Fatigue-induced increase in intracortical communication between mid/anterior insular and motor cortex during cycling exercise.

In the present study, intracortical communication between mid/anterior insular and motor cortex was investigated during a fatiguing cycling exercise. From 16 healthy male subjects performing a constant-load test at 60% peak oxygen consumption (VO(2peak)) until volitional exhaustion, electroencephalography data were analysed during repetitive, artefact-free periods of 1-min duration. To quantify fatigue-induced intracortical communication, mean intra-hemispheric lagged phase synchronization between mid/anterior insular and motor cortex was calculated: (i) at the beginning of cycling; (ii) at the end of cycling; and (iii) during recovery cycling. Results revealed significantly increased lagged phase synchronization at the end of cycling, which returned to baseline during recovery cycling after subjects' cessation of exercise. Following previous imaging studies reporting the mid/anterior insular cortex as an essential instance processing a variety of sensory stimuli and signalling forthcoming physiological threat, our results provide further evidence that during a fatiguing exercise this structure might not only integrate and evaluate sensory information from the periphery, but also act in communication with the motor cortex. To the best of our knowledge, this is the first study to empirically demonstrate that muscle fatigue leads to changes in interaction between structures of a brain's neural network.

Spinal opioid receptor-sensitive muscle afferents contribute to the fatigue-induced increase in intracortical inhibition in healthy humans.

We investigated the influence of spinal opioid receptor-sensitive muscle afferents on cortical changes following fatiguing unilateral knee-extensor exercise. On separate days, seven subjects performed an identical five sets of intermittent isometric right-quadriceps contractions, each consisting of eight submaximal contractions [63 ± 7% maximal voluntary contraction (MVC)] and one MVC. The exercise was performed following either lumbar interspinous saline injection or lumbar intrathecal fentanyl injection blocking the central projection of spinal opioid receptor-sensitive lower limb muscle afferents. To quantify exercise-induced peripheral fatigue, quadriceps twitch force (Q(tw,pot)) was assessed via supramaximal magnetic femoral nerve stimulation before and after exercise. Motor evoked potentials and cortical silent periods (CSPs) were evaluated via transcranial magnetic stimulation of the motor cortex during a 3% MVC pre-activation period immediately following exercise. End-exercise quadriceps fatigue was significant and similar in both conditions (Q(tw,pot) -35 and -39% for placebo and fentanyl, respectively; P = 0.38). Immediately following exercise on both days, motor evoked potentials were similar to those obtained prior to exercise. Compared with pre-exercise baseline, CSP in the placebo trial was 21 ± 5% longer postexercise (P < 0.01). In contrast, CSP following the fentanyl trial was not significantly prolonged compared with the pre-exercise baseline (6 ± 4%). Our findings suggest that the central effects of spinal opioid receptor-sensitive muscle afferents might facilitate the fatigue-induced increase in CSP. Furthermore, since the CSP is thought to reflect inhibitory intracortical interneuron activity, which may contribute to central fatigue, our findings imply that spinal opioid receptor-sensitive muscle afferents might influence central fatigue by facilitating intracortical inhibition.

Limitation of physical performance in a muscle fatiguing handgrip exercise is mediated by thalamo-insular activity.

In this study, we investigated central/supraspinal processes mediating cessation of a muscle fatiguing exercise. Fifteen male subjects performed 39 intermittent, isometric handgrip contractions (13 s on, 5-6 s off) with the dominant right hand while brain activation was assessed by means of functional magnetic resonance imaging (fMRI). An adaptive, partly stochastic protocol was designed such that in approximately 50% of the contraction trials the required force could not be held until the end of the trial (task failure trial). Trials performed in compliance with the force requirements (succeeded trial) were compared with task failure trials concerning neural activity during a small time window before task failure occurred. The data revealed significantly increased activation contralaterally in both the mid/anterior insular cortex and the thalamus during the investigated time window in the case of subsequent task failure. In accordance with other studies investigating sensations that alert the organism to urgent homeostatic imbalance such as air hunger, hunger for food, and pain, we assume that an increased thalamo-insular activation in the context of a fatigue-induced handgrip exercise could reflect increased homeostatic disturbance in the exercising muscle and may be of essential importance by mediating task failure to maintain the integrity of the organism.