Altered Reward Processing Research Articles

Social isolation enhances cued-reinstatement of sucrose and nicotine seeking, but this is reversed by a return to social housing

Physical or perceived (i.e. loneliness) social isolation is increasing in Western cultures. Unfortunately, social isolation is associated with a range of negative physical and mental health outcomes, including increased incidence of obesity and smoking. Here we monitored the impact of social isolation on a range of physical measures, and then tested whether social isolation in adult rats changes how reward-related stimuli motivate sucrose- or nicotine-seeking. Socially isolated rats showed elevated baseline CORT, gained significantly less weight across the study, were more active in response to a novel or familiar environment. Isolated rats also acquired nose-poking for a food pellet more rapidly, and showed increased susceptibility to cue-, but not reward-induced reinstatement. Notably, these effects are partially mitigated by a return to group housing, suggesting that they are not necessarily permanent, and that a return to a social setting can quickly reverse any deficits or changes associated with social isolation. This study advances our understanding of altered reward-processing in socially isolated individuals and reiterates the importance of socialisation in the treatment of disorders such as overeating and addiction.

Resting State Hypoconnectivity of Reward Networks in Binge Eating Disorder.

The clinical presentation of binge eating disorder (BED) and data emerging from task-based functional neuroimaging research suggests that this disorder may be associated with alterations in reward processing. However, there is a dearth of research investigating the functional organization of brain networks that mediate reward in BED. To address this gap, 27 adults with BED and 21 weight-matched healthy controls (WMC) completed a multimodel assessment consisting of a resting functional magnetic resonance imaging scan, behavioral tasks measuring reward-based decision-making (i.e., delay discounting and reversal learning), and self-report assessing clinical symptoms. A seed-based approach was employed to examine the resting state functional connectivity (rsFC) of the striatum (nucleus accumbens [NAcc] and ventral and dorsal caudate), a collection of regions implicated in reward processing. Compared with WMC, the BED group exhibited lower rsFC of striatal seeds, with frontal regions mediating executive functioning (e.g., superior frontal gyrus [SFG]) and posterior, parietal, and temporal regions implicated in emotional processing. Lower NAcc-SFG rsFC was associated with more difficulties with reversal learning and binge eating frequency in the BED group. Results suggest that hypoconnectivity of striatal networks that integrate self-regulation and reward processing may promote the clinical phenomenology of BED. Interventions for BED may benefit from targeting these circuit-based disturbances.

Reward motivation and cognitive flexibility in tau null-mutation mice

The reduction of tau or hyperphosphorylated tau (p-tau) has been proposed as a therapeutic strategy for Alzheimer's disease (AD) and frontotemporal dementia (FTD). Cognitive decline and sleep-wake dysregulation seen in AD and FTD patients are mimicked in transgenic and null-mutation mouse models of tauopathy. Alterations in the reward system are additional symptoms of AD and FTD. However, the role of tau in reward processes is not well understood. The present study aimed to examine reward and reward-motivated cognitive processes in male and female tau knockout (tau−/−) and wild-type mice using progressive ratio and reversal learning tasks. Tau−/− mice were heavier, ate more in the home cage, and reached criterion in operant lever training faster than wild-type mice. Tau−/− mice had a higher breakpoint in progressive ratio but were unimpaired in reversal learning or reward sensitivity. These data indicate that tau loss of function alters reward processing. This may help to explain aberrant reward-related behaviors in tauopathy patients and highlights a potentially important area for consideration in the development of anti-tau therapies.

