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This study examined whether an alteration in the effort–reward relationship, a theoretical framework based on cognitive neuroscience, could explain cognitive fatigue. Forty persons with MS and 40 healthy age- and education-matched cognitively healthy controls (HC) participated in a computerized switching task with orthogonal high- and low-demand (effort) and reward manipulations. We used the Visual Analog Scale of Fatigue (VAS-F) to assess subjective state fatigue before and after each condition during the task. We used mixed-effects models to estimate the association and interaction between effort and reward and their relationship to subjective fatigue and task performance. We found the high-demand condition was associated with increased VAS-F scores (p < .001), longer response times (RT) (p < .001) and lower accuracy (p < .001). The high-reward condition was associated with faster RT (p = .006) and higher accuracy (p = .03). There was no interaction effect between effort and reward on VAS-F scores or performance. Participants with MS reported higher VAS-F scores (p = .02). Across all conditions, participants with MS were slower (p < .001) and slower as a function of condition demand compared with HC (p < .001). This behavioural study did not find evidence that an effort–reward interaction is associated with cognitive fatigue. However, our findings support the role of effort in subjective cognitive fatigue and both effort and reward on task performance. In future studies, more salient reward manipulations could be necessary to identify effort–reward interactions on subjective cognitive fatigue.  相似文献   
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