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Disordered gambling: a behavioral addiction
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Disordered gambling: a behavioral addiction Luke Clark and Eve H Limbrick-Oldfield Developments in psychiatry have ratified the existence of behavioral addictions, that certain activities such as gambling or video-game play may be considered addictive in the absence of exogenous (i.e. drug-induced) stimulation of brain reinforcement circuitry. This article describes recent advances in understanding the neurobiological basis of behavioral addiction, with a focus on pathological gambling as the prototypical disorder. We describe positron emission tomography (PET) studies characterizing dopaminergic transmission, and functional imaging studies of reward processing and gambling-related cognitive distortions. The current evidence not only indicates changes in pathological gamblers in core circuitry implicated in drug addiction, but also highlights some subtle differences. Behavioral addictions can also provide experimental traction on distinguishing vulnerability markers for addictions from the active detrimental effects of chronic drug use. Address Department of Psychology, University of Cambridge, Cambridge, UK Corresponding author: Clark, Luke ([email protected])
Current Opinion in Neurobiology 2013, 23:655–659 This review comes from a themed issue on Addiction Edited by Barry Everitt and Ulrike Heberlein For a complete overview see the Issue and the Editorial Available online 1st February 2013 0959-4388/$ – see front matter, # 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.conb.2013.01.004
In the imminent DSM5, one of the major proposed modifications is the reclassification of pathological gambling from the Impulse Control Disorders category into a new category labeled ‘Addiction and Related Disorders’. This decision ratifies the concept of a behavioral addiction; that people may compulsively and dysfunctionally engage in an activity that does not involve exogenous drug administration, and that it is scientifically tractable to consider such conditions within an addictions framework. This decision for pathological gambling has been predicated by several lines of convergent evidence, showing overlap between this condition and drug addiction in terms of clinical phenomenology (e.g. withdrawal symptoms, comorbidity), heritability, and the neurobiological profile [1]. The past two years has seen particular strides in characterizing the neural systems that are dysregulated in pathological gambling, chiefly using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). As we www.sciencedirect.com
will review below, these studies strongly reinforce the notion of overlapping circuitry with drug addiction. They also highlight some subtle but provocative differences, which may ultimately provide insights into mechanisms of addiction that cannot be readily observed in neural systems compromised by drugs of abuse. Pathological gambling (to be renamed disordered gambling) is the only behavioral addiction to be recognized in the DSM5, and hence it is likely to serve as a ‘blueprint’ for research on other syndromes that include excessive video-gaming [2], Internet addiction [3], and compulsive shopping [4]. This overview will also highlight the nascent neurobiological findings on these conditions. Novel targets in obesity and/or binge eating may also benefit from an addictions model [5], but this is beyond the scope of the present article.
Neurochemistry Investigation of dopamine transmission has been a logical starting point for studies of pathological gambling. Early findings on the rates of dopamine polymorphisms in pathological gambling [6,7], and of plasma alterations in dopamine metabolites [8] were extended by a series of provocative case reports describing the sudden emergence of disordered gambling in patients with Parkinson’s Disease, linked to treatment with dopamine receptor agonist medications [9,10]. Large-scale studies have corroborated this phenomenon, as part of a constellation of reward-driven behaviors that also includes compulsive shopping and hypersexuality [11,12]. The likelihood of a patient developing problematic gambling as a side-effect is predicted by male gender, earlier age of PD onset, and familial or personal alcohol or nicotine problems, and may be primarily linked to D3-receptor preferent medications including pramipexole [13]. The fundamental question of how (or whether) these drug actions are altered by the Parkinsonian neuropathology remains unclear. The most direct approach for quantifying dopamine transmission in the human brain is via PET imaging of dopamine ligands. Building upon work by Volkow and others showing a robust reduction in striatal D2-receptor availability across different groups of substance users dependent on several distinct drugs [14–16], four recent papers have examined this marker in patients with primary (i.e. related) pathological gambling non-Parkinson’s [17,18,19,20]. Each study found no significant group difference in raclopride binding, although a number of correlative effects were observed, suggesting that dopamine transmission is nonetheless relevant to the illness. For example, baseline striatal D2-receptor binding was Current Opinion in Neurobiology 2013, 23:655–659
