Imaging Neurodegeneration: Steps Toward Brain Network-Based Pathophysiology and Its Potential for Multi-modal Imaging Diagnostics

Purpose: Multi-modal brain imaging provides different in vivo windows into the human brain and thereby different ways to characterize brain disorders. Particularly, resting-state functional magnetic resonance imaging facilitates the study of macroscopic intrinsic brain networks, which are critical for development and spread of neurodegenerative processes in different neurodegenerative diseases. The aim of the current study is to present and highlight some paradigmatic findings in intrinsic network-based pathophysiology of neurodegenerative diseases and its potential for new network-based multimodal tools in imaging diagnostics. Methods: Qualitative review of selected multi-modal imaging studies in neurodegenerative diseases particularly in Alzheimer’s disease (AD). Results: Functional connectivity of intrinsic brain networks is selectively and progressively impaired in AD, with changes likely starting before the onset of symptoms in fronto-parietal key networks such as default mode or attention networks. Patterns of distribution and development of both amyloid-β plaques and atrophy are linked with network connectivity changes, suggesting that start and spread of pathology interacts with network connectivity. Qualitatively similar findings have been observed in other neurodegenerative disorders, suggesting shared mechanisms of network-based pathophysiology across diseases. Conclusion: Spread of neurodegeneration is intimately linked with the functional connectivity of intrinsic brain networks. These pathophysiological insights pave the way for new multi-modal network-based tools to detect and characterize neurodegeneration in individual patients.