¹Taipei City Psychiatric Center, Department of Addiction Sciences, Taipei, Taiwan, ²National Yang Ming Chiao Tung University, Institute of Brain Science, Taipei, Taiwan, ³Taipei Veterans General Hospital, Department of Medical Research, Taipei, Taiwan, ⁴Taipei Veterans General Hospital, Department of Psychiatry, Taipei, Taiwan, ⁵Taipei Medical University, Department of Psychiatry, School of Medicine, College of Medicine, Taipei, Taiwan

Background: Gambling disorder (GD) involves disrupted reward processing and executive control due to abnormalities in cortico-striatal-thalamo-cortical circuits. Theta burst stimulation (TBS) has shown promise in modulating cortical excitability and neural connectivity; however, its effects on functional connectivity (FC) and clinical outcomes in GD remain understudied.

Aims & Objectives: This study aimed to evaluate the effects of combined TBS on the FC of the thalamus and putamen in patients with GD and explore its clinical benefits.

Method: Seventy-nine patients with GD were recruited, with 63 completing the study. Participants were randomized into a TBS group (n = 39) or sham group (n = 24). The TBS protocol consisted of 10 sessions combining intermittent TBS (iTBS) to the left dorsolateral prefrontal cortex and continuous TBS (cTBS) to the pre-supplementary motor area. Resting-state fMRI was conducted pre- and post-intervention in a subset of patients (TBS: n = 9; sham: n = 5). Functional connectivity (FC) and clinical outcomes (e.g., GSAS) were analyzed.

Results: Baseline sociodemographic and psychological variables showed no group differences. Combined TBS significantly decreased FC between the thalamus and the left frontal pole while increasing FC with the left inferior occipital gyrus and temporal pole. For the putamen, significant increases in FC were observed with the right middle temporal gyrus, right precuneus, and bilateral lateral occipital cortex. In contrast, decreases in FC were noted with reward-related regions, including the bilateral frontal pole, OFC, and insular cortex, as well as inter-putamen connectivity. For clinical outcomes, time effects in GSAS scores were significant (p < 0.01), but group (p = 0.179) and interaction effects (p = 0.868) were non-significant.

Discussion & Conclusions: The findings suggest that our combined TBS protocol can effectively enhancing executive control-related connectivity and reducing hyperconnectivity in reward-related regions. While symptom improvement was observed over time, no significant treatment-specific effects were detected in clinical outcomes. These findings highlight the potential of FC as a biomarker for TBS efficacy in GD. Future research should involve larger cohorts and explore the long-term clinical implications of these connectivity changes.