Smokers and ex-smokers have shared differences in the neural substrates for potential monetary gains and losses

Despite an increased understanding of nicotine addiction, there is a scarcity of research comparing the neural correlates of non-drug reward between smokers and ex-smokers. Long-term changes in reward-related brain functioning for non-drug incentives may elucidate patterns of functioning that potentially contribute to ongoing smoking behaviour in current smokers. Similarly, examining the effects of previous chronic nicotine exposure during a period of extended abstinence may reveal whether there are neural correlates responsible for non-drug reward processing that are different from current smokers

Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents.

Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use

Neural Correlates of Polysubstance Use: Differential and Interactive Effects of Alcohol and Cannabis on the Adolescent Brain

Two of the most commonly used and abused substances by adolescents in the United States are alcohol and cannabis, which are associated with adverse medical and psychiatric outcomes. Alcohol use and cannabis use during adolescence is also associated with an increased risk of alcohol use disorder (AUD) and/or cannabis use disorder (CUD) in adulthood as well as increased likelihood of relapse after successful treatment. Despite this, much of the previous work on the neurobiology of substance use disorders has focused on adult substance use. This work has shown that individuals with AUD and/or CUD show dysfunction within reward processing, emotion processing, and executive functioning neuro-circuitries. In this dissertation, we have utilized the Monetary Incentive Delay (MID), Affective Stroop (aST), and Optimistic Bias (OB) tasks in order to examine dysfunction in these neuro-circuitries related to AUD and CUD symptomatology in a group of adolescents from a residential treatment facility and the surrounding community. The current data indicate that dysfunction in reward processing, emotion processing, and executive functioning neuro-circuitries is associated with AUD symptomatology, primarily within the MID and aST. However, dysfunction in emotion processing and executive functioning neuro-circuitries is associated with CUD neuro-circuitries across all three tasks. Moreover, there are interactive effects of AUD and CUD symptom severity on emotional processing and executive functioning neuro-circuitries within the aST and OB tasks. These data indicate differential and interactive effects of AUD and CUD on various neuro-circuitries within the adolescent brain

Blunted ventral striatal responses to anticipated rewards foreshadow problematic drug use in novelty-seeking adolescents

Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use. We find that diminished BOLD activity in mesolimbic (ventral striatal and midbrain) and prefrontal cortical (dorsolateral prefrontal cortex) regions during reward anticipation at age 14 predicts problematic drug use at age 16. Lower psychometric conscientiousness and steeper discounting of future rewards at age 14 also predicts problematic drug use at age 16, but the neural responses independently predict more variance than psychometric measures. Together, these findings suggest that diminished neural responses to anticipated rewards in novelty-seeking adolescents may increase vulnerability to future problematic drug use

Structural and Functional Imaging Studies in Chronic Cannabis Users: A Systematic Review of Adolescent and Adult Findings

Background: The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. Methods: Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. Results: One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. Limitations: However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. Conclusion: Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives

Μελέτη της επίδρασης της ανταμοιβής στους νοητικούς μηχανισμούς λήψης απόφασης σε ασθενείς με σχιζοφρένεια και χρήστες κάνναβης

Η χρόνια χρήση κάνναβης και η σχιζοφρένεια πιστεύεται ότι επηρεάζουν τη διεργασία ανταμοιβής. Ενώ έχουν μελετηθεί και για τις δύο περιπτώσεις οι συμπεριφορικές και νευρικές επιδράσεις στη διεργασία κινήτρων, δεν έχει μελετηθεί η αλληλεπίδρασή τους, αν και η χρόνια χρήση κάνναβης είνα κοινή στους ασθενείς με σχιζοφρένεια. Στην παρούσα μελέτη ογδόντα εννέα συμμετέχοντες χωρισμένοι σε τέσσερις ομάδες (δείγμα χρόνιων χρηστών κάνναβης και μη χρηστών· ασθενείς με σχιζοφρένεια χρήστες κάνναβης και μη χρήστες) εξετέλεσαν μια άσκηση αποφάσεων διπλής επιλογής, αφού είχαν προηγηθεί σήματα κινήτρων (υψηλή/χαμηλή ανταμοιβή/τιμωρία ή ουδέτερο), ενώ παράλληλα σαρώνονταν με τη χρήση Λειτουργικού Μαγνητικού Συντονισμού (fMRI). Η αναμονή ανταμοιβής και τιμωρίας είχε ως αποτέλεσμα την ενεργοποίηση περιοχών ενδιαφέροντος, όπως του θαλάμου, των βασικών γαγγλίων, της αμυγδαλής και του νησιωτικού φλοιού. Η χρόνια χρήση κάνναβης και η σχιζοφρένεια είχαν αντίθετα αποτελέσματα αναφορικά με την ευαισθησία αναμονής ανταμοιβής. Ειδικότερα, οι χρήστες του δείγματος και οι ασθενείς μη χρήστες παρουσίασαν ταχύτερη συμπεριφορική απόκριση και αυξημένη δραστηριότητα στον πρόσθιο/οπίσθιο νησιωτικό φλοιό στα σήματα υψηλού μεγέθους σε σύγκριση με το δείγμα μη χρηστών και ασθενών χρηστών. Το ίδιο μοτίβο αλληλεπίδρασης παρατηρήθηκε στην ενεργοποίηση του δεξιού θαλάμου όσον αφορά στην ανταμοιβή έναντι των σημάτων τιμωρίας. Η μελέτη αυτή παρείχε αποδείξεις για την αλληλεπίδραση της χρόνιας χρήσης κάνναβης και σχιζοφρένειας στη διεργασία ανταμοιβής και τιμωρίας και αναδεικνύει την ανάγκη περαιτέρω μελλοντικής έρευνας λόγω της σπουδαιότητας αυτής της αλληλεπίδρασης στην παθοφυσιολογία αυτών των καταστάσεων και των κλινικών συνεπειών τους.Chronic cannabis use and schizophrenia are both thought to affect reward processing. While behavioural and neural effects on incentive processing have been investigated in both populations, their interaction has not been studied, although chronic cannabis use is common among schizophrenia patients. In the present study eighty-nine participants divided into four groups (control chronic cannabis users and non-users; schizophrenia patient cannabis users and non-users) performed a two-choice decision task, preceded by incentive cues (high/low reward/punishment or neutral), while being scanned using functional magnetic resonance imaging. Reward and punishment anticipation resulted in activation of regions of interest including the thalamus, striatum, amygdala and insula. Chronic cannabis use and schizophrenia had opposing effects on reward anticipation sensitivity. More specifically control users and patient non-users showed faster behavioural responses and increased activity in anterior/posterior insula for high magnitude cues compared to control non-users and patient users. The same interaction pattern was observed in the activation of the right thalamus for reward versus punishment cues. This study provided evidence for the interaction of chronic cannabis use and schizophrenia on reward and punishment processing and highlights the need for future research addressing the significance of this interaction for the pathophysiology of these conditions and its clinical consequences

