Reward, relief, and habit drinking profiles in treatment seeking individuals with an AUD.

AIMS: This study aimed to compare reward, relief, and habit treatment-seeking individuals on recent drinking, alcohol use disorder (AUD) phenomenology, and mood. The second aim of the study was to evaluate the predictive validity of reward, relief, and habit profiles. METHOD: Treatment-seeking individuals with an AUD (n = 169) were recruited to participate in a medication trial for AUD (NCT03594435). Reward, relief, and habit drinking groups were assessed using the UCLA Reward Relief Habit Drinking Scale. Group differences at baseline were evaluated using univariate analyses of variance. A subset of participants were enrolled in a 12-week, double-blind, placebo-controlled medication trial (n = 102), and provided longitudinal drinking and phenomenology data. The predictive validity of group membership was assessed using linear regression analyses. RESULTS: At baseline, individuals who drink primarily for relief had higher craving and negative mood than those who drink for reward and habit. Prospectively, membership in the relief drinking group predicted greater alcohol use, greater heavy drinking, and fewer days abstinent compared to those in the reward drinking group. Membership in the relief drinking group also predicted greater alcohol craving, more alcohol-related consequences, and more anxiety symptoms over 12 weeks compared to those in the reward drinking group. CONCLUSIONS: This study provides support for reward and relief drinking motive profiles in treatment-seeking individuals with an AUD. Membership in the relief drinking motive group was predictive of poorer drinking outcomes and more negative symptomology over 12 weeks, indicating that individuals who drink for relief may be a particularly vulnerable sub-population of individuals with AUD.

Effort-reward imbalance and sleep quality in railway locomotive stewards: a cross-sectional study.

OBJECTIVE: To assess the correlation between the effort-reward imbalance (ERI) and sleep quality among railway locomotive stewards. DESIGN: Cross-sectional study. SETTING: Lanzhou Bureau Group, China Railway, between July and August 2022. PARTICIPANTS: Railway locomotive stewards. PRIMARY AND SECONDARY OUTCOME MEASURES: Sleep quality was assessed using the Pittsburgh Sleep Quality Index Scale (PSQI), categorising scores of >14 as poor, 8-14 as fair and <8 as good. RESULTS: A total of 5738 valid questionnaires (mean age of 30.85±6.91 years and 5730 males) were included. The response rate was 92.27%. The PSQI score was 11.52±3.95; 2304 (40.15%) respondents had good sleep quality, 1590 (27.71%) had fair sleep quality and 1844 (32.14%) had poor sleep quality. Stepwise multivariable logistic regression analysis showed that, compared with poor sleep quality, Jiayuguan Locomotive Depot workers (OR 0.775, 95% CI 0.587 to 0.971, p=0.028), electric locomotive drivers (OR 0.499, 95% CI 0.316 to 0.786, p=0.003), passenger train locomotive drivers (OR 0.209, 95% CI 1.313 to 3.337, p=0.002), working <40 hours weekly (OR 2.291, 95% CI 1.686 to 3.112, p<0.001), working 40-50 hours weekly (OR 1.602, 95% CI 1.299 to 1.977, p<0.001), senior titles (OR 0.727, 95% CI 0.570 to 0.928, p=0.010), high effort/low reward (OR 2.812, 95% CI 2.218 to 3.564, p<0.001) and low overcommitment (OR 5.848, 95% CI 4.710 to 7.261, p<0.001) were independently associated with fair sleep quality. Electric locomotive drivers (OR 0.535, 95% CI 0.364 to 0.787, p=0.001), diesel locomotive drivers (OR 0.567, 95% CI 0.348 to 0.924, p=0.023), passenger train locomotive drivers (OR 1.471, 95% CI 1.005 to 2.155, p=0.047), working <40 hours weekly (OR 1.549, 95% CI 1.196 to 2.006, p=0.001), working 40-50 hours weekly (OR 1.340, 95% CI 1.141 to 1.574, p<0.001), high school diploma or less (OR 1.448, 95% CI 1.062 to 1.975, p=0.019), high effort/low reward (OR 1.237, 95% CI 1.006 to 1.521, p=0.044), balanced effort-reward (OR 0.653, 95% CI 0.478 to 0.892, p=0.007) and low overcommitment (OR 2.553, 95% CI 2.224 to 2.931, p<0.001) were independently associated with good sleep quality. CONCLUSION: The results revealed an acceptable ERI and poor sleep quality among railway stewards. ERI was correlated with sleep quality. Health education, lifestyle changes and improved work schedules may help boost sleep quality and well-being among railway locomotive stewards.

Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD. METHODS: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task. RESULTS: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group. CONCLUSIONS: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology).

Pulling the lever in a hurry: the influence of impulsivity and sensitivity to reward on moral decision-making under time pressure.

BACKGROUND: Making timely moral decisions can save a life. However, literature on how moral decisions are made under time pressure reports conflicting results. Moreover, it is unclear whether and how moral choices under time pressure may be influenced by personality traits like impulsivity and sensitivity to reward and punishment. METHODS: To address these gaps, in this study we employed a moral dilemma task, manipulating decision time between participants: one group (N = 25) was subjected to time pressure (TP), with 8 s maximum time for response (including the reading time), the other (N = 28) was left free to take all the time to respond (noTP). We measured type of choice (utilitarian vs. non-utilitarian), decision times, self-reported unpleasantness and arousal during decision-making, and participants' impulsivity and BIS-BAS sensitivity. RESULTS: We found no group effect on the type of choice, suggesting that time pressure per se did not influence moral decisions. However, impulsivity affected the impact of time pressure, in that individuals with higher cognitive instability showed slower response times under no time constraint. In addition, higher sensitivity to reward predicted a higher proportion of utilitarian choices regardless of the time available for decision. CONCLUSIONS: Results are discussed within the dual-process theory of moral judgement, revealing that the impact of time pressure on moral decision-making might be more complex and multifaceted than expected, potentially interacting with a specific facet of attentional impulsivity.

Are cash incentives always king? A randomized controlled trial evaluating hedonic versus cash incentives (TEH-C).

Introduction: Physical inactivity is a risk factor for obesity and non-communicable diseases. Despite myriad health and non-health benefits resulting from physical activity (PA), most individuals do not meet PA recommendations. Providing an incentive for meeting activity goals may increase activity levels. Classical economists argue that cash is the best incentive. Behavioral economists have posited that hedonic (pleasurable) incentives (e.g., massages, restaurant meals) may be superior to cash when incentives are offered over multiple time periods. To date, no studies have directly compared the effectiveness of cash versus hedonic incentives in promoting PA across multiple time periods. Methods: We conducted a two-arm, parallel, 4-month randomized controlled trial with healthy adults in Singapore where participants were randomized to either cash or hedonic incentives. Participants could earn up to SGD50 (≈USD37) in cash or hedonic incentives each month they met the study's step target of 10,000 steps daily on at least 20/25 days out of the first 28 days of a month. The primary objective was to compare the mean proportion of months that participants met the step target between the two arms. Results: By month 4, participants in the cash (N = 154) and hedonic incentive (N = 156) arms increased their mean daily steps by 870 (p < 0.001) and 1,000 steps (p < 0.001), respectively. The mean proportion of months the step target was achieved was 90.53 and 88.34 for participants in the cash and hedonic incentive arms respectively, but differences across arms were small and not statistically significant for this or any outcome assessed. Conclusion: Our findings suggest that both cash and hedonic incentives are effective at promoting physical activity but that neither strategy is clearly superior.Clinical trial registration: ClinicalTrials.gov, NCT04618757 registered on November 6, 2020.

Functional diversity of dopamine axons in prefrontal cortex during classical conditioning.

