, 2009), despite the decreased signal-to-noise ratio in the brainstem resulting from the effects of cardiac pulsation and respiratory movement. The response is unlikely to be an artifact of motion attributable to increased physiological arousal as the BOLD effect observed is decreasing with increasing uncertainty. While previous studies have demonstrated sensitivity of neuronal responses in locus coeruleus to unexpected changes in reward contingencies in rats and nonhuman primates (Aston-Jones et al., 1997 and Bouret and Sara, 2004) and have this website attributed phasic

changes in pupil diameter in human subjects correlating with unexpected uncertainty to the action of locus coeruleus (Nassar et al., 2012 and Preuschoff et al., 2011), this finding

represents neural evidence in humans for the claim that brain regions containing noradrenergic neurons are involved in the representation of Ruxolitinib cost unexpected uncertainty (Yu and Dayan, 2005). The neurophysiological literature (Aston-Jones et al., 1999 and Bouret and Sara, 2005) has noted a distinction between the phasic and tonic modes of LC activity. While the phasic mode has been associated with enhanced task engagement and performance, the tonic mode has been associated with increased distractibility, the shifting of attention, and exploratory behavior (Aston-Jones and Cohen, 2005, Aston-Jones et al., 1994 and Rajkowski et al., 1992). In addition, shifts from phasic to tonic LC mode have been noted during contingency changes in a target reversal task with nonhuman primates (Aston-Jones et al., 1997). In our task, Sodium butyrate however, a contingency change may not precipitate the shifting of attention to previously irrelevant

task stimuli or engagement in exploratory behavior, as may be the case in a target-reversal paradigm; rather it is possible that the contingency change signaled by high unexpected uncertainty brings about increased engagement with the outcome stimuli for the purpose of learning and thus recruitment of phasic LC mode, characterized by both relatively low baseline firing rate and high phasic responsiveness to task-relevant stimuli. Given that our BOLD signal appears to be more sensitive to baseline activity as opposed to phasic responsiveness, this effect could potentially manifest in the sustained decrease in BOLD signal that we observe under conditions of high unexpected uncertainty. Further investigation is required, however, to fully characterize how switching of LC mode relates to task demands and how it may influence the BOLD signal. Another key question for future research lies in determining which, if any, of the cortical representations of unexpected uncertainty observed here are dependent on efferent projection from locus coeruleus.