Structural and functional MRI signatures of Gambling Disorder: a case-control study
- 1Imperial College London
Abstract
Gambling disorder (GD) is a behavioural addiction that may help identify addiction-related neural features without the direct neurobiological effects of a primary substance of dependence. We examined regional grey matter volume (GMV) and resting-state functional connectivity (rsFC) in the same well-characterised sample. Eighteen men with GD and 21 matched healthy controls underwent high-resolution structural and resting-state functional MRI. GMV was quantified across 214 cortical and subcortical regions, and seed-based rsFC analyses focused on striatal subdivisions and mesocorticolimbic regions. Group differences were evaluated using permutation testing and cluster-corrected mixed-effects modelling. GD was associated with lower GMV in the ventromedial prefrontal cortex, orbitofrontal regions and other cortical and subcortical areas, alongside higher GMV in a subset of limbic and default-mode regions. Participants with GD also showed lower connectivity between the limbic striatum and the hippocampus, thalamus and putamen. In exploratory analyses, somatomotor connectivity was positively associated with gambling severity (Problem Gambling Severity Index: Spearman's rho = 0.71, p = 0.003, false-discovery-rate-adjusted q = 0.016). Structural and functional findings overlapped spatially in regions associated with valuation, memory, reward and habit formation, but regional GMV did not mediate group differences in rsFC. These findings are broadly consistent with corticostriatal models of GD and identify candidate circuit-level differences for independent replication. Larger, more diverse and longitudinal samples are required to establish their reproducibility, temporal direction and clinical relevance.
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BibTeX
@misc{zafar2026structural,
title = {{Structural and functional MRI signatures of Gambling Disorder: a case-control study}},
author = {R. Zafar and N. Ertl and L. Donegan and O. Downes and S. Suseelan and M. Siegel and E. Farrell and A. Cross and P. Adkins and V. Leonidaki and D. L. Kurtin and L. Paterson and M. Wall and H. Bowden-Jones and D. Nutt and D. Erritzoe},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.749325},
url = {https://www.biorxiv.org/content/10.64898/2026.09.09.749325v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Structural and functional MRI signatures of Gambling Disorder: a case-control study
AU - R. Zafar
AU - N. Ertl
AU - L. Donegan
AU - O. Downes
AU - S. Suseelan
AU - M. Siegel
AU - E. Farrell
AU - A. Cross
AU - P. Adkins
AU - V. Leonidaki
AU - D. L. Kurtin
AU - L. Paterson
AU - M. Wall
AU - H. Bowden-Jones
AU - D. Nutt
AU - D. Erritzoe
PY - 2026
DA - 2026/09/09
PB - bioRxiv
DO - 10.64898/2026.09.09.749325
UR - https://www.biorxiv.org/content/10.64898/2026.09.09.749325v1
AB - Gambling disorder (GD) is a behavioural addiction that may help identify addiction-related neural features without the direct neurobiological effects of a primary substance of dependence. We examined regional grey matter volume (GMV) and resting-state functional connectivity (rsFC) in the same well-characterised sample. Eighteen men with GD and 21 matched healthy controls underwent high-resolution structural and resting-state functional MRI. GMV was quantified across 214 cortical and subcortical regions, and seed-based rsFC analyses focused on striatal subdivisions and mesocorticolimbic regions. Group differences were evaluated using permutation testing and cluster-corrected mixed-effects modelling. GD was associated with lower GMV in the ventromedial prefrontal cortex, orbitofrontal regions and other cortical and subcortical areas, alongside higher GMV in a subset of limbic and default-mode regions. Participants with GD also showed lower connectivity between the limbic striatum and the hippocampus, thalamus and putamen. In exploratory analyses, somatomotor connectivity was positively associated with gambling severity (Problem Gambling Severity Index: Spearman's rho = 0.71, p = 0.003, false-discovery-rate-adjusted q = 0.016). Structural and functional findings overlapped spatially in regions associated with valuation, memory, reward and habit formation, but regional GMV did not mediate group differences in rsFC. These findings are broadly consistent with corticostriatal models of GD and identify candidate circuit-level differences for independent replication. Larger, more diverse and longitudinal samples are required to establish their reproducibility, temporal direction and clinical relevance.
ER -