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Purpose: Cancer-related fatigue (CRF) is the most reported side effect of cancer and its treatments. Mechanisms of CRF are multidimensional, including neuromuscular alterations leading to decreased muscle strength and endurance (i.e., fatigability). Recently, exercise fatigability and CRF have been related, while fatigability mechanisms remain unclear. Traditionally, fatigability is assessed from maximal voluntary contractions (MVC) decrease, but some authors hypothesized that the rate of force development (RFD) determined during a rapid contraction could also be an interesting indicator of functional alterations. However, to our knowledge, no study investigated RFD in cancer patients. The purpose of this study was to determine whether RFD, fatigability amplitude, and etiology are different between fatigued and non-fatigued cancer patients. Methods: Eighteen participants with cancer, divided in fatigued or non-fatigued groups according their CRF level, completed a 5-min all-out exercise in ankle plantar flexor muscles composed of 62 isometric MVC of 4 s with 1 s rest, to assess fatigability amplitude as the force–time relationship asymptote (FA). Before and after exercise, fatigability etiologies (i.e., voluntary activation (VA) and evoked forces by electrical stimulation (Db100)) were assessed as well as RFD in 50 and 100 ms (RFD50 and RFD100, respectively) during rapid contractions. Results: FA is significantly lower in fatigued group. Significant differences were found between pre- and post-exercise VA, Db100, RFD50, and RFD100 for both groups, with no statistical difference between groups. Conclusion: During treatments, fatigability is higher in fatigued patients; however, the mechanisms of fatigability and RFD alterations are similar in both groups. Trial registration: ClinicalTrials.gov, NCT04391543, May 2020. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate if a continuous muscle contraction (CON) is more fatiguing than an intermittent exercise (INT) performed until task failure. To get a more comprehensive picture of neuromuscular fatigability, in addition to the commonly used maximal voluntary contraction (MVC), we assessed the maximal torque sustainability (i.e., the ability to maintain a high level of torque for 1 min). Fourteen subjects performed a plantar flexors MVC of 1-min duration (MVC1-MIN) before and after CON or INT contractions at 40% MVC until task failure. Despite a greater torque-time integral for the INT task, a similar MVC reduction was found after both exercises. On the contrary, a greater torque loss during the MVC1-MIN was observed after the CON exercise and it was positively correlated to the mean exercise torque. These results reveal that, for exercises performed until exhaustion, the contraction pattern (i.e., CON vs. INT) affects the ability to maintain a high level of torque, but does not influence the maximal torque production capacity. Thus, we demonstrate that maximal torque production and sustainability are two distinct and complementary characteristics of neuromuscular fatigability. Consequently, when considering both capacities, it results that, an exhausting CON contraction is more fatiguing than an exhausting INT effort. This highlights the importance of simultaneously evaluating both capacities when exploring neuromuscular fatigability. [ABSTRACT FROM AUTHOR]

• The use of neuronavigated TMS should lead to superior targeting and stabilization of stimulus delivery. • The use of neuronavigated TMS does not influence the corticospinal responses in unfatigued and fatigued muscle, relative to a standardized function-guided procedure. • Function-guided procedure seems as accurate as neuronavigated TMS in the assessment of corticospinal excitability and inhibition in unfatigued and fatigued muscle, providing a trained investigator can reliably position and hold the TMS coil. In studying neuromuscular fatigability, researchers commonly use functional criteria to position and hold the transcranial magnetic stimulation (TMS) coil during testing sessions. This could influence the magnitude of corticospinal excitability and inhibition responses due to imprecise and unsteady positions of the coil. To reduce coil position and orientation variability, neuronavigated TMS (nTMS) could be used. We evaluated the accuracy of nTMS and a standardized function-guided procedure for maintaining TMS coil position both in unfatigued and fatigued knee extensors. Eighteen participants (10F/8M) volunteered in two identical and randomized sessions. Maximal and submaximal neuromuscular evaluations were performed with TMS three times before (PRE_1) and three times after (PRE_2) a 2 min resting session and one time immediately after (POST) a 2-min sustained maximal voluntary isometric contraction (MVIC). The located "hotspot" [the location that evoked the largest motor-evoked potential (MEP) responses in the rectus femoris ] was maintained either with or without nTMS. MEP, silent period (SP) and the distance between the "hotspot" and the actual coil position were recorded. A time × contraction intensity × testing session × muscle interaction was not observed for MEP, SP, and distance. Bland-Altman plots presented adequate agreements for MEP and SP. Spatial accuracy of TMS coil position over the motor cortex did not influence corticospinal excitability and inhibition in unfatigued and fatigued knee extensors. The variability in MEP and SP responses may be due to spontaneous fluctuations in corticospinal excitability and inhibition, and it is not altered by the spatial stability of the stimulation point. [ABSTRACT FROM AUTHOR]