The human functional connectome in neurodegenerative diseases: relationship to pathology and clinical progression

Introduction: Neurodegenerative diseases can be considered as 'disconnection syndromes,' in which a communication breakdown prompts cognitive or motor dysfunction. Mathematical models applied to functional resting-state MRI allow for the organization of the brain into nodes and edges, which interact to form the functional brain connectome. Areas covered: The authors discuss the recent applications of functional connectomics to neurodegenerative diseases, from preclinical diagnosis, to follow up along with the progressive changes in network organization, to the prediction of the progressive spread of neurodegeneration, to stratification of patients into prognostic groups, and to record responses to treatment. The authors searched PubMed using the terms 'neurodegenerative diseases' AND 'fMRI' AND 'functional connectome' OR 'functional connectivity' AND 'connectomics' OR 'graph metrics' OR 'graph analysis.' The time range covered the past 20 years. Expert opinion: Considering the great pathological and phenotypical heterogeneity of neurodegenerative diseases, identifying a common framework to diagnose, monitor and elaborate prognostic models is challenging. Graph analysis can describe the complexity of brain architectural rearrangements supporting the network-based hypothesis as unifying pathogenetic mechanism. Although a multidisciplinary team is needed to overcome the limit of methodologic complexity in clinical application, advanced methodologies are valuable tools to better characterize functional disconnection in neurodegeneration.