Guillaume Sescousse

Pathological Choice: The Neuroscience of Gambling and Gambling Addiction

Gambling is pertinent to neuroscience research for at least two reasons. First, gambling is a naturalistic and pervasive example of risky decision making, and thus gambling games can provide a paradigm for the investigation of human choice behavior and “irrationality.” Second, excessive gambling involvement (i.e., pathological gambling) is currently conceptualized as a behavioral addiction, and research on this condition may provide insights into addictive mechanisms in the absence of exogenous drug effects. This article is a summary of topics covered in a Society for Neuroscience minisymposium, focusing on recent advances in understanding the neural basis of gambling behavior, including translational findings in rodents and nonhuman primates, which have begun to delineate neural circuitry and neurochemistry involved.

Disruption of Reward Processing in Addiction : An Image-Based Meta-analysis of Functional Magnetic Resonance Imaging Studies

Importance Disrupted reward processing, mainly driven by striatal dysfunction, is a key characteristic of addictive behaviors. However, functional magnetic resonance imaging (fMRI) studies have reported conflicting results, with both hypoactivations and hyperactivations during anticipation and outcome notification of monetary rewards in addiction. Objective To determine the nature and direction of reward-processing disruptions during anticipation and outcome notification of monetary rewards in individuals with addiction using image-based meta-analyses of fMRI studies. Data Sources Relevant publications were identified searching PubMed (inclusion until March 2015) using the following terms: reward, fMRI, substance use, cocaine, cannabis, opiates, alcohol, nicotine, smokers, gambling, gamblers, gaming, and gamers. Authors of included articles were contacted to obtain statistical fMRI maps. Study Selection Inclusion criteria: reward task involving monetary reward anticipation and/or outcome; participants showing addictive behaviors; and healthy control group. Exclusion criteria: participants aged younger than 18 years; recreational substance use or gambling; participants at risk for addictive behaviors; and studies using the same patient data as other included studies. Data Extraction and Synthesis Study procedures were conducted in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. Using Seed-based d Mapping software, meta-analyses were performed using random-effect nonparametric statistics with group whole brain T-maps from individual studies as input. Analyses were performed across all addictions and for substance and gambling addictions separately. Main Outcomes and Measures Group differences (individuals with addiction vs control individuals) in reward-related brain activation during reward anticipation and outcome using fMRI (planned before data collection). Results Twenty-five studies were included in the meta-analysis, representing 643 individuals with addictive behaviors and 609 healthy control individuals. During reward anticipation, individuals with substance and gambling addictions showed decreased striatal activation compared with healthy control individuals. During reward outcome, individuals with substance addiction showed increased activation in the ventral striatum, whereas individuals with gambling addiction showed decreased activation in the dorsal striatum compared with healthy control individuals. Conclusions and Relevance Striatal hypoactivation in individuals with addiction during reward anticipation and in individuals with gambling addiction during reward outcome is in line with the reward-deficiency theory of addiction. However, the combination of hypoactivation during reward anticipation and hyperactivation during reward outcome in the striatum of individuals with substance addiction may be explained using learning-deficit theory.

Can Pornography be Addictive? An fMRI Study of Men Seeking Treatment for Problematic Pornography Use

Pornography consumption is highly prevalent, particularly among young adult males. For some individuals, problematic pornography use (PPU) is a reason for seeking treatment. Despite the pervasiveness of pornography, PPU appears under-investigated, including with respect to the underlying neural mechanisms. Using functional magnetic resonance imaging (fMRI), we examined ventral striatal responses to erotic and monetary stimuli, disentangling cue-related ‘wanting’ from reward-related ‘liking’ among 28 heterosexual males seeking treatment for PPU and 24 heterosexual males without PPU. Subjects engaged in an incentive delay task in the scanner, in which they received erotic or monetary rewards preceded by predictive cues. Blood-oxygen-level-dependent responses to erotic and monetary cues were analyzed and examined with respect to self-reported data on sexual activity collected over the 2 preceding months. Men with and without PPU differed in their striatal responses to cues predicting erotic pictures but not in their responses to erotic pictures. PPU subjects when compared with control subjects showed increased activation of ventral striatum specifically for cues predicting erotic pictures but not for cues predicting monetary gains. Relative sensitivity to cues predicting erotic pictures vs monetary gains was significantly related to the increased behavioral motivation to view erotic images (suggestive of higher ‘wanting’), severity of PPU, amount of pornography use per week, and number of weekly masturbations. Our findings suggest that, similar to what is observed in substance and gambling addictions, the neural and behavioral mechanisms associated with the anticipatory processing of cues specifically predicting erotic rewards relate importantly to clinically relevant features of PPU. These findings suggest that PPU may represent a behavioral addiction and that interventions helpful in targeting behavioral and substance addictions warrant consideration for adaptation and use in helping men with PPU.

