The potential of the human connectome as a biomarker of brain disease

The human connectome at the level of fiber tracts between brain regions has been shown to differ in patients with brain disorders compared to healthy control groups. Nonetheless, there is a potentially large number of different network organizations for individual patients that could lead to cognitive deficits prohibiting correct diagnosis. Therefore changes that can distinguish groups might not be sufficient to diagnose the disease that an individual patient suffers from and to indicate the best treatment option for that patient. We describe the challenges introduced by the large variability of connectomes within healthy subjects and patients and outline three common strategies to use connectomes as biomarkers of brain diseases. Finally, we propose a fourth option in using models of simulated brain activity (the dynamic connectome) based on structural connectivity rather than the structure (connectome) itself as a biomarker of disease. Dynamic connectomes, in addition to currently used structural, functional, or effective connectivity, could be an important future biomarker for clinical applications.