Neurodegeneration of brain networks in the amyotrophic lateral sclerosis–frontotemporal lobar degeneration (ALS–FTLD) continuum: evidence from MRI and MEG studies

Brain imaging techniques, especially those based on magnetic resonance imaging (MRI) and magnetoencephalography (MEG), have been increasingly applied to study multiple large-scale distributed brain networks in healthy people and neurological patients. With regard to neurodegenerative disorders, amyotrophic lateral sclerosis (ALS), clinically characterized by the predominant loss of motor neurons and progressive weakness of voluntary muscles, and frontotemporal lobar degeneration (FTLD), the second most common early-onset dementia, have been proven to share several clinical, neuropathological, genetic, and neuroimaging features. Specifically, overlapping or mildly diverging brain structural and functional connectivity patterns, mostly evaluated by advanced MRI techniques—such as diffusion tensor and resting-state functional MRI (DT–MRI, RS–fMRI)—have been described comparing several ALS and FTLD populations. Moreover, though only pioneering, promising clues on connectivity patterns in the ALS–FTLD continuum may derive from MEG investigations. We will herein overview the current state of knowledge concerning the most advanced neuroimaging findings associated with clinical and genetic patterns of neurodegeneration across the ALS–FTLD continuum, underlying the possibility that network-based approaches may be useful to develop novel biomarkers of disease for adequately designing and monitoring more appropriate treatment strategies.