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The properties of this pathway have frequently been observed to change during fatiguing exercise in ways that could influence the development of central fatigue (i.e. the progressive reduction in voluntary muscle activation). However, based on differences in motor cortical and motoneuronal excitability between exercise modalities (e.g. single\u2010joint\n                    <jats:italic>vs<\/jats:italic>\n                    . locomotor exercise), there is no characteristic response that allows for a categorical conclusion about the effect of these changes on functional impairments and performance limitations. Despite the lack of uniformity in findings during fatigue, there is strong evidence for marked \u2018inhibition\u2019 of motoneurones as a direct result of voluntary drive. Endogenous forms of neuromodulation, such as via serotonin released from neurones, can directly affect motoneuronal output and central fatigue. Exogenous forms of neuromodulation, such as brain stimulation, may achieve a similar effect, although the evidence is weak. Non\u2010invasive transcranial direct current stimulation can cause transient or long\u2010lasting changes in cortical excitability; however, variable results across studies cast doubt on its claimed capacity to enhance performance. Furthermore, with these studies, it is difficult to establish a cause\u2010and\u2010effect relationship between brain responsiveness and exercise performance. This review briefly summarizes changes in the corticomotoneuronal pathway during various types of exercise, and considers the relevance of these changes for the development of central fatigue, as well as the potential of non\u2010invasive brain stimulation to enhance motor cortical excitability, motoneuronal output and, ultimately, exercise performance.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15346-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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