Guido Van Wingen

Ahmed El Gazzar, Rajat Mani Thomas, Guido Van Wingen

Single subject prediction of brain disorders from neuroimaging data has gained increasing attention in recent years. Yet, for some heterogeneous disorders such as major depression disorder (MDD) and autism spectrum disorder (ASD), the performance of prediction models on large-scale multi-site datasets remains poor. We present a two-stage framework to improve the diagnosis of heterogeneous psychiatric disorders from resting-state functional magnetic resonance imaging (rs-fMRI). First, we propose a self-supervised mask prediction task on data from healthy individuals that can exploit differences between healthy controls and patients in clinical datasets. Next, we train a supervised classifier on the learned discriminative representations. To model rs-fMRI data, we develop Graph-S4; an extension to the recently proposed state-space model S4 to graph settings where the underlying graph structure is not known in advance. We show that combining the framework and Graph-S4 can significantly improve the diagnostic performance of neuroimaging-based single subject prediction models of MDD and ASD on three open-source multi-center rs-fMRI clinical datasets.

Ahmed ElGazzar, Rajat Thomas, Guido van Wingen

Graph Neural Networks (GNNs) have emerged as a powerful tool to learn from graph-structured data. A paramount example of such data is the brain, which operates as a network, from the micro-scale of neurons, to the macro-scale of regions. This organization deemed GNNs a natural tool of choice to model brain activity, and have consequently attracted a lot of attention in the neuroimaging community. Yet, the advantage of adopting these models over conventional methods has not yet been assessed in a systematic way to gauge if GNNs are capable of leveraging the underlying structure of the data to improve learning. In this work, we study and evaluate the performance of five popular GNN architectures in diagnosing major depression disorder and autism spectrum disorder in two multi-site clinical datasets, and sex classification on the UKBioBank, from functional brain scans under a general uniform framework. Our results show that GNNs fail to outperform kernel-based and structure-agnostic deep learning models, in which 1D CNNs outperform the other methods in all scenarios. We highlight that creating optimal graph structures for functional brain data is a major bottleneck hindering the performance of GNNs, where existing works use arbitrary measures to define the edges resulting in noisy graphs. We therefore propose to integrate graph diffusion into existing architectures and show that it can alleviate this problem and improve their performance. Our results call for increased moderation and rigorous validation when evaluating graph methods and advocate for more data-centeric approaches in developing GNNs for functional neuroimaging applications.

Ahmed El-Gazzar, Rajat Mani Thomas, Guido Van Wingen

Single-subject mapping of resting-state brain functional activity to non-imaging phenotypes is a major goal of neuroimaging. The large majority of learning approaches applied today rely either on static representations or on short-term temporal correlations. This is at odds with the nature of brain activity which is dynamic and exhibit both short- and long-range dependencies. Further, new sophisticated deep learning approaches have been developed and validated on single tasks/datasets. The application of these models for the study of a different targets typically require exhaustive hyperparameter search, model engineering and trial and error to obtain competitive results with simpler linear models. This in turn limit their adoption and hinder fair benchmarking in a rapidly developing area of research. To this end, we propose fMRI-S4; a versatile deep learning model for the classification of phenotypes and psychiatric disorders from the timecourses of resting-state functional magnetic resonance imaging scans. fMRI-S4 capture short- and long- range temporal dependencies in the signal using 1D convolutions and the recently introduced state-space models S4. The proposed architecture is lightweight, sample-efficient and robust across tasks/datasets. We validate fMRI-S4 on the tasks of diagnosing major depressive disorder (MDD), autism spectrum disorder (ASD) and sex classifcation on three multi-site rs-fMRI datasets. We show that fMRI-S4 can outperform existing methods on all three tasks and can be trained as a plug&play model without special hyperpararameter tuning for each setting

Jakub Frac, Alexander Schmatz, Qiang Li et al.

Functional magnetic resonance imaging (fMRI) analysis faces significant challenges due to limited dataset sizes and domain variability between studies. Traditional self-supervised learning methods inspired by computer vision often rely on positive and negative sample pairs, which can be problematic for neuroimaging data where defining appropriate contrasts is non-trivial. We propose adapting a recently developed Hierarchical Functional Maximal Correlation Algorithm (HFMCA) to graph-structured fMRI data, providing a theoretically grounded approach that measures statistical dependence via density ratio decomposition in a reproducing kernel Hilbert space (RKHS),and applies HFMCA-based pretraining to learn robust and generalizable representations. Evaluations across five neuroimaging datasets demonstrate that our adapted method produces competitive embeddings for various classification tasks and enables effective knowledge transfer to unseen datasets. Codebase and supplementary material can be found here: https://github.com/fr30/mri-eigenencoder

Tianzheng Hu, Qiang Li, Shu Liu et al.