Reward-Related Dorsal Striatal Activity Differences between Former and Current Cocaine Dependent Individuals during an Interactive Competitive Game

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses)

Cannabis dampens the effects of music in brain regions sensitive to reward and emotion

Background: Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here we investigate the effects of cannabis on listening to music - a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol (CBD), which may offset cannabis-related harms. Methods: Across three sessions, sixteen cannabis users inhaled cannabis with CBD, cannabis without CBD, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging (fMRI) within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (p<0.05). Results: Compared to placebo, cannabis without CBD dampened response to music in bilateral auditory cortex (right: p=0.005, left: p=0.008), right hippocampus/parahippocampal gyrus (p=0.025), right amygdala (p=0.025) and right ventral striatum (p=0.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (p=0.002) and increased functional connectivity with auditory cortex (right: p=0.000, left: p=0.000), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by CBD (right: p=0.003, left: p=0.030), and cannabis with CBD did not differ from placebo on any fMRI measures. Both types of cannabis increased ratings of wanting to listen to music (p<0.002) and enhanced sound perception (p<0.001). Conclusions: Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol

Drug and non-drug reward processing in cigarette and cannabis users

Most people who try psychoactive drugs never become addicted. Theoretically, hypersensitivity to drug rewards and hyposensitivity to non-drug rewards may contribute to the development of drug addiction. In chapter 1, I review this literature, focusing on the psychology and neuroscience of reward processing, in nicotine and cannabis addictions. In chapter 2, using a novel task (the DReaM-Choice), I demonstrate that dependent (n=20), compared with occasional smokers (n=20), had greater motivation for and liking of cigarettes, but displayed little evidence of a difference in non-drug reward processing. Surprisingly, I also show the effects of 12 hour abstinence on reward processing were similar in dependent and occasional smokers. I then report a functional magnetic-resonance-imaging (fMRI) experiment (chapter 3), in which dependent smokers (n=22) had greater behavioural motivation for cigarettes and a stronger neural response to winning cigarettes than occasional smokers (n=20). However, there were no differences between the groups in behavioural or neural processing of the non-drug reward (music). I attempted to lessen the motivation to smoke cigarettes in the study reported in chapter 4, by administering a dopamine D2/3 receptor agonist (0.5mg pramipexole) to both dependent (n=20) and occasional (n=20) smokers. Pramipexole had no impact on motivation to smoke cigarettes, though it did impair reward learning and effort-related decision-making for monetary reward. In chapter 5, I found that, in non-dependent cannabis users (n=17), acutely administered cannabis reduced motivation for monetary reward; an effect which was moderated by the presence of cannabidiol in the cannabis. In a separate study, I demonstrate that dependent cannabis users (n=20) had impaired reward learning, but were not amotivated, relative to non-dependent, drug-using controls (n=20). Finally, in chapter 6, I summarise my findings, discuss their theoretical and clinical implications, consider their limitations and suggest future research directions for the field of reward processing in addiction

Associations between regular cannabis use and brain resting-state functional connectivity in adolescents and adults

BACKGROUND/AIM: Cannabis use is highly prevalent in adolescents; however, little is known about its effects on adolescent brain function. METHOD: Resting-state functional magnetic resonance imaging was used in matched groups of regular cannabis users (N = 70, 35 adolescents: 16-17 years old, 35 adults: 26-29 years old) and non-regular-using controls (N = 70, 35 adolescents/35 adults). Pre-registered analyses examined the connectivity of seven major cortical and sub-cortical brain networks (default mode network, executive control network (ECN), salience network, hippocampal network and three striatal networks) using seed-based analysis methods with cross-sectional comparisons between user groups and age groups. RESULTS: The regular cannabis use group (across both age groups), relative to controls, showed localised increases in connectivity only in the ECN analysis. All networks showed localised connectivity differences based on age group, with the adolescents generally showing weaker connectivity than adults, consistent with the developmental effects. Mean connectivity across entire network regions of interest (ROIs) was also significantly decreased in the ECN in adolescents. However, there were no significant interactions found between age group and user group in any of the seed-based or ROI analyses. There were also no associations found between cannabis use frequency and any of the derived connectivity measures. CONCLUSION: Regular cannabis use is associated with changes in connectivity of the ECN, which may reflect allostatic or compensatory changes in response to regular cannabis intoxication. However, these associations were not significantly different in adolescents compared to adults