  Purpose: Critical torque (CT) and work done above it (W') are key predictors
of exercise performance associated with neuromuscular fatigue. The aim of the
present study was to understand the role of the metabolic cost of exercise in
determining exercise tolerance, CT and W' and the mechanisms of neuromuscular
fatigue.Methods: Twelve subjects performed four knee extension time-trials (6,
8, 10, and 12-minutes) using eccentric, isometric, or concentric contractions
(3 s-on/2 s-off at 90{\textdegree} or 30{\textdegree}/s) to modulate the
metabolic cost of exercise. Exercise performance was quantified by total
impulse and mean torque. CT and W' were determined using the linear
relationship between total impulse and contraction time. Cardiometabolic,
neuromuscular, and ventilatory responses were quantified. Neuromuscular
function was evaluated by maximal voluntary contraction, resting potentiated
single/doublet electrical stimulations, and superimposed single electrical
stimulation to quantify neuromuscular, peripheral, and central fatigue,
respectively.Results: Compared to isometric exercise, total impulse (+36 $\pm$
21%; P < 0.001), CT (+27 $\pm$ 30%; P < 0.001), and W' (+67 $\pm$ 99%; P <
0.001) were increased during eccentric exercise whereas total impulse (-25
$\pm$ 7%; P < 0.001), critical torque (-26 $\pm$ 15%; P < 0.001) and W' (-18
$\pm$ 19%; P < 0.001) were reduced in concentric exercise. Conversely, the
metabolic response and the degree of peripheral fatigue were reduced during
eccentric exercise whereas they were increased during concentric exercise. CT
was negatively associated with oxygen consumption gain (R2 = 0.636; P < 0.001)
and W' was negatively associated with rates of neuromuscular and peripheral
fatigue indices (R2 = [0.252-0.880]; P < 0.001).Conclusions: The contraction
mode influenced both CT and W', and consequently exercise tolerance, indicating
that the metabolic cost of contraction played a key role.
