Reward Processing Research Articles

Adolescent Internet Gaming Disorder and sensitivity to money and social rewards

Internet Gaming Disorder (IGD) is a behavioural addiction characterised by excessive exposure to addictive stimuli, resulting in reduced sensitivity of the brain's reward system towards everyday rewards. Online game addiction is prevalent among adolescents; however, it remains unclear if there are variations in reward processing patterns among adolescents with online game addiction.We compared differences in sensitivity to two types of rewards between patients with IGD and patients with Recreational Game Use (RGU) using the Monetary Incentive Delay (MID) paradigm and the Social Incentive Delay (SID) paradigm (Experiment 1). Additionally, we used a mixed reward latency paradigm, including both monetary and social rewards, to further explore the processing characteristics of IGD towards a mixture of these two rewards (Experiment 2).There were significant differences in the sensitivity of IGD and RGU to monetary and social rewards. Adolescents with IGD had significantly shorter reaction times to the four mixed rewards compared to RGU, while no significant differences were found between groups regarding sensitivity to specific individual rewards. However, the simultaneous presence of two rewards affected the processing speed and preference of adolescents with IGD.The reward processing characteristics observed in adolescents with online gaming disorder show specificity concerning the type and presentation of rewards, providing a theoretical foundation for diagnosing and treating adolescent online gaming addiction.

Experiential processing increases positive affect and decreases dampening appraisals during autobiographical memory recall in an anhedonic sample

Anhedonia is characterized by diminished reward processing, which may be explained in part by dampening appraisals, or thoughts that blunt positive emotions. Experiential processing, or attending to sensory and bodily experience, may curb dampening appraisals, as compared to analytical processing, or conceptually thinking about an event. In this study, 96 participants with elevated anhedonia completed writing tasks, in which they recalled positive autobiographical memories. Participants recalled the first memory as they naturally would to assess spontaneous use of processing mode and were then randomized to recall the second positive memory using either experiential, analytical, or control instructions. Both spontaneous and instructed experiential processing were associated with greater positive affect and less dampening compared to analytical processing. Clinical implications include savoring pleasant sensations to reduce dampening and enhance positive affect in anhedonia.

The Impact of Emotional Responses on Female Reproduction: Fibrinolysis in the Spotlight.

Fibrinolytic enzymes modify various substrates required for tissue remodeling, playing a crucial role in mechanisms underlying resilience, reward processing, ovulation, embryo implantation, and placentation. Individuals with low resilience and reduced reward responsiveness, when exposed to chronic stress, are at increased risk of experiencing a range of negative emotions. Chronic anxiety and melancholia are examples of negative emotions associated with hypercortisolism, while fear and atypical depression are characterized by systemic inflammation. Both cortisol and inflammatory cytokines stimulate the production of plasminogen activator inhibitor-1 (PAI-1), a potent fibrinolysis inhibitor. Chronic anxiety, fear, and depression are among the many hypofibrinolytic conditions increasing the risk of oligo-anovulation, miscarriage, fetal growth restriction, and preeclampsia. Although significant, the impact of negative emotions on implantation is not as obvious as on ovulation or placentation. Other hypofibrinolytic conditions that may affect female reproduction through mechanisms dependent or independent of PAI-1 include metabolic disturbances (e.g., due to consumption of highly palatable foods, often used to alleviate negative affect), inflammation, hyperhomocysteinemia, hypothyroidism, hypercortisolism, antiphospholipid antibodies, and the 4G allele of the PAI-1 gene. Benzodiazepines and antidepressants should be used with caution in the first trimester as this combination may cause malformations. Also, selective serotonin reuptake inhibitors have fibrinolytic properties that increase the risk of bleeding after surgical procedures. Psychological interventions, especially group therapy, are effective in the prevention of reproductive disorders. Controlled trials are needed to test the hypothesis that female reproductive health depends on psychological well-being, a balanced diet and physical activity, suppression of inflammation and autoantibodies, and homocysteine and hormonal homeostasis.

