Altered spreading of fast aperiodic brain waves relates to disease duration in Amyotrophic Lateral Sclerosis

Abstract

Abstract Amyotrophic lateral sclerosis (ALS) is a multisystem disorder, as supported by clinical, molecular and neuroimaging evidence. Functional connectivity (FC) studies show alterations in the topological organization of brain network in ALS patients, demonstrating a hyper-connectedness as the disease progresses. This functionally hyper-connected network can be linked to altered brain dynamics, since the brain activity is characterized by large-scale bursts of activations, defined as neuronal avalanches. The number of unique avalanche patterns (i.e., the size of the functional repertoire) might be used as a readout of brain flexibility. In fact, we have previously shown that the size of the functional repertoire is reduced in ALS and predicts clinical disability. However, this approach did not provide information on the spatio-temporal spreading of neuronal avalanches in the brain. In this work, we hypothesized that ALS patients would show an altered spreading of neuronal avalanches. To test our hypothesis, we obtained the source-reconstructed MEG signals from thirty-six ALS patients and forty-two healthy controls. Then, we used the construct of the avalanche transition matrix (ATM), which represents the probability that two brain regions are consecutively recruited in an avalanche, and used the corresponding network parameter nodal strength to quantify the changes in each region. In fact, this parameter provides key information about which brain regions are mostly involved in the spreading avalanches. Our work demonstrated that ALS patients present higher values of the nodal strength in both cortical and sub-cortical brain areas. Furthermore, the nodal strength correlates directly with disease duration.