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Neural activity related to the processing of increasing monetary reward in smokers and nonsmokers.

This study investigated the processing of increasing monetary reward in nonsmoking and smoking subjects. The choice of the subject populations has been motivated by the observation of differences between nonsmokers and smokers in response to rewarding stimuli in a previous study. Subjects performed a pattern recognition task with delayed response, while rCBF was measured with [H215O] PET. Correct responses to the task were reinforced with three different amounts of monetary reward. The subjects received the sum of the rewards at the end of the experiment. The results show that a cortico-subcortical loop, including the dorsolateral prefrontal cortex, the orbitofrontal cortex, the cingulate gyrus and the thalamus is involved in processing increasing monetary reward. Furthermore, the striatal response differentiates nonsmokers from smokers. Thus, we found significant correlations between rCBF increases in striatum and increasing monetary reward and between striatal rCBF increases and mood in nonsmokers, but not in smokers. Moreover, no significant mood changes among the different monetary rewards could be observed in smokers. We infer that the response of the striatum to reward is related to changes in subjective feelings. The differences between smokers and nonsmokers confirm our previous conclusions that the association between blood flow, performance, mood and amount of reward is more direct in nonsmokers.

Adult↗

Dissociation of reward anticipation and outcome with event-related fMRI.

Reward processing involves both appetitive and consummatory phases. We sought to examine whether reward anticipation vs outcomes would recruit different regions of ventral forebrain circuitry using event-related fMRI. Nine healthy volunteers participated in a monetary incentive delays task in which they either responded to a cued target for monetary reward, responded to a cued target for no reward, or did not respond to a cued target during scanning. Multiple regression analyses indicated that while anticipation of reward vs non-reward activated foci in the ventral striatum, reward vs non-reward outcomes activated foci in the ventromedial frontal cortex. These findings suggest that reward anticipation and outcomes may differentially recruit distinct regions that lie along the trajectory of ascending dopamine projections.

Adult↗

The dopamine D1 antagonist reduces ethanol reward for C57BL/6 mice.

BACKGROUND: Dopamine D1 antagonist effects on behaviors related to obtaining and consuming ethanol remain unclear. The highly selective D1 antagonist ecopipam (SCH 39166), which has no effect on the serotonin system, was used to evaluate the role of D1 receptors in ethanol reward and its potential for treating alcohol abuse by determining its effect on several measures of ethanol reward in C57BL/6 (B6) mice. METHODS: Ecopipam (0.025-0.2 mg/kg) effects on instrumental and contingent consummatory responses and on noncontingent consummatory responses for ethanol and water reward were determined in food-restricted male mice trained to lever-respond for 12% ethanol delivered on a fixed ratio-4 reinforcement schedule. The mice were tested for 15-min sessions under preprandial (high-hunger and low-thirst) and postprandial (low-hunger and high-thirst) test conditions. RESULTS: Ecopipam dose-dependently reduced instrumental and consummatory responses for ethanol and ethanol intake when tested under hunger- or thirst-motivated conditions with free access to water. Under thirst motivation with no access to an alternate fluid source, lever responses for ethanol and water were similar; however, ecopipam reduced responding for ethanol more than responding for water reward. When given concurrent free access to the same fluid delivered for lever pressing, animals made more contacts for ethanol than for water; ecopipam reduced free ethanol but not water contacts. CONCLUSIONS: Ecopipam attenuated ethanol reward at doses that did not affect water reward, indicating an effect independent of reductions in motor system function or general motivation and arousal. Ecopipam also reduced ethanol reward to the same degree under hunger, thirst, or sated conditions, again indicating that it affected ethanol reward at doses that did not grossly affect general motivational states. These data suggest that ecopipam may reduce ethanol reward with few side effects and that it warrants further investigation as a pharmacological tool for treating alcohol abuse.

Animals↗

Functional magnetic resonance imaging of reward prediction.

PURPOSE OF REVIEW: Technical and conceptual advances in functional magnetic resonance imaging now allow visualization of real-time changes in oxygenation of deep subcortical regions, leading to rapid advances in scientific characterization of the neural substrates that underlie reward prediction in humans. RECENT FINDINGS: Neuroimaging research over the past year has focused on determining the necessary neural substrates for reward prediction. SUMMARY: While the orbitofrontal cortex has long been implicated in modality-specific reward representation, the ventral striatum (particularly the nucleus accumbens) may play a role in modality-independent representations of predicted reward. On the other hand, the mesial prefrontal cortex appears to play a role in representing reward prediction error and the dorsal caudate in linking reward to behavior. Theoretically, future studies will need to establish the specificity of these responses to reward versus punishment and anticipation versus outcome. Clinically, current findings suggest that patients can predict reward without a prefrontal cortex, but should experience difficulty correcting their behavior when reward predictions are violated.

