Factors underlying the neurofunctional domains of the Addictions Neuroclinical Assessment assessed by a standardized neurocognitive battery.

The Addictions Neuroclinical Assessment (ANA) is a neurobiologically-informed framework designed to understand the etiology and heterogeneity of Alcohol Use Disorder (AUD). Previous studies validated the three neurofunctional domains of ANA: Incentive Salience (IS), Negative Emotionality (NE) and Executive Function (EF) using secondary data. The present cross-sectional observational study assessed these domains in an independent, prospective clinical sample. Adults across the drinking spectrum (N = 300) completed the ANA battery, a standardized collection of behavioral tasks and self-report assessments. Factor analyses were used to identify latent factors underlying each domain. Associations between identified domain factors were evaluated using structural equation models. Receiver operating characteristics analyses were used to determine factors with the strongest ability to classify individuals with problematic drinking and AUD. We found (1) two factors underlie the IS domain: alcohol motivation and alcohol insensitivity. (2) Three factors were identified for the NE domain: internalizing, externalizing, and psychological strength. (3) Five factors were found for the EF domain: inhibitory control, working memory, rumination, interoception, and impulsivity. (4) These ten factors showed varying degrees of cross-correlations, with alcohol motivation, internalizing, and impulsivity exhibiting the strongest correlations. (5) Alcohol motivation, alcohol insensitivity, and impulsivity showed the greatest ability in classifying individuals with problematic drinking and AUD. Thus, the present study identified unique factors underlying each ANA domain assessed using a standardized assessment battery. These results revealed additional dimensionality to the ANA domains, bringing together different constructs from the field into a single cohesive framework and advancing the field of addiction phenotyping. Future work will focus on identifying neurobiological correlates and identifying AUD subtypes based on these factors.

Sleep profiles of different psychiatric traits.

Disturbed sleep comes in many forms. While the key role of sleep in mental health is undisputed, our understanding of the type of sleeping problems that manifest in the early stages of psychiatric disorders is limited. A sample without psychiatric diagnoses (N = 440, 341 women, 97 men, 2 non-binaries; Mage = 32.1, SD = 9.4, range 18-77) underwent a comprehensive assessment, evaluating eight sleep features and 13 questionnaires on common psychiatric complaints. Results revealed that traits of affect disorders, generalized anxiety, and ADHD had the worst sleep profiles, while autism disorder, eating disorder, and impulsivity traits showed milder sleep issues. Mania was the only trait associated with an overall better sleep profile. Across traits, insomnia and fatigue dominated and sleep variability was least prominent. These findings provide support for both transdiagnostic and disorder-specific targets for prevention and treatment.

Potential association between suicide risk, aggression, impulsivity, and the somatosensory system.

Aggression and impulsivity are linked to suicidal behaviors, but their relationship to the suicidal crisis remains unclear. This magnetoencephalography (MEG) study investigated the link between aggression, impulsivity, and resting-state MEG power and connectivity. Four risk groups were enrolled: high-risk (HR; n = 14), who had a recent suicidal crisis; lower-risk (LR; n = 41), who had a history of suicide attempts but no suicide attempt or ideation in the past year; clinical control (CC; n = 38), who had anxiety/mood disorders but no suicidal history; and minimal risk (MR; n = 28), who had no psychiatric/suicidal history. No difference in resting-state MEG power was observed between the groups. Individuals in the HR group with high self-reported aggression and impulsivity scores had reduced MEG power in regions responsible for sensory/emotion regulation vs. those in the HR group with low scores. The HR group also showed downregulated bidirectional glutamatergic feedback between the precuneus (PRE) and insula (INS) compared to the LR, CC, and MR groups. High self-reported impulsivity was linked to reduced PRE to INS feedback, whereas high risk-taking impulsivity was linked to upregulated INS to postcentral gyrus (PCG) and PCG to INS feedback. These preliminary findings suggest that glutamatergic-mediated sensory and emotion-regulation processes may function as potential suicide risk markers.

The Mediating Effect of Coping Strategies and Emotion Regulation in the Relationship between Impulsivity, Metacognition, and Eating Disorders.