Frontoparietal hyperconnectivity during cognitive regulation in obsessive-compulsive disorder followed by reward valuation inflexibility

Obsessive-compulsive disorder (OCD) is characterized by cognitive deficits and altered reward processing systems. An imbalance between cognitive and reward pathways may explain the lack of control over obsessions followed by rewarding compulsive behaviors. While the processes of emotional cognitive regulation are widely studied in OCD, the mechanisms of cognitive regulation of reward are poorly described. Our goal was to investigate the OCD impact on cognitive regulation of reward at behavioral and neural functioning levels. OCD and control participants performed a functional magnetic resonance imaging task where they cognitively modulated their craving for food pictures under three cognitive regulation conditions: indulge/increase craving, distance/decrease craving, and natural/no regulation of craving. After regulation, the participants gave each picture a monetary value. We found that OCD patients had fixed food valuation scores while the control group modulated these values accordingly to the regulation conditions. Moreover, we observed frontoparietal hyperconnectivity during cognitive regulation. Our results suggest that OCD is characterized by deficits in cognitive regulation of internal states associated with inflexible behavior during reward processing. These findings bring new insights into the nature of compulsive behaviors in OCD.

Dissociation between binge eating behavior and incentive motivation

Binge-like eating behavior (BLE) has been characterized as an eating disorder in which subjects have an enhanced intake of food, mainly fats. However, intake of fats and carbohydrates may have differential effects on motivation. Previously it was shown that BLE produces an increase in operant responding for vegetable shortening. Our aim was to determine if BLE behavior induced with a sucrose solution would produce an increment in performance for sucrose reinforcers. Male Wistar rats were trained under an exponential progressive ratio schedule of sucrose reinforcement; thereafter, the limited access model was used to induce BLE. Finally, subjects were tested for increments in break points (BPs) in the progressive ratio schedule. We were unable to observe an increase in BPs after BLE. No increments in BPs were observed when a distinctive flavor (vanilla-flavored sucrose) was correlated with BLE induction and reinforcement, or when different types of ratio progression in the operant schedules were employed. However, rats adjusted their BPs according to reinforcer concentration after BLE induction, demonstrating that valuation (cost/benefit decision) of reinforcers was intact. Extent of training, alterations of reward processing after extended exposure to sucrose, and different mechanisms for processing high fat and high carbohydrate reinforcers are variables worth exploring to gain a better understanding of BLE behavior in rodent models.

经前期综合征与奖赏进程失调——来自脑电的证据

经前期综合征与奖赏进程失调——来自脑电的证据

Emotional Instability Relates to Ventral Striatum Activity During Reward Anticipation in Females.

Both non-emotional symptoms, such as inattention, and symptoms of emotional instability (EI) are partially co-varying and normally distributed in the general population. Attention Deficit Hyperactivity Disorder (ADHD), which is associated with both inattention and emotional instability, has been related to lower reward anticipation activation in the ventral striatum. However, it is not known whether non-emotional dysregulation, such as inattention, or EI—or both—are associated with this effect. We hypothesized that altered reward processing relates specifically to EI. To test this, 29 healthy participants were recruited to this functional MRI study (n = 15 females). Reward processing was studied using a modified version of the Monetary Incentive Delay (MID) task. Brown Attention-Deficit Disorder Scales questionnaire was used to assess EI and inattention symptoms on a trait level. We observed less ventral striatal activation during reward anticipation related to the EI trait in females, also when controlling for the inattention trait, but not in the whole sample or males only. Our study suggests the existence of sex differences in the relationship between reward processing and EI/inattention traits.

Aberrant salience and reward processing: a comparison of measures in schizophrenia and anxiety.

Aberrant salience may contribute to the development of schizophrenia symptoms via alterations in reward processing and motivation. However, tests of this hypothesis have yielded inconsistent results. These inconsistencies may reflect problems with the validity and specificity of measures of aberrant salience in schizophrenia. Therefore, we investigated relationships among measures of aberrant salience, reward, and motivation in schizophrenia and anxiety. Individuals with schizophrenia (n = 30), anxiety (n = 33) or unaffected by mental disorder (n = 30) completed measures of aberrant salience [Aberrant Salience Inventory (ASI), Salience Attribution Test (SAT)], motivation (Effort Expenditure for Reward Task), and reinforcer sensitivity (Stimulus Chase Task). Schizophrenia participants scored higher than anxiety (d = 0.71) and unaffected (d = 1.54) groups on the ASI and exhibited greater aberrant salience (d = 0.60) and lower adaptive salience (d = 0.98) than anxious participants on the SAT. There was no evidence of a correlation between measures of aberrant salience. Schizophrenia was associated with related deficits in motivated behaviour and maladaptive reward processing. However, these differences in reward processing did not correlate with aberrant salience measures. The results suggest that key measures of aberrant salience have limited specificity and validity. These problems may account for inconsistent findings reported in the literature.