Cognition↗

Long- and short-range reward expectancy in the primate orbitofrontal cortex.

The orbitofrontal cortex (OFC) is important in motivation and emotion. We previously reported reward expectancy-related delay activities during a delayed reaction time task in primate OFC neurons. To further investigate the significance of the OFC in motivational operations, we examined pre-instruction, baseline activities of OFC neurons in relation to reward expectancy during the delayed reaction time task. In this task, an instruction cue indicated whether reward would be present or absent in the trial. Each set of four consecutive trials constituted one block within which three different kinds of rewards and one trial with no reward were given in a fixed order that differed from the monkey's reward preference. We identified two types of OFC neurons with reward expectancy-related pre-instruction activities: Step-type neurons showed stepwise changes (increase or decrease) in pre-instruction activity toward the trial with a particular outcome, which usually was the most or least attractive within a block; Pref-type neurons showed pre-instruction activity changes according to the monkey's preference for each trial's outcome. We propose that Step-type and Pref-type neurons are related to long-range and short-range reward expectancies of a particular outcome, respectively. The OFC is considered to play important roles in goal-directed behaviour by adjusting the motivational level toward a certain (current or future) outcome of a particular motivational significance based on the two kinds of reward expectancy processes. Impairments in goal-directed behaviour by OFC patients may be caused by a lack of long-range expectancy or by a deficit in compromising between short-range and long-range expectancies.

Animals↗

Supplementary motor area encodes reward expectancy in eye-movement tasks.

Neural activity signifying the expectation of reward has been found recently in many parts of the brain, including midbrain and cortical structures. These signals can facilitate goal-directed behavior or the learning of new skills based on reinforcements. Here we show that neurons in the supplementary motor area (SMA), an area concerned with movements of the body and limbs, also carry a reward expectancy signal in the postsaccadic period of oculomotor tasks. While the monkeys performed blocks of memory-guided and object-based saccades, the neurons discharged a burst after a approximately 200-ms delay following the target-acquiring saccade in the memory task but often fired concurrently with the target-acquiring saccade in the object task. The hypothesis that this postsaccadic bursting activity reflects the expectation of a reward was tested with a series of manipulations to the memory-guided saccade task. It was found that although the timing of the bursting activity corresponds to a visual feedback stimulus, the visual feedback is not required for the neurons to discharge a burst. Second, blocks of no-reward trials reveal an extinction of the bursting activity as the monkeys come to understand that they would not be rewarded for properly generated saccades. Finally, the delivery of unexpected rewards confirmed that in many of the neurons, the activity is not related to a motor plan to acquire the reward (e.g., licking). Thus we conclude that reward expectancy is represented by the activity of SMA neurons, even in the context of an oculomotor task. These results suggest that the reward expectancy signal is broadcast over a large extent of motor cortex, and may facilitate the learning of new, coordinated behavior between different body parts.

Action Potentials↗

Functional properties of monkey caudate neurons. III. Activities related to expectation of target and reward.

1. The present paper reports complex neural activities in the monkey caudate nucleus that precede and anticipate visual stimuli and reward in learned visuomotor paradigms. These activities were revealed typically in the delayed saccade task in which memory and anticipation were required. We classified these activities according to their relationships to the task. 2. Activity related to expectation of a cue (n = 46) preceded the presentation of a spot of light (target cue) that signified the future location of saccade target. When the target cue was delayed, the activity was prolonged accordingly. The same spot of light was preceded by no activity if it acted as a distracting stimulus. 3. The sustained activity (n = 80) was a tonic discharge starting after the target cue as if holding the spatial information. 4. The activity related to expectation of target (n = 109) preceded the appearance of the target whose location was cued previously. It started with or after a saccade to the cued target location and ended with the appearance of the target. The activity was greater when the target was expected to appear in the contralateral visual field. 5. The activity related to expectation of reward (n = 57) preceded a task-specific reward. It started with the appearance of the final target and ended with the reward. In most cases, the activity was nonselective for how the monkey obtained the reward, i.e., by visual fixation only, by a saccade, or by a hand movement. The activity was dependent partly on visual fixation. 6. A few neurons showed tonic activity selectively before lever release and are thus considered to be related to the preparation of hand movements. 7. The activity related to breaking fixation (n = 33) occurred phasically if the monkey broke fixation, aborting the trial. 8. Activity related to reward (n = 104) was a phasic discharge that occurred before or after a reward of water was delivered. The activity was not simply related to a specific movement involved in the reward-obtaining behavior (eye, hand, or mouth movement). 9. Fixation-related activity (n = 72) was tonic activity continuing as long as the monkey attentively fixated a spot of light. It was dependent on reward expectancy in most cases. 10. The present results, together with those in the preceding papers, indicate that the activities of individual caudate neurons--sensory, motor, or cognitive--are dependent on specific contexts of learned behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Nucleus accumbens corticotropin-releasing factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive effects in stress?

