Fatigue following mild traumatic brain injury relates to visual processing and effort perception in the context of motor performance

INTRODUCTION: Following mild traumatic brain injury (mTBI), a substantial number of patients experience disabling fatigue for months after the initial injury. To date, the underlying mechanisms of fatigue remain unclear. Recently, it was shown that mTBI patients with persistent fatigue do not demonstrate increased performance fatigability (i.e., objective performance decline) during a sustained motor task. However, it is not known whether the neural activation required to sustain this performance is altered after mTBI. METHODS: Blood oxygen level-dependent (BOLD) fMRI data were acquired from 19 mTBI patients (>3 months post-injury) and 19 control participants during two motor tasks. Force was recorded from the index finger abductors of both hands during submaximal contractions and a 2-minute maximal voluntary contraction (MVC) with the right hand. Voluntary muscle activation (i.e., CNS drive) was indexed during the sustained MVC using peripheral nerve stimulation. Fatigue was quantified using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Questionnaire, task, and BOLD data were compared across groups, and linear regression was used to evaluate the relationship between BOLD-activity and fatigue in the mTBI group. RESULTS: The mTBI patients reported significantly higher levels of fatigue (FSS: 5.3 vs. 2.6, p < 0.001). Both mTBI- and control groups demonstrated significant performance fatigability during the sustained MVC, but no significant differences in task performance or BOLD-activity were observed between groups. However, mTBI patients reporting higher FSS scores showed increased BOLD-activity in the bilateral visual cortices (mainly extrastriate) and the left midcingulate gyrus. Furthermore, across all participants mean voluntary muscle activation during the sustained MVC correlated with long lasting post-contraction BOLD-activation in the right insula and midcingulate cortex. CONCLUSION: The fMRI findings suggest that self-reported fatigue in mTBI may relate to visual processing and effort perception. Long lasting activation associated with high levels of CNS drive might be related to changes in cortical homeostasis in the context of high effort.