Reward-related Processes Research Articles

The Angiotensin Antagonist Losartan Modulates Social Reward Motivation and Punishment Sensitivity via Modulating Midbrain-Striato-Frontal Circuits.

Social deficits and dysregulations in dopaminergic midbrain-striato-frontal circuits represent transdiagnostic symptoms across psychiatric disorders. Animal models suggest that interactions between the dopamine (DA) and renin-angiotensin system (RAS) may modulate learning and reward-related processes. The present study therefore examined the behavioral and neural effects of the Angiotensin II type 1 receptor (AT1R) antagonist losartan on social reward and punishment processing in humans. A preregistered randomized double-blind placebo-controlled between-subject pharmacological design was combined with a social incentive delay (SID) functional MRI (fMRI) paradigm during which subjects could avoid social punishment or gain social reward. Healthy volunteers received a single-dose of losartan (50 mg, n = 43, female = 17) or placebo (n = 44, female = 20). We evaluated reaction times (RTs) and emotional ratings as behavioral and activation and functional connectivity as neural outcomes. Relative to placebo, losartan modulated the reaction time and arousal differences between social punishment and social reward. On the neural level the losartan-enhanced motivational salience of social rewards was accompanied by stronger ventral striatum-prefrontal connectivity during reward anticipation. Losartan increased the reward-neutral difference in the ventral tegmental area (VTA) and attenuated VTA associated connectivity with the bilateral insula in response to punishment during the outcome phase. Thus, losartan modulated approach-avoidance motivation and emotional salience during social punishment versus social reward via modulating distinct core nodes of the midbrain-striato-frontal circuits. The findings document a modulatory role of the renin-angiotensin system in these circuits and associated social processes, suggesting a promising treatment target to alleviate social dysregulations.SIGNIFICANCE STATEMENT Social deficits and anhedonia characterize several mental disorders and have been linked to the midbrain-striato-frontal circuits of the brain. Based on initial findings from animal models we here combine the pharmacological blockade of the Angiotensin II type 1 receptor (AT1R) via losartan with functional MRI (fMRI) to demonstrate that AT1R blockade enhances the motivational salience of social rewards and attenuates the negative impact of social punishment via modulating the communication in the midbrain-striato-frontal circuits in humans. The findings demonstrate for the first time an important role of the AT1R in social reward processing in humans and render the AT1R as promising novel treatment target for social and motivational deficits in mental disorders.

Hypothalamic interaction with reward-related regions during subjective evaluation of foods

The reward system implemented in the midbrain, ventral striatum, orbitofrontal cortex, and ventromedial prefrontal cortex evaluates and compares various types of rewards given to the organisms. It has been suggested that autonomic factors influence reward-related processing via the hypothalamus, but how the hypothalamus modulates the reward system remains elusive. In this functional magnetic resonance imaging study, the hypothalamus was parcellated into individual hypothalamic nuclei performing different autonomic functions using boundary mapping parcellation analyses. The effective interaction during subjective evaluation of foods in a reward task was then investigated between the human hypothalamic nuclei and the reward-related regions. We found significant brain activity decrease in the paraventricular nucleus (PVH) and lateral nucleus in the hypothalamus in food evaluation compared with monetary evaluation. A psychophysiological interaction analysis revealed dual interactions between the PVH and (1) midbrain region and (2) ventromedial prefrontal cortex, with the former correlated with the stronger tendency of participants toward food-seeking. A dynamic causal modeling analysis further revealed unidirectional interactions from the PVH to the midbrain and ventromedial prefrontal cortex. These results suggest that the PVH in the human hypothalamus interacts with the reward-related regions in the cerebral cortex via multiple pathways (i.e., the midbrain pathway and ventromedial prefrontal pathway) to evaluate rewards for subsequent decision-making.

