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Background: The Alcohol and Addiction Research Domain Criteria (AARDoC) propose that alcohol use disorder is associated with neural dysfunction in three primary domains: incentive salience, negative emotionality, and executive function. Prior studies in heavy drinking samples have examined brain activation changes associated with alcohol and negative affect cues, representing the incentive salience and negative emotionality domains, respectively. Yet studies examining such cue‐induced changes in functional connectivity (FC) are relatively sparse. Methods: Nontreatment‐seeking heavy drinking adults (N = 149, 56.0% male, 48.6% non‐white, mean age 34.8 years (SD = 10.0)) underwent functional magnetic resonance imaging during presentation of alcohol, negative, and neutral pictures. We focused on FC changes involving the nucleus accumbens and amygdala in addition to activation and FC correlations with self‐reported AUD severity. Results: For alcohol cues versus neutral cues, we observed accumbens FC changes in the cerebellum and prefrontal cortex (PFC), and amygdala FC changes with occipital, parietal, and hippocampal regions. AUD severity correlated positively with activation in the cerebellum (p < 0.05), accumbens FC in the cingulate gyri, somatosensory gyri, and cerebellum (p < 0.05), and with amygdala FC in the PFC and inferior parietal lobule (p < 0.05) for alcohol cues versus neutral cues. For negative cues versus neutral cues, we observed accumbens FC changes in the lateral temporal, occipital, and parietal regions, and amygdala FC changes in the fusiform and lingual gyri (p < 0.05). Conclusions: The present findings provide empirical support for the AARDoC domains of incentive salience and negative emotionality and indicate that AUD severity is associated with salience and response control for reward cues. When covarying for differences in nonalcohol substance use and mood disorder diagnoses, AUD severity was also associated with emotional reactivity for negative cues. [ABSTRACT FROM AUTHOR]

Dopamine (DA) neurons of the dorsal raphe nucleus (DRN) were traditionally viewed as an extension of the ventral tegmental area (VTA) DA population. While the VTA DA population is known to play important roles in reward processing, emerging evidence now supports the view that DRN DA neurons are a specialized midbrain DA subsystem that performs distinct functions in parallel to the VTA DA population. Recent studies have shed new light on the roles of DRN DA neurons in encoding incentive salience and in regulating memory expression and arousal. Here, we review recent findings using mouse models about the physiology and behavioral functions of DRN DA neurons, highlight the engagement of DRN DA neurons and their upstream circuits in opioid addiction, and discuss emerging lines of investigation that reveal multifaceted heterogeneity among DRN DA neurons. Dopamine (DA) neurons of the dorsal raphe nucleus (DRN) have been classically viewed as a dorsal-caudal extension of the ventral tegmental area (VTA) DA population. Increasingly, however, the DRN DA population is seen as a distinct midbrain DA subpopulation that functions in parallel to the VTA DA subpopulations. Emerging reports using mouse models have demonstrated that DRN DA neurons encode incentive salience and function in both incentive memory expression and sleep regulation. DRN DA neurons and their upstream inputs also contribute to the neural substrate of opioid addiction. Recent studies revealed considerable morphological and transcriptional heterogeneity among DRN DA neurons. [ABSTRACT FROM AUTHOR]

Learning to respond appropriately to one's surrounding environment is fundamental to survival. Importantly, however, individuals vary in how they respond to cues in the environment and this variation may be a key determinant of psychopathology. The ability of seemingly neutral cues to promote maladaptive behavior is a hallmark of several psychiatric disorders including, substance use disorder, post-traumatic stress disorder, eating disorders and obsessive-compulsive disorder. Thus, it is important to uncover the neural mechanisms by which such cues are able to attain inordinate control and promote psychopathological behavior. Here, we suggest that glucocorticoids play a critical role in this process. Glucocorticoids are primarily recognized as the main hormone secreted in response to stress but are known to exert their effects across the body and the brain, and to affect learning and memory, cognition and reward-related behaviors, among other things. Here we speculate that glucocorticoids act to facilitate a dopamine-dependent form of cue-reward learning that appears to be relevant to a number of psychiatric conditions. Specifically, we propose to utilize the sign-tracker/goal-tracker animal model as a means to capture individual variation in stimulus-reward learning and to isolate the role of glucocorticoid-dopamine interactions in mediating these individual differences. It is hoped that this framework will lead to the discovery of novel mechanisms that contribute to complex neuropsychiatric disorders and their comorbidity. [ABSTRACT FROM AUTHOR]

Addiction management is complex, and it requires a bio-psycho-social perspective, that ought to consider the multiple etiological and developmental factors. Because of this, a large amount of resources has been allocated to assess the vulnerability to dependence, i.e., to identify the processes underlying the transition from substance use to dependence, as well as its course, in order to determine the key points in its prevention, treatment, and recovery. Consequently, knowledge \from neuroscience must be taken into account, which is why different initiatives have emerged with this objective, such as the “Research Domain Criteria” (RDoC), and the “Addiction Neuroclinical Assessment” (ANA). Particularly, neuropsychophysiological measures could be used as markers of cognitive and behavioral attributes or traits in alcohol dependence, and even trace clinical change. In this way, the aim of this narrative review is to provide an overview following ANA clinical framework, to the most robust findings in neuropsychophysiological changes in alcohol dependence, that underlie the main cognitive domains implicated in addiction: incentive salience, negative emotionality, and executive functioning. The most consistent results have been found in event-related potential (ERP) analysis, especially in the P3 component, that could show a wide clinical utility, mainly for the executive functions. The review also shows the usefulness of other components, implicated in affective and substance-related processing (P1, N1, or the late positive potential LPP), as well as event-related oscillations, such as theta power, with a possible use as vulnerability or clinical marker in alcohol dependence. Finally, new tools emerging from psychophysiology research, based on functional connectivity or brain graph analysis could help toward a better understanding of altered circuits in alcohol dependence, as well as communication efficiency and effort during mental operations. This review concludes with an examination of these tools as possible markers in the clinical field and discusses methodological differences, the need for more replicability studies and incipient lines of work. It also uses consistent findings in psychophysiology to draw possible treatment targets and cognitive profiles in alcohol dependence.