Midbrain dopamine neurons impact neural processing in the prefrontal cortex (PFC) through mesocortical projections. However, the signals conveyed by dopamine projections to the PFC remain unclear, particularly at the single-axon level. Here, we investigated dopaminergic axonal activity in the medial PFC (mPFC) during reward and aversive processing. By optimizing microprism-mediated two-photon calcium imaging of dopamine axon terminals, we found diverse activity in dopamine axons responsive to both reward and aversive stimuli. Some axons exhibited a preference for reward, while others favored aversive stimuli, and there was a strong bias for the latter at the population level. Long-term longitudinal imaging revealed that the preference was maintained in reward- and aversive-preferring axons throughout classical conditioning in which rewarding and aversive stimuli were paired with preceding auditory cues. However, as mice learned to discriminate reward or aversive cues, a cue activity preference gradually developed only in aversive-preferring axons. We inferred the trial-by-trial cue discrimination based on machine learning using anticipatory licking or facial expressions, and found that successful discrimination was accompanied by sharper selectivity for the aversive cue in aversive-preferring axons. Our findings indicate that a group of mesocortical dopamine axons encodes aversive-related signals, which are modulated by both classical conditioning across days and trial-by-trial discrimination within a day.

Nucleus accumbens neuronal ensembles vary with cocaine reinforcement in male and female rats.

Neuronal ensembles in the medial prefrontal cortex mediate cocaine self-administration via projections to the nucleus accumbens. We have recently shown that neuronal ensembles in the prelimbic cortex form rapidly to mediate cocaine self-administration. However, the role of neuronal ensembles within the nucleus accumbens in initial cocaine-seeking behaviour remains unknown. Here, we sought to expand the current literature by testing the necessity of the cocaine self-administration ensemble in the nucleus accumbens core (NAcCore) 1 day after male and female rats acquire cocaine self-administration by using the Daun02 inactivation procedure. We found that disrupting the NAcCore ensembles after a no-cocaine reward-seeking test increased subsequent cocaine seeking, while disrupting NAcCore ensembles following a cocaine self-administration session decreased subsequent cocaine seeking. We then characterized neuronal cell type in the NAcCore using RNAscope in situ hybridization. In the no-cocaine session, we saw reduced dopamine D1 type neuronal activation, while in the cocaine self-administration session, we found preferential dopamine D1 type neuronal activity in the NAcCore.

A dopamine mechanism for reward maximization.

Individual survival and evolutionary selection require biological organisms to maximize reward. Economic choice theories define the necessary and sufficient conditions, and neuronal signals of decision variables provide mechanistic explanations. Reinforcement learning (RL) formalisms use predictions, actions, and policies to maximize reward. Midbrain dopamine neurons code reward prediction errors (RPE) of subjective reward value suitable for RL. Electrical and optogenetic self-stimulation experiments demonstrate that monkeys and rodents repeat behaviors that result in dopamine excitation. Dopamine excitations reflect positive RPEs that increase reward predictions via RL; against increasing predictions, obtaining similar dopamine RPE signals again requires better rewards than before. The positive RPEs drive predictions higher again and thus advance a recursive reward-RPE-prediction iteration toward better and better rewards. Agents also avoid dopamine inhibitions that lower reward prediction via RL, which allows smaller rewards than before to elicit positive dopamine RPE signals and resume the iteration toward better rewards. In this way, dopamine RPE signals serve a causal mechanism that attracts agents via RL to the best rewards. The mechanism improves daily life and benefits evolutionary selection but may also induce restlessness and greed.

Evidence for socially influenced and potentially actively coordinated cooperation by bumblebees.