Dimensions of childhood maltreatment and adult risky behaviors: Differential affective and inhibitory control mechanisms

BackgroundWhile childhood maltreatment has been identified as a robust risk factor for a myriad of poor outcomes, significant gaps in our understanding still remain regarding mechanisms of this risk transmission across the lifespan. ObjectiveInformed by recent dimensional models, the objective of this study was to examine how unique dimensions of childhood maltreatment relate to adult risky behaviors via interactions between cognitive control and affective processes across Positive and Negative Valence Systems. Participants and settingOur sample consisted of 110 community adults (M/SDage = 31.92/10.58 years old, 52.7 % male). MethodsParticipants completed a neuropsychological test of inhibitory control and self-report measures of childhood maltreatment, recent adult risky behaviors, and indices of affective processing. ResultsModerated-mediation analyses revealed that childhood experiences of neglect and abuse exhibited distinct mechanisms of risk transmission related to adult risky behaviors. Specifically, disruptions in inhibitory control and reward-related processes were linked to adult risky behavior in the context of Childhood Deprivation (95%CI = −0.166/−0.002), whereas negative affective processes were associated with adult risky behavior in the context of Childhood Threat (95 % CI = 0.015/0.157). ConclusionsFindings provide empirical support for novel dimensional theories of childhood maltreatment and suggest that distinct regulatory processes are impacted by these early life experiences, which may confer risk into adulthood.

Developing attention deficits/hyperactivity disorder-virtual reality diagnostic tool with machine learning for children and adolescents.

The traditional diagnosis of Attention Deficits/Hyperactivity Disorder (ADHD) is through parent-child interviews and observations; therefore, innovative ADHD diagnostic tools that represent this digital era are needed. Virtual reality (VR) is a significant technology that can present a virtual immersive environment; it can provide an illusion of participation in an artificial milieu for children with ADHD. This study aimed to develop an ADHD-VR diagnostic tool construct (Research Domain Construct/RDC) based on the DSM5 ADHD diagnostic criteria, and using the RDC to develop a diagnostic tool with a machine learning (ML) application that can produce an intelligent model to receive some complex and multifaceted clinical data (ADHD clinical symptoms). We aimed to expand a model algorithm from the data, and finally make predictions by providing new data (output data) that have more accurate diagnostic value. This was an exploratory qualitative study and consisted of two stages. The first stage of the study applied the Delphi technique, and the goal was to translate ADHD symptoms based on DSM 5 diagnostic criteria into concrete behavior that can be observed among children in a classroom setting. This stage aimed to gather information, perceptions, consensus, and confirmation from experts. In this study, three rounds of Delphi were conducted. The second stage was to finalize the RDC of the ADHD-VR diagnostic tool with ML, based on the first-stage results. The results were transformed into concrete activities that could be applied in the programming of the ADHD-VR diagnostic tool, followed by starting to input data that were required to build the diagnostic tool. The second stage consisted of more than ten focus-group discussions (FGDs) before it could be transformed into the ADHD-VR diagnostic tool with the ML prototype. First-stage data analysis was performed using Microsoft Excel for Mac. Qualitative data were analyzed using conceptual content analysis with a manifest/latent analysis approach. From the first stage of the study, there were 13 examples of student behaviors that received more than 75% totally agreed or agreed from the experts. The RDC of the ADHD-VR diagnostic tool with machine learning application consisted of three domains and was divided into six sub-domains: reward-related processing, emotional lability, inhibitory, sustained attention, specific timing of playing in order, and arousal. In conclusion, the results of this study can be used as a reference for future studies in a similar context and content, that is, the ADHD-VR diagnostic tool with machine learning based on the constructed RDC.