Rationale: Prior research suggests that the neural pathway from the lateral hypothalamic area (LHA) to the paraventricular nucleus of the thalamus (PVT) mediates the attribution of incentive salience to Pavlovian reward cues. However, a causal role for the LHA and the neurotransmitters involved have not been demonstrated in this regard. Objectives: To examine (1) the role of LHA in the acquisition of Pavlovian conditioned approach (PavCA) behaviors, and (2) the role of PVT orexin 1 receptors (OX1r) and orexin 2 receptors (OX2r) in the expression of PavCA behaviors and conditioned reinforcement. Methods: Rats received excitotoxic lesions of the LHA prior to Pavlovian training. A separate cohort of rats characterized as sign-trackers (STs) or goal-trackers (GTs) received the OX1r antagonist SB-334867, or the OX2r antagonist TCS-OX2-29, into the PVT, to assess their effects on the expression of PavCA behavior and on the conditioned reinforcing properties of a Pavlovian reward cue. Results: LHA lesions attenuated the development of sign-tracking behavior. Administration of either the OX1r or OX2r antagonist into the PVT reduced sign-tracking behavior in STs. Further, OX2r antagonism reduced the conditioned reinforcing properties of a Pavlovian reward cue in STs. Conclusions: The LHA is necessary for the development of sign-tracking behavior; and blockade of orexin signaling in the PVT attenuates the expression of sign-tracking behavior and the conditioned reinforcing properties of a Pavlovian reward cue. Together, these data suggest that LHA orexin inputs to the PVT are a key component of the circuitry that encodes the incentive motivational value of reward cues. [ABSTRACT FROM AUTHOR]

Rationale: Environmental stimuli paired with alcohol can function as conditioned reinforcers (CRfs) and trigger relapse to alcohol-seeking. In animal models, pharmacological stressors can enhance alcohol consumption and reinstate alcohol-seeking, but it is unknown whether stress can potentiate the conditioned reinforcing properties of alcohol-paired stimuli. Objectives: We examined whether the pharmacological stressors, the α-2 adrenoreceptor antagonist yohimbine (vehicle, 1.25, 2.5 mg/kg; IP) and the K-opioid receptor agonist U50,488 (vehicle, 1.25, 2.5 mg/kg; SC), increase responding for conditioned reinforcement, and if their effects interact with the nature of the reward (alcohol vs. sucrose). We subsequently examined the effects of yohimbine (vehicle, 1.25, 2.5 mg/kg; IP) on responding for sensory reinforcement. Methods: Male Long-Evans underwent Pavlovian conditioning, wherein a tone-light conditioned stimulus (CS) was repeatedly paired with 12% EtOH or 21.7% sucrose. Next, tests of responding for a CRf were conducted. Responding on the CRf lever delivered the CS, whereas responding on the other lever had no consequences. In a separate cohort of rats, the effects of yohimbine on responding just for the sensory reinforcer were examined. Results: Both doses of yohimbine, but not U50,488, increased responding for conditioned reinforcement. This enhancement occurred independently of the nature of the reward used during Pavlovian conditioning. Yohimbine-enhanced responding for a CRf was reproducible and stable over five tests; it even persisted when the CS was omitted. Both doses of yohimbine also increased responding for sensory reinforcement. Conclusions: Yohimbine increases operant responding for a variety of sensory and conditioned reinforcers. This enhancement may be independent of its stress-like effects. [ABSTRACT FROM AUTHOR]

It has been argued that the dopaminergic system is involved in the attribution of motivational value to reward predictive cues as well as prediction error. To evaluate, dopamine neurons were recorded from male rats performing a Pavlovian approach task containing cues that have both "predictive" and "incentive" properties. All animals learned the predictive nature of the cue (illuminated lever entry into cage), but some also found the cue to be attractive and were motivated toward it ("sign-trackers," STs). "Goal-trackers" (GTs) predominantly approached the location of reward receptacle. Rats were implanted with tetrodes for neural electrophysiological recordings in the ventral tegmental area. Cells were characterized by spike waveform shape and firing rate. Firing rates and magnitudes of responses in relation to Pavlovian behaviors, cue presentation, and reward delivery were assessed. We identified 103 dopamine and 141 nondopamine neurons. GTs and STs both showed responses to the initial lever presentation (CS1) and lever retraction (CS2). However, higher firing rates were sustained during the lever interaction period only in STs. Further, dopamine cells of STs showed a significantly higher proportion of cells responding to both CS1 and CS2. These are the first results to show that neurons from the VTA encode both predictive and incentive cues, support an important role for dopamine neurons in the attribution of incentive salience to reward-paired cues, and underscore the consequences of potential differences in motivational behavior between individuals. [ABSTRACT FROM AUTHOR]

Background: The incentive sensitisation theory of addiction posits that drug-associated stimuli become imbued with incentive motivational properties, driving pathological drug seeking. However, pre-existing variability in the incentive salience to non-drug reward cues ('sign trackers' (STs); 'goal trackers' (GTs)) is also predictive of the desire for and relapse to cocaine and opioids. Here, we asked whether variation in propensity to attribute incentive salience to a food cue is predictive of reinstatement to the highly addictive psychostimulant methamphetamine (METH), and whether treatment with the promising anti-addiction therapy oxytocin differentially reduces METH behaviour between STs and GTs.Methods: Rats were trained to associate a Pavlovian cue with delivery of a sucrose pellet over 8 days. They then received jugular vein catheters for intravenous METH self-administration, followed by behavioural extinction, and cue-induced and METH-primed reinstatement to METH-seeking behaviours. Oxytocin was administered prior to self-administration and reinstatement tests.Results: Despite the self-administration of similar amounts of METH, STs reinstated more to METH cues than did GTs, yet METH-priming reinstated STs and GTs similarly. Furthermore, oxytocin attenuated cue-induced reinstatement more so in STs than in GTs, and reduced METH-primed reinstatement to a greater extent in the top quartile of reinstaters, indicating that oxytocin treatment may be most effective for those at highest risk of addiction.Conclusions: This pre-existing bias towards reward cues presents a possible tool to screen for METH addiction susceptibility and may be useful for understanding the neurobiology of addiction and for pharmacotherapeutic discovery. [ABSTRACT FROM AUTHOR]