BACKGROUND: Corticotropin-releasing factor (CRF) is typically considered to mediate aversive aspects of stress, fear and anxiety. However, CRF release in the brain is also elicited by natural rewards and incentive cues, raising the possibility that some CRF systems in the brain mediate an independent function of positive incentive motivation, such as amplifying incentive salience. Here we asked whether activation of a limbic CRF subsystem magnifies the increase in positive motivation for reward elicited by incentive cues previously associated with that reward, in a way that might exacerbate cue-triggered binge pursuit of food or other incentives? We assessed the impact of CRF microinjections into the medial shell of nucleus accumbens using a pure incentive version of Pavlovian-Instrumental transfer, a measure specifically sensitive to the incentive salience of reward cues (which it separates from influences of aversive stress, stress reduction, frustration and other traditional explanations for stress-increased behavior). Rats were first trained to press one of two levers to obtain sucrose pellets, and then separately conditioned to associate a Pavlovian cue with free sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250 or 500 ng/0.2 microl) or amphetamine (20 microg/0.2 microl). Lever pressing was assessed in the presence or absence of the Pavlovian cues during a half-hour test. RESULTS: Microinjections of the highest dose of CRF (500 ng) or amphetamine (20 microg) selectively enhanced the ability of Pavlovian reward cues to trigger phasic peaks of increased instrumental performance for a sucrose reward, each peak lasting a minute or so before decaying after the cue. Lever pressing was not enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or during the presentation without a cue, showing that the CRF enhancement could not be explained as a result of generalized motor arousal, frustration or stress, or by persistent attempts to ameliorate aversive states. CONCLUSION: We conclude that CRF in nucleus accumbens shell amplifies positive motivation for cued rewards, in particular by magnifying incentive salience that is attributed to Pavlovian cues previously associated with those rewards. CRF-induced magnification of incentive salience provides a novel explanation as to why stress may produce cue-triggered bursts of binge eating, drug addiction relapse, or other excessive pursuits of rewards.

Animals↗

Ventral pallidal representation of pavlovian cues and reward: population and rate codes.

We recorded neural activity in the ventral pallidum (VP) while rats learned a pavlovian reward association. Rats learned to distinguish a tone that predicted sucrose pellets (CS+) from a different tone that predicted nothing (CS-). Many VP units became responsive to CS+, but few units responded to CS-. When two CS+ were encountered sequentially, the earliest predictor of reward became most potent. Many VP units were also activated when the sucrose reward was received [unconditioned stimulus (UCS)]. These VP units for UCS remained responsive to sucrose reward after learning, even when sucrose was already predicted by CS+. Neural representation of reward learning and reward itself was characterized by population codes. The population of units that responded to CS+ increased with learning, whereas the population that responded to UCS did not change. A relative firing rate code also represented the identities of conditioned stimuli and UCS. Firing rate differences among stimuli were acquired early and remained stable during subsequent training, whereas population codes and behavioral conditioned responses continued to develop during subsequent training. Thus, the VP makes use of dynamic CS population and rate codes to encode pavlovian reward cues in reward learning and uses stable UCS population and firing codes to encode sucrose reward itself.

Acoustic Stimulation↗

The role of ventral frontostriatal circuitry in reward-based learning in humans.

This study examined changes in behavior and neural activity with reward learning. Using an event-related functional magnetic resonance imaging paradigm, we show that the nucleus accumbens, thalamus, and orbital frontal cortex are each sensitive to reward magnitude, with the accumbens showing the greatest discrimination between reward values. Mean reaction times were significantly faster to cues predicting the greatest reward and slower to cues predicting the smallest reward. This behavioral change over the course of the experiment was paralleled by a shift in peak in accumbens activity from anticipation of the reward (immediately after the response), to the cue predicting the reward. The orbitofrontal and thalamic regions peaked in anticipation of the reward throughout the experiment. Our findings suggest discrete functions of regions within basal ganglia thalamocortical circuitry in adjusting behavior to maximize reward.