Performing a Motor Action Enhances Social Reward Processing and Modulates the Neural Processing of Predictive Cues.

Associative learning affects many areas of human behavior. Recently, we showed that the neural response to monetary reward is enhanced by performing an action, suggesting interactions between neural systems controlling motor behavior and reward processing. Given that many psychiatric disorders are associated with social anhedonia, a key open question is whether such effects generalize to social rewards, and in how far they affect associative learning. We developed a novel task in which participants (n = 66) received social reward feedback and social punishment either by pressing a button or waiting. Predictive cues were linked to feedback valence with 80% accuracy. Using EEG, we measured the neural response to both predictive cues and social feedback. We found enhanced reward positivity for social reward preceded by an action, and an enhanced N2 for cues predicting negative feedback. Cue-locked P3 amplitude was reduced for cues associated with negative feedback in passive trials only, showing a modulation of outcome anticipation by performing a motor action. This was supported by connectivity analyses showing stronger directed theta synchronization, in line with increased top-down modulation of attention, in active compared with passive trials. These findings suggest that actively obtaining social feedback enhances reward sensitivity and modulates outcome anticipation.

Problematic Gaming and Gambling: A Systematic Review of Task-Specific EEG Protocols.

Even though gaming and gambling bear similar problematic behavioral aspects, there are no recognizable neurophysiological biomarkers or features characterizing and/or distinguishing these conditions. A systematic review of the literature with a focus on methods was performed in PubMed, Scopus, Web of Science (Web of Science Core Collection), EBSCOhost Research Databases (APA PsycINFO; APA PsycArticles; OpenDissertations; ERIC) databases. Following search terms were used to search the databases: ERP, "event related potential*", EP, "evoked potential*", SS, "steady state", EEG, electroencephal*; gam*. Data about the participants (total number, gender, age), main aim of the study and information about the experimental setup (experimental task description, stimuli used, ERPs measured (latency windows and placement of the electrodes), process evaluated) was extracted. A total of 24 studies were revised (problematic gaming - 16, pathological gambling - 8). The experimental protocols could be grouped into 3 main target domains (Cue-reactivity, General Information processing and Reward Processes & Risk Assessment). Sample-related limitations (small sample sizes, gender differences, differences between the groups regarding potential confounding variables) and heterogeneity regarding the experimental tasks, implementation and interpretation reviewed. Gambling-related research is highly focused on the investigation of the reward-related processes, whereas gaming-related research is mostly focused on the altered aspects of more general information processing. A vast heterogeneity regarding the ERP experimental paradigms being usedand lack of clear guidelines and standardized procedures prevents identification of measures capable to reliably discriminate or characterize the population susceptible to addictive behavior or being able to diagnose and monitor these disorders.

T38 - Differential Reward Processing Across Adolescent Temperamental Profiles Associated With Increased Risk of Substance Use

T38 - Differential Reward Processing Across Adolescent Temperamental Profiles Associated With Increased Risk of Substance Use

VTA μ-opioidergic neurons facilitate low sociability in protracted opioid withdrawal.

Opioids initiate dynamic maladaptation in brain reward and affect circuits that occur throughout chronic exposure and withdrawal that persist beyond cessation. Protracted withdrawal is characterized by negative affective behaviors such as heightened anxiety, irritability, dysphoria, and anhedonia, which pose a significant risk factor for relapse. While the ventral tegmental area (VTA) and mu-opioid receptors (MORs) are critical for opioid reinforcement, the specific contributions of VTAMOR neurons in mediating protracted withdrawal-induced negative affect is not fully understood. In our study, we elucidate the role of VTAMOR neurons in mediating negative affect and altered brain-wide neuronal activities following opioid exposure and withdrawal in male and female mice. Utilizing a chronic oral morphine administration model, we observe increased social deficit, anxiety-related, and despair-like behaviors during protracted withdrawal. VTAMOR neurons show heightened neuronal FOS activation at the onset of withdrawal and connect to an array of brain regions that mediate reward and affective processes. Viral re-expression of MORs selectively within the VTA of MOR knockout mice demonstrates that the disrupted social interaction observed during protracted withdrawal is facilitated by this neural population, without affecting other protracted withdrawal behaviors. Lastly, VTAMORs contribute to heightened neuronal FOS activation in the anterior cingulate cortex (ACC) in response to an acute morphine challenge, suggesting their unique role in modulating ACC-specific neuronal activity. These findings identify VTAMOR neurons as critical modulators of low sociability during protracted withdrawal and highlight their potential as a mechanistic target to alleviate negative affective behaviors associated with opioid withdrawal.