• Conditioned place preference (CPP) and intravenous drug self-administration (SA) derive from a common antecedent. • Although most manipulations produce concordant effects on CPP and SA, several manipulations produce discordant effects. • Discordant examples can be classified as driven by motivation or as simple parallel shifts in dose-response functions. Although developed from a common antecedent, conditioned place preference (CPP) and intravenous drug self-administration (SA) represent different behavioral paradigms, each with strong face validity. The field has treated results from these studies largely interchangeably; however, there is considerable evidence of opposite modulation of CPP vs. SA. This review outlines four manipulations that differentially affect CPP and SA based on alterations of motivation. These examples are contrasted with one example of differential CPP and SA results that can be explained by simple parallel shifts in dose-response functions. The final two examples have yet to be classified as motivation-based or parallel shifts. Important aspects, including motivation, volitional control of drug administration, reward, and the role of cues are discussed. One major conclusion of this paper is that explanations for apparent discrepancies between CPP and SA require full dose effect functions and assessment of PR breakpoints. Overall, this manuscript offers a more nuanced insight into how CPP and SA can be used to study different aspects of substance use disorders. [ABSTRACT FROM AUTHOR]

Previous research has implied that monetary reward to target location (a reward for spatial properties) can affect object‐based attention, but no study has directly investigated the influence of monetary objects (a reward for object properties) on object‐based attention. Thus, it is unclear whether and how monetary objects can affect object‐based attention. To experimentally investigate this problem, this study adapted the well‐established two‐rectangle paradigm. In Experiment 1, either two 100‐yuan notes or two 1‐yuan notes were presented to participants. We found an object‐based effect with faster responses to targets at an uncued position on the cued object compared to those at an equidistant position on the uncued object; the effect was similar in 100‐yuan and 1‐yuan note trials. In Experiment 2, two notes (one 100‐yuan and one 1‐yuan) were simultaneously presented to participants, and cue location (100‐yuan, 1‐yuan) was manipulated. We found a greater object‐based effect when the cue appeared on the 100‐yuan note than on the 1‐yuan note. These results suggest that the rewarding property of objects can affect object‐based attention by means of altering object salience. [ABSTRACT FROM AUTHOR]

Introduction: By improving our understanding of the neurobiological mechanisms underlying addiction, neuroimaging research is helping to identify new targets for personalized treatment interventions. When trying to quit, smokers with larger electrophysiological responses to cigarette-related, compared with pleasant, stimuli ("C > P") are more likely to relapse than smokers with the opposite brain reactivity profile ("P > C").Aim and Method: The goal was to (1) build a classification algorithm to identify smokers characterized by P > C or C > P neuroaffective profiles and (2) validate the algorithm's classification outcomes in an independent data set where we assessed both smokers' electrophysiological responses at baseline and smoking abstinence during a quit attempt. We built the classification algorithm applying discriminant function analysis on the event-related potentials evoked by emotional images in 180 smokers.Results: The predictive validity of the classifier showed promise in an independent data set that included new data from 177 smokers interested in quitting; the algorithm classified 111 smokers as P > C and 66 as C > P. The overall abstinence rate was low; 15 individuals (8.5% of the sample) achieved CO-verified 12-month abstinence. Although individuals classified as P > C were nearly 2.5 times more likely to be abstinent than smokers classified as C > P (12 vs. 3, or 11% vs. 4.5%), this result was nonsignificant, preliminary, and in need of confirmation in larger trials.Conclusion: These results suggest that psychophysiological techniques have the potential to advance our knowledge of the neurobiological underpinnings of nicotine addiction and improve clinical applications. However, larger sample sizes are necessary to reliably assess the predictive ability of our algorithm.Implications: We assessed the clinical relevance of a neuroimaging-based classification algorithm on an independent sample of smokers enrolled in a smoking cessation trial and found those with the tendency to attribute more relevance to rewards than cues were nearly 2.5 times more likely to be abstinent than smokers with the opposite brain reactivity profile (11% vs. 4.5%). Although this result was not statistically significant, it suggests our neuroimaging-based classification algorithm can potentially contribute to the development of new precision medicine interventions aimed at treating substance use disorders. Regardless, these findings are still preliminary and in need of confirmation in larger trials. [ABSTRACT FROM AUTHOR]

Addiction management is complex, and it requires a bio-psycho-social perspective, that ought to consider the multiple etiological and developmental factors. Because of this, a large amount of resources has been allocated to assess the vulnerability to dependence, i.e., to identify the processes underlying the transition from substance use to dependence, as well as its course, in order to determine the key points in its prevention, treatment, and recovery. Consequently, knowledge \from neuroscience must be taken into account, which is why different initiatives have emerged with this objective, such as the "Research Domain Criteria" (RDoC), and the "Addiction Neuroclinical Assessment" (ANA). Particularly, neuropsychophysiological measures could be used as markers of cognitive and behavioral attributes or traits in alcohol dependence, and even trace clinical change. In this way, the aim of this narrative review is to provide an overview following ANA clinical framework, to the most robust findings in neuropsychophysiological changes in alcohol dependence, that underlie the main cognitive domains implicated in addiction: incentive salience, negative emotionality, and executive functioning. The most consistent results have been found in event-related potential (ERP) analysis, especially in the P3 component, that could show a wide clinical utility, mainly for the executive functions. The review also shows the usefulness of other components, implicated in affective and substance-related processing (P1, N1, or the late positive potential LPP), as well as event-related oscillations, such as theta power, with a possible use as vulnerability or clinical marker in alcohol dependence. Finally, new tools emerging from psychophysiology research, based on functional connectivity or brain graph analysis could help toward a better understanding of altered circuits in alcohol dependence, as well as communication efficiency and effort during mental operations. This review concludes with an examination of these tools as possible markers in the clinical field and discusses methodological differences, the need for more replicability studies and incipient lines of work. It also uses consistent findings in psychophysiology to draw possible treatment targets and cognitive profiles in alcohol dependence. [ABSTRACT FROM AUTHOR]

The attention system is shaped by reward history, such that learned reward cues involuntarily draw attention. Recent research has begun to uncover the neural mechanisms by which learned reward cues compete for attention, implicating dopamine (DA) signaling within the dorsal striatum. How these elevated priority signals develop in the brain during the course of learning is less well understood, as is the relationship between value-based attention and the experience of reward during learning. We hypothesized that the magnitude of the striatal DA response to reward during learning contributes to the development of a learned attentional bias towards the cue that predicted it, and examined this hypothesis using positron emission tomography with [11C]raclopride. We measured changes in dopamine release for rewarded versus unrewarded visual search for color-defined targets as indicated by the density and distribution of the available D2/D3 receptors. We then tested for correlations of individual differences in this measure of reward-related DA release to individual differences in the degree to which previously reward-associated but currently task-irrelevant stimuli impair performance in an attention task (i.e., value-driven attentional bias), revealing a significant relationship in the right anterior caudate. The degree to which reward-related DA release was right hemisphere lateralized was also predictive of later attentional bias. Our findings provide support for the hypothesis that value-driven attentional bias can be predicted from reward-related DA release during learning.

