Network control theory applied to the human connectome: A study on variability and discriminability of fMRI...

Network control theory (NCT) models human connectomes as high-dimensional input-state-output stable systems where the efficiency of neural connections can be addressed by energy cost (of state transitions) and controllability (from/to reachable states). Different options are available to extract NCT features: initial/final states, control time horizon, structural (vs. functional), and static (vs. dynamic) connectivity measure. Leveraging the minimum control paradigm, assuming the Schur stability for discrete systems, we investigate intra- and inter-individual variability of NCT features, across different settings and datasets, and assess their potential as useful connectome metrics in clinical studies. NCT was applied to structural and functional MRI (fMRI), in a cohort of 82 cognitively unimpaired elderly subjects with normal or (age-related) sensorineural condition (hearing loss), and in young adults from the Human Connectome Project database. Results demonstrated low intra-individual and moderate within-group inter-individual variability of NCT features. The energy cost was related to the time horizon of the system but did not discriminate groups. Controllability analyses revealed significant group effects and acceptable discrimination between normal and disease-affected connectomes, particularly for the default-mode network. We provide a systematic evaluation of different settings for fMRI-derived NCT features that may help guiding clinical applications toward capturing neurologically meaningful changes in the human connectome.