Neural encoding of food and monetary reward delivery

Different types of rewards such as food and money can similarly drive our behavior owing to shared brain processes encoding their subjective value. However, while the value of money is abstract and needs to be learned, the value of food is rooted in the innate processing of sensory properties and nutritional utilization. Yet, the actual consumption of food and the receipt of money have never been directly contrasted in the same experiment, questioning what unique neural processes differentiate those reward types. To fill this gap, we examined the distinct and common neural responses to the delivery of food and monetary rewards during fMRI.In a novel experimental approach, we parametrically manipulated the subjective value of food and monetary rewards by modulating the quantities of administered palatable milkshake and monetary gains. The receipt of increasing amounts of milkshake and money recruited the ventral striatum and the ventromedial prefrontal cortex, previously associated with value encoding. Notably, the consumption and the subsequent evaluation of increasing quantities of milkshake relative to money revealed an extended recruitment of brain regions related to taste, somatosensory processing, and salience. Moreover, we detected a decline of reward encoding in the ventral tegmental area, nucleus accumbens, and vmPFC, indicating that these regions may be susceptible to time-dependent effects upon accumulation of food and money rewards.Relative to monetary gains, the consumption and evaluation of palatable milkshakes engaged complex neural processing over and above value tracking, emphasizing the critical contribution of taste and other sensory properties to the processing of food rewards. Furthermore, our results highlight the need to closely monitor metabolic states and neural responses to the accumulation of rewards to pinpoint the mechanisms underlying time-dependent dynamics of reward-related processing.

Selenium deficiency is associated with disease severity, disrupted reward processing, and increased suicide risk in patients with Anorexia Nervosa

Background & AimsPatients with Anorexia Nervosa (AN) present many nutritional deficiencies (macro- and often also micro-nutrients), possibly explained by their inadequate food intake. Previous studies reported that selenium (Se) deficiency is common in the general population. As Se can be easily added as a supplement, the goal of this study was to evaluate the clinical impact of Se deficiency in patients with AN. MethodsThis cross-sectional study concerned 153 patients with AN (92.9% women) followed at the Eating Disorder Unit of Lapeyronie Academic Hospital, Montpellier, France. Patients underwent an extensive neuropsychological assessment, and completed validated questionnaires. Blood samples were collected for Se quantification. Results were compared with the t-test, Mann-Whitney U, and Chi square tests, and univariate linear and multivariate logistic regression models. ResultsSe plasma levels were below the cut-off of 80 µg/L in 53.6% (N = 82) of patients. AN onset was earlier in patients with Se deficiency, (p = .005), whereas disease duration was comparable between groups (p = .77). General eating disorder symptomatology in the past 28 days (Eating Disorder Examination Questionnaire) was more severe in patients with Se deficiency (p = .010). The suicide risk (MINI International Neuropsychiatric Evaluation) tended to be higher (p = .037), and suicide attempt history was more frequent (28.39% vs 9.85%, p = .004) in patients with low Se levels. Se plasma concentration was negatively correlated with the performance in the temporal delayed discounting task (p = .006). ConclusionsOur findings suggest that in patients with AN, Se plasma concentration might be implicated in disease severity and suicide risk. The finding that Se deficiency in patients with AN was associated only with reward-related processes, but not with other psychological functions suggests the selective involvement of dopamine-related pathways. Our results suggest that it might be useful to monitor the plasma micronutrient profile in patients with AN. Future studies should determine whether Se supplementation in AN might improve clinical outcomes.

A bias toward the unknown: individual and environmental factors influencing exploratory behavior.

With limited resources, exploring new opportunities is crucial for survival. Exploring novel options, however, comes at the cost of uncertainty. Therefore, there is a trade‐off between exploiting options with a known beneficial outcome and exploring novel options with a potentially higher gain. Computational models have suggested that novelty may promote exploratory behavior by inducing a so‐called novelty bonus through reward‐related processes. So far, few studies have provided behavioral evidence for such a novelty bonus. In this study, we aimed to investigate whether spatial novelty can stimulate exploratory behavior (Experiment 1), and whether age, novelty‐seeking, and reduced action radius or social interactions due to COVID‐19 restrictions influenced the exploration–exploitation trade‐off (Experiment 2). In both experiments, we employed a novel paradigm in which participants made binary decisions between food items, while on rare trials, a surprise option was presented. Results from Experiment 1 are in line with a novelty bonus, with spatial novelty promoting exploratory behavior. In Experiment 2, we found that exploratory behavior declined with age, high novelty seekers made more exploratory choices than low novelty seekers, and participants with a smaller action radius made fewer exploratory choices. These findings are consistent with previous findings in animals and predictions from computational models.

Neurons in the Monkey's Subthalamic Nucleus Differentially Encode Motivation and Effort.