Cooperation is common in animals, yet the specific mechanisms driving collaborative behaviour in different species remain unclear. We investigated the proximate mechanisms underlying the cooperative behaviour of bumblebees in two different tasks, where bees had to simultaneously push a block in an arena or a door at the end of a tunnel for access to reward. In both tasks, when their partner's entry into the arena/tunnel was delayed, bees took longer to first push the block/door compared with control bees that learned to push alone. In the tunnel task, just before gaining access to reward, bees were more likely to face towards their partner than expected by chance or compared with controls. These results show that bumblebees' cooperative behaviour is not simply a by-product of individual efforts but is socially influenced. We discuss how bees' turning behaviours, e.g. turning around before first reaching the door when their partner was delayed and turning back towards the door in response to seeing their partner heading towards the door, suggest the potential for active coordination. However, because these behaviours could also be interpreted as combined responses to social and secondary reinforcement cues, future studies are needed to help clarify whether bumblebees truly use active coordination.

Dogs understand the role of a human partner in a cooperative task.

Humans are exceptionally flexible in cooperation, partly due to our ability to recognize the roles of cooperative partners. While some non-human animals understand the need for a partner in such interactions, it is unclear whether they grasp the consequences of their partner's actions and adjust accordingly. Previous studies utilizing economic games with non-human animals yielded mixed results. We investigated dogs, known for their close cooperation with humans, in a stag hunt game. Dogs could cooperate for better rewards or defect for lower ones, while their human partners would either cooperate, never cooperate, or act randomly. We control for attraction to food, side bias, and local enhancement. Dogs were more likely to coordinate with their partners when it led to better rewards, suggesting that they understood their partner's actions. By highlighting this cognitive skill in dogs, we advance our knowledge of the intricate mechanisms driving cooperative behavior in non-human animals.

Physiological paradigm for assessing reward prediction and extinction using cortical direct current potential responses in rats.

Anticipating positive outcomes is a core cognitive function in the process of reward prediction. However, no neurophysiological method objectively assesses reward prediction in basic medical research. In the present study, we established a physiological paradigm using cortical direct current (DC) potential responses in rats to assess reward prediction. This paradigm consisted of five daily 1-h sessions with two tones, wherein the rewarded tone was followed by electrical stimulation of the medial forebrain bundle (MFB) scheduled at 1000 ms later, whereas the unrewarded tone was not. On day 1, both tones induced a negative DC shift immediately after auditory responses, persisting up to MFB stimulation. This negative shift progressively increased and peaked on day 4. Starting from day 3, the negative shift from 600 to 1000 ms was significantly larger following the rewarded tone than that following the unrewarded tone. This negative DC shift was particularly prominent in the frontal cortex, suggesting its crucial role in discriminative reward prediction. During the extinction sessions, the shift diminished significantly on extinction day 1. These findings suggest that cortical DC potential is related to reward prediction and could be a valuable tool for evaluating animal models of depression, providing a testing system for anhedonia.

Multiplexed representation of others in the hippocampal CA1 subfield of female mice.

Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also represents the position of a conspecific performing a spatial task. However, whether this representation is allocentric, egocentric or mixed is less clear. In this study we investigated the representation of others during free behavior and in a task where female mice learned to follow a conspecific for a reward. We found that most cells represent the position of others relative to self-position (social-vector cells) rather than to the environment, with a prevalence of purely egocentric coding modulated by context and mouse identity. Learning of a pursuit task improved the tuning of social-vector cells, but their number remained invariant. Collectively, our results suggest that the hippocampus flexibly codes the position of others in multiple coordinate systems, albeit favoring the self as a reference point.

Sodium Bicarbonate Decreases Alcohol Consumption in Mice.

We previously reported that mice with low neuronal pH drink more alcohol, demonstrating the importance of pH for alcohol reward and motivation. In this study, we tested whether systemic pH affects alcohol consumption and if so, whether it occurs by changing the alcohol reward. C57BL/6J mice were given NaHCO3 to raise their blood pH, and the animals' alcohol consumption was measured in the drinking-in-the-dark and two-bottle free choice paradigms. Alcohol consumption was also assessed after suppressing the bitterness of NaHCO3 with sucrose. Alcohol reward was evaluated using a conditioned place preference. In addition, taste sensitivity was assessed by determining quinine and sucrose preference. The results revealed that a pH increase by NaHCO3 caused mice to decrease their alcohol consumption. The decrease in high alcohol contents (20%) was significant and observed at different ages, as well as in both males and females. Alcohol consumption was also decreased after suppressing NaHCO3 bitterness. Oral gavage of NaHCO3 did not alter quinine and sucrose preference. In the conditioned place preference, NaHCO3-treated mice spent less time in the alcohol-injected chamber. Conclusively, the results show that raising systemic pH with NaHCO3 decreases alcohol consumption, as it decreases the alcohol reward value.

