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At least 595 records · Page 33Linked to original sources
PubMed2002

Brain reward system activity in major depression and comorbid nicotine dependence.

Major depressive disorder (MDD) and nicotine dependence are highly comorbid. MDD patients may use nicotine to ameliorate depressive symptoms. The pathophysiology of the comorbidity of these two disorders is unknown. We hypothesized that a dysfunctional dopaminergic brain reward system (BRS) might be a neurobiological link between MDD and nicotine dependence and that smoking modulates the activity of the BRS by enhancing dopaminergic activity and relieving some depressive symptoms. Eighteen nicotine-dependent, nonmedicated subjects with Diagnostic and Statistical Manual of Mental Disorders (4th edition) diagnosis of MDD and 16 nicotine-dependent, control subjects participated in a double-blind, placebo-controlled, randomized parallel study. A single 30-mg oral dose of d-amphetamine (d-amph) was used to release dopamine and probe the activity of the BRS. The d-amph-mediated physiological and rewarding effects were assessed at baseline and post-treatment using standardized and validated questionnaires. Our results show that d-amph significantly increased blood pressure (p < 0.001). Subjective rewarding d-amph effects increased in both groups. Negative subjective effects were reported while on placebo during nonsmoking sessions. A significant correlation between depression severity (Hamilton depression scale) and d-amph rewarding effects was found in MDD smoker subjects (Addiction Research Center Inventory composite: r = 0.89, p < 0.000; profile of mood states composite: r = 0.71, p < 0.003; and visual analog scales composite: r = 0.78, p < 0.005). These data show that smoking did not modify the response to d-amph in MDD or control subjects, but decreased overall negative mood state during placebo sessions. Severity of depression was significantly correlated with increased rewarding effects of d-amph. Thus, although the BRS may be dysfunctional in MDD subjects, chronic nicotine use does not modify response to d-amph.

Adolescent↗
PubMed2004

Neuronal activity related to reward value and motivation in primate frontal cortex.

In several areas of the macaque brain, neurons fire during delayed-response tasks at a rate determined by the value of the reward expected at the end of the trial. The activity of these neurons might be related to the value of the expected reward or to the degree of motivation induced by expectation of the reward. We describe results indicating that the nature of reward-dependent activity varies across areas. Neuronal activity in orbitofrontal cortex represents the value of the expected reward, whereas neuronal activity in premotor cortex reflects the degree of motivation.

Action Potentials↗
PubMed2000

Modulation of brain reward circuitry by leptin.

Leptin, a hormone secreted by fat cells, suppresses food intake and promotes weight loss. To assess the action of this hormone on brain reward circuitry, changes in the rewarding effect of lateral hypothalamic stimulation were measured after leptin administration. At five stimulation sites near the fornix, the effectiveness of the rewarding electrical stimulation was enhanced by chronic food restriction and attenuated by intracerebroventricular infusion of leptin. In contrast, the rewarding effect of stimulating neighboring sites was insensitive to chronic food restriction and was enhanced by leptin in three of four cases. These opposing effects of leptin may mirror complementary changes in the rewarding effects of feeding and of competing behaviors.

Animals↗
PubMed2005

Orbitofrontal ensemble activity monitors licking and distinguishes among natural rewards.

The classification of rhythmic licking into clusters has proved to be useful for characterizing brain mechanisms that modulate the ingestion of natural rewards (sucrose and water). One cortical area that is responsive to rewarding stimuli is the orbitofrontal cortex (OFC). However, it is not presently known how OFC neurons respond while rodents freely lick for natural rewards and whether these responses are related to the structure of licking clusters. We addressed these issues by showing that temporary inactivation of the OFC decreases the duration and increases the number of clusters and that the activity of OFC neurons changed at precise times before, during, and after the cluster terminates. Furthermore, analysis of the activity of OFC neuronal ensembles showed that they could discriminate cluster onset from termination, predict when a behaving animal will begin a cluster, and distinguish and anticipate between natural rewards. These results provide a new role for the OFC in influencing licking clusters and anticipating specific rewards.

Animals↗
PubMed2004

Reward-related reversal learning after surgical excisions in orbito-frontal or dorsolateral prefrontal cortex in humans.