The understanding of the electrophysiological properties of the subthalamic nucleus (STN) neurons is crucial since it represents the main target of deep brain stimulation for the treatment of Parkinson's disease and obsessive-compulsive disorders. The study of its nonmotor properties could shed light on the cognitive and motivational alterations possibly encountered after stimulation. In this study, we recorded the activity of STN neurons in two male behaving monkeys (Macaca mulatta) while they performed a visuomotor motivational task in which visual cues indicated which amount of force was required to obtain which amount of reward. Our results evidenced force- and reward-modulated neurons. After the occurrence of the visual stimuli, the force-modulated neurons mainly fired when a high effort was required. Differently, the activity of the population of reward-modulated neurons encoded the motivational value of the stimuli. This population consisted of neurons increasing or decreasing their activity according to the motivational ranking of the task conditions. Both populations could play complementary roles, one in the implementation of the difficulty of the action and the other in enhancing or slowing its execution based on the subjective value of each condition.SIGNIFICANCE STATEMENT An increasing number of studies confers a role to the subthalamic nucleus (STN) in motivational and reward-related processes. However, the electrophysiological bases of such properties at the neuronal level remain unclear. The present study investigated the modulation of STN neuronal activity in monkeys performing a motivational task in which the force to produce and the reward obtained were manipulated. We found two main populations of neurons, one modulated by the effort required and the other integrating the motivational subjective value of the stimuli. This last population could help at improving decision-making to act or not, depending on the subjective value set by the motivational context. This highlights the pivotal role of STN in the valuation of cost/benefit for decision-making processes.

Pregestational oxycodone exposure does not impact future maternal care or drug preference in the postpartum mouse.

Females are uniquely sensitive to drugs of abuse at specific points in their reproductive cycle. Females' endogenous opioid system contributes to both reward-related processes and maternally relevant physiological functions, yet less is known about how adolescent opioid exposure impacts females' future behavior, ranging from parental caregiving to opioid preference. The present study explores 2 questions: (a) are there sex differences in response to adolescent oxycodone exposure, spontaneous withdrawal, and oxycodone preference in adulthood, and (b) to what extent does this pregestational opioid exposure alter females' future maternal caregiving behavior? Female and male mice received 12d of oxycodone or saline injections during mid/late adolescence, and drug was then withheld. Some females were then mated and experienced a drug-free pregnancy. Following parturition, females' maternal behavior and motivation were assessed. All mice then underwent a place conditioning procedure to assess the incentive value of oxycodone during adulthood. Mice displayed similar behavioral responses to oxycodone (e.g., sensitization) and patterns of withdrawal behaviors, independent of sex. Mice showed strong group preferences for the oxycodone-paired chamber, and the strength of these preferences did not differ by sex or maternal status. Postpartum females' maternal behavior and motivation were also similar despite adolescent drug history. Together, results did not suggest overt sex differences in response to adolescent oxycodone exposure and that, in females, a range of motivated behaviors may be relatively resilient to such perturbations during adolescence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neural Processing Dysfunctions During Fear Learning but Not Reward-Related Processing Characterize Depressed Individuals With High Levels of Repetitive Negative Thinking

BackgroundRepetitive negative thinking (RNT) is a symptom dimension of depression that is associated with a poorer prognosis in terms of higher recurrence, treatment resistance, residual symptoms, and disability. This investigation examined whether RNT is associated with aberrant reward processing and fear learning. MethodsVery high RNT (VH-RNT) (n = 60) and high RNT (H-RNT) (n = 60) propensity-matched individuals with depression (age, sex, race/ethnicity, income/employment, body mass index, depressive and anxiety symptom severity) participated in this study along with matched healthy comparison volunteers (n = 30). This propensity-matched sample was selected from the larger Tulsa 1000 study. Participants performed two functional magnetic resonance imaging tasks: the monetary incentive delay task probing reward processing and the fear conditioning task probing aversive learning and extinction. ResultsBoth VH-RNT and H-RNT groups showed lower neural activity than healthy comparison subjects in reward circuitry, including the inferior frontal gyrus (VH-RNT: β = −1.24, H-RNT: β = −1.28) and the cerebellum (VH-RNT: β = −0.93, H-RNT: β = −1.14). However, individuals with VH-RNT exhibited lower activation than those with H-RNT in central autonomic network components during fear conditioning (β = −0.84) and continued conditioned responses during early extinction in the postcentral cortex (β = 0.71). ConclusionsVH-RNT showed aberrant processing in fear conditioning during both learning and extinction phases compared with H-RNT. These findings demonstrate that dysfunctions of negative valence associated with RNT may be domain specific, which should be taken into account for identifying potential specific targets of intervention.