BACKGROUND: Risk factors for eating disorders are multifaceted and complex, so it is crucial to elucidate the role of executive functions, including impulsivity and metacognition, and coping strategies in the severity of eating behaviors. The study aims were threefold: (1) to analyze gender differences in impulsivity, metacognition, coping strategies, emotion regulation, and eating disorders; (2) to examine the correlation between the study variables; and (3) to test the mediating role of coping and emotion-regulation strategies in the relationship between metacognition, impulsivity, and eating disorders. METHODS: A total of 1076 participants (Mage = 21.78, SD = 5.10; 77.7% women) completed a set of questionnaires. Two mediation analyses were conducted to test the mediating role of coping strategies, including emotion regulation, in the relationship between executive functions (i.e., impulsivity and metacognition) and eating disorders. RESULTS: Women displayed higher coping strategies, specifically emotional expression, wishful thinking, and social support, whereas men presented greater social withdrawal. Mediational analyses showed a significant association between impulsivity, metacognition, and eating disorders, whose relationship was partially mediated by coping strategies and mainly by emotion regulation. CONCLUSION: Interventions based on coping strategies and emotion regulation could be a feasible and effective option to deal with eating disorders among the young population.

The Independent Contribution of Positive and Negative Metacognitions About Smoking to Urge to Smoke, Withdrawal Symptoms and Dependence in Smoking-Dependent Men.

Previous research has indicated that various factors, such as psychological distress, distress intolerance, anhedonia, impulsivity and smoking metacognitions, have been individually linked to the urge to smoke, withdrawal symptoms and dependence. However, these factors have not been collectively examined to determine whether smoking metacognitions independently and significantly contribute to these outcomes. Therefore, the aim of this study was to investigate the impact of distress intolerance, anhedonia, impulsivity and smoking metacognitions on the urge to smoke, withdrawal symptoms and dependency in men who are dependent on smoking. A total of 300 smoking-dependent men completed psychological scales and smoking-related measures. The findings of the study indicated that positive metacognitions about emotion regulation significantly predicted the urge to smoke, even when accounting for other significant predictors such as the number of daily cigarettes smoked, psychological distress, anhedonia and impulsivity. Furthermore, positive metacognitions about cognitive regulation were found to be a significant predictor of withdrawal symptoms, independent of other significant predictors such as psychological distress and the urge to smoke. Smoking dependence was predicted by negative metacognitions about uncontrollability beyond other significant predictors, including the number of daily cigarettes smoked and distress intolerance. These results highlight the role of metacognitions about smoking in both short- and long-term clinical outcomes related to smoking. Consequently, addressing such beliefs during treatment for smoking dependence should be an important therapeutic goal.

Impulsivity and inhibitory control in deficit and non-deficit schizophrenia.

BACKGROUND: There is conflicting evidence on impulsivity and its potential relationship with inhibitory control in schizophrenia. This study therefore aimed to identify differences in impulsivity and cognitive and motor inhibition between patients with deficit (DS) and non-deficit (NDS) schizophrenia and healthy controls (HC). We also explored the relationships between impulsivity and different dimensions of inhibitory control in all studied groups. METHODS: The sample comprised 28 DS patients, 45 NDS patients, and 39 age-matched HC. A neuropsychological battery was used. RESULTS: DS patients scored lower in venturesomeness, while those with NDS scored higher in impulsiveness compared to HC. In addition, both groups of patients scored higher on measures of cognitive and motor inhibition, including those relatively independent of information processing speed (although the results were slightly different after adjusting for IQ and/or years of education). Correlations between impulsivity and cognitive inhibition emerged in DS patients, while links between impulsivity and motor inhibition were observed in HC. CONCLUSIONS: Our results suggest the presence of deficits in experimentally assessed inhibitory control in schizophrenia patients, with predominant impulsivity in the NDS population. In addition, impulsivity may affect the cognitive control of inhibition in deficit schizophrenia. Nevertheless, due to the preliminary nature of these findings, they require further empirical verification in future research.