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negatively related to trait impulsivity [18]. Using an alternative ligand, the D3-preferent PHNO ligand, a positive correlation was observed between binding in substantia nigra and problem gambling severity [17]. Two of these studies additionally measured the extent of dopamine release (i.e. raclopride displacement) induced by a gambling task. There was again no overall group difference from controls, but a positive correlation with subjective excitement [20] and gambling severity [19]. Two further studies in patients with Parkinson’s Disease have also detected greater dopamine release in patients with the pathological gambling side-effect [21,22]. These effects contrast with evidence of blunted dopamine release in drug addiction [23,24], measuring raclopride displacement by a low-dose stimulant like methylphenidate. With the requisite caution in invoking the null hypothesis, the results in pathological gamblers are also pertinent to the unresolved chicken-and-egg debate in drug addiction: do dopaminergic abnormalities represent a pre-existing vulnerability or arise directly as a ‘toxic’ (or at least neuroadaptive) consequence of chronic drug use? The lack of effect in an illness that shares considerable vulnerability with drug addiction [25] supports longitudinal studies in experimental animals, that D2-receptor levels decrease following short-term stimulant administration [26,27]. Less is known about the integrity of other neurotransmitter systems in pathological gambling. In terms of therapeutic targets, it should be noted that dopamine receptor antagonists have shown limited efficacy in preliminary trials [28–30] — perhaps because D2-receptor reductions are only present in a subset of patients such as those with high impulsivity [18], suggesting avenues for tailored interventions. The form of pharmacotherapy with the strongest empirical support at present is the opioid receptor antagonists, which include naltrexone [31,32]. These drugs have been used in the clinical management of heroin and alcohol dependent patients for several decades. Using a gambling task in healthy volunteers, the opioid receptor antagonist naloxone attenuated the response in medial prefrontal cortex to monetary wins, and increased responses to monetary losses in insula and anterior cingulate, providing a potential mechanism for its action in pathological gambling [33]. Norepinephrine may also be implicated in the peripheral arousal associated with gambling; although the direction of effect is currently unclear. Using alpha-2 adrenergic probes, pathological gamblers showed a blunted neuroendocrine response to clonidine [34], but enhanced amygdala recruitment by yohimbine [35]. As PET ligands become more widely available for these systems, studies assessing the integrity of opioid and norepinephrine transmission in pathological gamblers are needed to elucidate the mechanisms underlying these preliminary treatment effects. Current Opinion in Neurobiology 2013, 23:655–659
Neuroimaging While structural brain changes have been widely observed in magnetic resonance imaging (MRI) studies in patients with drug addiction [36,37,38], these studies do not allow the neural signature of the addiction process to be isolated from the possible neurotoxic sequelae of chronic drug use. However, such atrophy should be absent in pathological gamblers, and two studies were unable to detect any significant differences in gray matter volume in pathological gamblers using voxel-based morphometry [39,36]. Using diffusion tensor imaging (DTI) to compare the white matter integrity of pathological gamblers to healthy controls, not only widespread reduced white matter integrity has been reported [39], but also reduced integrity of the corpus callosum [40]. Such structural differences could represent either a premorbid susceptibility, or reflect neuroadaptive changes as a result of chronic gambling behavior. A fruitful line of enquiry has used fMRI to examine neural activity during reinforcement processing and decisionmaking tasks, where the underlying circuitry in healthy volunteers is reasonably well delineated [41]. Early studies of pathological gamblers found reduced functional responses in the striatum [42] and medial PFC [43] relative to