Decreased reward circuit connectivity during reward anticipation in major depression

An important symptom of major depressive disorder (MDD) is the inability to experience pleasure, possibly due to a dysfunction of the reward system. Despite promising insights regarding impaired reward-related processing in MDD, circuit-level abnormalities remain largely unexplored. Furthermore, whereas studies contrasting experimental conditions from incentive tasks have revealed important information about reward processing, temporal difference modeling of reward-related prediction error (PE) signals might give a more accurate representation of the reward system. We used a monetary incentive delay task during functional MRI scanning to explore PE-related striatal and ventral tegmental area (VTA) activation in response to anticipation and delivery of monetary rewards in 24 individuals with MDD versus 24 healthy controls (HCs). Furthermore, we investigated group differences in temporal difference related connectivity with a generalized psychophysiological interaction (gPPI) analysis with the VTA, ventral striatum (VS) and dorsal striatum (DS) as seeds during reward versus neutral, both in anticipation and delivery. Relative to HCs, MDD patients displayed a trend-level (p = 0.052) decrease in temporal difference-related activation in the VS during reward anticipation and delivery combined. Moreover, gPPI analyses revealed that during reward anticipation, MDD patients exhibited decreased functional connectivity between the VS and anterior cingulate cortex / medial prefrontal cortex, anterior cingulate gyrus, angular/middle orbital gyrus, left insula, superior/middle frontal gyrus (SFG/MFG) and precuneus/superior occipital gyrus/cerebellum compared to HC. Moreover, MDD patients showed decreased functional connectivity between the VTA and left insula compared to HC during reward anticipation. Exploratory analysis separating medication free patients from patients using antidepressant revealed that these decreased functional connectivity patterns were mainly apparent in the MDD group that used antidepressants. These results suggest that MDD is characterized by alterations in reward circuit connectivity rather than isolated activation impairments. These findings represent an important extension of the existing literature since improved understanding of neural pathways underlying depression-related reward dysfunctions, may help currently unmet diagnostic and therapeutic efforts.

Changes in temporal discounting, hedonic hunger, and food addiction during recovery from substance misuse

Substance use disorders (SUDs) and obesity are both chronic, relapsing, remitting disorders that arise from a heightened preference for immediate-focused rewards (i.e., steep temporal discounting). During recovery from SUDs, overweight and obese outcomes are common as individuals may replace drug rewards for food rewards. However, little has been done to investigate the neuropsychological processes underlying food reward and addiction in individuals recovering from SUDs. Using data collected from the International Quit and Recovery Registry and Amazon Mechanical Turk, we aimed to elucidate the factors that influence the attraction to palatable foods in a population in recovery from substance misuse (n = 114) as well as a population with no history of substance misuse (n = 97). We hypothesized that individuals in recovery from substance misuse would have steeper temporal discounting, an increased drive for palatable foods (i.e., hedonic hunger), and greater food addiction symptoms than non-substance users. Contrary to our hypotheses, we found that individuals in recovery from SUDs show improved outcomes in temporal discounting, hedonic hunger, and food addiction symptoms. Moreover, recovery status and temporal discounting significantly predicted these outcomes. Our findings suggest that the enhanced executive control processes needed for successful SUD recovery may transfer to other reward-related processes such as food reward and consumption. Interventions targeted at improving executive function including episodic future thinking, meditation, or exercise, may be excellent ways to support a successful recovery and improve other reward-related processes, including food consumption, to decrease the risk of overweight or obese outcomes during recovery.