Behavioral proxies compete by the time courses of their rewards, including endogenous rewards.

Natural selection is slow, so behavioral goals must be based on patterns of reward. Addictions are rewarded in the same way as adaptive choice, so they can be distinguished only by their time course. In addition, the reward process is more plastic than is generally recognized, so abstract goals are shaped by the "legibility" of their proxies.

Aberrant effort-based reward dynamics in anhedonia.

Anhedonia is a transdiagnostic symptom and associated with a spectrum of reward deficits among which the motivational dysfunction is poorly understood. Previous studies have established the abnormal cost-benefit trade-off as a contributor to motivational deficits in anhedonia and its relevant psychiatric diseases. However, it remains elusive how the anhedonic neural dynamics underlying reward processing are modulated by effort expenditure. Using an effort-based monetary incentive delay task, the current event-related potential study examined the neural dynamics underlying the effort-reward interplay in anhedonia using a nonclinical sample who scored high or low on an anhedonia questionnaire. We found that effort prospectively decreased reward effect on the contingent variation negativity and the target-P3 but retrospectively enhanced outcome effect on the feedback-P3 following effort expenditure. Compared to the low-anhedonia group, the high-anhedonia group displayed a diminished effort effect on the target-P3 during effort expenditure and an increased effort-enhancement effect for neutral trials during the feedback-P3 period following effort expenditure. Our findings suggest that anhedonia is associated with an inefficient control and motivation allocation along the efforted-based reward dynamics from effort preparation to effort production.

Differential effects of acute and prolonged morphine withdrawal on motivational and goal-directed control over reward-seeking behaviour.

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.

Human mutations in high-confidence Tourette disorder genes affect sensorimotor behavior, reward learning, and striatal dopamine in mice.

Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous to human de novo variants in two high-confidence Tourette genes, CELSR3 and WWC1. Mice with human mutations in Celsr3 and Wwc1 exhibit cognitive and/or sensorimotor behavioral phenotypes consistent with TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition, occur in both male and female Celsr3 TD models. Wwc1 mice show reduced prepulse inhibition only in females. Repetitive motor behaviors, common to Celsr3 mice and more pronounced in females, include vertical rearing and grooming. Sensorimotor gating deficits and rearing are attenuated by aripiprazole, a partial agonist at dopamine type II receptors. Unsupervised machine learning reveals numerous changes to spontaneous motor behavior and less predictable patterns of movement. Continuous fixed-ratio reinforcement shows that Celsr3 TD mice have enhanced motor responding and reward learning. Electrically evoked striatal dopamine release, tested in one model, is greater. Brain development is otherwise grossly normal without signs of striatal interneuron loss. Altogether, mice expressing human mutations in high-confidence TD genes exhibit face and predictive validity. Reduced prepulse inhibition and repetitive motor behaviors are core behavioral phenotypes and are responsive to aripiprazole. Enhanced reward learning and motor responding occur alongside greater evoked dopamine release. Phenotypes can also vary by sex and show stronger affection in females, an unexpected finding considering males are more frequently affected in TD.

Financial incentive interventions for smoking cessation among Chinese smokers: study protocol for a cluster randomised controlled trial.