Graph analysis uncovers an opposing impact of methylphenidate on connectivity patterns within default mode network sub-divisions.

BACKGROUND: The Default Mode Network (DMN) is a central neural network, with recent evidence indicating that it is composed of functionally distinct sub-networks. Methylphenidate (MPH) administration has been shown before to modulate impulsive behavior, though it is not yet clear whether these effects relate to MPH-induced changes in DMN connectivity. To address this gap, we assessed the impact of MPH administration on functional connectivity patterns within and between distinct DMN sub-networks and tested putative relations to variability in sub-scales of impulsivity. METHODS: Fifty-five right-handed healthy adults underwent two resting-state functional MRI (rs-fMRI) scans, following acute administration of either MPH (20 mg) or placebo, via a randomized double-blind placebo-controlled design. Graph modularity analysis was implemented to fractionate the DMN into distinct sub-networks based on the impact of MPH (vs. placebo) on DMN connectivity patterns with other neural networks. RESULTS: MPH administration led to an overall decreased DMN connectivity, particularly with the auditory, cinguloopercular, and somatomotor networks, and increased connectivity with the parietomedial network. Graph analysis revealed that the DMN could be fractionated into two distinct sub-networks, with one exhibiting MPH-induced increased connectivity and the other decreased connectivity. Decreased connectivity of the DMN sub-network with the cinguloopercular network following MPH administration was associated with elevated impulsivity and non-planning impulsiveness. CONCLUSION: Current findings highlight the intricate effects of MPH administration on DMN rs-fMRI connectivity, uncovering its opposing impact on distinct DMN sub-divisions. MPH-induced dynamics in DMN connectivity patterns with other neural networks may account for some of the effects of MPH administration on impulsive behavior.

Neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence.

AIMS: Abuse of methamphetamine has aroused concern worldwide. Stimulant use and sexual behaviours have been linked in behavioural and epidemiological studies. Although methamphetamine-related neurofunctional differences are reported in previous studies, only few studies have examined neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence. METHODS: Neurofunctional changes were measured using a cue-reactivity task involving methamphetamine, sexual, and neutral cues in 20 methamphetamine abusers who were evaluated after a short- (1 week to 3 months) and long-term (10-15 months) abstinence. RESULTS: Five brain regions mainly involved in the occipital lobe and the parietal lobe were found with the group-by-condition interaction. Region-of-interest analyses found higher sexual-cue-related activation than other two activations in all five brain regions in the long-term methamphetamine abstinence group while no group differences were found. Negative relationships between motor impulsivity and methamphetamine- or sexual-cue-related activations in the left middle occipital gyrus, the superior parietal gyrus and the right angular gyrus were found. CONCLUSIONS: The findings suggested that methamphetamine abstinence may change the neural response of methamphetamine abusers to methamphetamine and sexual cues, and the neurofunction of the five brain regions reported in this study may partly recover with long-term methamphetamine abstinence. Given the use and relapse of methamphetamine for sexual purposes, the findings of this study may have particular clinical relevance.

Involvement of dopamine D3 receptor in impulsive choice decision-making in male rats.

Impulsive decision-making has been linked to impulse control disorders and substance use disorders. However, the neural mechanisms underlying impulsive choice are not fully understood. While previous PET imaging and autoradiography studies have shown involvement of dopamine and D2/3 receptors in impulsive behavior, the roles of distinct D1, D2, and D3 receptors in impulsive decision-making remain unclear. In this study, we used a food reward delay-discounting task (DDT) to identify low- and high-impulsive rats, in which low-impulsive rats exhibited preference for large delayed reward over small immediate rewards, while high-impulsive rats showed the opposite preference. We then examined D1, D2, and D3 receptor gene expression using RNAscope in situ hybridization assays. We found that high-impulsive male rats exhibited lower levels of D2 and D3, and particularly D3, receptor expression in the nucleus accumbens (NAc), with no significant changes in the insular, prelimbic, and infralimbic cortices. Based on these findings, we further explored the role of the D3 receptor in impulsive decision-making. Systemic administration of a selective D3 receptor agonist (FOB02-04) significantly reduced impulsive choices in high-impulsive rats but had no effects in low-impulsive rats. Conversely, a selective D3 receptor antagonist (VK4-116) produced increased both impulsive and omission choices in both groups of rats. These findings suggest that impulsive decision-making is associated with a reduction in D3 receptor expression in the NAc. Selective D3 receptor agonists, but not antagonists, may hold therapeutic potentials for mitigating impulsivity in high-impulsive subjects.

