Is Fatigue Response to Tdcs Mediated by Change in Affect? an Open-label Tdcs-Mri Study

Objective: 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. Background: 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. Design/Methods: In this open-label trial, participants with MS and fatigue (Fatigue Severity Score>36) were enrolled in an intervention of 20×20-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). Results: 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). Conclusions: 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. Disclosure: Dr. Pilloni has nothing to disclose. The institution of an immediate family member of Lillian Walton Masters has received research support from LANDENBERGER FAMILY FOUNDATION. The institution of an immediate family member of Lillian Walton Masters has received research support from NIH. Marco Muccio has nothing to disclose. Ms. Choi has nothing to disclose. Abhishek Datta has nothing to disclose. Marom Bikson has received intellectual property interests from a discovery or technology relating to health care. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lerhman. Dr. Krupp has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for medscape. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroLive. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Krupp has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Cleveland Clinic. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for MCIC. The institution of Dr. Krupp has received research support from Biogen. The institution of Dr. Krupp has received research support from National Multiple Sclerosis Society. Dr. Krupp has received intellectual property interests from a discovery or technology relating to health care. Yulin Ge has nothing to disclose. Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson & Johnson. Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springer Healthcare. Dr. Charvet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for YBrain. Dr. Charvet has stock in Johnson&Johnson.