INTRODUCTION: There is an urgent issue to relieve the burdens caused by tobacco use through feasible and effective smoking cessation interventions, particularly in a middle-income country with less accessible smoking cessation services and high demand for quitting smoking. Financial incentives have shown effective in changing health behaviours, thus needing to test its portability to a wider implementation and effectiveness of increasing smoking cessation rates. METHODS AND ANALYSIS: This is a three-arm cluster randomised controlled trial. 462 eligible participants will be assigned to 2 financial incentive groups-rewards or deposits, or the control group. All participants including those in the control group will receive text messages to help quitting smoking developed by the US National Cancer Institute over a 3-month intervention period. In addition to text messages, reward group participants will be rewarded with CNY200 and CNY400 (CNY100 approximately US$15) for sustained smoking abstinence at 1 month and 3 months follow-up assessments; participants in the deposit group will accumulate CNY200 and CNY600 in the deposit accounts after verified smoking abstinence at 1 month and 3 months follow-up assessments, and all the deposits will be given at once right after the 3-month follow-up visit. The primary outcome is biochemically verified smoking abstinence rate sustained for 6 months after enrolment. ETHICS AND DISSEMINATION: This trial protocol has been approved by the Ethics Committee of Peking University Health Science Centre (date: 23 February 2023; ethical approval number: IRB00001052-22172). Results and findings of this trial will be disseminated in peer-reviewed journals and professional conferences. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-2300069631.

Dextromethorphan moderates reward deficiency associated with central serotonin transporter availability in 3,4-methylenedioxy-methamphetamine-treated animals.

BACKGROUND: The neurotoxicity of 3,4-methylenedioxy-methamphetamine (MDMA) to the serotonergic system is well-documented. Dextromethorphan (DM), an antitussive drug, decreased morphine- or methamphetamine (MA)-induced reward in rats and may prevent MDMA-induced serotonergic deficiency in primates, as indicated by increased serotonin transporter (SERT) availability. We aimed to investigate the effects of DM on reward, behavioral sensitization, and neurotoxicity associated with loss of SERT induced by chronic MDMA administration in rats. METHODS: Conditioned place preference (CPP) and locomotor activity tests were used to evaluate drug-induced reward and behavioral sensitization; 4-[ 18 F]-ADAM/animal-PET and immunohistochemistry were used to explore the effects of DM on MDMA-induced loss of SERT. RESULTS: MDMA significantly reduced SERT binding in the rat brain; however, co-administration of DM significantly restored SERT, enhancing the recovery rate at day 14 by an average of ~23% compared to the MDMA group. In confirmation of the PET findings, immunochemistry revealed MDMA reduced SERT immunoactivity in all brain regions, whereas DM markedly increased the serotonergic fiber density after MDMA induction. CONCLUSION: Behavioral tests and in vivo longitudinal PET imaging demonstrated the CPP indexes and locomotor activities of the reward system correlate negatively with PET 4-[ 18 F]ADAM SERT activity in the reward system. Our findings suggest MDMA induces functional abnormalities in a network of brain regions important to decision-making processes and the motivation circuit. DM may exert neuroprotective effects to reverse MDMA-induced neurotoxicity.

Effort-cost decision-making associated with negative symptoms in schizophrenia and bipolar disorder.

Motivational deficits and reduced goal-directed behavior for external rewards have long been considered an important features of negative symptoms in patients with schizophrenia (SCZ). Negative symptoms have also a high prevalence in bipolar disorder (BP). We used a transdiagnostic approach in order to examine association between negative symptoms and effort allocation for monetary rewards. 41 patients with SCZ and 34 patients with BP were enrolled in the study along with 41 healthy controls (HC). Effort-Expenditure for Rewards Task (EEfRT) was used to measure subjects' effort allocation for monetary rewards. Generalized estimating equation models were used to analyze EEfRT choice behavior. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS). SCZ and BP groups expended lower effort to obtain a monetary rewards compared to HC. Severity of negative symptoms was negatively correlated with EEfRT performance in both diagnostic groups. Each diagnostic group showed lower effort allocation for monetary rewards compared to HC suggesting reduced motivation for monetary rewards. In addition, our results suggest that abnormal effort-based decision-making might be a transdiagnostic factor underlying negative symptoms.