Neurophysiological studies in primates and neuroimaging studies in humans suggest that the orbito-frontal cortex is involved in representing the reward value of stimuli and in the rapid learning and relearning of associations between visual stimuli and rewarding or punishing outcomes. In the present study, we tested patients with circumscribed surgical lesions in different regions of the frontal lobe on a new visual discrimination reversal test, which, in an fMRI study (O'Doherty, Kringelbach, Rolls, Hornak, & Andrews, 2001), produced bilateral orbito-frontal cortex activation in normal subjects. In this task, touching one of two simultaneously presented patterns produced reward or loss of imaginary money delivered on a probabilistic basis to minimize the usefulness of verbal strategies. A number of types of feedback were present on the screen. The main result was that the group of patients with bilateral orbito-frontal cortex lesions were severely impaired at the reversal task, in that they accumulated less money. These patients often failed to switch their choice of stimulus after a large loss and often did switch their choice although they had just received a reward. The investigation showed that bilateral lesions were required for this deficit, since patients with unilateral orbito-frontal cortex (or medial prefrontal cortex) lesions were not impaired in the probabilistic reversal task. The task ruled out a simple motor disinhibition as an explanation of the deficit in the bilateral orbito-frontal cortex patients, in that the patients were required to choose one of two stimuli on each trial. A comparison group of patients with dorsolateral prefrontal cortex lesions was in some cases able to do the task, and in other cases, was impaired. Posttest debriefing showed that all the dorsolateral prefrontal patients who were impaired at the task had failed to pay attention to the crucial feedback provided on the screen after each trial about the amount won or lost on each trial. In contrast, all dorsolateral patients who paid attention to this crucial feedback performed normally on the reversal task. Further, it was confirmed that the bilateral orbito-frontal cortex patients had also paid attention to this crucial feedback, but in contrast had still performed poorly at the task. The results thus show that the orbital prefrontal cortex is required bilaterally for monitoring changes in the reward value of stimuli and using this to guide behavior in the task; whereas the dorsolateral prefrontal cortex, if it produces deficits in the task, does so for reasons related to executive functions, such as the control of attention. Thus, the ability to determine which information is relevant when making a choice of pattern can be disrupted by a dorsolateral lesion on either side, whereas the ability to use this information to guide behavior is not disrupted by a unilateral lesion in either the left or the right orbito-frontal cortex, but is severely impaired by a bilateral lesion in this region. Because both abilities are important in many of the tasks and decisions that arise in the course of daily life, the present results are relevant to understanding the difficulties faced by patients after surgical excisions in different frontal brain regions.

Adult↗
PubMed2002

Long-term reward prediction in TD models of the dopamine system.

This article addresses the relationship between long-term reward predictions and slow-timescale neural activity in temporal difference (TD) models of the dopamine system. Such models attempt to explain how the activity of dopamine (DA) neurons relates to errors in the prediction of future rewards. Previous models have been mostly restricted to short-term predictions of rewards expected during a single, somewhat artificially defined trial. Also, the models focused exclusively on the phasic pause-and-burst activity of primate DA neurons; the neurons' slower, tonic background activity was assumed to be constant. This has led to difficulty in explaining the results of neurochemical experiments that measure indications of DA release on a slow timescale, results that seem at first glance inconsistent with a reward prediction model. In this article, we investigate a TD model of DA activity modified so as to enable it to make longer-term predictions about rewards expected far in the future. We show that these predictions manifest themselves as slow changes in the baseline error signal, which we associate with tonic DA activity. Using this model, we make new predictions about the behavior of the DA system in a number of experimental situations. Some of these predictions suggest new computational explanations for previously puzzling data, such as indications from microdialysis studies of elevated DA activity triggered by aversive events.

Animals↗
PubMed2004

A comparative developmental study of impulsivity in rats and humans: the role of reward sensitivity.

The present study was conducted to test the hypothesis that differences in reward sensitivity between adolescents and adults account for differences in impulsivity. In a comparative study, we examined preferences for various concentrations of sucrose solutions as an operational measure of reward sensitivity in adolescent and adult rats and humans. Humans also completed self-report measures of impulsivity and reward sensitivity. There was some indication that adolescents preferred sweeter solutions compared to adults. Also, adolescents scored substantially higher on impulsivity. However, adolescents and adults did not differ in self-ratings of reward sensitivity and personality scores were not consistently related to sucrose preferences. The data highlight some of the benefits and issues that arise with developing comparative measures in humans and animals. Future comparative research using alternative behavioral paradigms is necessary to determine if and how changes in reward sensitivity influence developmental shifts in impulsivity.

Adolescent↗
PubMed2006

Does occupational gender segregation influence the association of effort-reward imbalance with myocardial infarction in the SHEEP study?

