Common neurobiological and psychological underpinnings of gambling and substance-use disorders
Introduction
The application of neuroimaging to examine gambling disorder (GD) began approximately 20 years ago: the first decade of neuroimaging studies produced 5 original research investigations in this population. Since 2010, dozens of neuroimaging studies have examined neural processes in GD populations (this does not include hundreds of neuroimaging studies examining gambling-related tasks or other phenomena such as loss-chasing or risk-taking). In the past 5 years, there has been an increase not only in the number of neuroimaging studies in GD, but also a refinement in the cognitive constructs examined, as well as sophistication in the types of comparisons made. The current literature review examines recent findings in human GD studies using different neuroimaging methods with a focus on magnetic resonance imaging (MRI). The review focuses first on the construct of appetitive processing – one of the most researched GD areas. This review also appraises recent studies using clinical comparison groups and work examining the neurobiology of specific gambling feature, near-misses. The review also examines other neuroimaging modalities, namely structural-based studies as well as the application of repetitive transcranial magnetic imaging (rTMS) for GD treatment. The first author searched the literature for relevant manuscripts on the topic, and supplemented this approach with knowledge from abstracts and citations in relevant articles. The purpose of this literature review is to shed light on recent findings in GD and gambling neurobiology, but is not necessarily exhaustive.
The interest in using neuroimaging to study GD is multifold. First, it provides a means to understand brain mechanisms involved in this disorder. Second, as the first formal ‘non-substance’ or ‘behavioral’ addiction, GD has potential to clarify addiction risk factors by disentangling addiction mechanisms from drug-use confounds. Many features are shared between substance-based and non-substance-based addictive disorders including urges/craving, withdrawal and tolerance. Additionally, core concepts and transdiagnostic constructs including impulsivity and compulsivity show similar relationships with these disorders. While it is possible that brain alterations (both in function and structure) may occur as a consequence of disordered gambling, recent GD studies, through careful subgrouping of co-occurring drug use, are beginning to isolate brain changes that may relate uniquely to gambling from those that may relate to alcohol or polysubstance use (Zois et al., 2017). This is particularly relevant as other problematic behaviors, including internet gaming, binge-eating and compulsive sexual behaviors, are increasingly discussed and debated in the context of ‘behavioral addictions’(Fineberg et al., 2010; el-Guebaly et al., 2012; Leeman and Potenza, 2013; Fineberg et al., 2014; Long et al., 2015; Kessler et al., 2016; Kraus et al., 2016; Kuhn and Gallinat, 2016; Gentile et al., 2017; Hutson et al., 2018; Kowalewska et al., 2018; Vaccaro and Potenza, 2019; Brand et al., 2019).
With comparable features as substance-use disorders (SUDs; e.g., urges, tolerance, withdrawal), GD offers an important condition for understanding neural mechanisms, both shared and unique features. As such, non-substance-based addictions like GD may help delineate boundaries and overlaps in addiction-like features. Additionally, transitions from impulsive to compulsive behaviors may share neural substrates (el-Guebaly et al., 2012; Fineberg et al., 2010; Fineberg et al., 2014; Brand et al., 2019). A recent systematic review and meta-analysis of compulsivity-related neurocognitive performance in GD found deficits in specific subdomains of this construct (van Timmeren et al., 2018). In particular, on tasks assessing attentional set-shifting, such as the Wisconsin Card Sorting Task (WCST), individuals with GD demonstrate impairments in cognitive flexibility which are often additionally related to problem-gambling severity, gambling frequency and gambling urges (Leppink et al., 2016; van Timmeren et al., 2018). Neuroimaging studies in GD reveal alterations in prefrontal cortical areas during cognitive control including the dorsolateral prefrontal cortex, the anterior cingulate cortex and the ventromedial/orbitofrontal cortex (Leppink et al., 2016). These alterations may express themselves as generalized compulsive propensities that could relate to difficulties in flexibly moving attention and in perseverative tendencies that maintain maladaptive gambling behaviors (van Timmeren et al., 2018). It has been proposed that greater dorsal striatal activity to some gambling-related cues may relate to an increased susceptibility to form action-outcome associations in GD populations (Balodis et al., 2012a, Balodis et al., 2012b). Combined with heightened impulsive tendencies well documented in GD populations, transitions to compulsive behaviors may be accelerated in this population; such impulsivity-compulsivity transitions represent an important future direction for disordered gambling research (Balodis et al., 2012a, Balodis et al., 2012b). Future studies should directly examine this possibility both in humans and animal models.