Inflammation and Negative Symptoms of Schizophrenia: Implications for Reward Processing and Motivational Deficits.

Negative symptoms of schizophrenia are debilitating and chronic in nature, are difficult to treat, and contribute to poor functional outcomes. Motivational deficits are a core negative symptom and may involve alterations in reward processing, which involve subcortical regions such as the basal ganglia. More specifically, dopamine-rich regions like the ventral striatum, have been implicated in these reward-processing deficits. Inflammation is one mechanism that may underlie negative symptoms, and specifically motivational deficits, via the effects of inflammatory cytokines on the basal ganglia. Previous work has demonstrated that inflammatory stimuli decrease neural activity in the ventral striatum and decrease connectivity in reward-relevant neural circuitry. The immune system has been shown to be involved in the pathophysiology of schizophrenia, and inflammatory cytokines have been shown to be altered in patients with the disorder. This paper reviews the literature on associations between inflammatory markers and negative symptoms of schizophrenia as well as the role of anti-inflammatory drugs to target negative symptoms. We also review the literature on the role of inflammation and reward processing deficits in both healthy controls and individuals with depression. We use the literature on inflammation and depression as a basis for a model that explores potential mechanisms responsible for inflammation modulating certain aspects of negative symptoms in patients with schizophrenia. This approach may offer novel targets to treat these symptoms of the disorder that are significant barriers to functional recovery and do not respond well to available antipsychotic medications.

Mitogen-activated protein kinase phosphatase-2 deletion modifies ventral tegmental area function and connectivity and alters reward processing.

Mitogen-activated protein kinases (MAPKs) regulate normal brain functioning, and their dysfunction is implicated in a number of brain disorders. Thus, there is great interest in understanding the signalling systems that control MAPK functioning. One family of proteins that contribute to this process, the mitogen-activated protein kinase phosphatases (MKPs), directly inactivate MAPKs through dephosphorylation. Recent studies have identified novel functions of MKPs in foetal development, the immune system, cancer and synaptic plasticity and memory. In the present study, we performed an unbiased investigation using MKP-2-/- mice to assess whether MKP-2 plays a global role in modulating brain function. Local cerebral glucose utilization is significantly increased in the ventral tegmental area (VTA) of MKP-2-/- mice, with connectivity analysis revealing alterations in VTA functional connectivity, including a significant reduction in connectivity to the nucleus accumbens and hippocampus. In addition, spontaneous excitatory postsynaptic current frequency, but not amplitude, onto putative dopamine neurons in the VTA is increased in MKP-2-/- mice, which indicates that increased excitatory drive may account for the increased VTA glucose utilization. Consistent with modified VTA function and connectivity, in behavioural tests MKP-2-/- mice exhibited increased sucrose preference and impaired amphetamine-induced hyperlocomotion. Overall, these data reveal that MKP-2 plays a role in modulating VTA function and that its dysfunction may contribute to brain disorders in which altered reward processing is present.

Instrumental learning in a mouse model for obsessive-compulsive disorder: Impaired habit formation in Sapap3 mutants