The objective of this study was to investigate whether occupational gender segregation moderates the association between job stress in terms of effort-reward imbalance and the risk of myocardial infarction. This analysis was conducted in 1,381 cases and 1,697 referents of the Swedish SHEEP case control study aged 45-70 years. Information on myocardial infarction and biological coronary risk factors (e.g. hypertension, blood lipids) was achieved from clinical screenings. Information on socio-demographic variables, effort-reward imbalance, behavioral coronary risk factors (e.g., smoking), and additional coronary risk factors (e.g., diabetes, family history of coronary heart disease) was derived from well-tested standardized questionnaires. After adjustment for confounders the strongest association between overcommitment (the intrinsic component of effort-reward imbalance) and risk of belonging to the myocardial infarction group was found among women in male-dominated jobs (odds ratio [OR] = 2.71, 95% CI = 1.13-6.52) as compared to the remaining group (OR = 1.52, 95% CI = 1.01-2.31). Moreover, a significant interaction between pronounced overcommitment and male domination in relation to myocardial infarction was observed among women (OR = 2.44, 95% CI = 1.05-5.67). In men, an association between the ratio of effort and reward (the extrinsic component of the model) and risk of myocardial infarction was found for the majority, that is the group not working in women-dominated jobs (OR = 1.39, 95% CI = 1.04-1.86). Despite methodological limitations, this study gives preliminary evidence of a moderating effect of occupational gender segregation on the association of effort-reward imbalance (i.e., the intrinsic model component overcommitment) with acute myocardial infarction risk among women, but not among men.

Adult↗
PubMed2006

Is avoiding an aversive outcome rewarding? Neural substrates of avoidance learning in the human brain.

Avoidance learning poses a challenge for reinforcement-based theories of instrumental conditioning, because once an aversive outcome is successfully avoided an individual may no longer experience extrinsic reinforcement for their behavior. One possible account for this is to propose that avoiding an aversive outcome is in itself a reward, and thus avoidance behavior is positively reinforced on each trial when the aversive outcome is successfully avoided. In the present study we aimed to test this possibility by determining whether avoidance of an aversive outcome recruits the same neural circuitry as that elicited by a reward itself. We scanned 16 human participants with functional MRI while they performed an instrumental choice task, in which on each trial they chose from one of two actions in order to either win money or else avoid losing money. Neural activity in a region previously implicated in encoding stimulus reward value, the medial orbitofrontal cortex, was found to increase, not only following receipt of reward, but also following successful avoidance of an aversive outcome. This neural signal may itself act as an intrinsic reward, thereby serving to reinforce actions during instrumental avoidance.

Adult↗
PubMed2005

GABAA-mediated inhibition of basolateral amygdala blocks reward devaluation in macaques.

Amygdala ablation disrupts reinforcer "devaluation" in monkeys (Malkova et al., 1997). Here, we tested the hypothesis that transient inactivation of amygdala by the GABA(A) agonist muscimol (MUS), specifically during the period of reward satiation, would have a similar effect. Six pigtail macaques were trained on a visual object discrimination task in which 60 objects were associated with one of two specific food rewards. Subsequently, we evaluated the selective satiation-induced change (devaluation) in object preference in probe sessions. We also examined the effect of the amygdala inactivation during the probe sessions to determine whether the inactivation limited to the testing period (and not during the satiation period) is sufficient to impair the expression of reinforcer devaluation. MUS infusions were aimed at basolateral amygdala (BLA) in a pseudorandomized design; each monkey received MUS or saline either before or after selective satiation with each of the two food rewards (six infusions total). Under the control (saline) condition, the monkeys significantly shifted their preference from objects representing the sated food rewards to those representing the nonsated rewards (30% change). When BLA was inactivated during selective satiation (i.e., MUS infused before satiation), this devaluation effect was blocked. In contrast, MUS infusion after satiation, so that it was present just during the testing period, did not impair the shift in object preference (27% change). Thus, BLA is necessary for the appropriate registration of the change in the reinforcer value but not for the subsequent expression of the devaluation involving its transfer to secondary reinforcers.

Amygdala↗
PubMed2006

Preference for immediate over delayed rewards is associated with magnitude of ventral striatal activity.

