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This chapter discusses how the effects of sleep deprivation on the brain can be studied using functional magnetic resonance imaging (fMRI). Most contemporary functional brain imaging experiments are conducted using fMRI. This technique measures changes in blood oxygenation level dependent (BOLD) signal in capillaries and venules adjacent to neuronal clusters whose firing rate is modulated by task performance. Inference is most straightforward when the activated brain region participates in a circumscribed set of cognitive functions. For example, state related modulation of amygdala activity in response to affective pictures can be reasonably related to changes in emotional processing. Results of many fMRI experiments conducted on sleep-deprived subjects have consistently shown reduced superior parietal and lateral occipital activation during task performance. Results of more recent studies involve making decisions under uncertainty have shown that sleep-deprived persons tend toward riskier options, mirroring the behavior of patients with medial frontal damage.