BackgroundThe neural mechanisms that underlie post-stroke fatigue are poorly understood. Previous work show an inverse relationship between motor cortex excitability and post-stroke fatigue, however, it is unclear if the side of lesion influences this relationship. The left hemisphere plays a dominant role in motor control, therefore we hypothesised that left hemisphere strokes are more likely to show a significant inverse relationship between corticospinal excitability and fatigue.MethodsResting motor threshold (measure of corticospinal excitability) using transcranial magnetic stimulation was measured in the affected hemisphere of 98 stroke survivors. Fatigue was measured using the fatigue severity scale. The effect of fatigue and hemisphere affected on corticospinal excitability was analysed using a multiple linear regression.ResultsA multiple linear regression with trait fatigue as the outcome variable (F(4,93)=12.04, p < 0.001, adj R2 = 0.313) revealed that RMT was not a significant predictor of FSS-7 (β = −0.063, p = 0.706, CI[-0.394, 0.268]), while the interaction between lesioned hemisphere and RMT was a significant predictor of FSS-7 (β = 0.339, p = 0.039, CI[0.018, 0.659]). The additional explanatory variables of HADSDepression and sex were also significant predictors of FSS-7 (β = 903, p < 0.001, CI[0.584, 1.223] and β = 1.127, p = 0.002, CI[0.425, 1.830] respectively).ConclusionLower corticospinal excitability of the left hemisphere may indicate altered perception of effort and reduced sensory attenuation. This provides evidence to support the sensory attenuation model of fatigue.