The amygdala, OFC and MFC contribute to learning, in part, by evaluating feedback. In an effort to extend our understanding of the physiological mechanisms underlying affective processing, we developed an fMRI paradigm to reveal blood-oxygen-level dependent (BOLD) responses to visual images that signal reward. Each week, subjects learned to associate images of novel objects with a high or low probability of water reward. Areas responding to the value of recently learned reward-predictive images included MFC area 10m/32, ventrolateral prefrontal cortex area 12, and inferior temporal visual cortex (IT). The amygdala and OFC, each thought to be involved in value encoding, showed little such effect. Instead, these two areas primarily responded to visual stimulation and reward receipt, respectively. Our findings demonstrate the importance of ventrolateral prefrontal cortex, MFC, and IT in representing the values of recently learned visual images. Tastes and their associated values drive food consumption and influence choice behavior. To understand the neural mechanisms underlying reward-guided decision making and value learning, we characterized the gustatory system in subjects with fMRI while measuring licking to control for oral movements, and to assess preferences. Though anatomical data indicate that taste information from the ventroposteromedial nucleus of the thalamus (VPMpc) goes to gustatory cortex, physiological responses to taste are widespread in cortex, including in somatosensory cortex and OFC. To identify taste-responsive cortex, we delivered small quantities (0.1ml) of sucrose, citric acid, or distilled water in random order without any predictive cues (e.g., visual stimuli) to subjects while using event-related fMRI. In addition, we used an MRI-compatible lick sensor to measure subjects licking during the scans. fMRI signals associated with licking in the absence of fluid delivery were used to mask responses to fluid delivery/receipt and associated licking. Licking in the absence of fluid delivery and fluid receipt times for each tastant were incorporated into a general linear model to analyze fMRI data. By contrasting BOLD responses to either sweet or sour tastes to those from distilled water, and masking with BOLD signals associated with licking in the absence of fluid delivery, we identified taste responses in gustatory cortex, ventrolateral prefrontal cortex area 12o, OFC area 13b and somatosensory cortex area 3b in three subjects. Areas activated by fluid delivery in general as defined by a contrast of all tastes relative to baseline included medial OFC area 14, the ventral striatum, the ventral pallidum, the basal nucleus of amygdala, and the perirhinal cortex. Our findings of gustatory responses are in agreement with single unit neurophysiological recordings. Whole brain fMRI in combination with quantification of licking behavior and subjects choice preferences for different tastes will be used to identify brain regions that signal value. Previous work from our group has shown that the subgenual portion of the anterior cingulate cortex contributes to autonomic arousal during anticipation of positive (rewarding) events. Because the OFC is involved in stimulus-based reward learning, we wondered whether this region, too, contributed to either the learning or maintenance of autonomic arousal associated with positive events. Accordingly, we evaluated autonomic responses in subjects that had sustained bilateral excitotoxic lesions of OFC and controls. Subjects were trained on a task in which Pavlovian conditioning of stimulus-reward associations was superimposed on instrumental conditioning of active visual fixation. On some trials, one of two Pavlovian stimuli (CS+, CS-) was presented on the monitor screen for 1 s during the 4-s fixation period. The CS+ was always followed by a large fluid reward; the CS- led to no reward. We recorded pupil size as a measure of autonomic response. Controls exhibited an increased pupil size to the CS+, compared to the response to the CS-, within a couple of training sessions (2 +/- 1) and continued to show the conditioned pupil response in anticipation of reward across at least 4 consecutive sessions. By contrast, subjects with OFC lesions required more sessions (20 +/- 7 sessions) to acquire the conditioned autonomic response and three out of four failed to sustain it for 4 consecutive sessions even with an extended period of training (50 sessions). Training with a second set of stimuli yielded a similar result. Thus, the present results suggest that OFC is involved in acquiring appropriate autonomic responses to cues predicting positive events.

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10
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2016
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U.S. National Institute of Mental Health
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