Cortical neurodynamics changes mediate the efficacy of a personalized neuromodulation against multiple sclerosis fatigue

The people with multiple sclerosis (MS) often report that fatigue restricts their life. Nowadays, pharmacological treatments are poorly effective accompanied by relevant side effects. A 5-day transcranial direct current stimulation (tDCS) targeting the somatosensory representation of the whole body (S1) delivered through an electrode personalized based on the brain MRI was efficacious against MS fatigue (FaReMuS treatment). This proof of principle study tested whether possible changes of the functional organization of the primary sensorimotor network induced by FaReMuS partly explained the effected fatigue amelioration. We measured the brain activity at rest through electroencephalography equipped with a Functional Source Separation algorithm and we assessed the neurodynamics state of the primary somatosensory (S1) and motor (M1) cortices via the Fractal Dimension and their functional connectivity via the Mutual Information. The dynamics of the neuronal electric activity, more distorted in S1 than M1 before treatment, as well as the network connectivity, altered maximally between left and right M1 homologs, reverted to normal after FaReMuS. The intervention-related changes explained 48% of variance of fatigue reduction in the regression model. A personalized neuromodulation tuned in on specific anatomo-functional features of the impaired regions can be effective against fatigue.