Disrupted effective connectivity of the sensorimotor network in amyotrophic lateral sclerosis

Although dysfunctional sensorimotor network (SMN) has been frequently involved in the pathogenesis of amyotrophic lateral sclerosis (ALS), the causal relationship within this network remains unexplored. In this study, spectral dynamic causal modeling was applied to resting-state functional magnetic resonance imaging data to estimate the causal relationship of SMN in a cohort of 20 ALS patients and 21 healthy controls. The SMN components were first extracted using an independent component analysis, and then compared between the two groups to identify the abnormalities in SMN. In ALS patients, we found significant regional activity alterations in the left primary motor cortex (M1), the left primary somatosensory cortex (S1), and the right supplementary motor cortex (SMA). Among these regions, spectral DCM revealed missing closed-loop circuit between the left M1 and the right SMA, and lost projection from the right SMA to the left S1 in ALS. These findings may reflect the influences of the loss of motor neurons on motor function in ALS, and provide compelling evidence for a breakdown of the sensorimotor neural circuits in ALS. In conclusion, this study elucidates a neurobiological model that may explain the functional impairments of the SMN in ALS, and provides much deeper insights into the pathophysiology of this disease.