Subjects: Sixteen Caltech undergraduate and graduate students were recruited from the Caltech Social Science Experimental Laboratory database to participate in the study (13 males, 3 females). The mean (std. dev.) age was 23.5 years (6.2). Informed consent was obtained using a consent form approved by the Internal Review Board at Caltech. Subjects read written instructions before entering the scanner (included at the end of the supplements). After reading the instructions they completed a quiz to ensure comprehension of how their decisions affected their performance and earnings. They knew that at the end of the experiment, one trial from each of the three treatments would be chosen at random, and their choice on that trial would determine their pay. Their earnings were the total from the three randomly-chosen choices, plus $5 fee for participating.Behavioral task: Stimuli were presented through MRI compatible goggles (Resonance Technology). Choices were made using an MRI-compatible button box. For each choice, three options were given. Two of the options were bets on either side of a binary choice gamble that carried some uncertainty of paying either a positive sum or zero. The third option was the sure payoff that paid a certain positive amount of money. Subjects were allowed as much time as they desired in making their choice. Responses were made by pressing the button corresponding to the location of the options (left-middle-right) on the screen.The gambles were not played after each trial because then the degree of ambiguity would change over time as subjects learned from feedback about the event probabilities.1 Card-deck treatment: In the Card-Deck treatment, subjects take the sure payoff, or bet on either red or black card. The cards are blue in the presentation because the background was black, but conventional red and black playing cards were used to determine the actual payoff after the subject came out of the scanner. Subjects knew blue and black were equivalent. Full list of stimuli are presented in Table S1.Knowledge treatment: In the Knowledge treatment, subjects could take the sure payoff, or bet on whether the answer was Yes or No to the statement presented. Full list of stimuli are presented in Table S2. Informed Opponents treatment:In the Informed opponents treatment, subjects either take the sure payoff, or bet that a red or black card would be drawn. If they choose the bet, they play against an opponent that will sample from the an ambiguous deck the number of cards indicated on the screen.If the colors of the cards chosen by the subject and his/her opponent match, the bet does not take place and both earn the sure payoff instead. If the colors mismatch, the bet takes place, and the subject whose card matches the color of the card randomly chosen from the deck, wins the amount indicated on the screen, with the other subject earning 0.Note that because the opponent chooses a color after seeing a sample of cards, the opponent always has more information than the subject, in the "low-information...

MicroRNA-122 (miR-122), which accounts for 70% of the liver's total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined. We demonstrated that mice lacking the gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These mice exhibited a striking disparity in HCC incidence based on sex, with a male-to-female ratio of 3.9:1, which recapitulates the disease incidence in humans. Impaired expression of microsomal triglyceride transfer protein (MTTP) contributed to steatosis, which was reversed by in vivo restoration of Mttp expression. We found that hepatic fibrosis onset can be partially attributed to the action of a miR-122a target, the Klf6 transcript. In addition, Mir122a -/-livers exhibited disruptions in a range of pathways, many of which closely resemble the disruptions found in human HCC. Importantly, the reexpression of miR-122a reduced disease manifestation and tumor incidence in Mir122a -/-mice. This study demonstrates that mice with a targeted deletion of the Mir122a gene possess several key phenotypes of human liver diseases, which provides a rationale for the development of a unique therapy for the treatment of chronic liver disease and HCC.