The mediating role of trait impulsivity in the relation between cue-induced craving and functional connectivity within the salience network among abstinent patients with methamphetamine use disorder.

Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders.

Impulsivity is a stable, measurable, and predictive psychological trait.

Impulsivity is a personality construct frequently employed to explain and predict important human behaviors. Major inconsistencies in its definition and measurement, however, have led some researchers to call for an outright rejection of impulsivity as a psychological construct. We address this highly unsatisfactory state with a large-scale, preregistered study (N = 1,676) in which each participant completed 48 measures of impulsivity derived from 10 self-report scales and 10 behavioral tasks and reported frequencies of seven impulsivity-related behaviors (e.g., impulsive buying and social media usage); a subsample (N = 196) then completed a retest session 3 mo later. We found that correlations between self-report measures were substantially higher than those between behavioral tasks and between self-report measures and behavioral tasks. Bifactor analysis of these measures exacted one general factor of impulsivity I, akin to the general intelligence factor g, and six specific factors. Factor I was related mainly to self-report measures, had high test-retest reliability, and could predict impulsivity-related behaviors better than existing measures. We further developed a scale named the adjustable impulsivity scale (AIMS) to measure I. AIMS possesses excellent psychometric properties that are largely retained in shorter versions and could predict impulsivity-related behaviors equally well as I. These findings collectively support impulsivity as a stable, measurable, and predictive trait, indicating that it may be too early to reject it as a valid and useful psychological construct. The bifactorial structure of impulsivity and AIMS, meanwhile, significantly advance the conceptualization and measurement of construct impulsivity.

Dark Tetrad personality traits, paraphilic interests, and the role of impulsivity: an EEG-study using a Go/No-Go paradigm.

Maladaptive personality traits, such as 'dark personalities' are found to result in a diverse set of negative outcomes, including paraphilic interests and associated (illegal) behaviors. It is however unclear how these are exactly related, and if related, if then only those individuals higher on dark personality traits and higher impulsivity engage in paraphilic behaviors. In the current study, 50 participants were recruited to investigate the relationship between Dark Tetrad personality traits (i.e., narcissism, psychopathy, Machiavellianism and everyday sadism), paraphilic interests (arousal and behavior) and the moderating role of impulsivity. Personality and paraphilic interests were investigated through self-report questionnaires. Impulsivity was measured both through self-reported dysfunctional impulsivity and the P3 event related potential using electroencephalography during the Go/No-Go task (i.e. response inhibition). The results showed that there was a positive association between psychopathy, sadism and paraphilic interests. Whereas everyday sadism was associated with paraphilic (self-reported) arousal, psychopathy was associated with paraphilic behavior. Although P3 amplitude was not associated with paraphilic interests, self-reported dysfunctional impulsivity was associated with paraphilic behavior specifically. However, there was no moderating role of dysfunctional impulsivity and response inhibition (P3) in the relationship between psychopathy and paraphilic behavior. Findings indicate that the relation between specific dark personalities and paraphilic interests may be more complex than initially thought. Nevertheless, risk assessment and intervention approaches for paraphilia and related behavior both may benefit from incorporating Dark Tetrad and impulsivity measurements.

"Age of traumatic experience as a predictor of distorted body image in patients with eating disorders".

