This study investigates how the human brain responds to uncertainty in decision-making. Sixteen Caltech students participated in three treatments: Card-Deck, Knowledge, and Informed Opponents. In the Card-Deck treatment, participants chose between a sure payoff or a bet on red or black cards. In the Knowledge treatment, they chose between a sure payoff or answering a yes/no question. In the Informed Opponents treatment, they competed against an opponent who had more information about the card deck. Behavioral data were analyzed using a nonlinear stochastic choice model to estimate risk and ambiguity. The results showed that participants were more likely to choose the sure payoff in ambiguous situations, indicating ambiguity aversion. Functional MRI (fMRI) analysis revealed that the brain regions involved in processing risk and ambiguity included the dorsal striatum, ventral striatum, insula, and orbitofrontal cortex (OFC). The study also found that the OFC was sensitive to the degree of uncertainty, while the striatum showed activity related to expected reward. Lesion studies on patients with brain damage showed that damage to the OFC impaired decision-making under uncertainty, supporting the role of the OFC in processing ambiguity. The study also found that the dorsal striatum was involved in processing expected reward, with activity correlated with the expected value of decisions. The study highlights the neural mechanisms underlying decision-making under uncertainty, showing that different brain regions are involved in processing risk and ambiguity. The findings have implications for understanding decision-making in economics, finance, and law, where ambiguity and risk play important roles.This study investigates how the human brain responds to uncertainty in decision-making. Sixteen Caltech students participated in three treatments: Card-Deck, Knowledge, and Informed Opponents. In the Card-Deck treatment, participants chose between a sure payoff or a bet on red or black cards. In the Knowledge treatment, they chose between a sure payoff or answering a yes/no question. In the Informed Opponents treatment, they competed against an opponent who had more information about the card deck. Behavioral data were analyzed using a nonlinear stochastic choice model to estimate risk and ambiguity. The results showed that participants were more likely to choose the sure payoff in ambiguous situations, indicating ambiguity aversion. Functional MRI (fMRI) analysis revealed that the brain regions involved in processing risk and ambiguity included the dorsal striatum, ventral striatum, insula, and orbitofrontal cortex (OFC). The study also found that the OFC was sensitive to the degree of uncertainty, while the striatum showed activity related to expected reward. Lesion studies on patients with brain damage showed that damage to the OFC impaired decision-making under uncertainty, supporting the role of the OFC in processing ambiguity. The study also found that the dorsal striatum was involved in processing expected reward, with activity correlated with the expected value of decisions. The study highlights the neural mechanisms underlying decision-making under uncertainty, showing that different brain regions are involved in processing risk and ambiguity. The findings have implications for understanding decision-making in economics, finance, and law, where ambiguity and risk play important roles.