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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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: This study evaluated whether central motor drive during fatiguing exercise plays a role in determining performance and the development of neuromuscular fatigue during a subsequent endurance task., Methods: On separate days, 10 males completed three constant-load (80% peak power output), single-leg knee-extension trials to task failure in a randomized fashion. One trial was performed without preexisting quadriceps fatigue (CON), and two trials were performed with preexisting quadriceps fatigue induced either by voluntary (VOL; involving central motor drive) or electrically evoked (EVO; without central motor drive) quadriceps contractions (~20% maximal voluntary contraction (MVC)). Neuromuscular fatigue was assessed via pre-post changes in MVC, voluntary activation (VA), and quadriceps potentiated twitch force ( Qtw,pot ). Cardiorespiratory responses and rating of perceived exertion were also collected throughout the sessions. The two prefatiguing protocols were matched for peripheral fatigue and stopped when Qtw,pot declined by ~35%., Results: Time to exhaustion was shorter in EVO (4.3 ± 1.3 min) and VOL (4.7 ± 1.5 min) compared with CON (10.8 ± 3.6 min, P < 0.01) with no difference between EVO and VOL. ΔMVC (EVO: -47% ± 8%, VOL: -45% ± 8%, CON: -53% ± 8%), Δ Qtw,pot (EVO: -65% ± 7%, VOL: -59% ± 14%, CON: -64% ± 9%), and ΔVA (EVO: -9% ± 7%, VOL: -8% ± 5%, CON: -7% ± 5%) at the end of the dynamic task were not different between conditions (all P > 0.05). Compared with EVO (10.6 ± 1.7) and CON (6.8 ± 0.8), rating of perceived exertion was higher ( P = 0.05) at the beginning of VOL (12.2 ± 1.0)., Conclusions: These results suggest that central motor drive involvement during prior exercise plays a negligible role on the subsequent endurance performance. Therefore, our findings indicate that peripheral fatigue-mediated impairments are the primary determinants of high-intensity single-leg endurance performance., (Copyright © 2022 by the American College of Sports Medicine.)

Transcranial magnetic stimulation (TMS)-induced relaxation rate reflects intrinsic muscle contractile properties by interrupting the drive from the central nervous system during voluntary muscle contractions. To determine the appropriateness of knee-extensor muscle relaxation measurements induced by TMS, this study aimed to establish both the within- and between-session reliability before and after a fatiguing exercise bout. Eighteen participants (9 females, 9 males, age 25 ± 2 years, height 171 ± 9 cm, body mass 68.5 ± 13.5 kg) volunteered to participate in two identical sessions approximately 30 days apart. Maximal and submaximal neuromuscular evaluations were performed with TMS six times before (PRE) and at the end (POST) of a 2-min sustained maximal voluntary isometric contraction. Within- and between-session reliability of PRE values were assessed with intraclass correlation coefficient (ICC 2,1 , relative reliability), repeatability coefficient (absolute reliability), and coefficient of variation (variability). Test-retest reliability of post-exercise muscle relaxation rates was assessed with Bland-Altman plots. For both the absolute and normalized peak relaxation rates and time to peak relaxation, data demonstrated low variability (e.g. coefficient of variation ≤ 7.8%) and high reliability (e.g. ICC 2,1  ≥ 0.963). Bland-Altman plots showed low systematic errors. These findings establish the reliability of TMS-induced muscle relaxation rates in unfatigued and fatigued knee-extensor muscles, showing that TMS is a useful technique that researchers can use when investigating changes in muscle relaxation rates both in unfatigued and fatigued knee-extensor muscles., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: Given the increased level of fatigue frequently reported by patients with Parkinson's disease (PD), this study investigated the interaction between central and peripheral components of neuromuscular fatigue (NF) in this population compared with healthy peers., Methods: Changes in maximal voluntary activation (ΔVA, central fatigue) and potentiated twitch force (ΔQtw,pot, peripheral fatigue) pre-post exercise were determined via the interpolated twitch technique in 10 patients with PD and 10 healthy controls (CTRL) matched for age, sex, and physical activity. Pulmonary gas exchange, femoral blood flow, and quadriceps EMG were measured during a fatiguing exercise (85% of peak power output [PPO]). For a specific comparison, on another day, CTRL repeat the fatiguing test matching the time to failure (TTF) and PPO of PD., Results: At 85% of PPO (PD, 21 ± 7 W; CTRL, 37 ± 22 W), both groups have similar TTF (~5.9 min), pulmonary gas exchange, femoral blood flow, and EMG. After this exercise, the maximal voluntary contraction (MVC) force and Qtwpot decreased equally in both groups (-16%, P = 0.483; -43%, P = 0.932), whereas VA decreased in PD compared with CTRL (-3.8% vs -1.1%, P = 0.040). At the same PPO and TTF of PD (21 W; 5.4 min), CTRL showed a constant drop in MVC, and Qtwpot (-14%, P = 0.854; -39%, P = 0.540), instead VA decreased more in PD than in CTRL (-3.8% vs -0.7%, P = 0.028)., Conclusions: In PD, central NF seems exacerbated by the fatiguing task which, however, does not alter peripheral fatigue. This, besides the TTF like CTRL, suggests that physical activity may limit NF and counterbalance PD-induced degeneration through peripheral adaptations., (Copyright © 2021 by the American College of Sports Medicine.)

Muscle fatigue induced by voluntary exercise, which requires central motor drive, causes central fatigue that impairs endurance performance of a different, nonfatigued muscle. This study investigated the impact of quadriceps fatigue induced by electrically induced (no central motor drive) contractions on single-leg knee-extension (KE) performance of the subsequently exercising ipsilateral quadriceps. On two separate occasions, eight males completed constant-load (85% of maximal power-output) KE exercise to exhaustion. In a counterbalanced manner, subjects performed the KE exercise with no pre-existing quadriceps fatigue in the contralateral leg on one day (No-PreF), whereas on the other day, the same KE exercise was repeated following electrically induced quadriceps fatigue in the contralateral leg (PreF). Quadriceps fatigue was assessed by evaluating pre- to postexercise changes in potentiated twitch force (ΔQ tw,pot ; peripheral fatigue), and voluntary muscle activation (ΔVA; central fatigue). As reflected by the 57 ± 11% reduction in electrically evoked pulse force, the electrically induced fatigue protocol caused significant knee-extensors fatigue. KE endurance time to exhaustion was shorter during PreF compared with No-PreF (4.6 ± 1.2 vs 7.7 ± 2.4 min; P < 0.01). Although ΔQ tw,pot was significantly larger in No-PreF compared with PreF (-60% vs -52%, P < 0.05), ΔVA was greater in PreF (-14% vs -10%, P < 0.05). Taken together, electrically induced quadriceps fatigue in the contralateral leg limits KE endurance performance and the development of peripheral fatigue in the ipsilateral leg. These findings support the hypothesis that the crossover effect of central fatigue is mainly mediated by group III/IV muscle afferent feedback and suggest that impairments associated with central motor drive may only play a minor role in this phenomenon.