Inter-hemispheric inhibition in stroke survivors is related to fatigue and cortical excitability

Objective: Persistent post-stroke fatigue is a major debilitating condition that has been linked to low corticomotor excitability and aberrant attention, both phenomena that are associated with the inter-hemispheric inhibition balance in the brain. In this study, we examined the relationship between inter-hemispheric inhibitory effective connectivity, motor cortex excitability and chronic persistence of post-stroke fatigue. Methods: We tested eighteen non-depressed stroke survivors with minimal motoric and cognitive impairments using spectral dynamic causal modelling (spDCM) of resting state magnetic resonance imaging (rs-fMRI) and transcranial magnetic stimulation (TMS) measures of cortical excitability. We also assessed the levels of non-exercise induced, persistent fatigue using Fatigue Severity Scale (FSS) - a self-report questionnaire which has been widely applied and validated across different conditions. To understand neural effective connectivity mechanisms involved in fatigue and corticomotor excitability we examined the balance in inhibitory connectivity between homologue regions in M1, anterior insula, caudate and thalamus of the resting brain. Results: Inter-hemispheric inhibition balance between left and right M1 accounted for 67% of variability in the reported fatigue (R=.82, p<0.001). Inter-hemispheric inhibition balance in M1 also accounted for 54% of variability in the corticomotor excitability characterised by individual resting motor thresholds (R=.74, p<0.001), a measure that has been associated with subjective fatigue reports. Other examined inter-hemispheric connections did not show significant relationships with either fatigue or cortical excitability measures. Conclusion: Our findings suggest that the balance in inter-hemispheric effective connectivity between primary motor regions is involved in regulation of corticomotor excitability and could explain subjective post-stroke fatigue.