controls. However, in more recent studies that have teased apart the temporal dynamics within a trial, a more complicated pattern emerges. Using a probabilistic choice game to model anticipatory processing (the spin of a wheel of fortune), pathological gamblers showed greater activity during the anticipation of large rewards over small rewards in dorsal striatum [44]; dorsal striatum and OFC also tracked gain-related expected value to a greater extent in the pathological gamblers. However, using a modified version of the monetary-incentive delay task to separate anticipatory and outcome-related processing, signal reductions were observed in the same fronto-striatal circuitry in pathological gamblers at both anticipation and gain outcomes [45]. While these results seem to defy reconciliation, it should be noted that the literature on appetitive processing in drug addiction shows similar inconsistency (i.e. reports of hyperactivity or hypoactivity in the same regions) [46]. Several methodological features may prove critical. For example, while the two studies in pathological gambling both employed monetary rewards, images of money in a realistic card game [44] is very different from verbal feedback in a more abstract task [45], and the use of associated cues may drive incentive salience [47]. Sescousse et al. (personal communication) compared neural responses to both financial gains and a primary reward (erotica) in pathological gamblers, and in line with this hypothesis, hyporeactivity was observed for the erotic cues, contrasting with hyper-reactivity to the financial outcomes. In parallel with these case–control neuroimaging studies, other work has begun to investigate the neural substrates of various cognitive distortions relevant to gambling behavior, and which appear to be elevated in pathological www.sciencedirect.com
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gamblers [48]. Using a simulated slot machine task, it was seen that ‘near miss’ outcomes (i.e. unsuccessful gamblers who fall close to a jackpot) increased the subjective desire to gamble, and recruited overlapping neural circuitry (in ventral striatum and anterior insula) to the jackpot wins [49]. Using the same task in a group of regular players, the midbrain response to near misses covaried with the gambling severity [50], suggesting that this distortion may be magnified in pathological gamblers. The ‘Gambler’s Fallacy’ is a second distortion in the processing of random sequences, such as in a coin-flipping task. Following a run of one consecutive outcome (e.g. three consecutive heads), the Gambler’s Fallacy is to predict that the other outcome (tails) is due. Comparing trial-by-trial predictions based on the Gambler’s Fallacy or a reinforcement learning model, an fMRI study reported that the dorsal striatum distinguished these choice strategies [51]. Other work has implicated the lateral prefrontal cortex in regulating these choice switches following runs of the same outcome, such that direct current stimulation of this region exaggerated the Gambler’s Fallacy [52]. These studies have begun to capture the momentary cognitions that occur during a gambling episode, and which may precipitate compulsive risk-taking (see also [53]). It remains unclear whether parallels to these distortions exist in drug addiction, and it should be noted that these paradigms are validated primarily in nongamblers to date, and are largely unexplored in pathological gamblers. This work is also increasingly informed by models of human choice from behavioral economics. A recent cognitive study characterized the probability weighting function from Prospect Theory in pathological gamblers, showing a global elevation in risk-taking across the entirety of the probability distribution [54]. Using fMRI to quantify how the neural representation of reward varies as a function of either its delay (i.e. temporal discounting) or level of uncertainty (i.e. probability discounting), it was found that pathological gamblers showed stronger value representations in ventral striatum during delay discounting (as well as preference for immediate rewards), but weaker value representations in the same region during probability discounting (where they were less risk averse) [55]. In a group of Parkinson’s patients, it has been shown that dopamine receptor agonists have a differential effect on reward processing, dependent upon the susceptibility of the individual to compulsive behaviors, such as gambling. While the striatal response to positive prediction errors was increased by dopamine stimulation in susceptible individuals, the opposite pattern emerged for nonsusceptible individuals [56]. Collectively, these experiments implicate distortions in the value functions that relate reinforcement to both time and uncertainty in problem gamblers.
