Towards a scalable effective connectivity estimation in fMRI

Characterizing directed connections between brain regions is fundamental for understanding the brain’s network organization and how it supports cognitive processes. However, a reliable methodology allowing assessment of effective connectivity (EC) at the whole-brain level and across high-resolution parcellations has remained elusive. This limitation reflects a trade-off between model detail and scalability. Mechanistic approaches such as Dynamic Causal Modeling (DCM) provide a principled description of directed interactions but become impractical for large parcellations, whereas scalable methods based on linear-system inversion often fail to reliably recover key features of the underlying effective connectivity. Here, using data from the Human Connectome Project S1200 release, we show that the multivariate Ornstein-Uhlenbeck (mOU) approach for EC estimation can be adapted to yield EC estimates that are in broad agreement with those of an advanced DCM, at least when the spatial variability of the hemodynamic response falls within the physiological range characteristic of the healthy adult brain. Furthermore, thanks to its low computational cost, mOU can be easily scaled up to large neuroimaging cohorts and high-resolution parcellations. High-resolution, mOU-based EC outperforms functional connectivity for single-subject connectome fingerprinting. In addition, it enables a high-resolution characterization of the brain’s hierarchical organization and modular architecture by identifying directed interactions within and between communities and revealing driver and receiver regions. Overall, our methodology provides a reliable and scalable EC estimation pipeline of wide applicability to cognitive and network neuroscience.