Functional connectivity has been widely investigated to understand brain disease in clinical studies and imaging-based neuroscience, and analyzing changes in functional connectivity has proven to be valuable for understanding and computationally evaluating the effects on brain function caused by diseases or experimental stimuli. By using Mahalanobis data whitening prior to the use of dimensionality reduction algorithms, we are able to distill meaningful information from fMRI signals about subjects and the experimental stimuli used to prompt them. Furthermore, we offer an interpretation of Mahalanobis whitening as a two-stage de-individualization of data which is motivated by similarity as captured by the Bures distance, which is connected to quantum mechanics. These methods have potential to aid discoveries about the mechanisms that link brain function with cognition and behavior and may improve the accuracy and consistency of Alzheimer's diagnosis, especially in the preclinical stage of disease progression.

We present a connectome-informed LLM framework that encodes dynamic fMRI connectivity as temporal sequences, applies robust normalization, and maps these data into a representation suitable for a frozen pre-trained LLM for clinical prediction. Applied to early Alzheimer's detection, our method achieves sensitive prediction with error rates well below clinically recognized margins, with implications for timely Alzheimer's intervention.

The generation of connectional brain templates (CBTs) has recently garnered significant attention for its potential to identify unique connectivity patterns shared across individuals. However, existing methods for CBT learning such as conventional machine learning and graph neural networks (GNNs) are hindered by several limitations. These include: (i) poor interpretability due to their black-box nature, (ii) high computational cost, and (iii) an exclusive focus on structure and topology, overlooking the cognitive capacity of the generated CBT. To address these challenges, we introduce mCOCO (multi-sensory COgnitive COmputing), a novel framework that leverages Reservoir Computing (RC) to learn population-level functional CBT from BOLD (Blood-Oxygen-level-Dependent) signals. RC's dynamic system properties allow for tracking state changes over time, enhancing interpretability and enabling the modeling of brain-like dynamics, as demonstrated in prior literature. By integrating multi-sensory inputs (e.g., text, audio, and visual data), mCOCO captures not only structure and topology but also how brain regions process information and adapt to cognitive tasks such as sensory processing, all in a computationally efficient manner. Our mCOCO framework consists of two phases: (1) mapping BOLD signals into the reservoir to derive individual functional connectomes, which are then aggregated into a group-level CBT - an approach, to the best of our knowledge, not previously explored in functional connectivity studies - and (2) incorporating multi-sensory inputs through a cognitive reservoir, endowing the CBT with cognitive traits. Extensive evaluations show that our mCOCO-based template significantly outperforms GNN-based CBT in terms of centeredness, discriminativeness, topological soundness, and multi-sensory memory retention. Our source code is available at https://github.com/basiralab/mCOCO.

The human brain is a complex system, and understanding its mechanisms has been a long-standing challenge in neuroscience. The study of the functional connectome, which maps the functional connections between different brain regions, has provided valuable insights through various advanced analysis techniques developed over the years. Similarly, neural networks, inspired by the brain's architecture, have achieved notable success in diverse applications but are often noted for their lack of interpretability. In this paper, we propose a novel approach that bridges neural networks and human brain functions by leveraging brain-inspired techniques. Our approach, grounded in the insights from the functional connectome, offers scalable ways to characterize topology of large neural networks using stable statistical and machine learning techniques. Our empirical analysis demonstrates its capability to enhance the interpretability of neural networks, providing a deeper understanding of their underlying mechanisms.

The static synaptic connectivity of neuronal circuits stands in direct contrast to the dynamics of their function. As in changing community interactions, different neurons can participate actively in various combinations to effect behaviors at different times. We introduce an unsupervised approach to learn the dynamic affinities between neurons in live, behaving animals, and to reveal which communities form among neurons at different times. The inference occurs in two major steps. First, pairwise non-linear affinities between neuronal traces from brain-wide calcium activity are organized by non-negative tensor factorization (NTF). Each factor specifies which groups of neurons are most likely interacting for an inferred interval in time, and for which animals. Finally, a generative model that allows for weighted community detection is applied to the functional motifs produced by NTF to reveal a dynamic functional connectome. Since time codes the different experimental variables (e.g., application of chemical stimuli), this provides an atlas of neural motifs active during separate stages of an experiment (e.g., stimulus application or spontaneous behaviors). Results from our analysis are experimentally validated, confirming that our method is able to robustly predict causal interactions between neurons to generate behavior. Code is available at https://github.com/dyballa/dynamic-connectomes.