Internet and video-game addiction The DSM5 prerelease has also flagged ‘Internet addiction’ as a possible candidate for future inclusion in www.sciencedirect.com
the Addictions category. The evidence base on this syndrome is at an early stage, and derives predominantly from South Korea and China, where the prevalence of this condition seems particularly high, plausibly as a result of widespread high-speed Internet access. The condition is at present defined from a direct translation of the pathological gambling criteria [57], but clinical validity may prove superior for specific activities on the Internet such as online gambling, or multiplayer online video-games like ‘World of Warcraft’. Structural imaging studies of excessive Internet users have described gray matter reductions in the cingulate gyrus and insula cortex [58] and reduced white-matter diffusivity in the orbitofrontal region and cingulum [59]. Reduced striatal dopamine binding has also been reported in a raclopride PET study [60]. These results are perhaps surprising in light of the aforementioned PET and structural MRI data in pathological gamblers, although a distinct set of studies has explored neuroplasticity with motor-skill learning in the context of video-games [61] and it should be noted that most studies of Internet or gaming addiction are in adolescents or young adults, where effects may be more accurately described as an interaction with healthy maturation than an active pathological process. A relatively large European multicenter imaging study comparing frequent and infrequent video-game players at age 14 found increased striatal gray matter volume in the frequent players, which also predicted faster deliberation times in a gambling game [62]. Functional brain changes have been identified in excessive Internet/video-game users, including reactivity to game cues in the anterior cingulate and parahippocampal gyrus [63], and reductions in the error-related negativity [64] and response inhibition [65], each of which is broadly reminiscent of changes observed in drug addiction. Assuming that behavioral addictions arise from the interaction between properties of the behavior, and vulnerabilities of the individual, further consideration of the ‘structural characteristics’ [66] of video-games and other Internet activities that convey their abuse potential is required, within the same framework that cognitive distortions have been explored in gambling behavior.
Acknowledgements This work was supported by a Medical Research Council grant G1100554 to LC and was completed at the Behavioural and Clinical Neuroscience Institute, which is supported by a consortium award from the MRC and Wellcome Trust.
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Current Opinion in Neurobiology 2013, 23:655–659
Disordered gambling: a behavioral addiction Luke Clark and Eve H Limbrick-Oldfield Developments in psychiatry have ratified the existence of behavioral addictions, that certain activities such as gambling or video-game play may be considered addictive in the absence of exogenous (i.e. drug-induced) stimulation of brain reinforcement circuitry. This article describes recent advances in understanding the neurobiological basis of behavioral addiction, with a focus on pathological gambling as the prototypical disorder. We describe positron emission tomography (PET) studies characterizing dopaminergic transmission, and functional imaging studies of reward processing and gambling-related cognitive distortions. The current evidence not only indicates changes in pathological gamblers in core circuitry implicated in drug addiction, but also highlights some subtle differences. Behavioral addictions can also provide experimental traction on distinguishing vulnerability markers for addictions from the active detrimental effects of chronic drug use. Address Department of Psychology, University of Cambridge, Cambridge, UK Corresponding author: Clark, Luke ([email protected])
Current Opinion in Neurobiology 2013, 23:655–659 This review comes from a themed issue on Addiction Edited by Barry Everitt and Ulrike Heberlein For a complete overview see the Issue and the Editorial Available online 1st February 2013 0959-4388/$ – see front matter, # 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.conb.2013.01.004
In the imminent DSM5, one of the major proposed modifications is the reclassification of pathological gambling from the Impulse Control Disorders category into a new category labeled ‘Addiction and Related Disorders’. This decision ratifies the concept of a behavioral addiction; that people may compulsively and dysfunctionally engage in an activity that does not involve exogenous drug administration, and that it is scientifically tractable to consider such conditions within an addictions framework. This decision for pathological gambling has been predicated by several lines of convergent evidence, showing overlap between this condition and drug addiction in terms of clinical phenomenology (e.g. withdrawal symptoms, comorbidity), heritability, and the neurobiological profile [1]. The past two years has seen particular strides in characterizing the neural systems that are dysregulated in pathological gambling, chiefly using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). As we www.sciencedirect.com
will review below, these studies strongly reinforce the notion of overlapping circuitry with drug addiction. They also highlight some subtle but provocative differences, which may ultimately provide insights into mechanisms of addiction that cannot be readily observed in neural systems compromised by drugs of abuse. Pathological gambling (to be renamed disordered gambling) is the only behavioral addiction to be recognized in the DSM5, and hence it is likely to serve as a ‘blueprint’ for research on other syndromes that include excessive video-gaming [2], Internet addiction [3], and compulsive shopping [4]. This overview will also highlight the nascent neurobiological findings on these conditions. Novel targets in obesity and/or binge eating may also benefit from an addictions model [5], but this is beyond the scope of the present article.
