Limitations and future directions
reduced cerebellar excitability, decreased cerebellar excitability, fatigue
RECRUITMENT, CORTEX, BROWN
CBI reflects the connectivity between the cerebellum and the primary motor cortex (M1). Specifically, it is the result of Purkinje cell activation by the CS, leading to inhibition of the deep cerebellar nuclei, which in turn have an excitatory connection with M1 via thalamic nuclei (Another intrinsic limitation of using TMS as a technique to assess cerebellar excitability is that participants can find the stimulation over the cerebellum quite uncomfortable (Last, we observe that some individuals show CBI values >1 after the fatigue task, which may reflect facilitation of the MEP with cerebellar conditioning. We are unaware of a specific physiological mechanism underlying this observation and propose that these values may reflect a reduction in activity of Purkinje cells and noise in the MEP measurement.In conclusion, we aimed to understand how cerebellar excitability is modulated after a fatiguing task and its association with fatigue and performance. We demonstrated that reduced cerebellar excitability after a fatiguing task relates to milder fatigue but worse motor control. These results suggest that decreased cerebellar excitability minimizes fatigue at the expense of performance. We propose that the cerebellum may help regulate both performance and fatigue, but modulation of fatigue interplays with optimal motor control. Future work should test this hypothesis to better understand fatigue and develop effective treatment and rehabilitation strategies for this common and debilitating symptom.This work was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award Numbers R01HD053793 to PC and R01HD097619 to VSC, as well as the National Institutes of Mental Health under Award Numbers R56MH113627 and R01MH119086 to VSC. We report how we determined our sample size, all data exclusions, all inclusion/exclusion criteria, whether inclusion/exclusion criteria were established prior to data analysis, all manipulations, and all measures for this study. The conditions of our ethics approval do not permit public archiving of any anonymized data. Readers seeking access to the data should contact the corresponding author. Access will be granted to named individuals in accordance with ethical procedures governing the reuse of data. Specifically, requestors must complete a formal data sharing agreement. We thank Dr. Michael Brown for technical support; Dr. Manuel Anaya for help with recruitment and compensation of participants; and Dr. Amy Bastian for constructive feedback on the experimental design, analysis, and interpretation of these studies.The authors declare no competing financial interests.