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

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. Overlapping prefrontal dysfunctions underlie impairments in executive functioning and emergence of craving states in both SUDs and GD. Enhanced prefrontal activation induced by cues, in particular in DLPFC, ACC and mOFC (in red). Decreased prefrontal activity during executive functions in DLPFC, dmPFC and vmPFC (in blue). Targeting and amplifying prefrontal control circuits via DLPFC rTMS may enhance cognitive control over craving and improve executive functioning.