Neurochemistry Investigation of dopamine transmission has been a logical starting point for studies of pathological gambling. Early findings on the rates of dopamine polymorphisms in pathological gambling [6,7], and of plasma alterations in dopamine metabolites [8] were extended by a series of provocative case reports describing the sudden emergence of disordered gambling in patients with Parkinson’s Disease, linked to treatment with dopamine receptor agonist medications [9,10]. Large-scale studies have corroborated this phenomenon, as part of a constellation of reward-driven behaviors that also includes compulsive shopping and hypersexuality [11,12]. The likelihood of a patient developing problematic gambling as a side-effect is predicted by male gender, earlier age of PD onset, and familial or personal alcohol or nicotine problems, and may be primarily linked to D3-receptor preferent medications including pramipexole [13]. The fundamental question of how (or whether) these drug actions are altered by the Parkinsonian neuropathology remains unclear. The most direct approach for quantifying dopamine transmission in the human brain is via PET imaging of dopamine ligands. Building upon work by Volkow and others showing a robust reduction in striatal D2-receptor availability across different groups of substance users dependent on several distinct drugs [14–16], four recent papers have examined this marker in patients with primary (i.e. related) pathological gambling non-Parkinson’s [17,18,19,20]. Each study found no significant group difference in raclopride binding, although a number of correlative effects were observed, suggesting that dopamine transmission is nonetheless relevant to the illness. For example, baseline striatal D2-receptor binding was Current Opinion in Neurobiology 2013, 23:655–659
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negatively related to trait impulsivity [18]. Using an alternative ligand, the D3-preferent PHNO ligand, a positive correlation was observed between binding in substantia nigra and problem gambling severity [17]. Two of these studies additionally measured the extent of dopamine release (i.e. raclopride displacement) induced by a gambling task. There was again no overall group difference from controls, but a positive correlation with subjective excitement [20] and gambling severity [19]. Two further studies in patients with Parkinson’s Disease have also detected greater dopamine release in patients with the pathological gambling side-effect [21,22]. These effects contrast with evidence of blunted dopamine release in drug addiction [23,24], measuring raclopride displacement by a low-dose stimulant like methylphenidate. With the requisite caution in invoking the null hypothesis, the results in pathological gamblers are also pertinent to the unresolved chicken-and-egg debate in drug addiction: do dopaminergic abnormalities represent a pre-existing vulnerability or arise directly as a ‘toxic’ (or at least neuroadaptive) consequence of chronic drug use? The lack of effect in an illness that shares considerable vulnerability with drug addiction [25] supports longitudinal studies in experimental animals, that D2-receptor levels decrease following short-term stimulant administration [26,27]. Less is known about the integrity of other neurotransmitter systems in pathological gambling. In terms of therapeutic targets, it should be noted that dopamine receptor antagonists have shown limited efficacy in preliminary trials [28–30] — perhaps because D2-receptor reductions are only present in a subset of patients such as those with high impulsivity [18], suggesting avenues for tailored interventions. The form of pharmacotherapy with the strongest empirical support at present is the opioid receptor antagonists, which include naltrexone [31,32]. These drugs have been used in the clinical management of heroin and alcohol dependent patients for several decades. Using a gambling task in healthy volunteers, the opioid receptor antagonist naloxone attenuated the response in medial prefrontal cortex to monetary wins, and increased responses to monetary losses in insula and anterior cingulate, providing a potential mechanism for its action in pathological gambling [33]. Norepinephrine may also be implicated in the peripheral arousal associated with gambling; although the direction of effect is currently unclear. Using alpha-2 adrenergic probes, pathological gamblers showed a blunted neuroendocrine response to clonidine [34], but enhanced amygdala recruitment by yohimbine [35]. As PET ligands become more widely available for these systems, studies assessing the integrity of opioid and norepinephrine transmission in pathological gamblers are needed to elucidate the mechanisms underlying these preliminary treatment effects. Current Opinion in Neurobiology 2013, 23:655–659