Optogenetic stimulation of lateral hypothalamic orexin/dynorphin inputs in the ventral tegmental area potentiates mesolimbic dopamine neurotransmission and promotes reward-seeking behaviours

Reward and reinforcement processes are critical for survival and propagation of genes. While numerous brain systems underlie these processes, a cardinal role is ascribed to mesolimbic dopamine. However, ventral tegmental area (VTA) dopamine neurons receive complex innervation and various neuromodulatory factors, including input from lateral hypothalamic (LH) orexin/hypocretin neurons which also express and co-release the neuropeptide, dynorphin. Dynorphin in the VTA induces aversive conditioning through the Kappa opioid receptor (KOR) and decreases dopamine when administered intra-VTA. Exogenous application of orexin or orexin 1 receptor (oxR1) antagonists in the VTA bidirectionally modulates dopamine-driven motivation and reward-seeking behaviours, including the attribution of motivational value to primary rewards and associated conditioned stimuli. However, the effect of endogenous stimulation of LH orexin/dynorphin-containing projections to the VTA and the potential contribution of co-released dynorphin on mesolimbic dopamine and reward related processes remains uncharacterised. We combined optogenetic, electrochemical, and behavioural approaches to examine this. We found that optical stimulation of LH orexin/dynorphin inputs in the VTA potentiates mesolimbic dopamine neurotransmission in the nucleus accumbens (NAc) core, produces real time and conditioned place preference, and increases the food cue-directed orientation in a Pavlovian conditioning procedure. LH orexin/dynorphin potentiation of NAc dopamine release and real time place preference was blocked by an oxR1, but not KOR antagonist. Thus, rewarding effects associated with optical stimulation of LH orexin/dynorphin inputs in the VTA are predominantly driven by orexin rather than dynorphin.

Unique and Transdiagnostic Dimensions of Reward Functioning in Attention-Deficit/Hyperactivity Disorder and Alcohol Use Disorder Symptoms.

Contemporary theories of attention-deficit/hyperactivity disorder (ADHD) and alcohol use disorder (AUD) emphasize core dysfunctions in reward-related processes and behaviors as pathognomonic characteristics. However, to date, it is unclear which domains of reward functioning are unique to ADHD versus AUD symptom dimensions, and which represent underlying shared correlates. The current study employed secondary data analyses from a large community sample of emerging adults (N = 602; 57.3% female) and novel transdiagnostic modeling (i.e. bi-factor confirmatory factor analyses and structural equation modeling) of ADHD, AUD and shared symptom dimensions to identify unique and common reward-related dimensions: environmental suppressors, reward probability, hedonic capacity, proportionate substance-related reinforcement and delay discounting. The presence of environmental suppressors was the only reward-related construct that correlated with the underlying ADHD-AUD shared dimension. The AUD symptom dimension was uniquely associated with proportionate substance-related reinforcement, whereas the ADHD symptom dimension was uniquely associated with limited reward probability. No significant associations were found for delay discounting or hedonic capacity. These novel findings highlight specific aspects of reward-related functioning in ADHD, AUD and shared symptom dimensions. In so doing, this work meaningfully advances theoretical conceptualizations of these two commonly co-occurring presentations and suggests future directions for research on transdiagnostic correlates. Future longitudinal studies should include clinical samples with diagnoses of AUD and ADHD to further identify underlying correlates over time.

Mechanisms Underlying Motivational Dysfunction in Schizophrenia.

Negative symptoms are a debilitating feature of schizophrenia which are often resistant to pharmacological intervention. The mechanisms underlying them remain poorly understood, and diagnostic methods rely on phenotyping through validated questionnaires. Deeper endo-phenotyping is likely to be necessary in order to improve current understanding. In the last decade, valuable behavioural insights have been gained through the use of effort-based decision making (EBDM) tasks. These have highlighted impairments in reward-related processing in schizophrenia, particularly associated with negative symptom severity. Neuroimaging investigations have related these changes to dysfunction within specific brain networks including the ventral striatum (VS) and frontal brain regions. Here, we review the behavioural and neural evidence associated with negative symptoms, shedding light on potential underlying mechanisms and future therapeutic possibilities. Findings in the literature suggest that schizophrenia is characterised by impaired reward based learning and action selection, despite preserved hedonic responses. Associations between amotivation and reward-processing deficits have not always been clear, and may be mediated by factors including cognitive dysfunction or dysfunctional or self-defeatist beliefs. Successful endo-phenotyping of negative symptoms as a function of objective behavioural and neural measurements is crucial in advancing our understanding of this complex syndrome. Additionally, transdiagnostic research–leveraging findings from other brain disorders, including neurological ones–can shed valuable light on the possible common origins of motivation disorders across diseases and has important implications for future treatment development.