Nalmefene is approved for as-needed pharmacological treatment in alcohol use disorder (AUD) by the European Medicines Agency. While the cellular effects of nalmefene have been thoroughly investigated, data are very limited on how this agent influences neural signals associated with inhibitory control and the visual analysis of environmental cues. This double-blind crossover study assessed the behavioral and neural effects of acute nalmefene administration in patients diagnosed with AUD. In experiment 1, we validated our experimental paradigm (electroencephalography combined with a modified Go/NoGo task using images of alcoholic and nonalcoholic drinks as prime stimuli) in 20 healthy adults to ensure that our protocol is suitable for assessing the behavioral and neural aspects of executive control. In experiment 2, we recruited 19 patients with AUD, and in a double-blind crossover design, we investigated the effects of nalmefene versus placebo on task performance (response accuracy, the sensitivity index, and reaction times), visual responses to appetitive cues (occipital P1, N1, and P2 components), and electrophysiological markers of conflict detection and response inhibition (frontal N2 and P3 waveforms). Under placebo, patients produced faster reaction times to alcohol-primed Go stimuli, an effect that was weak despite being statistically significant. However, the effect of alcoholic cues on the speed of response initiation disappeared after receiving nalmefene. We found no placebo versus nalmefene difference regarding our patients’ ability to accurately inhibit responses to NoGo stimuli or for occipital and frontal event-related potentials. Our results suggest that nalmefene might be potent in reducing the vigor to act upon alcoholic cues in AUD patients, but this effect is most probably mediated via subcortical (rather than cortical) neural circuits.

Cues in the environment can elicit complex emotional states, and thereby maladaptive behavior, as a function of their ascribed value. Here we capture individual variation in the propensity to attribute motivational value to reward-cues using the sign-tracker/goal-tracker animal model. Goal-trackers attribute predictive value to reward-cues, and sign-trackers attribute both predictive and incentive value. Using chemogenetics and microdialysis, we show that, in sign-trackers, stimulation of the neuronal pathway from the prelimbic cortex (PrL) to the paraventricular nucleus of the thalamus (PVT) decreases the incentive value of a reward-cue. In contrast, in goal-trackers, inhibition of the PrL-PVT pathway increases both the incentive value and dopamine levels in the nucleus accumbens shell. The PrL-PVT pathway, therefore, exerts top-down control over the dopamine-dependent process of incentive salience attribution. These results highlight PrL-PVT pathway as a potential target for treating psychopathologies associated with the attribution of excessive incentive value to reward-cues, including addiction.

• There is individual variation in the effects of sleep loss on reward circuitry. • This individual variation has been difficult to study in preclinical animal models. • There exists a Sign/Goal Tracker model of individual differences in cued motivation. • There is overlapping circuitry responsible for both sleep and ST/GT behavior. • ST/GT model can be used to study individual variation in sleep-reward interactions. Individuals differ widely in their drug-craving behaviors. One reason for these differences involves sleep. Sleep disturbances lead to an increased risk of substance use disorders and relapse in only some individuals. While animal studies have examined the impact of sleep on reward circuitry, few have addressed the role of individual differences in the effects of altered sleep. There does, however, exist a rodent model of individual differences in reward-seeking behavior: the sign/goal-tracker model of Pavlovian conditioned approach. In this model, only some rats show the key behavioral traits associated with addiction, including impulsivity and poor attentional control, making this an ideal model system to examine individually distinct sleep-reward interactions. Here, we describe how the limbic neural circuits responsible for individual differences in incentive motivation overlap with those involved in sleep-wake regulation, and how this model can elucidate the common underlying mechanisms. Consideration of individual differences in preclinical models would improve our understanding of how sleep interacts with motivational systems, and why sleep deprivation contributes to addiction in only select individuals. [ABSTRACT FROM AUTHOR]

• Alcohol cues are attributed with incentive salience in humans and non-human animals. • Alcohol can render the incentive salience circuitry sensitized to alcohol cues. • Humans and non-human animals can exhibit sensitized reactivity to alcohol cues. • Incentive salience sensitization may drive alcohol use disorder (AUD) in some people. • More work is needed on the role of this neuropsychological mechanism in alcohol use and AUD. The incentive salience sensitization (ISS) theory of addiction holds that addictive behavior stems from the ability of drugs to progressively sensitize the brain circuitry that mediates attribution of incentive salience (IS) to reward-predictive cues and its behavioral manifestations. In this article, we establish the plausibility of ISS as an etiological pathway to alcohol use disorder (AUD). We provide a comprehensive and critical review of evidence for: (1) the ability of alcohol to sensitize the brain circuitry of IS attribution and expression; and (2) attribution of IS to alcohol-predictive cues and its sensitization in humans and non-human animals. We point out gaps in the literature and how these might be addressed. We also highlight how individuals with different alcohol subjective response phenotypes may differ in susceptibility to ISS as a pathway to AUD. Finally, we discuss important implications of this neuropsychological mechanism in AUD for psychological and pharmacological interventions attempting to attenuate alcohol craving and cue reactivity. [ABSTRACT FROM AUTHOR]

Nalmefene is approved for as-needed pharmacological treatment in alcohol use disorder (AUD) by the European Medicines Agency. While the cellular effects of nalmefene have been thoroughly investigated, data are very limited on how this agent influences neural signals associated with inhibitory control and the visual analysis of environmental cues. This double-blind crossover study assessed the behavioral and neural effects of acute nalmefene administration in patients diagnosed with AUD. In experiment 1, we validated our experimental paradigm (electroencephalography combined with a modified Go/NoGo task using images of alcoholic and nonalcoholic drinks as prime stimuli) in 20 healthy adults to ensure that our protocol is suitable for assessing the behavioral and neural aspects of executive control. In experiment 2, we recruited 19 patients with AUD, and in a double-blind crossover design, we investigated the effects of nalmefene versus placebo on task performance (response accuracy, the sensitivity index, and reaction times), visual responses to appetitive cues (occipital P1, N1, and P2 components), and electrophysiological markers of conflict detection and response inhibition (frontal N2 and P3 waveforms). Under placebo, patients produced faster reaction times to alcohol-primed Go stimuli, an effect that was weak despite being statistically significant. However, the effect of alcoholic cues on the speed of response initiation disappeared after receiving nalmefene. We found no placebo versus nalmefene difference regarding our patients' ability to accurately inhibit responses to NoGo stimuli or for occipital and frontal event-related potentials. Our results suggest that nalmefene might be potent in reducing the vigor to act upon alcoholic cues in AUD patients, but this effect is most probably mediated via subcortical (rather than cortical) neural circuits. [ABSTRACT FROM AUTHOR]

