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Discounting of delayed rewards in opioid-dependent outpatients: exponential or hyperbolic discounting functions?

Recent theories of substance abuse have used value discounting of delayed rewards to partly explain the decision to take drugs. Normative-economic theory holds that an exponential function describes the effects of delay on discounting, whereas the matching law posits a hyperbolic discounting function. The ability of these functions to describe 18 human heroin-dependent individuals' monetary- and heroin-reward delay-discounting functions was assessed. In the 1st condition, participants chose between immediate and delayed hypothetical monetary rewards. Delayed rewards were $1,000, and the immediate reward amount was adjusted until choices reflected indifference. In the 2nd condition, participants chose between immediate and delayed heroin (the delayed amount was that which each participant reported he or she could purchase with $1,000). The hyperbolic function produced significantly higher R2 values and significantly lower sums of squared error values. Consistent with previous findings, delayed heroin rewards were discounted at a significantly higher rate than were delayed monetary rewards.

Adult↗

Retrospective and prospective coding for predicted reward in the sensory thalamus.

Reward is important for shaping goal-directed behaviour. After stimulus-reward associative learning, an organism can assess the motivational value of the incoming stimuli on the basis of past experience (retrospective processing), and predict forthcoming rewarding events (prospective processing). The traditional role of the sensory thalamus is to relay current sensory information to cortex. Here we find that non-primary thalamic neurons respond to reward-related events in two ways. The early, phasic responses occurred shortly after the onset of the stimuli and depended on the sensory modality. Their magnitudes resisted extinction and correlated with the learning experience. The late responses gradually increased during the cue and delay periods, and peaked just before delivery of the reward. These responses were independent of sensory modality and were modulated by the value and timing of the reward. These observations provide new evidence that single thalamic neurons can code for the acquired significance of sensory stimuli in the early responses (retrospective coding) and predict upcoming reward value in the late responses (prospective coding).

Animals↗

Prediction of immediate and future rewards differentially recruits cortico-basal ganglia loops.

Evaluation of both immediate and future outcomes of one's actions is a critical requirement for intelligent behavior. Using functional magnetic resonance imaging (fMRI), we investigated brain mechanisms for reward prediction at different time scales in a Markov decision task. When human subjects learned actions on the basis of immediate rewards, significant activity was seen in the lateral orbitofrontal cortex and the striatum. When subjects learned to act in order to obtain large future rewards while incurring small immediate losses, the dorsolateral prefrontal cortex, inferior parietal cortex, dorsal raphe nucleus and cerebellum were also activated. Computational model-based regression analysis using the predicted future rewards and prediction errors estimated from subjects' performance data revealed graded maps of time scale within the insula and the striatum: ventroanterior regions were involved in predicting immediate rewards and dorsoposterior regions were involved in predicting future rewards. These results suggest differential involvement of the cortico-basal ganglia loops in reward prediction at different time scales.

Adult↗

Blockade of mesolimbic dopamine transmission dramatically increases sensitivity to the rewarding effects of nicotine in the ventral tegmental area.

Nicotine produces rewarding and aversive motivational effects in humans and other animal species. Here, we report that the mammalian ventral tegmental area (VTA) represents a critical neural substrate for the mediation of both the rewarding and aversive properties of nicotine. We demonstrate that direct infusions of nicotine into the VTA can produce both rewarding and aversive motivational effects. While the rewarding effects of higher doses of nicotine were not attenuated by dopamine (DA) receptor blockade, blockade of mesolimbic DA signalling with either systemic or intra-nucleus accumbens (NAc) neuroleptic pretreatment potentiated the sensitivity to nicotine's rewarding properties over a three-order-of-magnitude dose range. Furthermore, the behavioural effects of lower doses of intra-VTA nicotine were reversed, switching the motivational valence of nicotine from aversive to rewarding. Our results suggest that blockade of mesolimbic DA signalling induced by neuroleptic medications may block selectively the aversive properties of nicotine, thus increasing the vulnerability to nicotine's rewarding and addictive properties by inducing a unique, drug-vulnerable phenotype.

