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Functional MRI provides a reproducible, non-invasive, and flexible means to study inter-individual variation in performance impairment in the setting of sleep deprivation (SD). An important long-term goal of studying inter-individual differences in responses to SD is to elucidate phenotypes that predict how an individual perform in an operational setting after being sleep deprived. The seemingly contradictory findings regarding the benefit of greater activation in areas of the brain led one to examine whether evaluating shifts in activation across states would prove a reliable marker of inter-individual variability in behavior. The thalamus plays an important part in mediating arousal and attention, which in turn have substantial effects on behavioral performance. Thalamic activation is less reliably reproducible across scan sessions than frontoparietal activation. More complex decision making tasks, where different strategies may be engaged, allow some latitude regarding which neural circuits are engaged and are potentially less at risk of use-dependent effects.