Drug and behavioural addictions are characterized by an intense and focused pursuit of a single reward above all others. Pursuit of the addictive reward is often compulsively sought despite adverse consequences and better alternative outcomes. Here, we explored the ability of the central amygdala (CeA) to powerfully bias choice, causing specific rewards to be almost compulsively preferred. Rats were trained on an operant choice task in which they could choose to respond on either of the two levers to receive a sucrose reward, one of which was paired with optogenetic stimulation of the CeA using channelrhodopsin‐2 (ChR2). Rats developed an almost exclusive preference for the laser‐paired reward over the otherwise equal unpaired reward. We found that this preference for stimulation‐paired reward persists even when a much larger sucrose reward is offered as an alternative (contingency management) or when this preferred reward is paired with adverse consequences such as progressively larger electric foot shock, time delays or effort requirements. We also report that when challenged with foot shock, a small proportion of these animals (≈20%) retained an exclusive laser‐paired reward preference, whereas others began to seek the alternate reward when the shock reached high levels. Lastly, we confirmed that optogenetic CeA stimulation was not independently rewarding if delivered in the absence of a paired sucrose reward. These results suggest a role for the CeA in focusing motivation and desire to excessive levels, generating addiction‐like behaviour that persists in the face of more rewarding alternatives and adverse consequences. [ABSTRACT FROM AUTHOR]

Background: Considerable evidence indicates that a low level of subjective response to alcohol's acute effects (i.e., low sensitivity) is associated with enhanced risk for alcohol use disorder (AUD). Recent work suggests that the highest risk response profile consists of blunted sensitivity to alcohol's sedation‐like effects, coupled with enhanced sensitivity to alcohol's stimulation‐like effects (i.e., differential sensitivity). A largely separate body of work indicates that enhanced reactivity to alcohol‐related cues is associated with increased AUD risk. Aims: The current research examined the extent to which variability in alcohol response phenotypes is associated with enhanced P3 event‐related potential (ERP) responses to alcohol‐related pictures (ACR‐P3), and whether this reactivity varies according to depicted drinking contexts. Methods: Eighty young adults (aged 18 to 33 years) completed a self‐report measure of alcohol sensitivity (the Alcohol Sensitivity Questionnaire) and viewed images depicting drinking in naturalistic contexts, alcohol and nonalcohol beverages in isolation (devoid of naturalistic drinking context), and neutral nonbeverage control images while ERPs were recorded. Results: Results indicated that blunted sensitivity to alcohol's sedative‐like effects was differentially associated with enhanced ACR‐P3 but reduced P3 reactivity to nonalcohol cues. Variation in sensitivity to alcohol's stimulant‐like effects was not associated with differential ACR‐P3. Contrary to predictions, these effects were not potentiated by drinking contexts. Conclusions: The current results replicate and extend previous work linking low alcohol sensitivity with enhanced incentive salience for alcohol‐related cues and suggest that cues depicting drinking contexts are less likely to differentiate high‐risk from low‐risk drinkers. [ABSTRACT FROM AUTHOR]

Reward uncertainty is a common characteristic of gambling and may powerfully enhance attraction to gambling-related cues, thus promoting maladaptive gambling behaviors in susceptible individuals. The co-occurrence of gambling disorder with tobacco use disorder (60.4%) suggests a common mechanism for their pathology, and comorbid anxiety (41.3%) might further promote the maintenance of these behaviors. However, it is unknown how nicotine or anxiety might contribute to cue and reward attraction, or promote disordered gambling behavior. In the present study, we investigated the effects of nicotine (0.4 mg/kg, SC) on the desire for uncertain rewards and their cues in male and female Sprague-Dawley rats. During an autoshaping task, rats learned to associate a lever + tone cue with the delivery of sucrose pellet rewards under either certain or uncertain (probability and magnitude) reward conditions. Subsequently, we tested the ability of gambling-like cues to serve as a conditioned reinforcer, and to promote motivation for sucrose rewards during a progressive ratio task. Finally, anxiety behavior was measured to examine its interaction with nicotine and uncertainty. Here, we found that nicotine enhanced attraction to the magazine under certain but not uncertain reward conditions, and increased cue-triggered behaviors. Conversely, in the progressive ratio task, exposure to uncertain conditions and nicotine enhanced motivation for reward, compared with certain conditions. These results suggest that nicotine may interact with both certain and uncertain reward conditions to increase cue-triggered behavior and enhance motivation for rewards, providing possible insight into the comorbid relationship between pathological gambling and tobacco use. [ABSTRACT FROM AUTHOR]

• DREADD inhibition of the NAcLSh → VP projection reduces sign-tracking behavior. • DREADD inhibition of the VP → NAcLSh does not affect sign-tracking behavior. • Neither projection inhibition reduces consumption of food rewards. Sign-tracking behavior, in which animals interact with a cue that predicts reward, provides an example of how incentive salience can be attributed to cues and elicit motivation. The nucleus accumbens (NAc) and ventral pallidum (VP) are two regions involved in cue-driven motivation. The VP, and NAc subregions including the medial shell and core, are critical for sign-tracking. Further, connections between the medial shell and VP are known to participate in sign-tracking and other motivated behaviors. The NAc lateral shell (NAcLSh) is a distinct and understudied subdivision of the NAc, and its contribution to the process by which reward cues acquire value remains unclear. The NAcLSh has been implicated in reward-directed behavior, and has reciprocal connections with the VP, suggesting that NAcLSh and VP interactions could be important mechanisms for incentive salience. Here, we use DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and an intersectional viral delivery strategy to produce a biased inhibition of NAcLSh neurons projecting to the VP, and vice versa. We find that disruption of connections from NAcLSh to VP reduces sign-tracking behavior while not affecting consumption of food rewards. In contrast, VP to NAcLSh disruption affected neither sign-tracking nor reward consumption, but did produce a greater shift in animals' behavior more towards the reward source when it was available. These findings indicate that the NAcLSh → VP pathway plays an important role in guiding animals towards reward cues, while VP → NAcLSh back-projections may not and may instead bias motivated behavior towards rewards. [ABSTRACT FROM AUTHOR]