Animals↗

Changes in reward-induced brain activation in opiate addicts.

Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with H(2)(15)O positron emission tomography (PET) during a visuo-spatial recognition task with delayed response in control subjects and in opiate addicts participating in a methadone program. Three conditions were defined by the types of feedback: nonsense feedback; nonmonetary reinforcement; or monetary reward, received by the subjects for a correct response. We found in the control subjects rCBF increases in regions associated with the meso-striatal and meso-corticolimbic circuits in response to both monetary reward and nonmonetary reinforcement. In opiate addicts, these regions were activated only in response to monetary reward. Furthermore, nonmonetary reinforcement elicited rCBF increases in limbic regions of the opiate addicts that were not activated in the control subjects. Because psychoactive drugs serve as rewards and directly affect regions of the dopaminergic system like the striatum, we conclude that the differences in rCBF increases between controls and addicts can be attributed to an adaptive consequence of the addiction process.

Adult↗

Development and validation of the Amsterdam Motives for Drinking Scale (AMDS): an attempt to distinguish relief and reward drinkers.

UNLABELLED: Determination of alcoholic subtypes is a promising strategy for patient treatment matching with anti-craving interventions. The aim of this study is to develop and validate a questionnaire on drinking motives that can distinguish relief and reward drinkers. METHODS: A 103-item self-report questionnaire was developed: the Amsterdam Motives for Drinking Scale (AMDS). The AMDS was tested in two samples of alcoholics (Sample A: n = 251; Sample B: n = 197). The psychometric properties were examined in Sample A and cross-validated in B. RESULTS: The AMDS consists of a relief scale and a reward scale, both containing distinct subscales. All (sub)scales had good internal consistency. However, the relief and reward scales were highly correlated (Sample A: r = 0.84, P < 0.01; Sample B: r = 0.76, P < 0.01), and convergent and divergent validity was only partly confirmed. The lowest correlations were found between the relief subscale 'stress and vulnerability' and the reward subscale 'stimulation seeking' (Sample A: r = 0.33, P < 0.01; Sample B: r = 0.13, P > 0.01). CONCLUSIONS: The AMDS reliably measures two types of motives. However, the relief and reward scales are highly correlated. Lower correlations were found only at the subscale level. It is concluded that most treatment-seeking alcoholics have both relief and reward motives. More research is needed on the relationship between motives for drinking and other phenotypic, endophenotypic and genetic indicators of relief and reward drinking, and appropriate cut-off points. Only than we can draw firm conclusions regarding the potential of drinking motives for patient treatment matching.

Adult↗

Reward-quality dependent anticipation in rat nucleus accumbens.

Single unit recording in rat nucleus accumbens (NAcc) was used to ascertain NAcc neuronal activity in mediating of reward including its anticipation. Of the 103 neurons investigated, 63% showed some response in connection with the task activity. Of these, 20 units responded during delivery of the primary reward (food and/or water) and five responded during the time period preceding reward if the reward was delayed (four to food, one to water). These result suggest that NAcc neurons responded not only to the delivery of primary reward and task inducing anticipation of reward, but also represent the difference of reward quality between food and water specifically.

Animals↗

Effects of monetary reward and punishment on stimulus-preceding negativity.

This study examined the effects of emotional valence on stimulus-preceding negativity (SPN) using reward and fine. A time estimation task under reward, punishment, combined, and control conditions was performed. Participants were rewarded for accurate responses in the reward condition, and were fined for incorrect estimations in the punishment condition. in the combined condition, correct responses were rewarded and incorrect responses were fined. In the control condition, neither a reward nor fine was used. Results showed a significant interaction of condition x hemisphere. The SPN at the left hemisphere was increased in the reward condition. For the punishment effect, although it evoked right hemisphere dominance, no conditional difference was apparent at the right hemisphere. These results suggest that the SPN is affected by positive emotion: The left hemisphere activation might represent a pleasant emotion accompanying monetary gain.

Adult↗

Visual responses to reward-related cues in inferior parietal lobule.

