Behavioral and Neural Correlates of Post-STROKE Fatigue: A Randomized Controlled Trial Protocol

Introduction Post-stroke fatigue (PSF) is highly prevalent and lacks of effective management. Recent evidence suggest the use of transcranial direct current stimulation (tDCS) to reduce PSF. However, the effect was not lasting and the working mechanisms was unclear. The purpose of this study is to determine the behavioral and neurophysiological effects of five daily sessions of tDCS on PSF. Methods and analysis This will be a double-blind randomized controlled trial targeting an enrollment of 32 participants with subacute-chronic stroke and significant fatigue (average Fatigue Severity Scale (FSS) > 4). Participants will be equally randomized to either anodal tDCS or sham tDCS groups. The anodal tDCS group will receive 20 minutes of 2-mA anodal tDCS applied to the ipsilesional primary motor cortex (M1) for five consecutive days. The sham tDCS group will receive the same protocol except there will be no active current delivered. Outcome assessments will take place at baseline (prior to randomization), immediately after the intervention, and at one-month follow-up. The primary behavioral outcome will be the FSS and the primary neurophysiological outcome will be an input-output curve of motor cortex excitability derived using transcranial magnetic stimulation. Secondary behavioral outcomes will include Fatigue Scale for Motor and Cognitive Function, Visual Analog Scale-Fatigue, Borg Rating of Perceived Exertion, and Paas Mental Effort Rating Scale. Secondary neurophysiological outcome will be the functional connectivity of the fronto-striato-thalamic network acquired using resting state functional Magnetic Resonance Imaging (MRI). Repeated measure ANOVA or ANCOVA will be conducted for all outcomes to compare the change between groups. Discussion Little is known about effective treatments for PSF and the underlying mechanisms of PSF. tDCS is a promising tool to provide targeted intervention to reduce PSF symptoms. However, its lasting effect and working mechanism on PSF is elusive. The results of this clinical trial will offer critical information for PSF management and investigation. Trial registration This trial was registered in February 1 2024 with ClinicalTrials.gov under the registration number NCT06088914.