#3097 Temporal and spectral dynamics of reward and risk processing in the amygdala revealed with stereo-EEG recordings in epilepsy

Objectives/AimsTo examine the temporal and spectral characteristics of local field potentials recorded from the amygdala in epilepsy in the context of the anticipation and receipt of rewards and losses using an incentive learning task and a risky decision-making task.Methods16 Epilepsy patients completed two tasks. In the monetary incentive delay (MID) task, patients saw reward and loss cues which indicated whether money could be won or lost depending on whether a subsequent response was or was not quick/accurate enough, respectively. This was compared with neutral cues where responses were neither rewarded nor punished regardless of response.In the risk task, patients were presented with two face down cards with values ranging from 1 to 10. When the first card is revealed, patients have to choose whether to bet or not bet that the second card is higher. After the card is revealed, patients receive a monetary reward if it is higher and a loss if it is lower. If patients do not bet, they receive nothing.ResultsIn both tasks, patients showed larger left amygdala theta band oscillatory activity to the receipt of monetary rewards compared to no money. In contrast, there were no significant responses to monetary losses. During the decision phase of the risk task, there was increased theta activity when patients chose to bet instead of not betting and when the decision had low risk (card <= 5) compared to high risk (card above 5). There were no effects of uncertainty.ConclusionsThe combined results of these two studies embellish our understanding of the role of the amygdala in motivation and decision-making processes and lend further support for its role in reward related processes rather than its often cited fear-related functions (Baxter & Murray, 2002; Murray, 2007). Theta activation is linked to cognitive processes in frontal cortices and coupled to MTL activity (Helfrich & Knight, 2016). As left amygdala theta activation was only recruited when patients were making their bet and not just anticipating reward, the pattern of results lend support to its role in cognition-emotion interactions specific to risk and reward but not uncertainty. Indeed, the hemispheric asymmetry is highly consistent with EEG studies showing left prefrontal dominance in reward processing (Manssuer et al., 2021).

Developing and feasibility testing of the Indonesian computer-based game prototype for children with attention deficit/hyperactivity disorder

The aim of this study was to develop an Indonesian computer-based game prototype, including feasibility testing, targeted on attention deficit/hypersensitivity disorder (ADHD) clinical symptoms and executive function. The study comprised five steps. The first to third steps used an exploratory qualitative research design. The Delphi technique with FGD was applied to collect qualitative data. During the study, seven experts participated in ten FGDs. Feasibility testing was conducted as a one group pre- and post-test design that included ten children with drug-naïve ADHD without other mental or physical disorders. Feasibility data were collected before and after 20 training sessions with the Indonesian computer-based game prototype. The framework analysis was performed for qualitative data. Quantitative data were analyzed using the paired t-test, Pearson's correlation and Spearman's rank-order correlation. Outputs of the exploratory qualitative study were the Indonesian computer-based game prototype constructs and general agreements of the prototype,. The Indonesian computer-based game prototype construct comprised six components: reward-related processing, control inhibition, improved sustained attention, specific timing, increased arousal, and improved emotional regulation. After 20 sessions of training, several indicators decreased significantly, such as CATPRS-teacher rating (18.5 [5.31] vs. 12.9 [5.51], p = 0.047), BRIEF-GEC (64.80 [10.21] vs. 57.50 [7.51], p = 0.02), BRIEF-MI (66.1 [7.61] vs. 58.4 [7.56], p = 0.014), BRIEF-Initiate (66.6 [10.15] vs. 54.1 [6.49], p = 0.008), BRIEF-Working Memory (68.0 [6.89] vs. 60.9 [10.05], p = 0.02), and BRIEF-Organization of Material (60.7 [12.88] vs. 49.3 [11.79], p = 0.04). There was a low to moderate correlation between CATPRS-teacher and -parent rating and several BRIEF domains. Feasibility testing output also included the training procedure guideline. The present study indicated that the Indonesian computer-based game prototype could be used as a framework to develop a fixed computer-based game intervention for children with ADHD. However, further randomized controlled studies need to be conducted to show its effectiveness.

