our approaches in the homogeneous and publicly available Human Connectome Project (HCP) dataset on a supervised binary classification task. We hope that our methodological advances relative to previous "connectomic" measures can ultimately be clinically and computationally relevant by leading to a more nuanced understanding of the brain dynamics in health and disease. Such understanding of the brain can fundamentally reduce the constant specialised clinical expertise in order to accurately understand brain variability.