Neuroimaging While structural brain changes have been widely observed in magnetic resonance imaging (MRI) studies in patients with drug addiction [36,37,38], these studies do not allow the neural signature of the addiction process to be isolated from the possible neurotoxic sequelae of chronic drug use. However, such atrophy should be absent in pathological gamblers, and two studies were unable to detect any significant differences in gray matter volume in pathological gamblers using voxel-based morphometry [39,36]. Using diffusion tensor imaging (DTI) to compare the white matter integrity of pathological gamblers to healthy controls, not only widespread reduced white matter integrity has been reported [39], but also reduced integrity of the corpus callosum [40]. Such structural differences could represent either a premorbid susceptibility, or reflect neuroadaptive changes as a result of chronic gambling behavior. A fruitful line of enquiry has used fMRI to examine neural activity during reinforcement processing and decisionmaking tasks, where the underlying circuitry in healthy volunteers is reasonably well delineated [41]. Early studies of pathological gamblers found reduced functional responses in the striatum [42] and medial PFC [43] relative to controls. However, in more recent studies that have teased apart the temporal dynamics within a trial, a more complicated pattern emerges. Using a probabilistic choice game to model anticipatory processing (the spin of a wheel of fortune), pathological gamblers showed greater activity during the anticipation of large rewards over small rewards in dorsal striatum [44]; dorsal striatum and OFC also tracked gain-related expected value to a greater extent in the pathological gamblers. However, using a modified version of the monetary-incentive delay task to separate anticipatory and outcome-related processing, signal reductions were observed in the same fronto-striatal circuitry in pathological gamblers at both anticipation and gain outcomes [45]. While these results seem to defy reconciliation, it should be noted that the literature on appetitive processing in drug addiction shows similar inconsistency (i.e. reports of hyperactivity or hypoactivity in the same regions) [46]. Several methodological features may prove critical. For example, while the two studies in pathological gambling both employed monetary rewards, images of money in a realistic card game [44] is very different from verbal feedback in a more abstract task [45], and the use of associated cues may drive incentive salience [47]. Sescousse et al. (personal communication) compared neural responses to both financial gains and a primary reward (erotica) in pathological gamblers, and in line with this hypothesis, hyporeactivity was observed for the erotic cues, contrasting with hyper-reactivity to the financial outcomes. In parallel with these case–control neuroimaging studies, other work has begun to investigate the neural substrates of various cognitive distortions relevant to gambling behavior, and which appear to be elevated in pathological www.sciencedirect.com
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gamblers [48]. Using a simulated slot machine task, it was seen that ‘near miss’ outcomes (i.e. unsuccessful gamblers who fall close to a jackpot) increased the subjective desire to gamble, and recruited overlapping neural circuitry (in ventral striatum and anterior insula) to the jackpot wins [49]. Using the same task in a group of regular players, the midbrain response to near misses covaried with the gambling severity [50], suggesting that this distortion may be magnified in pathological gamblers. The ‘Gambler’s Fallacy’ is a second distortion in the processing of random sequences, such as in a coin-flipping task. Following a run of one consecutive outcome (e.g. three consecutive heads), the Gambler’s Fallacy is to predict that the other outcome (tails) is due. Comparing trial-by-trial predictions based on the Gambler’s Fallacy or a reinforcement learning model, an fMRI study reported that the dorsal striatum distinguished these choice strategies [51]. Other work has implicated the lateral prefrontal cortex in regulating these choice switches following runs of the same outcome, such that direct current