Haploinsufficiency of the Parkinson's disease gene synaptojanin1 is associated with abnormal responses to psychomotor stimulants and mesolimbic dopamine signaling.

The synaptojanin-1 (SYNJ1) gene is known to be important for dopamine-related disorders. Recent evidence has demonstrated that Synj1 deficient mice (Synj1 +/-) have impairments in dopaminergic synaptic vesicular recycling. However, less is known about how Synj1 deficits affect the mesolimbic system, reward processing, and motivated behavior. To examine the role of the Synj1 gene in motivated behavior, we subjected male and female Synj1 +/- and Synj1 +/+ mice to a battery of behavioral tests evaluating hedonic responses, effortful responding, and responses to psychomotor stimulants. We observed that Synj1 +/- mice exhibit few differences in reward processing and motivated behavior, with normal hedonic responses and motivated responding for sucrose. However, male but not female Synj1 +/- demonstrated an attenuated conditioned place preference for cocaine that could not be attributed to deficits in spatial memory. To further understand the dopamine signaling underlying the attenuated response to cocaine in these mutant mice, we recorded nucleus accumbens dopamine in response to cocaine and observed that Synj1 +/- male and female mice took longer to reach peak dopamine release following experimenter-administered cocaine. However, female mice also showed slower decay in accumbens dopamine that appear to be linked to differences in cocaine-induced DAT responses. These findings demonstrate that SYNJ1 deficiencies result in abnormal mesolimbic DA signaling which has not previously been demonstrated. Our work also highlights the need to develop targeted therapeutics capable of restoring deficits in DAT function, which may be effective for reversing the pathologies associated with Synj1 mutations.

CREB-Binding Protein Regulates Cocaine- and Amphetamine-Regulated Transcript Peptide Expression in the Lateral Hypothalamus: Implication in Reward and Reinforcement.

Neuropeptide cocaine- and amphetamine-regulated transcript peptide (CARTp) is known to play an important role in reward processing. The rats conditioned to intra-cranial self-stimulation (ICSS) showed massive upregulation of CART protein and mRNA in the vicinity of the electrode implanted to deliver the electric current directly at the lateral hypothalamus (LH)-medial forebrain bundle (MFB) area. However, the underlying mechanisms leading to the upregulation of CART in ICSS animals remain elusive. We tested the putative role of CREB-binding protein (CBP), an epigenetic enzyme with intrinsic histone acetyltransferase (HAT) activity, in regulating CART expression during ICSS. An electrode was implanted in LH-MFB and the rats were conditioned to self-stimulation in an operant chamber. CBP siRNA was delivered ipsilaterally in the LH-MFB to knock-down CBP and the effects on lever press activity were monitored. While ICSS-conditioned rats showed distinct increase in CART, CBP and pCREB levels, enhanced CBP binding and histone acetylation (H3K9ac) were noticed on the CART promoter in chromatin immunoprecipitation assay. Direct infusion of CBP siRNA in the LH-MFB lowered lever press activity, CBP levels, histone acetylation at the CART promoter, and CART mRNA and peptide expression. Co-infusion of CARTp in LH-MFB rescued the waning effects of CBP siRNA on self-stimulation. We suggest that CBP-mediated histone acetylation may play a causal role in CART expression in LH, which in turn may drive the positive reinforcement of lever press activity.