Adult↗

Previous cocaine exposure makes rats hypersensitive to both delay and reward magnitude.

Animals prefer an immediate over a delayed reward, just as they prefer a large over a small reward. Exposure to psychostimulants causes long-lasting changes in structures critical for this behavior and might disrupt normal time-discounting performance. To test this hypothesis, we exposed rats to cocaine daily for 2 weeks (30 mg/kg, i.p.). Approximately 6 weeks later, we tested them on a variant of a time-discounting task, in which the rats responded to one of two locations to obtain reward while we independently manipulated the delay to reward and reward magnitude. Performance did not differ between cocaine-treated and saline-treated (control) rats when delay lengths and reward magnitudes were equal at the two locations. However, cocaine-treated rats were significantly more likely to shift their responding when we increased the delay or reward size asymmetrically. Furthermore, they were slower to respond and made more errors when forced to the side associated with the lower value. We conclude that previous exposure to cocaine makes choice behavior hypersensitive to differences in the time to and size of available rewards, consistent with a general effect of cocaine exposure on reward valuation mechanisms.

Animals↗

Effectiveness of video of conspecifics as a reward for socially housed bonnet macaques (Macaca radiata).

Two experiments were conducted to examine the effectiveness of presenting brief video of conspecifics to socially housed bonnet macaques as a reward for performing a joystick task. Using a joystick, subjects tracked a moving target with the cursor on a computer monitor. In Exp. 1, subjects completed significantly more joystick trials for food reward than for video reward or no reward. Subjects also preferred viewing video of another group (Other Group Video) to receiving no reward or to viewing video of their own group (Own Group Video). In Exp. 2, subjects were given two reward conditions, video of a familiar social group or video of a new social group. Two monkeys contributed the vast majority of trials, and both responded more frequently when the reward was video of the new social group. Results of these two experiments suggest that viewing video of conspecifics may serve as an effective reward for at least some socially housed primates and suggests that novelty of the individuals depicted in the video is an important factor contributing to the reward value of video.

Animals↗

Dissociable neural responses in human reward systems.

Reward is one of the most important influences shaping behavior. Single-unit recording and lesion studies in experimental animals have implicated a number of regions in response to reinforcing stimuli, in particular regions of the extended limbic system and the ventral striatum. In this experiment, functional neuroimaging was used to assess neural response within human reward systems under different psychological contexts. Nine healthy volunteers were scanned using functional magnetic resonance imaging during the performance of a gambling task with financial rewards and penalties. We demonstrated neural sensitivity of midbrain and ventral striatal regions to financial rewards and hippocampal sensitivity to financial penalties. Furthermore, we show that neural responses in globus pallidus, thalamus, and subgenual cingulate were specific to high reward levels occurring in the context of increasing reward. Responses to both reward level in the context of increasing reward and penalty level in the context of increasing penalty were seen in caudate, insula, and ventral prefrontal cortex. These results demonstrate dissociable neural responses to rewards and penalties that are dependent on the psychological context in which they are experienced.

Brain↗

[Psychological stress and rewarding effect of alcohol].

It has long been postulated that an interaction between ethanol and stress may play an important role in the etiology of alcoholism. In the present review, we focused on an interaction between ethanol and stress in the mechanism of psychological dependence on ethanol. Ethanol with conditioned fear stress (CFS), but not without the stress, induced a significant place preference. These results suggest that psychological stress may play an important role in the rewarding effect of ethanol. It has been hypothesized that activation of the mesolimbic dopamine system mediated by the endogenous opioid system may be particularly important in the rewarding mechanism of ethanol. It appeared that mu- and delta-opioid receptors might play critical roles in the development of the rewarding effect of ethanol under the stress. Under psychological stress, the rewarding effect of ethanol through the activation of mu- and/or delta-opioid receptors was found to results the activation of dopamine D1 and/or D2 receptors. Additionally, a subtype of serotonin (5-HT) receptors, 5-HT3 receptor, was shown to be involved in the rewarding mechanism of ethanol through the activation of mu- and delta-opioid receptors. In conclusion, psychological stress may be an important factor in the development of the rewarding effect of ethanol and may potentiate the rewarding mechanism. 5-HT3 receptor, is likely to be involved in the rewarding mechanism of ethanol under stress. Dopamine D1 and D2 receptors may also be implicated in the rewarding mechanism of ethanol under stress.

