Brain Plasticity Effects of Neuromodulation Against Multiple Sclerosis Fatigue

Abstract

RationaleWe recently reported on the efficacy of a personalized transcranial direct current stimulation (tDCS) treatment in reducing multiple sclerosis (MS) fatigue. The result supports the notion that interventions targeted at modifying abnormal excitability within the sensorimotor network could represent valid non-pharmacological treatments.ObjectiveThe present work aimed at assessing whether the mentioned intervention also induces changes in the excitability of sensorimotor cortical areas.MethodTwo separate groups of fatigued MS patients were given a 5-day tDCS treatments targeting, respectively, the whole body somatosensory areas (S1wb) and the hand sensorimotor areas (SM1hand). The study had a double blind, sham-controlled, randomized, cross-over (Real vs. Sham) design. Before and after each treatment, we measured fatigue levels (by the modified fatigue impact scale, mFIS), motor evoked potentials (MEPs) in response to transcranial magnetic stimulation and somatosensory evoked potentials (SEPs) in response to median nerve stimulation. We took MEPs and SEPs as measures of the excitability of the primary motor area (M1) and the primary somatosensory area (S1), respectively.ResultsThe Real S1wb treatment produced a 27% reduction of the mFIS baseline level, while the SM1hand treatment showed no difference between Real and Sham stimulations. M1 excitability increased on average 6% of the baseline in the S1wb group and 40% in the SM1hand group. Observed SEP changes were not significant and we found no association between M1 excitability changes and mFIS decrease.ConclusionThe tDCS treatment was more effective against MS fatigue when the electrode was focused on the bilateral whole body somatosensory area. Changes in S1 and M1 excitability did not correlate with symptoms amelioration.SignificanceThe neuromodulation treatment that proved effective against MS fatigue induced only minor variations of the motor cortex excitability, not enough to explain the beneficial effects of the intervention.

The Tolerability and Efficacy of 4 mA Transcranial Direct Current Stimulation on Leg Muscle Fatigability

“…Other studies in PwMS also showed no significant improvements on fatigue questionnaires from unilateral prefrontal or parietal tDCS stimulation applied daily for five consecutive days [29][30][31]. However, tDCS applied daily for five consecutive days over the primary somatosensory cortex (S1) bilaterally [32][33][34], the primary motor cortex (M1) bilaterally [35], and the sensorimotor cortex bilaterally [33], showed significant fatigue improvements. The discrepancy in the results might be related to the differences in stimulation targets, protocol duration (single session vs. five daily sessions) and the adapted current intensity applied in these studies (e.g., all of these protocols used intensities ≤2 mA).…”

Fatigue in multiple sclerosis – Insights into evaluation and management

“…However, the stimulation site differed among studies, in which the targets were chosen as follows: bilateral primary motor cortex [56], bilateral primary sensory cortex [222,223], bilateral sensorimotor cortex [223] left dorsolateral prefrontal cortex (DLPFC) [25,192], or right posterior parietal cortex (PPC) [25]. While stimulation of bilateral sensory and/or motor cortices [56,222,223] resulted in significant fatigue improvement compared to sham, efficacy of the DLPFC stimulation showed discrepancy among studies. In fact, our team found a significant fatigue reduction following left prefrontal cortex stimulation [25]; but this was not the case in the work done by Saiote et al where the whole group analysis failed to document any difference between active and sham conditions [192].…”

Beyond rehabilitation in MS: Insights from non-invasive brain stimulation

“…Bilateral tDCS over M1 has been applied for 5 days in 25 MS subjects with chronic fatigue in a cross-over study, with significant decrease in 65% of subjects after real versus 30% after sham stimulation; the effect persisted after 3 weeks. 29 Tecchio et al 30,31 obtained positive results applying anodal tDCS bilaterally over the whole somatosensory area. Anodal tDCS over the left dorsolateral prefrontal cortex (L-DLPFC) significantly ameliorated fatigue in two sham-controlled studies.…”

“…35 Finally, no effect on fatigue has been obtained from anodal tDCS of the right posterior parietal cortex. 32 Besides heterogeneity in clinical features of participants and stimulation site, inconsistent results obtained with tDCS may also be related to the relatively short intervention, from up to 5 days in most studies [29][30][31][32]34 to 20 days, 33 and the lack of a behavioral intervention.…”