stimulation of this region exaggerated the Gambler’s Fallacy [52]. These studies have begun to capture the momentary cognitions that occur during a gambling episode, and which may precipitate compulsive risk-taking (see also [53]). It remains unclear whether parallels to these distortions exist in drug addiction, and it should be noted that these paradigms are validated primarily in nongamblers to date, and are largely unexplored in pathological gamblers. This work is also increasingly informed by models of human choice from behavioral economics. A recent cognitive study characterized the probability weighting function from Prospect Theory in pathological gamblers, showing a global elevation in risk-taking across the entirety of the probability distribution [54]. Using fMRI to quantify how the neural representation of reward varies as a function of either its delay (i.e. temporal discounting) or level of uncertainty (i.e. probability discounting), it was found that pathological gamblers showed stronger value representations in ventral striatum during delay discounting (as well as preference for immediate rewards), but weaker value representations in the same region during probability discounting (where they were less risk averse) [55]. In a group of Parkinson’s patients, it has been shown that dopamine receptor agonists have a differential effect on reward processing, dependent upon the susceptibility of the individual to compulsive behaviors, such as gambling. While the striatal response to positive prediction errors was increased by dopamine stimulation in susceptible individuals, the opposite pattern emerged for nonsusceptible individuals [56]. Collectively, these experiments implicate distortions in the value functions that relate reinforcement to both time and uncertainty in problem gamblers.
Internet and video-game addiction The DSM5 prerelease has also flagged ‘Internet addiction’ as a possible candidate for future inclusion in www.sciencedirect.com
the Addictions category. The evidence base on this syndrome is at an early stage, and derives predominantly from South Korea and China, where the prevalence of this condition seems particularly high, plausibly as a result of widespread high-speed Internet access. The condition is at present defined from a direct translation of the pathological gambling criteria [57], but clinical validity may prove superior for specific activities on the Internet such as online gambling, or multiplayer online video-games like ‘World of Warcraft’. Structural imaging studies of excessive Internet users have described gray matter reductions in the cingulate gyrus and insula cortex [58] and reduced white-matter diffusivity in the orbitofrontal region and cingulum [59]. Reduced striatal dopamine binding has also been reported in a raclopride PET study [60]. These results are perhaps surprising in light of the aforementioned PET and structural MRI data in pathological gamblers, although a distinct set of studies has explored neuroplasticity with motor-skill learning in the context of video-games [61] and it should be noted that most studies of Internet or gaming addiction are in adolescents or young adults, where effects may be more accurately described as an interaction with healthy maturation than an active pathological process. A relatively large European multicenter imaging study comparing frequent and infrequent video-game players at age 14 found increased striatal gray matter volume in the frequent players, which also predicted faster deliberation times in a gambling game [62]. Functional brain changes have been identified in excessive Internet/video-game users, including reactivity to game cues in the anterior cingulate and parahippocampal gyrus [63], and reductions in the error-related negativity [64] and response inhibition [65], each of which is broadly reminiscent of changes observed in drug addiction. Assuming that behavioral addictions arise from the interaction between properties of the behavior, and vulnerabilities of the individual, further consideration of the ‘structural characteristics’ [66] of video-games and other Internet activities that convey their abuse potential is required, within the same framework that cognitive distortions have been explored in gambling behavior.
Acknowledgements This work was supported by a Medical Research Council grant G1100554 to LC and was completed at the Behavioural and Clinical Neuroscience Institute, which is supported by a consortium award from the MRC and Wellcome Trust.
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