Fatigue, effort perception and central activation failure in chronic stroke survivors: a TMS and fMRI investigation

Fatigue is commonly seen in stroke survivors and the most common manifestation of fatigue is the requirement of high effort for activities of daily life. In this study we set out to identify the neural correlates of perceived effort and central activation failure, a neurophysiological measure correlated with perceived effort. Methods: Twelve chronic stroke survivors participated in this study. Fatigue levels were quantified using the Fatigue Severity Scale -7, perceived effort was quantified using a 1-10 numerical rating scale while performing an isometric biceps hold task, Central Activation Failure was quantified using the modified twitch interpolation technique using Transcranial Magnetic Stimulation and functional Magnetic Resonance Imaging was used to measure blood-oxygen-level dependent signal (BOLD) from the brain while the participant performed a hand grip task. Analysis: Following standard pre-processing procedures for fMRI data using SPM software, co-variance of BOLD signal with perceived effort levels and central activation failure was evaluated. Correlation analysis was performed between measures of fatigue and effort. Results: The main findings of this study were 1) high fatigue was associated with high perceived effort 2) higher perceived effort was associated with greater increase in BOLD fMRI activity in pre-SMA and the ipsilateral inferior frontal gyrus with increasing force 3) greater Central Activation Failure was associated with higher increase in BOLD fMRI activity in bilateral caudate, contralateral superior frontal gyrus and pre-motor cortices with increasing force.