Influence of reinforcement learning on the inhibitory control of Internet gaming disorder.

Reward processing dysfunction and inhibition control deficiency have been observed in Internet gaming disorder (IGD). However, it is still unclear whether the previous reinforcement learning depends on reward/punishment feedback influences on the cognitive inhibitory control of IGD. This study compared the differences between an IGD group and healthy people without game experiences in the probability selection task and the subsequent stop signal task by the method of behavioral experiments, in order to explore whether the reward learning ability is impaired in the IGD group. We also discuss the influence of previous reward learning on subsequent inhibition control. The results showed that (1) during the reward learning phase, the IGD group's accuracy was significantly lower than that of the control group; (2) compared with the control group, the IGD group's reaction times were longer in the transfer phase; (3) for no-go trials of the inhibitory control phase after reward learning, the accuracy of the reward-related stimulation in the IGD group was lower than that of punishment-related or neutral stimulation, but there was no significant difference among the three conditions in the control group. These findings indicated that the reinforcement learning ability of the IGD group was impaired, which further caused the abnormal response to reinforcement stimuli.

Des-acyl ghrelin reduces alcohol intake and alcohol-induced reward in rodents

The mechanisms contributing to alcohol use disorder (AUD) are complex and the orexigenic peptide ghrelin, which enhances alcohol reward, is implied as a crucial modulator. The major proportion of circulating ghrelin is however the non-octanoylated form of ghrelin, des-acyl ghrelin (DAG), whose role in reward processes is unknown. As recent studies show that DAG decreases food intake, we hypothesize that DAG attenuates alcohol-related responses in animal models. Acute and repeated DAG treatment dose-dependently decreased alcohol drinking in male and female rats. In these alcohol-consuming male rats, repeated DAG treatment causes higher levels of dopamine metabolites in the ventral tegmental area, an area central to reward processing. The role of DAG in reward processing is further supported as DAG prevents alcohol-induced locomotor stimulation, reward in the conditioned place preference paradigm, and dopamine release in the nucleus accumbens in male rodents. On the contrary, DAG does not alter the memory of alcohol reward or affect neurotransmission in the hippocampus, an area central to memory. Further, circulating DAG levels are positively correlated with alcohol drinking in female but not male rats. Studies were conducted in attempts to identify tentative targets of DAG, which currently are unknown. Data from these recombinant cell system revealed that DAG does not bind to either of the monoamine transporters, 5HT2A, CB1, or µ-opioid receptors. Collectively, our data show that DAG attenuates alcohol-related responses in rodents, an effect opposite to that of ghrelin, and contributes towards a deeper insight into behaviors regulated by the ghrelinergic signaling pathway.

Linking social reward responsiveness and affective responses to the social environment: An ecological momentary assessment study.

Social support is a key predictor of well-being, but not everyone experiences mental health benefits from receiving it. However, given that a growing number of interventions are based on social support, it is crucial to identify the features that make individuals more likely to benefit from social ties. Emerging evidence suggests that neural responses to positive social feedback (i.e., social reward) might relate to individual differences in social functioning, but potential mechanisms linking these neural responses to psychological outcomes are yet unclear. This study examined whether neural correlates of social reward processing, indexed by the reward positivity (RewP), relate to individuals' affective experience following self-reported real-world positive social support events. To this aim, 193 university students (71% females) underwent an EEG assessment during the Island Getaway task and completed a 10-day ecological momentary assessment where participants reported their positive and negative affects (PA, NA) nine times a day and the count of daily positive and negative events. Experiencing a higher number of social support positive events was associated with higher PA. The RewP moderated this association, such that individuals with greater neural response to social feedback at baseline had a stronger positive association between social support positive events count and PA. Individual differences in the RewP to social feedback might be one indicator of the likelihood of experiencing positive affect when receiving social support.

Dopamine Release Dynamics in the Nucleus Accumbens Are Modulated by the Timing of Electrical Stimulation Pulses When Applied to the Medial Forebrain Bundle and Medial Prefrontal Cortex.