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Curiosity has been described as the "wick in the candle of learning" but its underlying mechanisms are not well-understood. We scanned subjects with fMRI while they read trivia questions. The level of curiosity when reading questions is correlated with activity in caudate regions previously suggested to be involved in anticipated reward or encoding prediction error. This finding led to a behavioral study showing that subjects spend more scarce resources (either limited tokens, or waiting time) to find out answers when they are more curious. The fMRI also showed that curiosity increases activity in memory areas when subjects guess incorrectly, which suggests that curiosity may enhance memory for surprising new information. This prediction about memory enhancement is confirmed in a behavioral study-higher curiosity in the initial session is correlated with better recall of surprising answers 10 days later.Keywords: Neuroimaging, Memory, Learning, Brain 2 Curiosity is the complex feeling and cognition accompanying the desire to learn what is unknown. Curiosity can be both helpful and dangerous. It plays a critical role in motivating learning and discovery, especially by creative professionals, increasing the world's store of knowledge. Einstein, for example, once said, "I have no special talents. I am only passionately curious (Hoffmann, 1972)." The dangerous side of curiosity is its association with exploratory behaviors with harmful consequences. An ancient example is the mythical Pandora, who opened a box that unleashed misfortunes on the world. In modern times, technology such as the Internet augments both good and bad effects of curiosity, by putting both enormous amounts of information and potentially dangerous social encounters a mouse click away.Despite its importance, the psychological and neural underpinnings of human curiosity remain poorly understood. Philosophers and psychologists have described curiosity as an appetite for knowledge, a drive like hunger and thirst (Loewenstein, 1994), the hunger pang of an 'info-vore' (Biederman & Vessel, 2006), and "the wick in the candle of learning" (William Arthur Ward). In reinforcement learning a "novelty bonus" is used to motivate the choice of unexplored strategies (Kakade & Dayan, 2002).Curiosity can be thought of as the psychological manifestation of such a novelty bonus.A theory guiding our research holds that curiosity arises from an incongruity or 'information gap'-a discrepancy between what one knows and what one wants to know (Loewenstein, 1994). The theory assumes that the aspired level of knowledge increases sharply with a small increase in knowledge, so that the information gap grows with initial learning. When one is sufficiently knowledgeable, however, the gap shrinks and curiosity falls. If curiosity is like a hunger for knowledge, then a small "priming dose" of information increases the hunger, and the decrease in curiosity from knowing a lot is like being satiated by information.In the information-gap theory, the object of curiosity is a...

Research on emotion regulation has focused upon observers' ability to regulate their emotional reaction to stimuli such as affective pictures, but many other aspects of our affective experience are also potentially amenable to intentional cognitive regulation. In the domain of decision-making, recent work has demonstrated a role for emotions in choice, although such work has generally remained agnostic about the specific role of emotion. Combining psychologically-derived cognitive strategies, physiological measurements of arousal, and an economic model of behavior, this study examined changes in choices (specifically, loss aversion) and physiological correlates of behavior as the result of an intentional cognitive regulation strategy. Participants were on average more aroused per dollar to losses relative to gains, as measured with skin conductance response, and the difference in arousal to losses versus gains correlated with behavioral loss aversion across subjects. These results suggest a specific role for arousal responses in loss aversion. Most importantly, the intentional cognitive regulation strategy, which emphasized ''perspective-taking,'' uniquely reduced both behavioral loss aversion and arousal to losses relative to gains, largely by influencing arousal to losses. Our results confirm previous research demonstrating loss aversion while providing new evidence characterizing individual differences and arousal correlates and illustrating the effectiveness of intentional regulation strategies in reducing loss aversion both behaviorally and physiologically.arousal ͉ emotion regulation ͉ decision-making W e are not at the whim of our emotions-rather, research on emotion regulation suggests we have a degree of control over our affective state and can reduce or enhance the emotional impact of a given stimulus in real time (1). We are able to do this intentionally, and when doing so, we not only report decreased negative affect (1-3) but also show signs of decreased physiological responding (4, 5) and decreased activity in brain areas that are closely linked to emotions and affect (1-3). Emotion regulation research so far has primarily used pictures (1-5), but any stimulus that results in an emotional response could theoretically be the target of regulation. We propose to examine a specific role for emotions in economic choice behavior and to observe the effects of an intentional cognitive regulation strategy on both behavior and associated emotional responses.It is widely acknowledged that emotion plays a role in decisionmaking, drawing on evidence from numerous behavioral studies using emotional stimuli as well as physiological, neuroimaging, and lesion studies. For example, one study demonstrated that irrelevant emotional states induced by film clips could eliminate or even reverse the endowment effect (higher selling than buying prices) in subsequent choices (6). Another study on consumption behavior of drinks showed that the subliminal presentation of emotional faces not only altered participants' ratings ...