It has been hypothesized that maladaptive habit formation contributes to compulsivity in psychiatric disorders such as obsessive-compulsive disorder (OCD). Here, we used an established animal model of OCD, Sapap3 knockout mice (SAPAP3-/-), to investigate the balance of goal-directed and habitual behavior in compulsive individuals and if altered habit formation is associated with compulsive-like behavior. We subjected 24 SAPAP3-/- and 24 wildtype littermates (WT) to two different schedules of reinforcement in a within-subjects design: a random-ratio (RR) schedule to promote goal-directedness, and a random-interval (RI) schedule, known to facilitate habitual responding. SAPAP3-/- acquired responding under both schedules, but showed lower response rates and fewer attempts to collect food pellets than WT, indicative of altered reward processing. As expected, WT were sensitive to sensory-specific satiety (outcome devaluation) following RR training, but not RI training, demonstrating schedule-specific acquisition of goal-directed and habitual responding, respectively. In contrast, SAPAP3-/- were sensitive to outcome devaluation after both RR and RI training, suggesting decreased engagement of a habitual response strategy. No linear relation was observed between increased grooming and behavior during the outcome devaluation test in SAPAP3-/-. Together, our findings demonstrate altered reward processing and impaired habit learning in SAPAP3-/-. We report a diminished propensity to form habits in these mice, which albeit inconsistent with the predominant idea of excessive habit formation in OCD, nonetheless points at dysregulation of behavioral automation in the context of compulsivity. Thus, the habit hypothesis of compulsivity should be updated to state that an imbalance of habitual and goal-directed responding in either direction can contribute to the development of compulsive behavior.

Dopamine agonist treatment increases sensitivity to gamble outcomes in the hippocampus in de novo Parkinson’s disease

BackgroundParkinson’s disease is associated with severe nigro-striatal dopamine depletion, leading to motor dysfunction and altered reward processing. We previously showed that drug-naïve patients with Parkinson’s disease had a consistent attenuation of reward signalling in the mesolimbic and mesocortical system. Here, we address the neurobiological effects of dopaminergic therapy on reward sensitivity in the mesolimbic circuitry, and how this may contribute to neuropsychiatric symptoms. ObjectivesWe tested the hypothesis that (1) dopaminergic treatment would restore the attenuated, mesolimbic and mesocortical responses to reward; and (2) restoration of reward responsivity by dopaminergic treatment would predict motor performance and the emergence of impulse control symptoms. MethodsIn 11 drug-naïve Parkinson patients, we prospectively assessed treatment-induced changes in reward processing before, and eight weeks after initiation of monotherapy with dopamine agonists. They were compared to 10 non-medicated healthy controls who were also measured longitudinally. We used whole-brain functional magnetic resonance imaging at 3 Tesla to assess the reward responsivity of the brain to monetary gains and losses, while participants performed a simple consequential gambling task. ResultsIn patients, dopaminergic treatment improved clinical motor symptoms without significantly changing task performance. Dopamine agonist therapy induced a stronger reward responsivity in the right hippocampus with higher doses being less effective. None of the patients developed impulse control disorders in the follow-up period of four years. ConclusionsShort-term treatment with first-ever dopaminergic medication partially restores deficient reward-related processing in the hippocampus in de novo Parkinson’s disease.

Is monetary reward processing altered in drug-naïve youth with a behavioral addiction? Findings from internet gaming disorder.

Current models of addiction biology highlight altered neural responses to non-drug rewards as a central feature of addiction. However, given that drugs of abuse can directly impact reward-related dopamine circuitry, it is difficult to determine the extent to which reward processing alterations are a trait feature of individuals with addictions, or primarily a consequence of exogenous drug exposure. Examining individuals with behavioral addictions is one promising approach for disentangling neural features of addiction from the direct effects of substance exposure. The current fMRI study compared neural responses during monetary reward processing between drug naïve young adults with a behavioral addiction, internet gaming disorder (IGD; n=22), and healthy controls (n=27) using a monetary incentive delay task. Relative to controls, individuals with IGD exhibited blunted caudate activity associated with loss magnitude at the outcome stage, but did not differ from controls in neural activity at other stages. These findings suggest that decreased loss sensitivity might be a critical feature of IGD, whereas alterations in gain processing may be less characteristic of individuals with IGD, relative to those with substance use disorders. Therefore, classic theories of altered reward processing in substance use disorders should be translated to behavioral addictions with caution.

Structural and functional brain correlates of altered taste processing in anorexia nervosa: A systematic review.

