Topology Assisted Clustering of Temporal fMRI Brain Networks With Use-Case in Mitigating Non-Neural Multi-Site Variability

Using temporal analysis of fMRI (functional Magnetic Resonance Imaging) data, we can characterize dynamic changes in brain connectivity over time. However, dynamic temporal analysis of fMRI data is challenging due to the high dimensionality of the datasets. Another fundamental challenge of dynamic temporal analysis of fMRI is the presence of non-neural artifacts that add sources of variation in the data that are not directly related to brain activity. For example, when data are acquired at different scanners at different temporal sampling rates and later analyzed as a single dataset, we have to contend with different number of image snapshots for different subjects. Also, high-frequency scans lead to more fine-grained temporal snapshotting than low-frequency scans. These factors can obscure true neural signals and lead to inconsistent characterization of dynamic brain connectivity across scans. Existing graph-based solutions often struggle with parameter sensitivity, since their outcomes depend heavily on selecting an arbitrary correlation threshold for defining network edges. In contrast, topological data analysis (TDA) sweeps across all threshold values to track the persistence of connectivity features, making it more robust for capturing fine-grained temporal dynamics. Clustering methods become imperative in this context as they offer a powerful means to uncover underlying structures within the high-dimensional temporal data.We address these challenges by developing a topological data analysis based temporal clustering pipeline targeted for dynamic functional connectivity derived from fMRI datasets that can preserve the dynamics of the temporal datasets and mask out the non-neural variability induced by varying sampling rates. The TDA-based pipeline extracts robust features that are invariant to non-neural noise and uses them to perform temporal clustering. We evaluate our framework by performing temporal clustering of resting-state fMRI-derived dynamic functional connectivity brain networks obtained from 316 subjects, each of whom was scanned thrice using different temporal sampling periods. The efficacy of our TDA-based pipeline is compared against three alternative approaches: direct time-series clustering, PCA-based dimensionality reduction and clustering, and a traditional fully connected network analysis pipeline with MDS-based dimensionality reduction. Additionally, we demonstrate that for a majority of cases, the number of clusters remains consistent for the same subjects scanned at different temporal sampling rates– showcasing the greater robustness of our TDA-based pipeline compared to other pipelines. The TDA pipeline achieved higher overlaps (59 %) in optimal cluster numbers across sampling cohorts, as well as higher pairwise similarity (74-77 %) between subjects’ cluster solutions. This indicates that incorporating network topology via TDA enables more robust clustering of temporal fMRI datasets despite changes in sampling rates.Furthermore, we validate our method on a clinical dataset (ADHD-200). The TDA-based pipeline successfully captures consistent clustering patterns across different sites and scanning protocols, with higher stability of cluster assignments (> 80% similarity) and better separation of subject-level dynamics compared to existing approaches. This reinforces the method’s robustness in multi-site, multi-condition settings. Our results demonstrate that incorporating network topology via TDA significantly enhances the reliability of temporal clustering in fMRI studies, offering a robust framework for studying brain dynamics across heterogeneous acquisition settings. INDEX TERMS  Temporal fMRI, topological data analysis, persistent homology.