In spite of years of research, the mechanisms that underlie the development of schizophrenia, as well as its relapse, symptomatology, and treatment, continue to be a mystery. The absence of appropriate analytic tools to deal with the variable and complicated nature of schizophrenia may be one of the factors that contribute to the development of this disorder. Deep learning is a subfield of artificial intelligence that was inspired by the nervous system. In recent years, deep learning has made it easier to model and analyse complicated, high-dimensional, and nonlinear systems. Research on schizophrenia is one of the many areas of study that has been revolutionised as a result of the outstanding accuracy that deep learning algorithms have demonstrated in classification and prediction tasks. Deep learning has the potential to become a powerful tool for understanding the mechanisms that are at the root of schizophrenia. In addition, a growing variety of techniques aimed at improving model interpretability and causal reasoning are contributing to this trend. Using multi-site fMRI data and a variety of deep learning approaches, this study seeks to identify different types of schizophrenia. Our proposed method of temporal aggregation of the 4D fMRI data outperforms existing work. In addition, this study aims to shed light on the strength of connections between various brain areas in schizophrenia individuals.

Resting-state functional MRI (rsfMRI) yields functional connectomes that can serve as cognitive fingerprints of individuals. Connectomic fingerprints have proven useful in many machine learning tasks, such as predicting subject-specific behavioral traits or task-evoked activity. In this work, we propose a surface-based convolutional neural network (BrainSurfCNN) model to predict individual task contrasts from their resting-state fingerprints. We introduce a reconstructive-contrastive loss that enforces subject-specificity of model outputs while minimizing predictive error. The proposed approach significantly improves the accuracy of predicted contrasts over a well-established baseline.

Population imaging markedly increased the size of functional-imaging datasets, shedding new light on the neural basis of inter-individual differences. Analyzing these large data entails new scalability challenges, computational and statistical. For this reason, brain images are typically summarized in a few signals, for instance reducing voxel-level measures with brain atlases or functional modes. A good choice of the corresponding brain networks is important, as most data analyses start from these reduced signals. We contribute finely-resolved atlases of functional modes, comprising from 64 to 1024 networks. These dictionaries of functional modes (DiFuMo) are trained on millions of fMRI functional brain volumes of total size 2.4TB, spanned over 27 studies and many research groups. We demonstrate the benefits of extracting reduced signals on our fine-grain atlases for many classic functional data analysis pipelines: stimuli decoding from 12,334 brain responses, standard GLM analysis of fMRI across sessions and individuals, extraction of resting-state functional-connectomes biomarkers for 2,500 individuals, data compression and meta-analysis over more than 15,000 statistical maps. In each of these analysis scenarii, we compare the performance of our functional atlases with that of other popular references, and to a simple voxel-level analysis. Results highlight the importance of using high-dimensional "soft" functional atlases, to represent and analyse brain activity while capturing its functional gradients. Analyses on high-dimensional modes achieve similar statistical performance as at the voxel level, but with much reduced computational cost and higher interpretability. In addition to making them available, we provide meaningful names for these modes, based on their anatomical location. It will facilitate reporting of results.

Michaela Cordova, a research associate and lab manager at Oregon Health and Science University, begins by "de-metaling": removing rings, watches, gadgets and other sources of metal, double-checking her pockets for overlooked objects that could, in her words, "fly in." Then she enters the scanning room, raises and lowers the bed, and waves a head coil in the general direction of the viewing window and the iPad camera that's enabling this virtual lab tour (I'm watching from thousands of miles away in Massachusetts). Her voice is mildly distorted by the microphone embedded in the MRI scanner, which from my slightly blurry vantage point looks less like an industrial cannoli than a beast with a glowing blue mouth. I can't help but think that eerie description might resonate with her usual clientele. Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

Substantial evidence indicates that major psychiatric disorders are associated with distributed neural dysconnectivity, leading to strong interest in using neuroimaging methods to accurately predict disorder status. In this work, we are specifically interested in a multivariate approach that uses features derived from whole-brain resting state functional connectomes. However, functional connectomes reside in a high dimensional space, which complicates model interpretation and introduces numerous statistical and computational challenges. Traditional feature selection techniques are used to reduce data dimensionality, but are blind to the spatial structure of the connectomes. We propose a regularization framework where the 6-D structure of the functional connectome is explicitly taken into account via the fused Lasso or the GraphNet regularizer. Our method only restricts the loss function to be convex and margin-based, allowing non-differentiable loss functions such as the hinge-loss to be used. Using the fused Lasso or GraphNet regularizer with the hinge-loss leads to a structured sparse support vector machine (SVM) with embedded feature selection. We introduce a novel efficient optimization algorithm based on the augmented Lagrangian and the classical alternating direction method, which can solve both fused Lasso and GraphNet regularized SVM with very little modification. We also demonstrate that the inner subproblems of the algorithm can be solved efficiently in analytic form by coupling the variable splitting strategy with a data augmentation scheme. Experiments on simulated data and resting state scans from a large schizophrenia dataset show that our proposed approach can identify predictive regions that are spatially contiguous in the 6-D "connectome space," offering an additional layer of interpretability that could provide new insights about various disease processes.