Reward-Related Neural Circuitry in Depressed and Anxious Adolescents: A Human Connectome Project

Although depression and anxiety often have distinct etiologies, they frequently co-occur in adolescence. Recent initiatives have underscored the importance of developing new ways of classifying mental illness based on underlying neural dimensions that cut across traditional diagnostic boundaries. Accordingly, the aim of the study was to clarify reward-related neural circuitry that may characterize depressed-anxious youth. The Boston Adolescent Neuroimaging of Depression and Anxiety Human Connectome Project tested group differences regarding subcortical volume and nucleus accumbens activation during an incentive processing task among 14- to 17-year-old adolescents presenting with a primary depressive and/or anxiety disorder (n= 129) or no lifetime history of mental disorders (n= 64). In addition, multimodal modeling examined predictors of depression and anxiety symptom change over a 6-month follow-up period. Our findings highlighted considerable convergence. Relative to healthy youth, depressed-anxious adolescents exhibited reduced nucleus accumbens volume and activation following reward receipt. These findings remained when removing all medicated participants (∼59% of depressed-anxious youth). Subgroup analyses comparing anxious-only, depressed-anxious, and healthy youth also were largely consistent. Multimodal modeling showed that only structural alterations predicted depressive symptoms over time. Multimodal findings highlight alterations within nucleus accumbens structure and function that characterize depressed-anxious adolescents. In the current hypothesis-driven analyses, however, only reduced nucleus accumbens volume predicted depressive symptoms over time. An important next step will be to clarify why structural alterations have an impact on reward-related processes and associated symptoms.

Toward a holistic view of value and social processing in the amygdala: Insights from primate behavioral neurophysiology

Located medially within the temporal lobes, the amygdala is a formation of heterogenous nuclei that has emerged as a target for investigations into the neural bases of both primitive and complex behaviors. Although modern neuroscience has eschewed the practice of assigning broad functions to distinct brain regions, the amygdala has classically been associated with regulating negative emotional processes (such as fear or aggression), primarily through research performed in rodent models. Contemporary studies, particularly those in non-human primate models, have provided evidence for a role of the amygdala in other aspects of cognition such as valuation of stimuli or shaping social behaviors. Consequently, many modern perspectives now also emphasize the amygdala’s role in processing positive affect and social behaviors. Importantly, several recent experiments have examined the intersection of two seemingly autonomous domains; how both valence/value and social stimuli are simultaneously represented in the amygdala. Results from these studies suggest that there is an overlap between valence/value processing and the processing of social behaviors at the level of single neurons. These findings have prompted researchers investigating the neurophysiological mechanisms underlying social interactions to question what contributions reward-related processes in the amygdala make in shaping social behaviors. In this review, we will examine evidence, primarily from primate neurophysiology, suggesting that value-related processes in the amygdala interact with the processing of social stimuli, and explore holistic hypotheses about how these amygdalar interactions might be instantiated.

An Empirically Derived Three-Domain Model of Binge Eating Behavior

Several factors, identified in various psychological models and theories, have been linked to binge-eating (BE) behaviors. Though commonalities exist between these theories, the main functional domains that contribute to the development and maintenance of these behaviors remain unclear. Here, we applied a data-driven dimension reduction approach to a broad community sample to develop an empirically based model of BE behaviors. We hypothesized that impairments in BE behavior are related to three broad functional domains shown to underlie addictive and impulsive behavior: 1) reward-related processing, 2) negative emotionality and 3) cognitive control.