Endogenous cortisol levels are associated with an imbalanced striatal sensitivity to monetary versus non-monetary cues in pathological gamblers

Pathological gambling is a behavioral addiction characterized by a chronic failure to resist the urge to gamble. It shares many similarities with drug addiction. Glucocorticoid hormones including cortisol are thought to play a key role in the vulnerability to addictive behaviors, by acting on the mesolimbic reward pathway. Based on our previous report of an imbalanced sensitivity to monetary versus non-monetary incentives in the ventral striatum of pathological gamblers (PGs), we investigated whether this imbalance was mediated by individual differences in endogenous cortisol levels. We used functional magnetic resonance imaging (fMRI) and examined the relationship between cortisol levels and the neural responses to monetary versus non-monetary cues, while PGs and healthy controls were engaged in an incentive delay task manipulating both monetary and erotic rewards. We found a positive correlation between cortisol levels and ventral striatal responses to monetary versus erotic cues in PGs, but not in healthy controls. This indicates that the ventral striatum is a key region where cortisol modulates incentive motivation for gambling versus non-gambling related stimuli in PGs. Our results extend the proposed role of glucocorticoid hormones in drug addiction to behavioral addiction, and help understand the impact of cortisol on reward incentive processing in PGs.

Visual Sexual Stimuli-Cue or Reward? A Perspective for Interpreting Brain Imaging Findings on Human Sexual Behaviors.

There is an increasing number of neuroimaging studies using visual sexual stimuli (VSS), especially within the emerging field of research on compulsive sexual behaviors (CSB). A central question in this field is whether behaviors such as excessive pornography consumption share common brain mechanisms with widely studied substance and behavioral addictions. Depending on how VSS are conceptualized, different predictions can be formulated within the frameworks of Reinforcement Learning or Incentive Salience Theory, where a crucial distinction is made between conditioned and unconditioned stimuli (related to reward anticipation vs. reward consumption, respectively). Surveying 40 recent human neuroimaging studies we show existing ambiguity about the conceptualization of VSS. Therefore, we feel that it is important to address the question of whether VSS should be considered as conditioned stimuli (cue) or unconditioned stimuli (reward). Here we present our own perspective, which is that in most laboratory settings VSS play a role of reward, as evidenced by: (1) experience of pleasure while watching VSS, possibly accompanied by genital reaction; (2) reward-related brain activity correlated with these pleasurable feelings in response to VSS; (3) a willingness to exert effort to view VSS similarly as for other rewarding stimuli such as money; and (4) conditioning for cues predictive of VSS. We hope that this perspective article will initiate a scientific discussion on this important and overlooked topic and increase attention for appropriate interpretations of results of human neuroimaging studies using VSS.

