Distinct neuropsychological processes may mediate decision-making under uncertainty with known and unknown probability in gain and loss frames Keigo Inukai, Taiki Takahashi * Department of Behavioral Science, Hokkaido University, N10 W7 Kita-ku, Sapporo 060-0810, Japan Received 6 February 2006; accepted 10 February 2006 Summary Decision-making under uncertainty has been studied in psychiatry, economic psychology, and neuroeco- nomics. Psychiatric patients (e.g., drug addicts) often show low degrees of aversion to potential danger. Investigation into neuropsychological processing underlying decision under uncertainty is important for medical treatments of neuropsychiatric disorders. In economic decision theory, choices under uncertainty with and without known probabilities of outcomes have been discriminated. Regarding decision-making under uncertainty with known probabilities (risk), Kahnemann–Tversky’s prospect theory revealed that people tend to avoid uncertainty in potential gains (i.e., risk-aversion in a gain-frame); on the contrary, prefer uncertainty in potential losses (i.e., risk-seeking in a loss-frame). Regarding choices between possible gains with known and unknown probabilities, Ellsberg demonstrated that, in a gain-frame, people tend to avoid uncertainty with unknown probabilities, more dramatically than uncertainty with known probabilities. This can be explained by risk/uncertainty aversion in the gain-frame, suggesting that uncertainty with known and unknown probabilities (i.e., risk and Knightian uncertainty, respectively) may possibly be processed by similar neuropsychological processing in the gain-frame. However, in spite of accumulating evidence in neuroimaging and neuroeconomic studies, it is still unknown whether probability and Knightian uncertainty in the loss- frame are mediated by similar neuropsychological processes as well. We propose that distinct neuropsychological processes may mediate potential losses with known and unknown probabilities, based on recent findings in neuroeconomics and our experiment. Importance of examining subjects’ degree of Knightian uncertainty aversion for the prediction/treatment of drug addicts’ risky behavior (e.g., needle-sharing) is also discussed.  c 2006 Elsevier Ltd. All rights reserved. Background Two types/degrees of uncertainty with respect to risky decision-making Impulsivity and risky decision-making are core deficits in neuropsychiatric illnesses such as drug-dependence, attention-deficit-hyperactivity 0306-9877/$ - see front matter  c 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.mehy.2006.02.014 * Corresponding author. Tel.: +81 488741307. E-mail addresses: taikitakahashi_neuroeconomics@hotmail. com, taiki103@hotmail.com (T. Takahashi). Medical Hypotheses (2006) 67, 283–286 http://intl.elsevierhealth.com/journals/mehy