A sample of 263 neurones was recorded in area 7a of the parietal lobe, in a monkey performing a reach task to visual targets displayed on a touch-sensitive videomonitor. The task had been operantly conditioned on food or juice rewards, and 78 (30%) of the units showed activity changes linked in some way to the reward. For most of these cells, the response was to the approach of the trainer's hand with the food reward. This specific visual response was similar irrespective of the direction of approach. Six cells increased discharge as soon as the task was completed in apparent anticipation of the reward. Another two neurones responded to missing a reward: they fired vigorously if the videoscreen was blanked in mid-trial because a target was not correctly touched. In many cases (40/78) the same cells responding to some aspect of the reward also responded to visual cues given during the task, especially the presentation of the target location. Reward-related activity in area 7a probably results from an integration of the visual and limbic inputs to this region, such that visual information which foretells behaviourally important events is emphasized.

Animals↗

High effort, low reward, and cardiovascular risk factors in employed Swedish men and women: baseline results from the WOLF Study.

STUDY OBJECTIVE: To examine associations between measures of work stress (that is, the combination of high effort and low reward) and cardiovascular risk factors. DESIGN: Cross sectional first screening of a prospective cohort study. SETTING AND PARTICIPANTS: The study was conducted among 5720 healthy employed men and women living in the greater Stockholm area aged 19-70 years. All analyses were restricted to subjects with complete data (n = 4958). The investigation of associations between indicators of effort-reward imbalance and cardiovascular risk factors was restricted to the age group 30-55 years (n = 3427). MAIN RESULTS: Subjects reporting high effort and low reward at work had a higher prevalence of well known risk factors for coronary heart disease. After adjustment for relevant confounders, associations between a measure of extrinsic effort and reward (the effort-reward ratio) and hypertension (multivariate prevalence odds ratio (POR) 1.62-1.68), increased total cholesterol (upper tertile 220 mg/dl)(POR = 1.24) and the total cholesterol/high density lipoprotein(HDL)-cholesterol ratio (upper tertile 4.61)(POR 1.26-1.30) were found among men. Among women a measure of high intrinsic effort (immersion) was related to increased low density lipoprotein (LDL)-cholesterol (upper tertile 130 mg/dl)(POR 1.37-1.39). Analyses of variance showed increasing mean values of LDL cholesterol with an increasing degree of the effort-reward ratio among men and increased LDL-cholesterol among women with high levels of intrinsic effort (upper tertile of immersion). CONCLUSIONS: Findings lend support to the hypothesis that effort-reward imbalance represents a specific constellation of stressful experience at work related to cardiovascular risk. The relation was not explained by relevant confounders (for example, lack of physical exercise, body weight, cigarette smoking).

Adult↗

Opioid reward mechanisms: a key role in drug abuse?

There is increasing evidence to implicate the mesolimbic dopamine system in the rewarding effects of drugs of abuse such as opioids, psychostimulants, and alcohol, and in addition endogenous opioids may play a key role in the underlying adaptive mechanisms. Opioid agonists with affinity for mu and delta opioid receptors are rewarding, whereas opioid agonists with affinity for kappa receptors are aversive. These opposing motivational effects are paralleled by an increase and decrease, respectively, of dopamine release in the nucleus accumbens. Opposite effects are induced in response to selective antagonists for these different receptor types, pointing to tonically active endogenous opioid reward mechanisms. Withdrawal from chronic morphine results in sensitization for opioid reward; an effect that is counteracted by kappa opioid agonists. The rewarding effects of psychostimulants such as cocaine and amphetamine, mediated by the mesolimbic dopamine pathway, are modulated by opioid mechanisms in both directions: sensitization by morphine pretreatment, inhibition by kappa receptor agonists. A modulatory role of endogenous opioids is also suggested from biochemical data, showing increased dynorphin and kappa receptor expression after chronic cocaine treatment. Alcohol reward involves the mesolimbic reward system also, and opioids modulate this behaviour. Naltrexone as well as selective mu and delta opioid receptor antagonists decrease alcohol consumption in operant conditioning models. Biochemical approaches point to a functional deficit of endogenous opioids in genetic models exhibiting high prevalence for alcohol intake. The therapeutic implications of these data are discussed.

