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The neurobiological mechanisms of Total Sleep Deprivation (TSD) - induced changes in executive control function were investigated. Fourteen participants were measured by functional magnetic resonance imaging (fMRI) with the visual Go/No-go task after normal sleep and following 36 hours of TSD. The TSD-induced positive and negative blood oxygenation level-dependent (BOLD) signals compared with that after a normal night’s sleep (NORM). The areas activated with positive BOLD signals include the superior prefrontal cortex and inferior prefrontal cortex, with negative BOLD signals in the anterior cingulated cortex (ACC) and right lingual gyrus. Increased activation may be related to the compensatory response since more attention resources are needed to perform the Go/No-go task after 36 hours of TSD and the decreased activation in the ACC may reflect the impact of executive control function by the TSD.