Discounting future outcomes as a function of their deferred availability underlies much of human decision making. Discounting, or preference for immediate over delayed rewards of larger value, is often associated with impulsivity and is a risk factor for addictive disorders such as pathological gambling, cigarette smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in mediating behavioral responses and physiological states associated with reward, and dysregulation of the VS contributes to addiction, perhaps by affecting impulsive decision-making. Behavioral tests of delay discounting (DD), which index preference for smaller immediate over larger delayed rewards, covary with impulsive tendencies in humans. In the current study, we examined the relationship between individual differences in DD, measured in a behavioral assessment, and VS activity measured with blood oxygenation level-dependent functional magnetic resonance imaging, in 45 adult volunteers. VS activity was determined using a task involving positive and negative feedback with monetary reward. Analyses revealed that individual differences in DD correlate positively with magnitude of VS activation in response to both positive and negative feedback, compared with a no-feedback control condition. Variability in DD was also associated with differential VS activation in response to positive, compared with negative, feedback. Collectively, our results suggest that increased preference for smaller immediate over larger delayed rewards reflects both a relatively indiscriminate and hyper-reactive VS circuitry. They also highlight a specific neurocognitive mechanism that may contribute to increased risk for addiction.

Adult↗
PubMed2006

Two brain sites for cannabinoid reward.

The recent findings that Delta9tetrahydrocannabinol (Delta9THC), the active agent in marijuana and hashish, (1) is self-administered intravenously, (2) potentiates the rewarding effects of electrical brain stimulation, and (3) can establish conditioned place preferences in laboratory animals, suggest that these drugs activate biologically primitive brain reward mechanisms. Here, we identify two chemical trigger zones for stimulant and rewarding actions of Delta9THC. Microinjections of Delta9THC into the posterior ventral tegmental area (VTA) or into the shell of the nucleus accumbens (NAS) increased locomotion, and rats learned to lever-press for injections of Delta9THC into each of these regions. Substitution of vehicle for drug or treatment with a cannabinoid CB1 receptor antagonist caused response cessation. Microinjections of Delta9THC into the posterior VTA and into the posterior shell of NAS established conditioned place preferences. Injections into the core of the NAS, the anterior VTA, or dorsal to the VTA were ineffective. These findings link the sites of rewarding action of Delta9THC to brain regions where such drugs as amphetamines, cocaine, heroin, and nicotine are also thought to have their sites of rewarding action.

Analysis of Variance↗
PubMed2007

Involvement of non-NMDA glutamate receptors in central amygdala in synaptic actions of ethanol and ethanol-induced reward behavior.

The central nucleus of the amygdala (CeA) plays a critical role in positive emotional responses that involve stimulus-reward learning and are induced by the reinforcing effects of many drugs of abuse, including alcohol. Behavioral studies have implicated CeA as a key brain structure in alcohol reward, but the underlying mechanisms are still poorly understood. Recent studies have demonstrated that both NMDA and non-NMDA receptors in CeA neurons are targets of acute and chronic alcohol in naive and alcohol-dependent animals. However, little is known about the role of CeA non-NMDA receptors in synaptic actions of alcohol and, particularly, in the behavior of alcohol reward. In the present study with both whole-cell voltage-clamp recordings in CeA slices in vitro and analysis of an animal model of conditioned place preference (CPP) in vivo, we investigated the synaptic mechanisms for actions of acute and chronic ethanol on CeA non-NMDA receptor functions and their contribution to ethanol-induced reward behavior. Acute ethanol significantly inhibited evoked and miniature synaptic currents mediated by non-NMDA receptors through inhibitions of both postsynaptic non-NMDA receptors and presynaptic glutamate release involving N-type Ca2+ channels. CeA neurons from rats exhibiting the ethanol-induced CPP behavior showed a significant increase in non-NMDA synaptic transmission. Blockade of this increased synaptic transmission through CeA microinjection abolished the CPP behavior. These results suggest that acute alcohol inhibits CeA non-NMDA synaptic transmission through both presynaptic and postsynaptic mechanisms, and chronic alcohol upregulates this synaptic activity, which is required for the alcohol-induced reward behavior.

Amygdala↗
PubMed2004

Dopamine transmission in the human striatum during monetary reward tasks.

