Abstract

BackgroundCognitive impairment is a core symptom that profoundly impacts the lives of people with multiple sclerosis (PwMS). Since the existing disease modifying therapies can only stabilize, but not actively treat, cognition in PwMS, there is an unmet need to expand approaches to treat these cognitive symptoms. Transcranial alternating current stimulation (tACS) permits frequency-specific entrainment of neural oscillations intrinsic to cognitive activity. However, the effects of the tACS on cognitive function in PwMS have not yet been assessed. We aimed to evaluate the potential efficacy of applying frontal theta-tACS to improve information processing speed in PwMS. Methods60 PwMS with cognitive complaints were enrolled in a double-blinded, randomized, controlled trial with three stimulation groups: 2 mA, 1 mA, or sham control. A single session of theta-tACS was applied while participants were engaged in a cognitive program which has shown to improve processing speed in PwMS. tACS effects were examined by the Symbol Digit Modalities Test (SDMT). Tolerability, side effects and acceptability were measured. Results1 mA groups had a significantly higher SDMT score after stimulation compared to their pre-stimulation score, 2 mA group showed a marginally significant improvement of their SDMT score, while the SDMT score in the sham group did not change. Overall, 49% of the stimulation group participants showed a clinically meaningful SDMT improvement (4+-point increase). ConclusiontACS is a well-tolerated, non-pharmacological intervention. Based on the positive effects observed in the current study of a single session of tACS applied during cognitive engagement, the effects of repeated tACS on cognitive function in PwMS merit further research. Trial RegistrationClinicalTrials.gov NCT04466228.

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