A master regulator of opioid reward in the ventral prefrontal cortex.

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express µ-opioid receptors (µORs). Disrupting µOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.

Social interaction-induced fear memory reduction: exploring the influence of dopamine and oxytocin receptors on memory updating.

It has been well established that a consolidated memory can be updated during the plastic state induced by reactivation. This updating process opens the possibility to modify maladaptive memory. In the present study, we evaluated whether fear memory could be updated to less-aversive level by incorporating hedonic information during reactivation. Thus, male rats were fear conditioned and, during retrieval, a female was presented as a social rewarding stimulus. We found that memory reactivation with a female (but not a male) reduces fear expression within-session and in the test, without presenting reinstatement or spontaneous recovery. Interestingly, this intervention impaired extinction. Finally, we demonstrated that this emotional remodeling to eliminate fear expression requires the activation of dopamine and oxytocin receptors during retrieval. Hence, these results shed new lights on the memory updating process and suggests that the exposure to natural rewarding information such as a female during retrieval reduces a previously consolidated fear memory.

General mechanisms of task engagement in the primate frontal cortex.

Staying engaged is necessary to maintain goal-directed behaviors. Despite this, engagement exhibits continuous, intrinsic fluctuations. Even in experimental settings, animals, unlike most humans, repeatedly and spontaneously move between periods of complete task engagement and disengagement. We, therefore, looked at behavior in male macaques (macaca mulatta) in four tasks while recording fMRI signals. We identified consistent autocorrelation in task disengagement. This made it possible to build models capturing task-independent engagement. We identified task general patterns of neural activity linked to impending sudden task disengagement in mid-cingulate gyrus. By contrast, activity centered in perigenual anterior cingulate cortex (pgACC) was associated with maintenance of performance across tasks. Importantly, we carefully controlled for task-specific factors such as the reward history and other motivational effects, such as response vigor, in our analyses. Moreover, we showed pgACC activity had a causal link to task engagement: transcranial ultrasound stimulation of pgACC changed task engagement patterns.

Are lateralized and bold fish optimistic or pessimistic?

Cognitive bias is defined as the influence of emotions on cognitive processes. The concept of the cognitive judgement bias has its origins in human psychology but has been applied to animals over the past 2 decades. In this study we were interested in determining if laterality and personality traits, which are known to influence learning style, might also be correlated with a cognitive bias in the three-spined sticklebacks (Gasterosteus aculeatus). We used the judgement bias test with the go/no-go procedure where fish were first trained to discriminate between a black and white card and, after reaching a minimum learning criterion, tested their response to an ambiguous card (grey). Optimistic subjects were expected to have a high expectation of reward associated with an ambiguous stimulus, whereas pessimistic subjects a high expectation of non-reward. We used an emergence and a mirror test to quantify boldness and laterality, respectively. We hypothesised that male, bolder and more strongly lateralized fish would be more optimistic than female, shy and less strongly lateralised fish. We found that males and more strongly lateralized fish were more optimistic than females and less strongly lateralized fish. In addition, bold males were more optimistic than shy males as we predicted, but females showed the opposite pattern. Finally, fish trained on the black colour card learned the training task faster than those trained on a white card. Our results indicate that both laterality and personality traits are linked to animals' internal states (pessimistic or optimistic outlooks) which likely has broad implications for understanding animal behaviour particularly in a welfare context.

Two Distinct Neuronal Populations in the Rat Parafascicular Nucleus Oppositely Encode the Engagement in Stimulus-driven Reward-seeking.

BACKGROUND: The thalamus is a phylogenetically well-preserved structure. Known to densely contact cortical regions, its role in the transmission of sensory information to the striatal complex has been widely reconsidered in recent years. METHODS: The parafascicular nucleus of the thalamus (Pf) has been implicated in the orientation of attention toward salient sensory stimuli. In a stimulus-driven reward-seeking task, we sought to characterize the electrophysiological activity of Pf neurons in rats. RESULTS: We observed a predominance of excitatory over inhibitory responses for all events in the task. Neurons responded more strongly to the stimulus compared to lever-pressing and reward collecting, confirming the strong involvement of the Pf in sensory information processing. The use of long sessions allowed us to compare neuronal responses to stimuli between trials when animals were engaged in action and those when they were not. We distinguished two populations of neurons with opposite responses: MOTIV+ neurons responded more intensely to stimuli followed by a behavioral response than those that were not. Conversely, MOTIV- neurons responded more strongly when the animal did not respond to the stimulus. In addition, the latency of excitation of MOTIV- neurons was shorter than that of MOTIV+ neurons. CONCLUSION: Through this encoding, the Pf could perform an early selection of environmental stimuli transmitted to the striatum according to motivational level.

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.

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.

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.

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.

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.

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).

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.

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.

Loss of glycine receptors in the nucleus accumbens and ethanol reward in an Alzheimer´s Disease mouse model.

