The central fatigue theory proposes that force output during fatiguing exercise is limited in order to maintaining homeostasis in advance of tissue damage. As methylphenidate (MPH) has been shown to enhance physical performance, it has been proposed that this medication alters the central fatigue mechanisms of the motor cortex. This study evaluated the neural underpinnings related to the ergogenic effects of MPH.

This double-blind, crossover study involved 15 right-handed subjects, randomized to receive 20 mg of MPH or placebo. The participants were asked to perform 40 grip trials with a visual display of their grip strength. The subjects began the task at a target force of 70% of their maximum voluntary contraction. Test failure was defined as falling below the target force by more than 10% after having reached the target. All sessions were conducted with concurrent functional magnetic resonance imaging (fMRI). Aso assessed were a measurement of task-dependent change in neural coupling (PPI), and a key region implicated in mental fatigue (OFC).

The mean forces achieved in all trials were significantly higher in the MPH group than in the placebo group (P＝0.032). The MPH condition resulted in an increase in left IC-left hand motor cortex coupling (PPI) and a decrease in bilateral OFC-left IC coupling during grip.

This study found that methylphenidate improved force production and brain connectivity during a fatiguing handgrip task.