A growing body of empirical literature indicates altered taste perception in individuals with anorexia nervosa (AN). However, it remains unknown whether the observed impairments in the neural processing of taste stimuli represent etiopathogenetic factors of AN or whether they are a secondary consequence of malnutrition. In the current systematic review, scientific studies were identified using the MEDLINE, PsycINFO, and Scopus databases. A supplemental search was performed by searches through reference lists of the relevant publications and via Google Scholar. On the basis of the searches conducted, 16 publications were identified and included in this literature review. The results of those studies point to disturbances in the structure and functioning of brain regions involved in taste processing in AN. The findings of the reviewed studies suggest that altered reward, interoceptive, and cognitive-emotional processing may contribute to abnormal taste processing in AN.

Goal-directed vs. habitual instrumental behavior during reward processing in anorexia nervosa: an fMRI study

Previous studies have proposed that altered reward processing and elevated cognitive control underlie the etiology of anorexia nervosa (AN). A newly debated notion suggests altered habit learning and an overreliance on habits may contribute to the persistence of AN. In weight-recovered AN patients, we previously found neuroimaging-based evidence for unaltered reward processing, but elevated cognitive control. In order to differentiate between state versus trait factors, we here contrast the aforementioned hypotheses in a sample of acutely underweight AN (acAN) patients. 37 acAN patients and 37 closely matched healthy controls (HC) underwent a functional MRI while performing an established instrumental motivation task. We found no group differences with respect to neural responses during the anticipation or receipt of reward. However, the behavioral response data showed a bimodal distribution, indicative for a goal-directed (gAN) and a habit-driven (hAN) patient subgroup. Additional analyses revealed decreased mOFC activation during reward anticipation in hAN, which would be in line with a habit-driven response. These findings provide a new perspective on the debate regarding the notion of increased goal-directed versus habitual behavior in AN. If replicable, the observed dissociation between gAN and hAN might help to tailor therapeutic approaches to individual patient characteristics.

Neural reward processing in paediatric Tourette syndrome and/or attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is the most common comorbidity in individuals with Tourette syndrome (TS). Yet, it is unclear to what extent TS and ADHD show overlapping or distinct neural abnormalities. ADHD has been associated with altered reward processing, but there are very few studies on reward processing in TS. This study assessed neural activation of basal ganglia and thalamus during reward anticipation and receipt in children with TS and/or ADHD. We analysed mean activations of a priori specified regions of interest during an fMRI monetary incentive delay task. Data was used from 124 children aged 8–12 years (TS n = 47, of which 29 had comorbid ADHD; ADHD n = 29; healthy controls n = 48). ADHD severity across ADHD and TS groups and healthy controls was marginally related to hypoactivation of the right nucleus accumbens during reward anticipation; this effect was not moderated by TS diagnosis. We detected no associations of neural activation with TS. The association between ADHD severity and hypoactivation of the right nucleus accumbens during reward anticipation, independent of the presence or absence of TS, is in line with the view of nucleus accumbens hypoactivation as a dimensional, neurofunctional marker of ADHD severity, transcending the boundaries of primary diagnosis.

Reward (BIS/BAS) mechanisms and fatigue in patients on chronic hemodialysis

ABSTRACT Recently, it has been demonstrated that chronic inflammation could have a role on fatigue onset in chronic hemodialysis (HD). Research on neuro-immune interactions highlighted that an alteration of basal ganglia functioning, secondary to chronic inflammation, may translate in a reduced motivation and altered reward processes in chronic diseases. This study investigated a possible correlation between fatigue severity and reward mechanisms, that regulate motivational dispositions, in HD patients. Evaluation scales were administered to ninety-four patients on HD (54 Male, 40 Female; Mdage = 67±26.5; Dialytic Mdage in years = 4±6.3. Fatigue was assessed by using Fatigue Severity Scale (FSS). Behavioural Inhibition System (BIS) and Behavioural Activation System (BAS) Scale was administered to investigate approach/avoidance behaviours. Anxiety and depression were measured by State-Trait Anxiety Inventory (STAI-Y) and Beck Depression Inventory (BDI-II). Results show that the distribution of HD patients for FSS score did not show a normal pattern. FSS score was significantly higher in patients with high BIS Z-score than in patients with low and medium BIS Z-score. BDI score and STAI-Y scores were similar among BIS Z-score groups of patients. Findings suggest that in patients on chronic hemodialysis there is a correlation between fatigue severity symptoms and motivational disposition mechanisms that predispose to action inhibition.