Previous studies have demonstrated the ability of the [11C]raclopride positron emission tomography (PET) technique to measure behaviorally induced changes in endogenous dopamine transmission in humans. However, these studies have lacked well matched sensorimotor control conditions, making it difficult to know what sensory, cognitive, or motor features contributed to changes in dopaminergic activity. Here we report on [11C]raclopride PET studies in which healthy humans performed card selection tasks for monetary rewards. During separate scans, subjects completed a variable ratio (VR) reward schedule with a 25% reward rate in which they did not know the outcome of their responses in advance, a fixed ratio (FR) 25% reward schedule in which outcomes were fully predictable, and a sensorimotor control (SC) condition involving similar sensory and motor demands but no rewards. Relative to the SC condition, the FR schedule produced only modest increases in dopamine transmission and no decreases relative to the SC condition. In contrast, the VR schedule produced significant increases in dopamine transmission in the left medial caudate nucleus while simultaneously producing significant decreases in other areas of the caudate and putamen. These data indicate: (1) the feasibility of measuring alterations in dopamine transmission even after controlling for sensorimotor features and (2) the complex and regionally specific influence of VR schedules on dopamine transmission. The implications of these results are discussed in relation to conflicting models of dopaminergic functioning arising from studies using electrophysiological and microdialysis techniques in animals.

Adult↗
PubMed2006

Effects of reward and behavioral context on neural activity in the primate inferior colliculus.

Neural activity in the inferior colliculus (IC) likely plays an integral role in the processing of various auditory parameters, such as sound location and frequency. However, little is known about the extent to which IC neural activity may be influenced by the context in which sounds are presented. In this study, we examined neural activity of IC neurons in the rhesus monkey during an auditory task in which a sound served as a localization target for a saccade. Correct performance was rewarded, and the magnitude of the reward was varied in some experiments. Neural activity was also assessed during a task in which the monkey maintained fixation of a light while ignoring the sound, as well as when sounds were presented in the absence of any task. We report that neural activity increased late in the trial in the saccade task in 58% of neurons and that the level of activity throughout the trials could be modulated by reward magnitude for many neurons. The late-trial neural activity similarly increased in the fixation task in 39% of the neurons tested for this task but was not observed when sounds were presented in the absence of a behavioral task and reward. Together, these results suggest that a reward-related signal influences neural activity in the IC.

Acoustic Stimulation↗
PubMed2001

Effect of response effort on the reward value of distinctively flavored food pellets.

This study was designed to test whether distinctively flavored food pellets, used as rewards for lever-pressing by rats, would acquire different reward values as a function of the differential effort involved in making the lever pressing response which would be predictable from the concept of cognitive dissonance. Subjects were seven Long-Evans strain hooded rats, 301-308 days old at the start of the study and had had their body weights reduced to 80%, of their free-feeding weights. Testing was done in a Y-maze, with food pellets associated with the difficult lever-press response serving as the reward for one choice and pellets associated with the easy lever-press response for the other. Analysis showed there was no preference in the choice of either the "easy" or the "difficult" pellets, the choice not being significantly different from chance. This indicated that the effort involved in making a response did not affect the reward strength of food pellets when used to reward a response with a different topography.

Animals↗
PubMed2003

"Justification of effort" in rats: effects of physical and discriminative effort on reward value.

The justification of effort is the tendency for humans to justify the amount of work they have put into an achievement by increasing the perceived value of that achievement after the effort has been expended. A positive effect of effort on reward value has also been reported for pigeons and starlings. The present study examined the effects of different amounts of required physical and discriminative effort on primary reward value in rats. On each day of training, rats underwent one high-effort training session and one low-effort training session in an operant chamber to earn either a grape-flavored reward pellet or a bacon-flavored reward pellet. Half of the rats exerted high effort to earn the grape pellets and low effort to earn the bacon pellets, with the arrangement reversed for the other half. On each test trial, each rat had the opportunity to consume 3 pellets of each flavor at the choice point in a T-maze. Analysis indicated no significant difference between the frequency of high-effort flavor choices and low-effort flavor choices. A positive effect of effort on reward value was not demonstrated in this experiment.

Animals↗
PubMed2004

Effect of upcoming reward type when rats press a lever for ethanol.

Rats' operant responding for sucrose rewards in the 1st half of a session can vary directly with the conditions of reward in the 2nd half. The authors investigated whether that induction effect represented an animal model of emotive states. Rats pressed a lever for either ethanol or sucrose rewards in the 1st half of a 40-min session. The reward in the 2nd half of the session was, across conditions, 1% sucrose, a food pellet, or the same reinforcer delivered in the 1st half. When subjects responded for sucrose, upcoming reward type had little influence on responding in the 1st half of the session. However, when subjects responded for ethanol, upcoming 1% sucrose and food-pellet reinforcement both produced increases in responding. The results suggest that the procedure produced different emotive states, but further work is needed to support such a model. The results also have potential applied implications.

Affect↗