The timing of trauma exposure is a risk factor for the development of psychopathology in adulthood. We aim to assess the presence of adverse life events (ALEs) before age 13 in patients with eating disorders (ED). Specifically, we examined the relationship between exposure to interpersonal trauma before the age of 13 and body image distortion (BID), impulsivity, and perfectionism. We conducted a cross-sectional, retrospective study in which 79 outpatients with ED were consecutively enrolled. Assessment was performed using the Traumatic Life Event Questionnaire, Contour Drawing Rating Scale, and Eating Disorder Inventory. Linear regression models were used to analyze the predictive role of interpersonal trauma before age 13 on BID perfectionism and impulsivity. Seventy-two patients (91.1%) reported ALEs throughout their lives. Patients with trauma before age 13 (55.6%) overestimated their shape. Patients with ED and bulimic symptoms had significantly higher BID levels. Interpersonal trauma predicted higher levels of impulsivity and perfectionism. Experiencing interpersonal ALEs before age 13 may be a risk factor for the development of BID, impulsivity, and perfectionism in adulthood. Body image can be modified during childhood through interventions focused on identifying stressful relationships.

Childhood is important for the construction of self-image. When people feel threatened in relationships they trust, they feel ashamed and guilty. These emotions could lead to ED and BID. To explore this, we conducted a study on how ALEs during childhood influence the way we perceive our bodies. We asked participants with ED to close their eyes and sense their bodies. We then invited them to choose a shape from a list of nine figures with different shapes. Participants who experienced childhood trauma chose a shape that was distorted with respect to their actual figure. We believe that closing the eyes connects people to their inner emotions and influences their body appreciation. This will help patients identify and treat negative emotions so that they feel more comfortable with their bodies.

Neurocognitive training enhances the outcomes of children with attention deficit hyperactivity disorder: A preliminary study.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by diverse clinical manifestations including inattention, hyperactivity and impulsivity. OBJECTIVE: The present study aims to investigate the effects of neurocognitive training (NT), a personalized and specialized exercise programme on symptoms, attention and dynamic balance in treatment-naïve children diagnosed with ADHD. METHODS: Fourteen treatment-naïve children aged 7-12 years diagnosed with ADHD were enrolled in the intervention group. The NT intervention was administered weekly for 10 consecutive weeks, supplemented by a structured home exercise programme for 6 days a week over the same 10-week period. ADHD-related symptoms, attention and dynamic balance were assessed in pre-treatment, post-treatment, 6 months, and 12 months. Fifteen typically developing (TD) children, matched for age, underwent evaluation only once to establish baseline normative values. RESULTS: Following the NT (post-treatment), significant improvements were observed in hyperactivity-impulsivity scores, oppositional-defiant behaviours and dynamic balance when compared to the TD children (p < 0.05). In the ADHD group, a significant difference was found in the long term (12-month follow-up) in hyperactivity-impulsivity, oppositional-defiant behaviours and dynamic balance (p < 0.05). CONCLUSION: The findings suggest that the NT yields favourable effects on hyperactivity-impulsivity, oppositional defiant behaviours and dynamic balance in children diagnosed with ADHD, with these improvements appearing to be sustained over the long term. CLINICAL TRIAL REGISTRATION NUMBER: NCT04707040.

The Role of Anxiety and Depression in the Relationship Among Emotional Eating, Sleep Quality, and Impulsivity.

ABSTRACT: The aim of this study was to investigate the relationship among sleep quality, impulsivity, anxiety, and depression in individuals with emotional eating behavior. The study was designed as a cross-sectional study. The study included 92 individuals (age 31.29 ± 9.17; female, 67.4% [ n = 62]; male, 32.6% [ n = 30]) with symptoms of emotional eating but no previous psychiatric diagnosis or treatment. Participants were administered a Structured Clinical Interview for DSM-5 Disorders interview form, a sociodemographic data form, the Emotional Eating Scale, the Beck Depression Scale, the Barratt Impulsivity Scale, the Beck Anxiety Scale, and the Pittsburgh Sleep Quality Index Scale. Emotional eating is positively correlated with anxiety ( r = 0.377, p = 0.001), depression ( r = 0.375, p = 0.001), impulsivity ( r = 0.250, p = 0.016), and poor sleep quality ( r = 0.478, p = 0.001). Obese individuals (defined as having a body mass index of 30 or higher) showed higher emotional eating ( z = -2.552, p = 0.016) and poorer sleep quality ( z = -2.089, p = 0.044) than nonobese individuals, and women showed higher emotional eating ( t = 2116, p = 0.037) and poorer sleep quality ( z = -2537, p = 0.010) than men. Poor sleep quality was associated with emotional eating. In this relationship, poor sleep quality influenced emotional eating through all mediators, including anxiety and depression ( B = 3.491; standardized effect, 0.485; p = 0.001). Poor sleep quality directly influenced emotional eating ( B = 2.806; standardized effect, 0.390; p = 0.001). The findings of the study suggest that emotional eating is associated with higher levels of anxiety, depression, impulsivity, and sleep problems, especially in women. It suggests that the interrelationships of psychological factors associated with emotional eating should be investigated.