Neurophysiological activity following rewards and losses among female adolescents and young adults with borderline personality disorder.

Borderline personality disorder (BPD) is a complex and debilitating psychiatric illness. Prior research in adults has shown that neurophysiological deficits in feedback processing and learning from rewards may be central to the development of BPD; however, little research has examined these markers in adolescents and young adults with BPD. The present study used event-related potentials and time-frequency decomposition analysis to probe neural responses to wins and losses in a guessing task among 68 females (13 to 23 years old) either with BPD (n = 35) or no history of mental disorders (healthy control [HC]; n = 33). Participants completed a guessing task wherein they won and lost money at equal frequencies while electroencephalogram (EEG) data were acquired. Adolescents and young adults with BPD showed a smaller differentiation between wins and losses in the reward positivity (RewP) relative to HCs. Using time-frequency decomposition, we isolated distinct frequency bands sensitive to wins (delta = < 3Hz) and losses (theta = 4 Hz to 7 Hz). Compared with BPD participants, HCs showed significantly larger delta power to wins, specifically. The groups did not differ in delta power to losses, nor theta power to wins or losses. Collectively, findings implicate altered reward processing in the pathophysiology of BPD and may inform early identification and targeted intervention. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Reward-Related Striatal Responses Following Stress in Healthy Individuals and Patients With Bipolar Disorder

BackgroundStress has a major impact on the onset and recurrence of mood episodes in bipolar disorder (BD), but the underlying mechanisms remain unknown. Previous studies have shown distinct time-dependent effects of stress on reward processing in healthy individuals. Impaired reward processing is a core characteristic of BD, and altered reward processing during recovery from stress could influence the development and course of bipolar disorder. MethodsWe investigated brain responses during reward processing 50 minutes after stress using functional magnetic resonance imaging in 40 healthy control subjects and 40 patients with euthymic BD assigned to either an acute stress test (Trier Social Stress Test) or a no-stress condition. ResultsAcute stress increased cortisol levels in both healthy control subjects and patients with BD. Ventral striatal responses to reward outcome were increased in healthy control subjects during stress recovery but not in patients with BD. For anticipation, no differences were found between the groups following stress. ConclusionsFor the first time, we show altered reward processing in patients with BD during the recovery phase of stress. These data suggest reduced neural flexibility of hedonic signaling in response to environmental challenges. This may increase the susceptibility to stressful life events in the future and play a role in the development of further psychopathology in the longer term.

Diminished Value Discrimination in Obsessive-Compulsive Disorder: A Prospect Theory Model of Decision-Making Under Risk.

Introduction: It has been hypothesized that people diagnosed with anxiety and obsessive-compulsive disorder (OCD) exhibit behavioral aberrations when faced with the potential for negative outcomes, but the specific cognitive aspects of decision-making that may be altered have not been systematically studied in clinical populations. Here, we studied decision-making in a clinical cohort using a task that allows for examination of the decision weights and values associated with different choice outcomes. Methods: Patients diagnosed with OCD (n = 10), generalized anxiety disorder (n = 15), social anxiety disorder (n = 14), and healthy controls (n = 20) were given a decision-making task and choices were modeled using a cumulative prospect theory framework. Results: We found OCD patients to have lower value discrimination than controls, as well as less optimal performance on the task, an effect that was mostly driven by trials with only positive outcomes. Discussion: Our results shed light on the cognitive processes that drive altered decision-making under risk in OCD. Specifically, they demonstrate that OCD patients have diminished sensitivity to positive outcomes, which might be associated with risk aversion and altered learning of gain. These findings also extend prior reports, suggesting that altered cognitive processing during decision-making is linked to altered perception of value, but not probability, in these patients.