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Previous functional magnetic resonance imaging investigations of second-order uncertainty in humans have drawn on an economic concept of ambiguity, where action-outcome associations in a gamble are either known (unambiguous) or completely unknown (ambiguous). Here, we relaxed the constraints associated with a purely categorical concept of ambiguity and varied the second-order uncertainty of gambles continuously, quantified as entropy over second-order probabilities. We show that second-order uncertainty influences decisions in a pessimistic way by biasing second-order probabilities, and that second-order uncertainty is negatively correlated with posterior cingulate cortex activity. The category of ambiguous (compared with nonambiguous) gambles also biased choice in a similar direction, but was associated with distinct activation of a posterior parietal cortical area; an activation that we show reflects a different computational mechanism. Our findings indicate that behavioral and neural responses to second-order uncertainty are distinct from those associated with ambiguity and may call for a reappraisal of previous data.<\/jats:p>","DOI":"10.1523\/jneurosci.1452-10.2011","type":"journal-article","created":{"date-parts":[[2011,3,30]],"date-time":"2011-03-30T17:30:22Z","timestamp":1301506222000},"page":"4811-4820","source":"Crossref","is-referenced-by-count":91,"title":["The Known Unknowns: Neural Representation of Second-Order Uncertainty, and Ambiguity"],"prefix":"10.1523","volume":"31","author":[{"given":"Dominik R.","family":"Bach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Hulme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"Penny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond 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