Animals↗

Neural correlates of rewarded and unrewarded eye movements in the primate caudate nucleus.

The prospect of immediate reward elicits goal-oriented behavior. However, animals often have to perform actions that do not immediately lead to reward in the pursuit of a long-term goal. Here we identify neural activity in monkey caudate nucleus that specifically correlates with rewarded and unrewarded eye movements. The monkey performed a visually guided saccade task in which only one position was associated with positive reinforcement. To advance in the experimental session, however, the monkey had no choice but to complete a saccade to an unrewarded position as well as to a rewarded position. Some caudate saccadic neurons showed enhanced activity around the time of the saccade in rewarded trials (rewarded-saccade neurons). Another subset of neurons discharged selectively around the execution of the saccade in unrewarded trials (unrewarded-saccade neurons). In both rewarded and unrewarded trials, stronger activity of these neurons was associated with reduced saccade latency. These results suggest that both rewarded and unrewarded saccades are facilitated by caudate saccadic activity. The neuronal activity of unrewarded-saccade neurons might reflect the required execution of unrewarded eye movements on the way to future reward.

Action Potentials↗

Coding of predicted reward omission by dopamine neurons in a conditioned inhibition paradigm.

Animals learn not only about stimuli that predict reward but also about those that signal the omission of an expected reward. We used a conditioned inhibition paradigm derived from animal learning theory to train a discrimination between a visual stimulus that predicted reward (conditioned excitor) and a second stimulus that predicted the omission of reward (conditioned inhibitor). Performing the discrimination required attention to both the conditioned excitor and the inhibitor; however, dopamine neurons showed very different responses to the two classes of stimuli. Conditioned inhibitors elicited considerable depressions in 48 of 69 neurons (median of 35% below baseline) and minor activations in 29 of 69 neurons (69% above baseline), whereas reward-predicting excitors induced pure activations in all 69 neurons tested (242% above baseline), thereby demonstrating that the neurons discriminated between conditioned stimuli predicting reward versus nonreward. The discriminative responses to stimuli with differential reward-predicting but common attentional functions indicate differential neural coding of reward prediction and attention. The neuronal responses appear to reflect reward prediction errors, thus suggesting an extension of the correspondence between learning theory and activity of single dopamine neurons to the prediction of nonreward.

Animals↗

Differential effect of naloxone on food and self-stimulation rewarded acquisition of a behavioral response pattern.

The involvement of endogenous opioids in self-stimulation reward was investigated by repeated administration of the opioid antagonist naloxone to rats during acquisition of a behavioral response pattern that was rewarded with electrical (self-)stimulation of the ventral tegmental area. A control experiment was performed using food deprived rats in which a comparable response pattern was rewarded with food pellets. The response patterns consisted of gradually decreasing amounts of reward per response, which could be reset to maximal reward by another response. It was found that naloxone disrupted the acquisition of the stimulation rewarded response pattern, while it did not influence the food rewarded behavior. It is suggested that endorphin systems are actively involved in the acquisition of self-stimulation reward procedures, and that this involvement may be specific for self-stimulation reward.

Animals↗

Support and rewards for scholarly activity in family medicine: a national survey.

BACKGROUND AND OBJECTIVES: This survey examined how time is allotted for family medicine faculty to pursue scholarly activities and how these activities are rewarded. METHODS: A survey was sent to all directors of family practice residency programs (n = 373) and chairs of family medicine departments (n = 112). Four primary questions were asked: 1) How is faculty time allotted for scholarly activities? 2) Does the residency or department use an explicit reward system? 3) What activities are rewarded? and 4) What rewards are used? RESULTS: A total of 363 surveys were returned, for a response rate of 75%. Forty-nine percent of respondents have regular, protected faculty time for scholarly activities. Faculty at university-based residencies and departments were more likely to have protected time (68/93, 73%) than faculty at community-based residencies (93/238, 39%). Thirty-eight percent of respondents have an explicit reward system. Activities rewarded and rewards used are department and program-type specific. CONCLUSIONS: Only 39% of community-based residencies and 73% of university programs allot regular protected time for faculty. The majority of programs and departments do not have an explicit reward system. Further studies are needed to determine if the use of protected time and reward systems enhance scholarly productivity.

Career Mobility↗