Alterations in cognitive and non-cognitive cerebral functions characterize Alzheimer's disease (AD). Cortical and hippocampal impairments related to extracellular accumulation of Aß in AD animal models have been extensively investigated. However, recent reports have also implicated intracellular Aß in limbic regions, such as the nucleus accumbens (nAc). Accumbal neurons express high levels of inhibitory glycine receptors (GlyRs) that are allosterically modulated by ethanol and have a role in controlling its intake. In the present study, we investigated how GlyRs in the 2xTg mice (AD model) affect nAc functions and ethanol intake behavior. Using transgenic and control aged-matched litter mates, we found that the GlyRα2 subunit was significantly decreased in AD mice (6-month-old). We also examined intracellular calcium dynamics using the fluorescent calcium protein reporter GCaMP in slice photometry. We also found that the calcium signal mediated by GlyRs, but not GABAAR, was also reduced in AD neurons. Additionally, ethanol potentiation was significantly decreased in accumbal neurons in the AD mice. Finally, we performed drinking in the dark (DID) experiments and found that 2xTg mice consumed less ethanol on the last day of DID, in agreement with a lower blood ethanol concentration. 2xTg mice also showed lower sucrose consumption, indicating that overall food reward was altered. In conclusion, the data support the role of GlyRs in nAc neuron excitability and a decreased glycinergic activity in the 2xTg mice that might lead to impairment in reward processing at an early stage of the disease.

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.

The neurocomputational link between defensive cardiac states and approach-avoidance arbitration under threat.

Avoidance, a hallmark of anxiety-related psychopathology, often comes at a cost; avoiding threat may forgo the possibility of a reward. Theories predict that optimal approach-avoidance arbitration depends on threat-induced psychophysiological states, like freezing-related bradycardia. Here we used model-based fMRI analyses to investigate whether and how bradycardia states are linked to the neurocomputational underpinnings of approach-avoidance arbitration under varying reward and threat magnitudes. We show that bradycardia states are associated with increased threat-induced avoidance and more pronounced reward-threat value comparison (i.e., a stronger tendency to approach vs. avoid when expected reward outweighs threat). An amygdala-striatal-prefrontal circuit supports approach-avoidance arbitration under threat, with specific involvement of the amygdala and dorsal anterior cingulate (dACC) in integrating reward-threat value and bradycardia states. These findings highlight the role of human freezing states in value-based decision making, relevant for optimal threat coping. They point to a specific role for amygdala/dACC in state-value integration under threat.

Mindfulness and inhibitory control: Insights from the stop signal task with neutral and reward-associated stimuli.

Mindfulness has been linked to enhanced inhibitory control, yet the dynamics of this relationship, especially in reward situations, are not well understood. Our cross-sectional study aimed to explore the relationship between trait mindfulness and a performance measure of inhibitory control as a function of reward context operationalized by stimuli characteristics, and temporal inhibitory demands. Thirty-six individuals aged 19 to 41 filled out the Mindful Attention Awareness Scale (MAAS) and performed a stop signal task (SST), that included both neutral (stone images) and reward-related (money images) stimuli. The SST encompassed four conditions: neutral go/neutral stop, neutral go/reward stop, reward go/neutral stop, and reward go/reward stop, requiring participants to suppress reactions either during or after encountering reward-related stimuli. The relevant index of inhibitory control is the stop signal reaction time (SSRT), a performance measure of inhibitory control. Our findings showed no notable variation in the relationship between the MAAS score and SSRT across the different conditions. However, there was an overall significant effect of MAAS score on SSRT, irrespective of condition. Results may reflect the benefit of mindfulness on inhibitory control after generalized reward exposure.

Understanding the Role of Naive Learners in Cultural Change.

AbstractA change to a population's social network is a change to the substrate of cultural transmission, affecting behavioral diversity and adaptive cultural evolution. While features of network structure such as population size and density have been well studied, less is understood about the influence of social processes such as population turnover-or the repeated replacement of individuals by naive individuals. Experimental data have led to the hypothesis that naive learners can drive cultural evolution by better assessing the relative value of behaviors, although this hypothesis has been expressed only verbally. We conducted a formal exploration of this hypothesis using a generative model that concurrently simulated its two key ingredients: social transmission and reinforcement learning. We simulated competition between high- and low-reward behaviors while varying turnover magnitude and tempo. Variation in turnover influenced changes in the distributions of cultural behaviors, irrespective of initial knowledge-state conditions. We found optimal turnover regimes that amplified the production of higher reward behaviors through two key mechanisms: repertoire composition and enhanced valuation by agents that knew both behaviors. These effects depended on network and learning parameters. Our model provides formal theoretical support for, and predictions about, the hypothesis that naive learners can shape cultural change through their enhanced sampling ability. By moving from experimental data to theory, we illuminate an underdiscussed generative process that can lead to changes in cultural behavior, arising from an interaction between social dynamics and learning.

Investment in nursing reaps rewards.

Sam Foster, Executive Director of Professional Practice, Nursing and Midwifery Council, considers the potential of nurses to improve their local health systems and, through those, the societies in which they live.