TY - JOUR JF - PLoS Computational Biology A1 - De Alteriis, Giuseppe A1 - Sherwood, Oliver A1 - Ciaramella, Alessandro A1 - Leech, Robert A1 - Cabral, Joana A1 - Turkheimer, Federico E A1 - Expert, Paul ID - discovery10206272 N2 - A crucial challenge in neuroscience involves characterising brain dynamics from high-dimensional brain recordings. Dynamic Functional Connectivity (dFC) is an analysis paradigm that aims to address this challenge. dFC consists of a time-varying matrix (dFC matrix) expressing how pairwise interactions across brain areas change over time. However, the main dFC approaches have been developed and applied mostly empirically, lacking a common theoretical framework and a clear view on the interpretation of the results derived from the dFC matrices. Moreover, the dFC community has not been using the most efficient algorithms to compute and process the matrices efficiently, which has prevented dFC from showing its full potential with high-dimensional datasets and/or real-time applications. In this paper, we introduce the Dynamic Symmetric Connectivity Matrix analysis framework (DySCo), with its associated repository. DySCo is a framework that presents the most commonly used dFC measures in a common language and implements them in a computationally efficient way. This allows the study of brain activity at different spatio-temporal scales, down to the voxel level. DySCo provides a single framework that allows to: (1) Use dFC as a tool to capture the spatio-temporal interaction patterns of data in a form that is easily translatable across different imaging modalities. (2) Provide a comprehensive set of measures to quantify the properties and evolution of dFC over time: the amount of connectivity, the similarity between matrices, and their informational complexity. By using and combining the DySCo measures it is possible to perform a full dFC analysis. (3) Leverage the Temporal Covariance EVD algorithm (TCEVD) to compute and store the eigenvectors and values of the dFC matrices, and then also compute the DySCo measures from the EVD. Developing the framework in the eigenvector space is orders of magnitude faster and more memory efficient than naïve algorithms in the matrix space, without loss of information. The methodology developed here is validated on both a synthetic dataset and a rest/N-back task experimental paradigm from the fMRI Human Connectome Project dataset. We show that all the proposed measures are sensitive to changes in brain configurations and consistent across time and subjects. To illustrate the computational efficiency of the DySCo toolbox, we performed the analysis at the voxel level, a task which is computationally demanding but easily afforded by the TCEVD. SN - 1553-7358 PB - Public Library of Science (PLoS) UR - https://doi.org/10.1371/journal.pcbi.1012795 N1 - Copyright: © 2025 Alteriis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. IS - 3 TI - DySCo: A general framework for dynamic functional connectivity AV - public Y1 - 2025/03// VL - 21 ER -