Neural Correlates of Reactive Inhibition in Gambling Disorder: An FMRI Study with Transcranial Magnetic Stimulation (TMS)

Gambling Disorder (GD) is a condition characterized by a persistent and recurrent pattern of problematic gambling behavior. Despite significant advances in understanding the neurobiological correlates of Gambling Disorder phenomenological manifestation, there are still several unanswered questions regarding the pathophysiological mechanisms underlying GD. There is substantial evidence from fMRI studies on the role of pre-SMA stimulation in psychiatric conditions with impairments in response inhibition such as behavioral addictions on enhancing the activity of the brain circuitry involving the right inferior (IFG) and middle frontal gyrus (MFG) (two cortical areas are differentially associated with two distinct aspects of control inhibition). In this study we utilized task-related functional Magnetic Resonance Imaging (fMRI) to explore the impact of continuous Theta-Burst Stimulation (cTBS) on the pre-Supplementary Motor Area (pre-SMA) in patients with Gambling Disorder (GD). Four GD patients underwent cTBS on bilateral pre-SMA, administered with the MagVenture MagPro R30 stimulator with add-on theta-burst option (MagVenture INC.) using a Cool D-B80 figure-of-eight coil. cTBS consists of bursts of 3 pulses separated by 20 ms (i.e., 50 Hz) delivered repeatedly at theta frequency on the pre-SMA bilaterally. Changes in Functional Connectivity (FC) were assessed before and after Real or Sham treatment using CONN functional connectivity toolbox and Statistical Parametric Mapping (SPM). The study aimed to determine whether cTBS influences the functional connectivity between pre-SMA and right prefrontal areas, specifically the right Inferior Frontal Gyrus (rIFG) and right Middle Frontal Gyrus (rMFG), and whether these changes correlate with treatment outcomes. Results indicated that real cTBS treatment increased functional connectivity between pre-SMA and both rIFG and rMFG, suggesting enhanced control inhibition. This was associated with a reduction in Gambling Disorder symptom severity, assessed with the Pathological Gambling version of the Yale-Brown Obsessive-Compulsive Scale (PG-YBOCS) and the Gambling Urges Questionnaire (GUQ), indicating a treatment response. Conversely, sham cTBS did not elicit the same positive FC changes in the reactive control inhibition network, aligning with behavioral measures. The study highlighted the potential of cTBS on pre-SMA in modulating inhibitory control circuit. Overall, this preliminary investigation provides a foundation for future investigations into the neurobiological mechanisms underlying GD and the potential efficacy of TMS interventions.