Resting‐state fMRI functional connectome of C9orf72 mutation status

Abstract

Abstract Objective The resting‐state functional connectome has not been extensively investigated in amyotrophic lateral sclerosis (ALS) spectrum disease, in particular in relationship with patients' genetic status. Methods Here we studied the network‐to‐network connectivity of 19 ALS patients carrying the C9orf72 hexanucleotide repeat expansion (C9orf72+), 19 ALS patients not affected by C9orf72 mutation (C9orf72−), and 19 ALS‐mimic patients (ALSm) well‐matched for demographic and clinical variables. Results When compared with ALSm, we observed greater connectivity of the default mode and frontoparietal networks with the visual network for C9orf72+ patients (P = 0.001). Moreover, the whole‐connectome showed greater node degree (P < 0.001), while sensorimotor cortices resulted isolated in C9orf72+. Interpretation Our results suggest a crucial involvement of extra‐motor functions in ALS spectrum disease. In particular, alterations of the visual cortex may have a pathogenic role in C9orf72‐related ALS. The prominent feature of these patients would be increased visual system connectivity with the networks responsible of the functional balance between internal and external attention.