Group III/IV locomotor muscle afferents alter motor cortical and corticospinal excitability and promote central fatigue during cycling exercise

•In the absence of fatigue: Group III/IV muscle afferents facilitate motor cortex.•In presence of fatigue: Group III/IV muscle afferents disfacilitate motor cortex.•Group III/IV muscle afferents promote central fatigue during endurance exercise.

ObjectiveTo investigate the influence of group III/IV muscle afferents on the development of central fatigue and corticospinal excitability during exercise.MethodsFourteen males performed cycling-exercise both under control-conditions (CTRL) and with lumbar intrathecal fentanyl (FENT) impairing feedback from leg muscle afferents. Transcranial magnetic- and cervicomedullary stimulation was used to monitor cortical versus spinal excitability.ResultsWhile fentanyl-blockade during non-fatiguing cycling had no effect on motor-evoked potentials (MEPs), cervicomedullary-evoked motor potentials (CMEPs) were 13 ± 3% higher (P < 0.05), resulting in a decrease in MEP/CMEP (P < 0.05). Although the pre- to post-exercise reduction in resting twitch was greater in FENT vs. CTRL (−53 ± 3% vs. −39 ± 3%; P < 0.01), the reduction in voluntary muscle activation was smaller (−2 ± 2% vs. −10 ± 2%; P < 0.05). Compared to the start of fatiguing exercise, MEPs and CMEPs were unchanged at exhaustion in CTRL. In contrast, MEPs and MEP/CMEP increased 13 ± 3% and 25 ± 6% in FENT (P < 0.05).ConclusionDuring non-fatiguing exercise, group III/IV muscle afferents disfacilitate, or inhibit, spinal motoneurons and facilitate motor cortical cells. In contrast, during exhaustive exercise, group III/IV muscle afferents disfacilitate/inhibit the motor cortex and promote central fatigue.SignificanceGroup III/IV muscle afferents influence corticospinal excitability and central fatigue during whole-body exercise in humans.