Alcohols↗

Neuronal activity in the rodent dorsal striatum in sequential navigation: separation of spatial and reward responses on the multiple T task.

The striatum plays an important role in "habitual" learning and memory and has been hypothesized to implement a reinforcement-learning algorithm to select actions to perform given the current sensory input. Many experimental approaches to striatal activity have made use of temporally structured tasks, which imply that the striatal representation is temporal. To test this assumption, we recorded neurons in the dorsal striatum of rats running a sequential navigation task: the multiple T maze. Rats navigated a sequence of four T maze turns to receive food rewards delivered in two locations. The responses of neurons that fired phasically were examined. Task-responsive phasic neurons were active as rats ran on the maze (maze-responsive) or during reward receipt (reward-responsive). Neither maze- nor reward-responsive neurons encoded simple motor commands: maze-responses were not well correlated with the shape of the rat's path and most reward-responsive neurons did not fire at similar rates at both food-delivery sites. Maze-responsive neurons were active at one or more locations on the maze, but these responses did not cluster at spatial landmarks such as turns. Across sessions the activity of maze-responsive neurons was highly correlated when rats ran the same maze. Maze-responses encoded the location of the rat on the maze and imply a spatial representation in the striatum in a task with prominent spatial demands. Maze-responsive and reward-responsive neurons were two separate populations, suggesting a divergence in striatal information processing of navigation and reward.

Algorithms↗

Effects of expectations for different reward magnitudes on neuronal activity in primate striatum.

In behavioral science, it is well known that humans and nonhuman animals are highly sensitive to differences in reward magnitude when choosing an outcome from a set of alternatives. We know that a realm of behavioral reactions is altered when animals begin to expect different levels of reward outcome. Our present aim was to investigate how the expectation for different magnitudes of reward influences behavior-related neurophysiology in the anterior striatum. In a spatial delayed response task, different instruction pictures are presented to the monkey. Each image represents a different magnitude of juice. By reaching to the spatial location where an instruction picture was presented, animals could receive the particular liquid amount designated by the stimulus. Reliable preferences in reward choice trials and differences in anticipatory licks, performance errors, and reaction times indicated that animals differentially expected the various reward amounts predicted by the instruction cues. A total of 374 of 2,000 neurons in the anterior parts of the caudate nucleus, putamen, and ventral striatum showed five forms of task-related activation during the preparation or execution of movement and activations preceding or following the liquid drop delivery. Approximately one-half of these striatal neurons showed differing response levels dependent on the magnitude of liquid to be received. Results of a linear regression analysis showed that reward magnitude and single cell discharge rate were related in a subset of neurons by a monotonic positive or negative relationship. Overall, these data support the idea that the striatum utilizes expectancies that contain precise information concerning the predicted, forthcoming level of reward in directing general behavioral reactions.

Animals↗

Hypothalamic neuron involvement in integration of reward, aversion, and cue signals.

