Effects on Corticospinal Tract Homology of Faremus Personalized Neuromodulation Relieving Fatigue in Multiple Sclerosis: A Proof-of-Concept Study

Abstract

Objectives: Fatigue in multiple sclerosis (MS) is a frequent and invalidating symptom, which can be relieved by non-invasive neuromodulation, which presents only negligible side effects. A 5-day transcranial direct-current stimulation, 15 min per day, anodically targeting the somatosensory representation of the whole body against a larger occipital cathode was efficacious against MS fatigue (fatigue relief in multiple sclerosis, Faremus treatment). The present proof-of-concept study tested the working hypothesis that Faremus S1 neuromodulation modifies the homology of the dominant and non-dominant corticospinal (CST) circuit recruitment. Methods: CST homology was assessed via the Fréchet distance between the morphologies of motor potentials (MEPs) evoked by transcranial magnetic stimulation in the homologous left- and right-hand muscles of 10 fatigued MS patients before and after Faremus. Results: In the absence of any change in MEP features either as differences between the two body sides or as an effect of the treatment, Faremus changed in physiological direction the CST’s homology. Faremus effects on homology were more evident than recruitment changes within the dominant and non-dominant sides. Conclusions: The Faremus-related CST changes extend the relevance of the balance between hemispheric homologs to the homology between body sides. With this work, we contribute to the development of new network-sensitive measures that can provide new insights into the mechanisms of neuronal functional patterning underlying relevant symptoms.

Musician's dystonia: an opinion on novel treatment strategies

“…We note that in that intervention, the targets of neuromodulation were left vs. right primary sensorimotor homologs, whereas bilateral alterations are typically observed in task-specific focal dystonia (Melgari et al, 2013 ; Dresel et al, 2014 ), suggesting the appropriateness of a bilateral intervention. On this basis, we believe that the proposed S1 neuromodulation (Tecchio et al, 2014 ; Cancelli et al, 2018 ) can offer a promising therapeutic enrichment, inducing bilateral rather than unilateral facilitation, and focusing the facilitatory effects on somatosensory rather than sensorimotor areas supporting the physiological sensorimotor integration processing (Porcaro et al, 2019 ; Padalino et al, 2021 ; Bertoli et al, 2023 ).…”

Functional balance at rest of hemispheric homologs assessed via normalized compression distance

“…Recent findings show that as right-hand dominance increases, the similarity in the homologous corticospinal tracts’ recruitment patterns also increases ( Pagliara et al, 2023 ). Furthermore, a neuromodulation intervention relieving chronic fatigue normalized these inter-lateral balances ( Bertoli et al, 2023 ). This underscores the potential of using resting-state indices to evaluate hemispheric homology, particularly for chronic symptom management.…”

“…The inter-hemispheric balance is crucial in chronic conditions such as fatigue ( Cogliati Dezza et al, 2015 ; Ondobaka et al, 2022 ), and it influences the severity of stroke ( Deco and Corbetta, 2011 ; Pellegrino et al, 2012 ; Zappasodi et al, 2014 ; Soleimani et al, 2023 ) and aging ( Cottone et al, 2013 ). In particular, neuromodulation interventions aimed at relieving fatigue have been observed to restore the physiological homology of primary motor areas ( Porcaro et al, 2019 ) and of the cortico-spinal tracts ( Bertoli et al, 2023 ).…”

Personalized strategies of neurostimulation: from static biomarkers to dynamic closed-loop assessment of neural function

“…Previous trials have shown promising results on the efficacy of Faremus ( Tecchio et al, 2016 ; Cancelli et al, 2018b ). Recently, the authors reached an average improvement in fatigue levels of 27%, which is considered clinically significant ( Bertoli et al, 2023 ). The ongoing adaptation and personalized nature of Faremus allow for long-term effectiveness and the potential to explore fatigue re-emergence over time.…”

“…Moreover, personalized neurostimulation interventions have revealed alterations in neural connectivity as Faremus-induced neurostimulation have been demonstrated to have an impact in the connectivity between dominant and non-dominant corticospinal tracts. This emphasized the specific effect that personalized interventions can have on an individual’s neural connectivity and organization ( Porcaro et al, 2019 ), highlighting the importance of tailoring treatments to target the central nervous system in conditions such as MS fatigue ( Bertoli et al, 2023 ).…”