Vigilance Improves in People with Multiple Sclerosis (MS) and Fatigue following Repeated Dorsolateral Prefrontal Cortex Transcranial Direct Current Stimulation (tDCS) Sessions Paired with Cognitive Training Delivered at Home
Leigh Charvet1, Lillian Walton Masters3, Claire Choi4, Marco Muccio2, Yulin Ge2, Lauren Krupp1, Giuseppina Pilloni1
1Neurology, 2Radiology, NYU Grossman School of Medicine, 3Thomas Jefferson University, 4SUNY Downstate

To determine the efficacy of at-home transcranial direct current stimulation (tDCS) in people with multiple sclerosis (MS)-associated fatigue. 


Fatigue in cognitive functioning is frequently reported in people with MS. Attentional vigilance, measured by response time and its variability across a period of sustained performance, can serve as an objective marker of self-reported cognitive fatigue. The dorsolateral prefrontal cortex (DLPFC) is a known substrate associated with self-reported fatigue and vigilance. 


People with MS and fatigue (Fatigue Severity Scale>36) and without severe cognitive impairment (z-score Symbol Digit Modality Test [SDMT] > -3.0) were enrolled in an open-label study to receive 20x20-minute daily at-home sessions of tDCS paired with adaptive cognitive training (aCT, Posit Science’s BrainHQ) using a remotely supervised protocol. Stimulation was administered over the DLPFC (anode F3, cathode F4) for 20 minutes at 2.0 mA. Attentional vigilance was measured by reaction time and variability on continuous performance tasks (Cogstate). Age was controlled by adjusting to normative z-scores to create a single composite vigilance z-score. 


Participants were n=24 (63% female, ages 22 to 71 years, and median Expanded Disability Status Scale (EDSS) score of 3.2 [1.0-6.5]). The intervention was safe and well tolerated, with n= 23/24 (96%) of them completing all 20 sessions. No significant improvement in SDMT was shown at the end of the intervention (-0.53±1.50 vs. -0.24±-1.45, p=0.101). However, the combined intervention of active tDCS and aCT led to an improvement in vigilance composite score (time and variability, mean z-score improvement: -0.89±1.94, p=0.036) as well as reaction time specific (mean detection (DET) z-score improvement: -0.46±1.02, p=0.038; mean identification (IDN) z-score improvement: -0.83±1.28, p=0.04).


Delivered as an at-home intervention, left DLPFC tDCS paired with aCT improves attentional vigilance in people with MS and fatigue. Vigilance can therefore provide an objective measure of cognitive fatigue in MS.