Rationale: Previous work has identified that different forms of Pavlovian conditioned approach, sign-tracking and goal-tracking, are governed by distinct neurochemical mechanisms when compared in animals predisposed to learning one form vs. the other. Objectives: The present study aimed to investigate whether these are also neurochemically distinct processes in a population of animals capable of developing either response when this is manipulated via the use of distinct conditioned stimuli (CS). Methods: Rats were trained on one of two Pavlovian conditioning procedures in which the CS was either a lever, which elicits sign-tracking, or an auditory click, which elicits goal-tracking. The differential involvement of dopamine D1- and D2-receptors (D1R; D2R) in the acquisition of approach types was investigated via systemic administration of antagonists selective to one or both receptor subtypes during Pavlovian training. Results: Results indicate that dopaminergic signalling is important for the acquisition of both sign-tracking and goal-tracking responses. However, whilst development of sign-tracking to a lever depends on activity at both D1R and D2R, development of goal-tracking in response to a click was shown to depend only on activity at D1R. Conclusions: We suggest that the importance of D1R activity in both sign- and goal-tracking acquisition reflects a general role in learning Pavlovian associations, which aligns with data implicating dopamine in prediction error processes. In contrast, the selective involvement of D2R activity in sign-tracking acquisition may reflect its importance in motivational processes such as incentive salience attribution. [ABSTRACT FROM AUTHOR]

Abstract Midbrain dopamine (DA) neurons play a crucial role in the formation of conditioned associations between environmental cues and appetitive events. Activation of N-methyl- d -aspartate (NMDA) receptors is a key mechanism responsible for the generation of conditioned responses of DA neurons to reward cues. Here, we tested the effects of the cell type-specific inactivation of NMDA receptors in DA neurons in adult mice on stimulus-reward learning. Animals were trained in a Pavlovian learning paradigm in which they had to learn the predictive value of two conditioned stimuli, one of which (CS+) was paired with the delivery of a water reward. Over the course of conditioning, mutant mice learned that the CS+ predicted reward availability, and they approached the reward receptacle more frequently during CS+ trials than CS- trials. However, conditioned responses to the CS+ were weaker in the mutant mice, possibly indicating that they did not attribute incentive salience to the CS+. To further assess whether the attribution of incentive salience was impaired by the mutation, animals were tested in a conditioned reinforcement test. The test revealed that mutant mice made fewer instrumental responses paired with CS+ presentation, confirming that the CS+ had a weaker incentive value. Taken together, these results indicate that reward prediction learning does occur in the absence of NMDA receptors in DA neurons, but the ability of reward-paired cues to invigorate and reinforce behavior is attenuated. [ABSTRACT FROM AUTHOR]

Abstract Despite considerable evidence of higher rates of alcohol use disorders (AUDs) in men than in women, there is a dearth of research into the underlying causes of this disparity. As the gap in high risk drinking between men and women closes, it is critical to disentangle the biological factors that may place men and women at different risk for the development of AUDs as well as AUD-associated health problems. While sex differences in alcohol drinking have been reported in animal models and in human alcoholics, it increasingly seems that consummatory behavior may be dissociated from propensity toward inflexible and cue-elicited drug seeking and taking that characterize alcohol use disorders. While much of this work was initially performed in males a growing, yet limited, body of literature suggests that there are sex differences in both cue reactivity, and further, the relationship between cue reactivity and the maintenance of addictive behavior, indicating that males may be at greater risk for the development of a subset of addiction-related behaviors independent of alcohol consumption. Here, we will review the current literature on sex effects on the relationship between incentive motivation and addictive behavior and discuss unanswered questions that we expect will inform the development of individualized and sex-specific treatment and prevention strategies for AUDs. We believe that a greater understanding of how sex interacts with in cue reactivity to independently mediate the drug taking and risk for the development of uncontrolled drug or alcohol-seeking and -taking will inform the development of individualized treatment and prevention strategies for addiction. Highlights • Rates of alcohol use disorders are higher in men than in women, though this gap is closing. • Cue-mediated drug and alcohol seeking may be related to difficulty in terminating drinking. • Sex differences are present in the relationship between incentive motivation and drug seeking. • Males may be at greater risk for cue-mediated alcohol seeking. [ABSTRACT FROM AUTHOR]

'Wanting' and 'liking' are mediated by distinct brain reward systems but their dissociation in human appetite and overeating remains debated. Further, the influence of socioemotional cues on food reward is little explored. We examined these issues in overweight/obese (OW/OB) and normal-weight (NW) participants who watched food images varying in palatability in the same time as videoclips of avatars looking at the food images while displaying facial expressions (happy, disgust or neutral) with their gaze directed only toward the food or consecutively toward the food and participants. We measured heart rate (HR) deceleration as an index of attentional/incentive salience, facial EMG activity as an index of hedonic or disgust reactions, and self-report of wanting and liking. OW/OB participants exhibited a larger HR deceleration to palatable food pictures than NW participants suggesting that they attributed greater incentive salience to food cues. However, in contrast to NW participants, they did not display increased hedonic facial reactions to the liked food cues. Subjective ratings of wanting and liking did not differentiate the two groups. Further, OW/OB participants had more pronounced HR deceleration than NW participants to palatable food cues when they watched avatars' happy faces gazing at the food. In line with the "incentive-sensitization" hypothesis, our data suggest that incentive salience attribution and not hedonic reactivity is increased in OW/OB individuals and that happy faces, as social reward cues, potentiate implicit wanting in OW/OB people. [ABSTRACT FROM AUTHOR]

