Is Fatigue Response to tDCS Mediated by Change in Affect? An Open-label tDCS-MRI Study
Giuseppina Pilloni1, Lillian Walton Masters3, Marco Muccio2, Claire Choi4, Abhishek Datta5, Marom Bikson6, Lauren Krupp1, Yulin Ge2, Leigh Charvet1
1Neurology, 2Radiology, NYU Grossman School of Medicine, 3Thomas Jefferson University, 4SUNY Downstate, 5Research and Development, Soterix Medical Inc, 6Biomedical Engineering, City College of New York
To evaluate a real-time brain metabolic biomarker of fatigue by measuring neuronal response to transcranial direct current stimulation (tDCS) and the corresponding link to negative and positive affect changes.

Repeated tDCS sessions targeting the dorsolateral prefrontal cortex (DLPFC) have been found to reduce the symptom of fatigue in patients with multiple sclerosis (MS) and other neurological conditions. DLPFC tDCS has been also shown to reduce negative affect and improve positive affect and is an effective treatment for major depression.

In this open-label trial, participants with MS and fatigue (Fatigue Severity Score>36) were enrolled in an intervention of 20x20-minute daily at-home tDCS sessions (2.0 mA, anode F3/cathode F4) paired with cognitive training. tDCS-MRI scans at baseline and follow-up were performed to measure real-time cerebral metabolic rate of oxygen (CMRO2) response to tDCS. tDCS-MRI was performed in a 3T scanner while wearing an MRI-compatible tDCS device. T2-Relaxation-Under-Spin-Tagging and phase contrast sequences were performed across 3 phases: pre-tDCS (current: 0mA), during tDCS (2mA), and post-tDCS (0mA). Self-reported outcomes assessed at baseline and follow-up were: self-reported fatigue (Modified Fatigue Impact Scale; MFIS), and affect (Positive and Negative Affect Schedule).
Participants were n=26 (58% female; age 48±11 years; median Expanded Disability Status Scale score of 3.5). Twenty daily sessions of tDCS led to a significant improvement in fatigue (51.7±13.9vs36.4±13.4, p<0.001) and a reduction in negative affect (13.6±5.2vs11.1±2.9, p=0.03). Fatigue reduction corresponded to increased positive affect (r=0.493, p=0.024). At baseline and follow-up, we found that CMRO2 increased significantly after tDCS (mean change baseline: 15.03±13.3ml/100g/min, p<0.001; mean change follow-up: 14.3±12.1ml/100g/min, p<0.001), and a greater neuronal response to tDCS at baseline (CMRO2) corresponded with a greater reduction in fatigue (MFIS; r=0.470, p=0.024). 

Fatigue reduction following tDCS is mediated by changes in affect and corresponds to simultaneous increases in tDCS-induced neuronal oxygen metabolic rate in patients with MS.