Structural and functional brain connectome in motor neuron diseases: A multicenter MRI study

Objective: To investigate structural and functional neural organization in amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) patients. Methods: 173 ALS, 38 PLS, 28 PMA sporadic patients and 79 healthy controls were recruited from three Italian centers. Subjects underwent clinical, neuropsychological and brain MRI evaluations. Using graph analysis and connectomics, global and lobar topological network properties and regional structural and functional brain connectivity were assessed. The association between structural and functional network organization and clinical/cognitive data was investigated. Results: Compared to healthy controls, ALS and PLS patients showed altered structural global network properties, as well as local topological alterations and decreased structural connectivity in sensorimotor, basal ganglia, frontal and parietal areas. PMA patients showed preserved global structure. Patient groups did not show significant alterations of functional network topological properties relative to controls. Increased local functional connectivity was observed in ALS patients in the precentral, middle and superior frontal areas, and in PLS patients in the sensorimotor, basal ganglia and temporal networks. In both ALS and PLS patients, structural connectivity alterations correlated with motor impairment, while functional connectivity disruption was closely related to executive dysfunctions and behavioral disturbances. Conclusions: This multicenter study showed widespread motor/extra-motor network degeneration in ALS and PLS, suggesting that graph analysis and connectomics might represent a powerful approach to detect upper motor neuron degeneration, extra-motor brain changes and network reorganization associated with the disease. Network-based advanced MRI provides an objective in vivo assessment of motor neuron diseases, delivering potential prognostic markers.