The Topological Architecture of Brain Identity

Simone Poetto, Haily Merritt, Andrea Santoro, Giovanni Rabuffo, Karolina Finc, Demian A Battaglia, Francesco Vaccarino, Manish Saggar, Andrea Brovelli, Giovanni Petri

Abstract: p>Accurately identifying individuals from brain activity—functional fingerprinting—is a powerful tool for understanding individual variability and detecting brain disorders. Most current approaches rely on functional connectivity (FC), which measures pairwise correlations between brain regions. However, FC is limited in capturing the higher-order, multiscale structure of brain organization. Here, we propose a novel fingerprinting method based on homological scaffolds, a topological repre-sentation derived from persistent homology of resting-state fMRI data. Using data from the Human Connectome Project (<i>n</i> = 100), we show that scaffold-based fingerprints achieve near-perfect identification accuracy ( <i>∼</i> 100%), outperforming FC-based methods (90%), and remain robust across preprocessing pipelines, atlas choices, and even with drastically shortened scan durations. Unlike FC, in which fingerprinting features localize within networks, scaffolds derive their discriminative power from inter-network connections, revealing the existence of individual mesoscale organizational signatures. Finally, we show that scaffolds bridge redundancy and synergy by balancing redundant information along high-FC border edges with synergistic interactions across the topological voids they enclose. These findings establish topological scaffolds as a powerful tool for capturing individual variability, revealing that unique signatures of brain organization are encoded in the interplay between mesoscale network integration and information dynamics.</p>

External IDs:doi:10.1101/2025.06.20.660792