Highlights • Single prolonged stress (SPS) decreases the acquisition of sign-tracking behavior. • SPS increases the acquisition of goal-tracking behavior. • SPS attenuates cue-induced reinstatement of cocaine-seeking behavior. • SPS blocks K+-evoked dopamine release in the nucleus accumbens. Abstract Exposure to prolonged, uncontrollable stress reduces reward-seeking behavior, resulting in anhedonia in neuropsychiatric disorders, such as posttraumatic stress disorder. However, it is unclear to what degree stressed subjects lose interest in rewards themselves or in reward-related cues that instigate reward-seeking behavior. In the present study, we investigated the effects of single prolonged stress (SPS) on cue-directed behavior in two different procedures: Pavlovian conditioned approach (PCA) and cue-induced reinstatement of cocaine-seeking. In Experiment 1, rats were exposed to SPS and tested for the acquisition of sign-tracking (cue-directed) and goal-tracking (reward-directed) behaviors during a PCA procedure. In Experiment 2, rats were exposed to SPS and tested for the expression of sign- and goal-tracking as well as cue-induced reinstatement of cocaine-seeking. Because dopaminergic activity in the nucleus accumbens is known to play a central role in many cue-directed behaviors, including both sign-tracking and cue-induced reinstatement, Experiment 3 used in vivo microdialysis to measure the effect of SPS on baseline and evoked dopamine levels in the nucleus accumbens. SPS decreased sign-tracking and increased goal-tracking during the acquisition of PCA behavior without affecting reward consumption. In addition, SPS decreased cue-induced reinstatement without affecting cocaine self-administration. Finally, SPS decreased evoked but not baseline levels of dopamine in the nucleus accumbens. These results suggest that SPS decreases the motivational, but not consummatory, aspects of reward-seeking behavior, which may result from long-term, SPS-induced reductions in dopamine release in the nucleus accumbens. [ABSTRACT FROM AUTHOR]

Abstract Not all individuals attribute incentive salience to conditional stimuli. For some, reward-cues are more motivating than are actual rewards. Individuals disproportionately attracted to reward-cues are referred to as sign-trackers whereas those attracted to actual rewards are referred to as goal-trackers. In nonhuman animals, sign-tracking is associated with addiction, impulsivity, behavioral persistence, and reinstatement of misbehavior, whereas goal-tracking is associated with intact inhibitory control, reward focus, and the ability to extinguish learned behaviors. In humans, psychopathy is a personality trait that exhibits many sign-tracking characteristics, leading to self- and other-destructive behaviors. Thus, incentive salience may be useful for defining patterns of antisocial behavior within psychopathy. [ABSTRACT FROM AUTHOR]

Many individuals sporadically and circumstantially sample addictive drugs, yet few become addicted. The individual vulnerabilities underlying the development of addiction are not well understood. Correlational findings show that early life adversity is associated with a greater propensity to develop drug addiction. However, the mechanisms by which early life adversity increases addiction vulnerability are unknown. Separate lines of research have found that several traits are associated with addiction. Here, we examined the effects of early life adversity on addiction-related traits in adulthood. We weaned male and female Sprague-Dawley rats (postnatal day – PND21) and randomly assigned them to either a non-adversity group (N-ADV) or an adversity group (ADV). ADV rats experienced adversity from PND 21-35, they were: a) singly housed, b) food restricted for 12 h/day, c) subjected to forced-swim sessions, and d) restrained and exposed to predator odour (1 h). As adults, rats were tested for impulsivity, anxiety-like behaviour, novelty preference, and attribution of incentive salience to a reward cue. ADV rats showed enhanced novelty preference and attributed greater incentive value to a reward cue. Compared to N-ADV rats, a greater proportion of ADV rats expressed multiple addiction risk traits. Furthermore, fewer ADV rats expressed no addiction risk traits. This effect was most evident in female ADV rats. [ABSTRACT FROM AUTHOR]

Highlights • In a serial sign-tracking paradigm (distal lever → proximal lever → food reward), animals bias responding toward the distal lever. • Previous work shows that extinction of the proximal lever leads to reduced responding toward the distal lever. • Here we show that distal lever extinction leads to reduced responding on the proximal lever. • We argue that sign-tracking levers in serial sequence share a representational association. Abstract Sign-tracking is a phenomenon whereby cues that predict rewards come to acquire their own motivational value (incentive salience) and attract appetitive behavior. Typically, sign-tracking paradigms have used single auditory, visual, or lever cues presented prior to a reward delivery. Yet, real world examples of events often can be predicted by a sequence of cues. We have shown that animals will sign-track to multiple cues presented in temporal sequence, and with time develop a bias in responding toward a reward distal cue over a reward proximal cue. Further, extinction of responding to the reward proximal cue directly decreases responding to the reward distal cue. One possible explanation of this result is that serial cues become representationally linked with one another. Here we provide further support of this by showing that extinction of responding to a reward distal cue directly reduces responding to a reward proximal cue. We suggest that the incentive salience of one cue can influence the incentive salience of the other cue. [ABSTRACT FROM AUTHOR]

Highlights • We studied rats' preference for discriminative vs non-discriminative alternatives. • We manipulated each alternative's probability of reinforcement, in order to evaluate the generality of rats' optimality. • We manipulated the characteristics of the predictor of non-reinforcement in the discriminative alternative. • Rats behaved optimally, despite variations in the ratio between probabilities of reinforcement of the two alternatives. • Rats behaved optimally, regardless of the characteristics of the predictor of non-reinforcement. Abstract Previous research has shown that pigeons and other birds display a strong and consistent preference for an alternative of reinforcement that presents stimuli that allow to discriminate whether a reinforcer will be delivered or not, even when its probability of reinforcement is lower than that of another alternative without those stimuli. In contrast, most of the studies performed with rats report that they show the opposite preference, choosing the alternative with higher probability of reinforcement. To explain these opposite preferences, it has been proposed that rats and pigeons have a differential sensitivity to the conditioned inhibition that emerges from the stimulus that predicts non-reinforcement: While it does not have an impact in pigeons, it strongly influences rats´ preferences. Alternatively, it was recently proposed that there is not a fundamental difference in the behavior of rats and pigeons, but that the procedure employed to evaluate each of these species has generated the difference; in particular, it was proposed that both species prefer the discriminative alternative when the discriminative stimuli have incentive salience. Two recent studies provide support for each of these hypotheses, so that the available evidence does not allow to distinguish between them. In the present report, we present three studies that systematically explore the influence of the procedural differences between the studies with discrepant results. The obtained results provide support for the following ideas: a) there is a fundamental difference between pigeons and rats in their choice behavior in the "suboptimal choice procedure", b) considering the incentive salience of the discriminative stimuli does not resolve it, and c) rats' optimality is a consistent phenomenon, which resists manipulations in reinforcement probabilities and the absence of conditioned inhibitors in the discriminative alternative. [ABSTRACT FROM AUTHOR]