Early neuroimaging studies in GD examined gambling-related cue-reactivity, particularly in the context of reward-based decision-making. However, recent studies have examined arguably more specific GD cognitive constructs, such as anticipatory processing, near-misses and value-based decision-making. Additionally, current neuroimaging studies have directly compared clinical groups with addictive disorders, including evaluations not only with SUDs but also with other disorders of impulse control such as binge-eating disorder (BED) or food addiction. These direct comparisons are in line with research efforts to consider constructs beyond diagnostic boundaries and provide a deeper understanding of pathophysiological mechanisms of addiction. One study has contrasted disorders with phenotypically different behavioral patterns (Majuri et al., 2017), having implications for disorder conceptualization. In addition, study stimuli are also moving beyond monetary cues to include natural rewards such as food or erotic stimuli (Sescousse et al., 2013; Majuri et al., 2017). These studies have the potential to highlight alterations in generalized reward processing that may act as precursor or maintenance factors in GD. Some GD studies already suggest differential reward sensitivities at both the motivational and hedonic levels to natural rewards (e.g. food or erotic cues), which provide some indication of core pathophysiological mechanisms in behavioral addictions (Sescousse et al., 2013), and similar approaches have been applied successfully to other behaviors proposed to have addictive potential like problematic pornography viewing (Gola et al., 2017).
This review will highlight recent neuroimaging studies in GD, including relevant constructs and novel neuromodulation techniques under study in GD.
Section snippets
Appetitive processing studies: seemingly conflicting findings and ongoing discussions
To date, most neuroimaging studies in GD have focused on appetitive processing, in particular with monetary cues and rewards. Some of the first fMRI studies in GD involved cue-exposures using tasks that were successful in increasing ratings of gambling urges; however, neuroimaging findings have been seemingly mixed. Early studies reported relatively diminished striatal and ventromedial prefrontal cortex (vmPFC) recruitment (Potenza et al., 2003; Reuter et al., 2005; de Greck et al., 2010)
Moving beyond monetary/gambling cues
To date, few neuroimaging studies of GD have directly examined reactivity to non-monetary/gambling cues. These types of studies are important as they shed light on whether imbalances in cue reactivity may be driven by hypersensitivity to monetary cues or reduced sensitivity to other types of reward. This has implications for understanding developmental and maintenance factors in GD. One study applied a modified incentive delay task in which participants anticipated viewing gambling or erotic
MRI-based structural studies
Initial grey-matter volume studies in GD presented seemingly ambiguous findings. Several studies reported no differences with healthy control groups (van Holst et al., 2012a, van Holst et al., 2012b, van Holst et al., 2012c; Fuentes et al., 2015) or increased ventral striatum and prefrontal cortex volumes using voxel-based morphometry (VBM) (Koehler et al., 2015). A region-of-interest approach identified smaller amygdalar and hippocampal volumes in GD that were linked to behavioral-inhibition
Funding and acknowledgments
This work was supported in part by the Gambling Research Exchange of Ontario (GREO); the Peter Boris Centre for Addictions Research; R01 DA019039 from the National Institutes of Health; the Connecticut Mental Health Center; and a Center of Excellence in Gambling Research Award from the National Center for Responsible Gaming.
Declaration of Competing Interest
The authors have no pertinent disclosures or conflict of interest. Over the past three years, Dr. Potenza has received financial support (to Yale or personally) for the following. He has consulted for and advised Game Day Data, Addiction Policy Forum, and Opiant Therapeutics; received research support from the Mohegan Sun Casino and the National Center for Responsible Gaming; consulted for or advised legal and gambling entities on issues related to impulse control and addictive behaviors;
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