Electrical brain stimulation has been used in vivo and in vitro to investigate neural circuitry. Historically, stimulation parameters such as amplitude, frequency, and pulse width were varied to investigate their effects on neurotransmitter release and behavior. These experiments have traditionally employed fixed-frequency stimulation patterns, but it has previously been found that neurons are more precisely tuned to variable input. Introducing variability into the interpulse interval of stimulation pulses will inform on how dopaminergic release can be modulated by variability in pulse timing. Here, dopaminergic release in rats is monitored in the nucleus accumbens (NAc), a key dopaminergic center which plays a role in learning and motivation, by fast-scan cyclic voltammetry. Dopaminergic release in the NAc could also be modulated by stimulation region due to differences in connectivity. We targeted two regions for stimulation─the medial forebrain bundle (MFB) and the medial prefrontal cortex (mPFC)─due to their involvement in reward processing and projections to the NAc. Our goal is to investigate how variable interpulse interval stimulation patterns delivered to these regions affect the time course of dopamine release in the NAc. We found that stimulating the MFB with these variable stimulation patterns saw a highly responsive, frequency-driven dopaminergic response. In contrast, variable stimulation patterns applied to the mPFC were not as sensitive to the variable frequency changes. This work will help inform on how stimulation patterns can be tuned specifically to the stimulation region to improve the efficiency of electrical stimulation and control dopamine release.

From anticipation to action: A RCT on mental imagery exercises in daily life as a motivational amplifier for individuals with depressive symptoms.

Encouraging engagement in rewarding or pleasant activities is one of the most important treatment goals for depression. Mental imagery exercises have been shown to increase the motivation for planned behaviour in the lab but it is unclear whether this is also the case in daily life. Therefore, we aimed to investigate the effect of mental imagery exercises on motivation and behaviour in daily life. Participants with depressive symptoms (N = 59) were randomly assigned to a group receiving mental imagery (MI) exercises or a control group receiving relaxation (RE) exercises via study phones. We employed an experience sampling design with 10 assessments per day for 10days (three days baseline, four days with two exercises per day and three days post-intervention). Data was analysed using t-tests and multilevel linear regression analyses. As predicted, MI exercises enhanced motivation and reward anticipation during the intervention phase compared to RE. However, MI did not enhance active behaviour or strengthen the temporal association from reward anticipation (t-1) to active behaviour (t). Mental imagery exercises can act as a motivational amplifier but its effects on behaviour and real-life reward processes remain to be elucidated.

Cellular and circuit architecture of the lateral septum for reward processing

The lateral septum (LS) is composed of heterogeneous cell types that are important for various motivated behaviors. However, the transcriptional profiles, spatial arrangement, function, and connectivity of these cell types have not been systematically studied. Using single-nucleus RNA sequencing, we delineated diverse genetically defined cell types in the LS that play distinct roles in reward processing. Notably, we found that estrogen receptor 1 (Esr1)-expressing neurons in the ventral LS (LSEsr1) are key drivers of reward seeking via projections to the ventral tegmental area, and these neurons play an essential role in methamphetamine (METH) reward and METH-seeking behavior. Extended exposure to METH increases the excitability of LSEsr1 neurons by upregulating hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, thereby contributing to METH-induced locomotor sensitization. These insights not only elucidate the intricate molecular, circuit, and functional architecture of the septal region in reward processing but also reveal a neural pathway critical for METH reward and behavioral sensitization.

Behavioral Activation and Brain Network Changes in Depression.

