Neural correlates of cue‐ and stress‐induced craving in gambling disorders: implications for transcranial magnetic stimulation interventions

Abstract

Gambling disorder (GD), currently considered a behavioral addiction, shows substantial similarities with substance use disorders (SUDs) in terms of neurobiology and phenomenology. These similarities have been recognized in the DSM‐5, although several relevant differences still exist in the diagnostic criteria, in particular, with regard to the role of cue‐ and stress‐ induced craving. Craving, recently included as a new criterion for SUDs diagnosis only, is a key construct also in the pathophysiology of GD. Furthermore, brain imaging studies indicate that similar alterations in cortico‐limbic‐striatal and prefrontal control circuits underlie the emergence of craving states in both disorders. This has important implications for the identification of neurobiologically based anti‐craving interventions, which may be used for both GD and SUDs. In this regard, a novel neuromodulation intervention, named repetitive transcranial magnetic stimulation (rTMS), is emerging as a promising treatment for craving in SUDs, and could potentially be effective also in treating gambling urges. Here, we review the clinical neurobiological research on GD, with a specific emphasis on the neural circuits implicated in cue‐ and stress‐craving, taking SUDs as the major comparative example. Furthermore, we describe the studies that have evaluated rTMS as a therapeutic tool for targeting and restoring the neural alterations underlying gambling urge. The manuscript concludes discussing some of the limitations of the current studies, and suggests directions for future rTMS research in GD.

Considering Motor Excitability During Action Preparation in Gambling Disorder: A Transcranial Magnetic Stimulation Study

“…Yet, it is noteworthy that structural and functional prefrontal alterations still exist in GDPs (84)(85)(86)(87)(88), even in the absence of any substance use disorder comorbidity (89). In particular, an increasing literature has led to consider the neuromodulation of the dorsolateral prefrontal cortex, using high-frequency repetitive TMS, as a potential treatment for GD (66), with encouraging results in terms of craving reduction (90-92), but not regarding inhibitory control (93). That being said, the absence of deficit in preparatory suppression reported in GDPs makes it an unlikely common vulnerability marker of whether one is going to develop an addiction or not.…”

“…The fifth edition of the DSM recently reclassified pathological gambling from the “Impulse Control Disorder” category to the newly established “Substance-related and Addictive Disorders” section ( 39 ). Such a decision implies that this substance-free gambling addiction shares many features with addictions to substances ( 64 – 66 ). In this context, extensive work is being dedicated to understanding these similarities and to identifying vulnerability markers that may be common to all addictive disorders, with one particularly promising candidate being a lack of inhibitory control.…”

Clinical Improvements in Comorbid Gambling/Cocaine Use Disorder (GD/CUD) Patients Undergoing Repetitive Transcranial Magnetic Stimulation (rTMS)

“…A prevalence rate of 10.3% has been reported for gambling disorder (GD) diagnosis in substance use disorders (SUD) patients [2,3], while GD patients have a 57.5% prevalence for substance-related disorder comorbidity [4,5]. Despite the differences observed in cue and stress-related craving, GD shares some of the neurobiological substrates, psychological processes, and behavioral manifestations of SUDs [6,7,8]. Compelling evidence supports that both GD and SUDs are sustained by impaired neuroplasticity and dysfunctions within reward, stress and cognitive-control systems.…”

Effective Treatment and Support for Problem Gambling

“…Research on the use of brain stimulation for treating gambling problems is somewhat inconclusive and subject to several limitations, including small sample sizes, inconsistencies in study design and treatment protocols, and lack of information about the mechanisms of action and change. 84 Future research on brain stimulation should include large, demographically representative samples, 81,83 and should investigate the long term effects of brain stimulation, 83 especially whether multiple sessions can decrease problem gambling symptoms for a longer period of time. 82…”