The incentive-motivational salience acquired by a Pavlovian conditioned stimulus (CS) is reflected by its ability to strengthen the performance of a separately learned instrumental action exerted to obtain an outcome, a phenomenon known as Pavlovian-Instrumental transfer (PIT). By means of a PIT paradigm, the present study addressed whether the CS motivational properties vary dynamically with the value of the associated outcome. Previous studies on human PIT and outcome devaluation have provided mixed results, showing that in some cases post-training devaluation leaves PIT unaffected when outcomes are palatable foods or drugs, and when the devalued outcome is not consumed immediately. In Experiment 1, thirsty participants first learned to squeeze a rubber bulb to accumulate a beverage (plain water or sugary drink); then participants learned Pavlovian associations between cues and the beverage. When tested in extinction, a PIT effect emerged as expected. In Experiment 2, the PIT effect emerged even despite participants quenched their thirst before the test phase. Our results suggest that the incentive properties of a CS can surprisingly and irrationally endure the devaluation of the associated outcome even when plain water is used as reward, and thirst is quenched by immediate reward consumption. This result may provide important insights in the understanding of the psychological mechanisms underlying different types of addiction. [ABSTRACT FROM AUTHOR]

Background: Three key domains including negative emotionality, incentive salience, and executive function form the core functional elements of addictive behaviors. Variables related to these broader domains have been studied extensively in relation to one another; however, no studies to date, have examined models including variables from all three domains, in relation to nicotine dependence. Method: Smokers (N = 117), 65.8% female, 78% white, mean age of 44.4 (SD = 10.8), enrolled in a smoking cessation program completed measures of negative affect (a component of negative emotionality), urge to smoke (incentive salience), and working memory (WM; a core executive function), during a baseline assessment period prior to initiating treatment. Results: Negative affect was associated with greater urge to smoke, and this elevated urge to smoke was associated with higher levels of nicotine dependence. Further, a significant moderated mediation indicated that WM moderated the relationship between increased urge to smoke and nicotine dependence. For those with low to average WM, urge to smoke was significantly related to nicotine dependence; however, for those with higher WM (+1 SD), urge to smoke stemming from negative affect was not associated with nicotine dependence. Conclusions: To our knowledge, this is the first reported relationship between negative affect, urge to smoke, WM, and nicotine dependence. Although preliminary, results indicate that WM may moderate the relationship between urge to smoke associated with negative affect and nicotine dependence. Treatments targeting WM may be particularly useful for individuals with average to low WM who experience urge to smoke related to negative affect. [ABSTRACT FROM AUTHOR]

Alcohol addiction, affecting approximately four percent of the population, contributes significantly to the global burden of diseases and is a substantial cost to the society. The neurochemical mechanisms regulating alcohol mediated behaviors is complex and in more recent years a new physiological role of the gut-brain peptides, traditionally known to regulate appetite and food intake, have been suggested. Indeed, regulators of alcohol-mediated behaviors. One of these gut-brain peptides is the annorexigenic peptide glucagon-like peptide-1 (GLP-1), Preclinical studies show that GLP-1 receptor activation, either by GLP-1 or analogues, attenuate the ability of alcohol to activate the mesolimbic dopamine system as well as decrease alcohol consumption and operant self-administration. In further support for the endogenous GLP-1 system in addiction processes are the experimental data showing that a GLP-1 receptor antagonist increases alcohol intake. Moreover, GLP-1 receptor agonists prevent the ability of other addictive drugs to activate the mesolimbic dopamine system. The number of clinical studies is limited, but show i) that genetic variation in the GLP-1 receptor gene is associated with alcohol addiction as well as increased alcohol infusion in humans, ii) that plasma levels of GLP-1 are associated with the subjective experience of cocaine and iii) that a GLP-1 receptor agonist reduces alcohol intake in patients with type-2 diabetes mellitus. These experimental and clinical studies raises the concern that clinically available GLP-1 receptor agonists deserves to be tested as potential treatments of patients with addictive disorders including alcohol addiction. This article is part of the Special Issue entitled ‘Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.’ [ABSTRACT FROM AUTHOR]

Previous research has found that the attention of social drinkers is preferentially oriented towards alcohol-related stimuli (attentional capture). This is argued to play a role in escalating craving for alcohol that can result in hazardous drinking. According to incentive theories of drug addiction, the stimuli associated with the drug reward acquire learned incentive salience and grab attention. However, it is not clear whether the mechanism by which this bias is created is a voluntary or an automatic one, although some evidence suggests a stimulus-driven mechanism. Here, we test for the first time whether this attentional capture could reflect an involuntary consequence of a goal-driven mechanism. Across three experiments, participants were given search goals to detect either an alcoholic or a non-alcoholic object (target) in a stream of briefly presented objects unrelated to the target. Prior to the target, a task-irrelevant parafoveal distractor appeared. This could either be congruent or incongruent with the current search goal. Applying a meta-analysis, we combined the results across the three experiments and found consistent evidence of goal-driven attentional capture, whereby alcohol distractors impeded target detection when the search goal was for alcohol. By contrast, alcohol distractors did not interfere with target detection, whilst participants were searching for a non-alcoholic category. A separate experiment revealed that the goal-driven capture effect was not found when participants held alcohol features active in memory but did not intentionally search for them. These findings suggest a strong goal-driven account of attentional capture by alcohol cues in social drinkers. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) patients who are treated with dopamine replacement therapy are at risk of developing impulse control disorders (ICDs) (such as gambling, binge eating, and others). According to recent evidence, compulsive reward seeking in ICDs may arise from an excessive attribution of incentive salience (or 'wanting') to rewards.Objectives: In this study, we tested this hypothesis in patients with PD who developed binge eating (BE).Methods: Patients with BE, patients without BE, and healthy controls performed different experimental tasks assessing food liking and wanting. Participants first rated the degree of liking and wanting for different foods using explicit self-report measures. They then performed an affective priming task that measured participants' affective reactions towards foods (liking), and a grip-force task that assessed their motivation for food rewards (wanting). All participants also completed several questionnaires assessing impulsivity, reward sensitivity, anxiety and depression, and underwent a neuropsychological evaluation.Results: Patients with BE displayed an altered liking for sweet foods compared to controls but not to patients without BE. Furthermore, this difference emerged only when implicit measures were used. Importantly, an increased wanting was not associated with binge eating even if wanting, but not liking scores significantly correlated with LED levodopa, confirming the hypothesis of a distinction between the two components of rewards. Lastly, binge eating was associated with depression and lower working memory scores.Conclusions: Take together these results suggest that binge eating in PD is associated with cognitive abnormalities, and to lesser extent affective abnormalities, but not with an increased incentive salience. [ABSTRACT FROM AUTHOR]