The development of diagnostic models is gaining traction in the field of psychiatric disorders. Recently, machine learning classifiers based on resting-state functional magnetic resonance imaging (rs-fMRI) have been developed to identify brain biomarkers that differentiate psychiatric disorders from healthy controls. However, conventional machine learning-based diagnostic models often depend on extensive feature engineering, which introduces bias through manual intervention. While deep learning models are expected to operate without manual involvement, their lack of interpretability poses significant challenges in obtaining explainable and reliable brain biomarkers to support diagnostic decisions, ultimately limiting their clinical applicability. In this study, we introduce an end-to-end innovative graph neural network framework named BrainIB++, which applies the information bottleneck (IB) principle to identify the most informative data-driven brain regions as subgraphs during model training for interpretation. We evaluate the performance of our model against nine established brain network classification methods across three multi-cohort schizophrenia datasets. It consistently demonstrates superior diagnostic accuracy and exhibits generalizability to unseen data. Furthermore, the subgraphs identified by our model also correspond with established clinical biomarkers in schizophrenia, particularly emphasizing abnormalities in the visual, sensorimotor, and higher cognition brain functional network. This alignment enhances the model's interpretability and underscores its relevance for real-world diagnostic applications.

Ahmed El-Gazzar, Rajat Mani Thomas, Guido van Wingen

The characterisation of the brain as a functional network in which the connections between brain regions are represented by correlation values across time series has been very popular in the last years. Although this representation has advanced our understanding of brain function, it represents a simplified model of brain connectivity that has a complex dynamic spatio-temporal nature. Oversimplification of the data may hinder the merits of applying advanced non-linear feature extraction algorithms. To this end, we propose a dynamic adaptive spatio-temporal graph convolution (DAST-GCN) model to overcome the shortcomings of pre-defined static correlation-based graph structures. The proposed approach allows end-to-end inference of dynamic connections between brain regions via layer-wise graph structure learning module while mapping brain connectivity to a phenotype in a supervised learning framework. This leverages the computational power of the model, data and targets to represent brain connectivity, and could enable the identification of potential biomarkers for the supervised target in question. We evaluate our pipeline on the UKBiobank dataset for age and gender classification tasks from resting-state functional scans and show that it outperforms currently adapted linear and non-linear methods in neuroimaging. Further, we assess the generalizability of the inferred graph structure by transferring the pre-trained graph to an independent dataset for the same task. Our results demonstrate the task-robustness of the graph against different scanning parameters and demographics.

Ahmed El-Gazzar, Mirjam Quaak, Leonardo Cerliani et al.

Functional Magnetic Resonance Imaging (fMRI) captures the temporal dynamics of neural activity as a function of spatial location in the brain. Thus, fMRI scans are represented as 4-Dimensional (3-space + 1-time) tensors. And it is widely believed that the spatio-temporal patterns in fMRI manifests as behaviour and clinical symptoms. Because of the high dimensionality ($\sim$ 1 Million) of fMRI, and the added constraints of limited cardinality of data sets, extracting such patterns are challenging. A standard approach to overcome these hurdles is to reduce the dimensionality of the data by either summarizing activation over time or space at the expense of possible loss of useful information. Here, we introduce an end-to-end algorithm capable of extracting spatiotemporal features from the full 4-D data using 3-D CNNs and 3-D Convolutional LSTMs. We evaluate our proposed model on the publicly available ABIDE dataset to demonstrate the capability of our model to classify Autism Spectrum Disorder (ASD) from resting-state fMRI data. Our results show that the proposed model achieves state of the art results on single sites with F1-scores of 0.78 and 0.7 on NYU and UM sites, respectively.

Ahmed El Gazzar, Leonardo Cerliani, Guido van Wingen et al.

Deep learning methods are increasingly being used with neuroimaging data like structural and function magnetic resonance imaging (MRI) to predict the diagnosis of neuropsychiatric and neurological disorders. For psychiatric disorders in particular, it is believed that one of the most promising modality is the resting-state functional MRI (rsfMRI), which captures the intrinsic connectivity between regions in the brain. Because rsfMRI data points are inherently high-dimensional (~1M), it is impossible to process the entire input in its raw form. In this paper, we propose a very simple transformation of the rsfMRI images that captures all of the temporal dynamics of the signal but sub-samples its spatial extent. As a result, we use a very simple 1-D convolutional network which is fast to train, requires minimal preprocessing and performs at par with the state-of-the-art on the classification of Autism spectrum disorders.