The lateral hypothalamus (LHA) is involved in integrative functions related to emotion, reward, aversion, and learning. It is, however, unclear whether the medial forebrain bundle (MFB) forms a substrate common to the anterior and posterior hypothalamic areas or whether information regarding rewarding and aversive stimuli converges on and is integrated by the same hypothalamic neuron. In the present study, unit activity in the LHA and lateral preoptic-anterior hypothalamic area (lPOA-AHA) of the rat was recorded during discrimination learning of cue tone stimuli (CTS) that predicted glucose or intracranial self-stimulation (ICSS) as rewarding stimuli, or electric shock or tail pinch as aversive stimuli, using identical behavior, licking. We examined functional differences between the LHA and lPOA-AHA. In positive reinforcement experiments a rat was rewarded by glucose or ICSS only when it licked a spout presented in front of its mouth. The threshold current for ICSS was used. In negative reinforcement experiments an aversive stimulus, either electric shock or tail pinch was applied if the rat did not lick the spout. The strengths of electric shock and tail pinch were selected to produce an avoidance ratio less than 20-30%, averaged in all trials. The activity of 507 LHA and 249 lPOA-AHA neurons was analyzed during both glucose and ICSS trials. The effects of both glucose and ICSS on the same LHA or lPOA-AHA neuron were usually in the same direction, i.e., either both excitatory or both inhibitory. Of 143 LHA and 44 lPOA-AHA neurons that responded to both rewards, the responses of 117 (81.8%) LHA and 35 (79.5%) lPOA-AHA neurons to both stimuli were similar. The activity of 131 LHA and 153 lPOA-AHA neurons was analyzed in both electric shock and tail pinch trials. The effects of both electric shock and tail pinch on the same LHA or lPOA-AHA neuron were usually in the same direction. Of 29 LHA and 27 lPOA-AHA neurons that responded to both aversive stimuli, the responses of 28 (96.6%) LHA and 25 (92.6%) lPOA-AHA neurons to both were similar. The activity of 170 LHA and 195 lPOA-AHA neurons in response to both rewarding glucose and/or ICSS stimulation and aversive electric shock and/or tail pinch was analyzed. About one-third of the neurons in each area were reward specific (57/170 in LHA; 63/195 in lPOA-AHA), whereas relatively few were aversion specific in each area (21/170 in LHA; 15/195 in lPOA-AHA).(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Functional involvement of catecholamines in reward-related neuronal activity of the monkey amygdala.

Neuronal activity was studied in the behaving active monkey to elucidate the functional significance of catecholamines (CA) in the amygdala during reward-related behavior, and the effects of noradrenaline (NA), dopamine (DA), and their antagonists, electrophoretically applied, were examined using multibarreled electrode techniques. The operant food intake task had four phases: 1) cue light on to signal the start of bar pressing, 2) execution of high fixed-ratio bar pressing (FR 20), 3) short cue tone triggered by the last bar press to signal the presentation of food, and 4) ingestion, reward. More than half of the 292 cells tested (198, 68%) changed activity during the task. Most changes occurred during the bar press and/or reward periods (164/198, 83%), the former affecting neuronal activity more (127/198, 64%) than the latter (70/198, 35%). Phasic responses to the cue light and cue tone were observed in 62 cells (31%) and 19 cells (10%), respectively. The effects of NA and DA were studied in 199 and 177 cells, respectively. Of these, 90 cells (46%) responded to NA, 87 (97%) with a decrease of firing, and only 3 (3%) with an increase, whereas 40 (26%) responded to DA by increasing (28 cells, 70%) or decreasing (18 cells, 30%) activity. The inhibitory effect of NA was blocked by alpha- and/or beta-adrenoceptive antagonists. Task-related activity changes occurred significantly more often among DA sensitive cells than among DA insensitive cells. CA sensitivity and task-related neuronal activity were functionally correlated only in the reward period. Activity of NA sensitive cells decreased in this period more frequently than insensitive cells, and DA sensitive cells increased more often than insensitive cells. Application of a beta-adrenoceptive antagonist or a DA antagonist attenuated the activity changes during the reward period. Application of a alpha-adrenoceptive antagonist had no effect on the reward-related neuronal activity changes. When grouped according to recording site, centromedial cells had a significantly higher occurrence of task-related activity changes than those in the basolateral parts of the amygdala. The bar-press responsive and reward-related cells, the firing of which decreased, were found more often in the centromedial than in the basolateral division, although the numbers of cells that responded to sensory cues were not different in the two parts. Catecholaminergic involvement in the task-related activity changes was also different.(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗

Modifications of reward expectation-related neuronal activity during learning in primate striatum.

