{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:08:10Z","timestamp":1789139290580,"version":"build-2803163510"},"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FWO-WEAVE","award":["G095422N"],"award-info":[{"award-number":["G095422N"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Mental fatigue (MF) significantly affects both cognitive and physical performance. However, the precise mechanisms, particularly concerning neurotransmission, require further investigation. An implication of the role of dopamine (DA) and noradrenaline (NA) is stated, but empirical evidence for this theory still needs to be provided. To address this gap, we aim to investigate the role of brain neurotransmission in elucidating if, and how prolonged cognitive activity induces MF and its subsequent impact on cognitive performance.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>This study (registration number: G095422N) will adopt a randomized cross-over design with sixteen healthy participants aged 18\u201335 years. The sessions include a familiarization, two experimental (DA: 20mg Methylphenidate; NA: 8mg Reboxetine) conditions, and one placebo (lactose tablet: 10mg) condition. A 60-minute individualized Stroop task will be used to investigate whether, and how the onset of MF changes under the influence of reuptake inhibitors. Attention and response inhibition will be assessed before and after the MF-inducing task using a Go\/NoGo task. The integration of physiological (electroencephalography, heart rate), behavioral (attention, response inhibition), and subjective indicators (scales and questionnaires) will be used to detect the underlying mechanisms holistically. Data analysis will involve linear mixed models with significance at p&lt;0.05.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Discussion<\/jats:title>\n<jats:p>The integration of diverse techniques and analyses offers a comprehensive perspective on the onset and impact of MF, introducing a novel approach. Future research plans involve extending this protocol to explore the connection between brain neurotransmission and physical fatigue. This protocol will further advance our understanding of the complex interplay between the brain and fatigue.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0310271","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T17:27:59Z","timestamp":1725989279000},"page":"e0310271","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["The interplay of brain neurotransmission and mental fatigue: A research protocol"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2637-3510","authenticated-orcid":true,"given":"Y. 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