Behavioral activation (BA) is a well-established method of evidence-based treatment for depression. There are clear links between the neural mechanisms underlying reward processing and BA treatment for depressive symptoms, including anhedonia; however, integrated interpretations of these two domains are lacking. Here we examine brain imaging studies involving BA treatments to investigate how changes in brain networks, including the reward networks, mediate the therapeutic effects of BA, and whether brain circuits are predictors of BA treatment responses. Increased activation of the prefrontal and subcortical regions associated with reward processing has been reported after BA treatment. Activation of these regions improves anhedonia. Conversely, some studies have found decreased activation of prefrontal regions after BA treatment in response to cognitive control stimuli in sad contexts, which indicates that the therapeutic mechanism of BA may involve disengagement from negative or sad contexts. Furthermore, the decrease in resting-state functional connectivity of the default-mode network after BA treatment appears to facilitate the ability to counteract depressive rumination, thereby promoting enjoyable and valuable activities. Conflicting results suggest that an intact neural response to rewards or defective reward functioning is predictive of the efficacy of BA treatments. Increasing the benefits of BA treatments requires identification of the unique individual characteristics determining which of these conflicting findings are relevant for the personalized treatment of each individual with depression.

Lack of Bmal1 leads to changes in rhythmicity and impairs motivation towards natural stimuli.

Maintaining proper circadian rhythms is essential for coordinating biological functions in mammals. This study investigates the effects of daily arrhythmicity using Bmal1-knockout (KO) mice as a model, aiming to understand behavioural and motivational implications. By employing a new mathematical analysis based on entropy divergence, we identified disrupted intricate activity patterns in mice derived by the complete absence of BMAL1 and quantified the difference regarding the activity oscillation's complexity. Changes in locomotor activity coincided with disturbances in circadian gene expression patterns. Additionally, we found a dysregulated gene expression profile particularly in brain nuclei like the ventral striatum, impacting genes related to reward and motivation. Further investigation revealed that arrhythmic mice exhibited heightened motivation for food and water rewards, indicating a link between circadian disruptions and the reward system. This research sheds light on how circadian clock alterations impact the gene expression regulating the reward system and how this, in turn, can lead to altered seeking behaviour and motivation for natural rewards. In summary, the present study contributes to our understanding of how reward processing is under the regulation of circadian clock machinery.

System-level Probabilistic Remaining Useful Life Prognostics and Predictive Inspection Planning for Wind Turbines

Wind energy plays a crucial role in the energy transition. However, it is often seen as an unreliable source of energy, with many production peaks and lows. Some of the drivers of uncertainty in energy production are the unexpected wind turbine (WT) failures and associated unscheduled maintenance. To support an effective health management and maintenance planning of WTs, we propose an integrated data-driven framework for Remaining Useful Life (RUL) prognostics and inspection planning of WTs. We propose a Long-short term memory (LSTM) neural network with Monte Carlo dropout to estimate the distribution of the RUL of WTs, i.e. we develop probabilistic prognostics. Different from existing studies focused on prognostics for single components, we consider the simultaneous health-monitoring of multiple components of the WTs, thus seeing the turbine as an integrated system. The obtained prognostics are further included into a stochastic planning model which determines optimal moments for inspections. For this, we pose the problem of WT inspections as a renewal reward process. We illustrate our framework for four offshore WTs which are continuously monitored by Supervisory Control and Data Acquisition (SCADA) systems. The results show that LSTMs are able to estimate well the RUL of the WTs, even in the early phase of their usage. We also show that the prognostics are informative for maintenance planning and are conducive to conservative inspections.

Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats.

Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression. In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests. Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients. No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies. While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa.

The Use of Ketamine for the Treatment of Anhedonia in Depression.

Anhedonia, a complex symptom rooted in deficits across reward processes, is primarily linked to depression and schizophrenia but transcends diagnostic boundaries across various mental disorders. Its presence correlates with poorer clinical outcomes, including an increased risk of suicide and diminished response to treatment. The neurobiological underpinnings of anhedonia remain incompletely understood despite advancements in biomarkers and imaging that contribute to deeper insights. Ketamine, known for its rapid-acting antidepressant properties, appears to possess antianhedonic effects through a mechanism of action not fully elucidated. This effect appears to be independent of its antidepressant properties. Explorations into alternative antianhedonic treatments have been underway, yet lingering questions persist, underscoring the imperative need for ongoing research to advance the field.