This study investigated neuronal activity in the anterior striatum while monkeys repeatedly learned to associate new instruction stimuli with known behavioral reactions and reinforcers. In a delayed go-nogo task with several trial types, an initial picture instructed the animal to execute or withhold a reaching movement and to expect a liquid reward or not. During learning, new instruction pictures were presented, and animals guessed and performed one of the trial types according to a trial-and-error strategy. Learning of a large number of pictures resulted in a learning set in which learning took place in a few trials and correct performance exceeded 80% in the first 60-90 trials. About 200 task-related striatal neurons studied in both familiar and learning conditions showed three forms of changes during learning. Activations related to the preparation and execution of behavioral reactions and the expectation of reward were maintained in many neurons but occurred in inappropriate trial types when behavioral errors were made. The activations became appropriate for individual trial types when the animals' behavior adapted to the new task contingencies. In particular, reward expectation-related activations occurred initially in both rewarded and unrewarded movement trials and became subsequently restricted to rewarded trials. These changes occurred in parallel with the visible adaptation of reward expectations by the animals. The second learning change consisted in decreases of task-related activations that were either restricted to the initial trials of new learning problems or persisted during the subsequent consolidation phase. They probably reflected reductions in the expectation and preparation of upcoming task events, including reward. The third learning change consisted in transient or sustained increases of activations. These might reflect the increased attention accompanying learning and serve to induce synaptic changes underlying the behavioral adaptations. Both decreases and increases often induced changes in the trial selective occurrence of activations. In conclusion, neurons in anterior striatum showed changes related to adaptations or reductions of expectations in new task situations and displayed activations that might serve to induce structural changes during learning.

Animals↗

Response differences in monkey TE and perirhinal cortex: stimulus association related to reward schedules.

Anatomic and behavioral evidence shows that TE and perirhinal cortices are two directly connected but distinct inferior temporal areas. Despite this distinctness, physiological properties of neurons in these two areas generally have been similar with neurons in both areas showing selectivity for complex visual patterns and showing response modulations related to behavioral context in the sequential delayed match-to-sample (DMS) trials, attention, and stimulus familiarity. Here we identify physiological differences in the neuronal activity of these two areas. We recorded single neurons from area TE and perirhinal cortex while the monkeys performed a simple behavioral task using randomly interleaved visually cued reward schedules of one, two, or three DMS trials. The monkeys used the cue's relation to the reward schedule (indicated by the brightness) to adjust their behavioral performance. They performed most quickly and most accurately in trials in which reward was immediately forthcoming and progressively less well as more intermediate trials remained. Thus the monkeys appeared more motivated as they progressed through the trial schedule. Neurons in both TE and perirhinal cortex responded to both the visual cues related to the reward schedules and the stimulus patterns used in the DMS trials. As expected, neurons in both areas showed response selectivity to the DMS patterns, and significant, but small, modulations related to the behavioral context in the DMS trial. However, TE and perirhinal neurons showed strikingly different response properties. The latency distribution of perirhinal responses was centered 66 ms later than the distribution of TE responses, a larger difference than the 10-15 ms usually found in sequentially connected visual cortical areas. In TE, cue-related responses were related to the cue's brightness. In perirhinal cortex, cue-related responses were related to the trial schedules independently of the cue's brightness. For example, some perirhinal neurons responded in the first trial of any reward schedule including the one trial schedule, whereas other neurons failed to respond in the first trial but respond in the last trial of any schedule. The majority of perirhinal neurons had more complicated relations to the schedule. The cue-related activity of TE neurons is interpreted most parsimoniously as a response to the stimulus brightness, whereas the cue-related activity of perirhinal neurons is interpreted most parsimoniously as carrying associative information about the animal's progress through the reward schedule. Perirhinal cortex may be part of a system gauging the relation between work schedules and rewards.

Animals↗

Tracking the hemodynamic responses to reward and punishment in the striatum.

Research suggests that the basal ganglia complex is a major component of the neural circuitry that mediates reward-related processing. However, human studies have not yet characterized the response of the basal ganglia to an isolated reward, as has been done in animals. We developed an event-related functional magnetic resonance imaging paradigm to identify brain areas that are activated after presentation of a reward. Subjects guessed whether the value of a card was higher or lower than the number 5, with monetary rewards as an incentive for correct guesses. They received reward, punishment, or neutral feedback on different trials. Regions in the dorsal and ventral striatum were activated by the paradigm, showing differential responses to reward and punishment. Activation was sustained following a reward feedback, but decreased below baseline following a punishment feedback.

Adult↗