The role of the habenula in the transition from reward to misery in substance use and mood disorders

The habenula (Hb) is an evolutionary well-conserved structure located in the epithalamus. The Hb receives inputs from the septum, basal ganglia, hypothalamus, anterior cingulate and medial prefrontal cortex, and projects to several midbrain centers, most importantly the inhibitory rostromedial tegmental nucleus (RMTg) and the excitatory interpeduncular nucleus (IPN), which regulate the activity of midbrain monoaminergic nuclei. The Hb is postulated to play a key role in reward and aversion processing across species, including humans, and to be implicated in the different stages of transition from recreational drug intake to addiction and co-morbid mood disorders. The Hb is divided into two anatomically and functionally distinct nuclei, the lateral (LHb) and the medial (MHb), which are primarily involved in reward-seeking (LHb) and misery-fleeing (MHb) behavior by controlling the RMTg and IPN, respectively. This review provides a neuroanatomical description of the Hb, discusses preclinical and human findings regarding its role in the development of addiction and co-morbid mood disorders, and addresses future directions in this area.

Sex, Impulsivity, and Anxiety: Interplay between Ventral Striatum and Amygdala Reactivity in Sexual Behaviors

Comorbidity of mood/anxiety disorders and addictive behaviors is widely reported in the clinical literature. Many psychological models of addictive and risk behaviors assume an appetitive component (related to impulsivity) and/or a mood regulation component (related to anxiety; [Verheul et al., 1999

Amplified Striatal Responses to Near-Miss Outcomes in Pathological Gamblers

Near-misses in gambling games are losing events that come close to a win. Near-misses were previously shown to recruit reward-related brain regions including the ventral striatum, and to invigorate gambling behavior, supposedly by fostering an illusion of control. Given that pathological gamblers are particularly vulnerable to such cognitive illusions, their persistent gambling behavior might result from an amplified striatal sensitivity to near-misses. In addition, animal studies have shown that behavioral responses to near-miss-like events are sensitive to dopamine, but this dopaminergic influence has not been tested in humans. To investigate these hypotheses, we recruited 22 pathological gamblers and 22 healthy controls who played a slot machine task delivering wins, near-misses and full-misses, inside an fMRI scanner. Each participant played the task twice, once under placebo and once under a dopamine D2 receptor antagonist (sulpiride 400 mg), in a double-blind, counter-balanced design. Participants were asked about their motivation to continue gambling throughout the task. Across all participants, near-misses elicited higher motivation to continue gambling and increased striatal responses compared with full-misses. Crucially, pathological gamblers showed amplified striatal responses to near-misses compared with controls. These group differences were not observed following win outcomes. In contrast to our hypothesis, sulpiride did not induce any reliable modulation of brain responses to near-misses. Together, our results demonstrate that pathological gamblers have amplified brain responses to near-misses, which likely contribute to their persistent gambling behavior. However, there is no evidence that these responses are influenced by dopamine. These results have implications for treatment and gambling regulation.

Increased Striatal Dopamine Synthesis Capacity in Gambling Addiction

BACKGROUND The hypothesis that dopamine plays an important role in the pathophysiology of pathological gambling is pervasive. However, there is little to no direct evidence for a categorical difference between pathological gamblers and healthy control subjects in terms of dopamine transmission in a drug-free state. Here we provide evidence for this hypothesis by comparing dopamine synthesis capacity in the dorsal and ventral parts of the striatum in 13 pathological gamblers and 15 healthy control subjects. METHODS This was achieved using [18F]fluoro-levo-dihydroxyphenylalanine dynamic positron emission tomography scans and striatal regions of interest that were hand-drawn based on visual inspection of individual structural magnetic resonance imaging scans. RESULTS Our results show that dopamine synthesis capacity was increased in pathological gamblers compared with healthy control subjects. Dopamine synthesis was 16% higher in the caudate body, 17% higher in the dorsal putamen, and 17% higher in the ventral striatum in pathological gamblers compared with control subjects. Moreover, dopamine synthesis capacity in the dorsal putamen and caudate head was positively correlated with gambling distortions in pathological gamblers. CONCLUSIONS Taken together, these results provide empirical evidence for increased striatal dopamine synthesis in pathological gambling.

Gambling Rats and Gambling Addiction: Reconciling the Role of Dopamine in Irrationality

Pathological gambling is a behavioral addiction that is characterized by excessive (monetary) risk-taking in the face of negative consequences, like bankruptcy or relationship problems. Brain dopamine has been suggested to play an important role in both risky behaviors and gambling addiction. Yet,