Associations between behavioral and self-reported impulsivity, brain structure, and genetic influences in middle childhood.

Impulsivity undergoes a normative developmental trajectory from childhood to adulthood and is thought to be driven by maturation of brain structure. However, few large-scale studies have assessed associations between impulsivity, brain structure, and genetic susceptibility in children. In 9112 children ages 9-10 from the ABCD study, we explored relationships among impulsivity (UPPS-P impulsive behavior scale; delay discounting), brain structure (cortical thickness (CT), cortical volume (CV), and cortical area (CA)), and polygenic scores for externalizing behavior (PGSEXT). Both higher UPPS-P total scores and more severe delay-discounting had widespread, low-magnitude associations with smaller CA in frontal and temporal regions. No associations were seen between impulsivity and CV or CT. Additionally, higher PGSEXT was associated with both higher UPPS-P scores and with smaller CA and CV in frontal and temporal regions, but in non-overlapping cortical regions, underscoring the complex interplay between genetics and brain structure in influencing impulsivity. These findings indicate that, within large-scale population data, CA is significantly yet weakly associated with each of these impulsivity measures and with polygenic risk for externalizing behaviors, but in distinct brain regions. Future work should longitudinally assess these associations through adolescence, and examine associated functional outcomes, such as future substance use and psychopathology.

The relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder: A systematic review and Meta-analysis.

BACKGROUND: This systematic review and meta-analysis explored the relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder (OCD). METHODS: We searched Pubmed, Scopus, Cochrane Library and PsychINFO databases until February 2023 for studies comparing patients with OCD and healthy controls on cognitive tests of compulsivity and impulsivity. The study followed PRISMA guidelines and was pre-registered on PROSPERO (CRD42021299017). RESULTS: Meta-analyses of 112 studies involving 8313 participants (4289 patients with OCD and 4024 healthy controls) identified significant impairments in compulsivity (g = -0.58, [95%CI -0.68, -0.47]; k = 76) and impulsivity (g = -0.48, [95%CI -0.57, -0.38]; k = 63); no significant difference between impairments. Medication use and comorbid psychiatric disorders were not significantly related to impairments. No associations were revealed with OCD severity, depression/anxiety, or illness duration. CONCLUSION: Cognitive phenotypes of compulsivity and impulsivity in patients with OCD appear to be orthogonal to clinical variables, including severity of OCD symptomatology. Their clinical impact is poorly understood and may require different clinical assessment tools and interventions.

Orbitostriatal encoding of reward delayed gratification and impulsivity in chronic pain.

Central robust network functional rearrangement is a characteristic of several neurological conditions, including chronic pain. Preclinical and clinical studies have shown the importance of pain-induced dysfunction in both orbitofrontal cortex (OFC) and nucleus accumbens (NAc) brain regions for the emergence of cognitive deficits. Outcome information processing recruits the orbitostriatal circuitry, a pivotal pathway regarding context-dependent reward value encoding. The current literature reveals the existence of structural and functional changes in the orbitostriatal crosstalk in chronic pain conditions, which have emerged as a possible underlying cause for reward and time discrimination impairments observed in individuals affected by such disturbances. However, more comprehensive investigations are needed to elucidate the underlying disturbances that underpin disease development. In this review article, we aim to provide a comprehensive view of the orbitostriatal mechanisms underlying time-reward dependent behaviors, and integrate previous findings on local and network malplasticity under the framework of the chronic pain sphere.