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Structural reductions of Auditory–Temporoparietal Association Cortex in Cannabis Users: Relevance to Neural Systems Implicated in Auditory Hallucinations

Miguel Quintanilla, Ihsan M. Salloum, Alan N. Francis

preprint DOI: 10.21203/rs.3.rs-10029365/v1 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Observational cohort
Sample size 660
Population Cannabis users and non-users from the Human Connectome Project
Measures FreeSurfer-derived cortical thickness measures, delay discounting AUC-200 and AUC-40K
Topics Cannabis
Key findings Cannabis users had significantly thinner cortex in bilateral superior temporal gyrus, angular gyrus, supramarginal gyrus, and right Heschl's gyrus, with effect sizes around d = -0.24 to -0.31. They also showed a trend toward steeper delay discounting, and older cannabis users exhibited accelerated thinning in right supramarginal gyrus and banks of the superior temporal sulcus.

Abstract

Abstract Background Cannabis use is a well-established environmental risk factor for psychosis and auditory hallucinations, yet the neurobiological mechanisms underlying this association remain incompletely understood. Neuroimaging studies of psychotic disorders have consistently implicated structural abnormalities within auditory and temporoparietal cortical networks involved in speech perception, sensory integration, and reality monitoring. We hypothesized that cannabis use would be associated with cortical thinning within these regions and with behavioral alterations relevant to psychosis vulnerability.

Methods: Using data from the Human Connectome Project (HCP; N = 1,206), we identified 330 cannabis users and matched to 330 non-users on age and sex using greedy nearest-neighbor matching. Cortical thickness was compared across bilateral superior temporal gyrus (STG), Heschl's gyrus (HG), banks of the superior temporal sulcus (BanksSTS), supramarginal gyrus (SMG), and angular gyrus (AG) using FreeSurfer-derived measures from 3T structural MRI. Delay discounting performance was also compared between groups, and structure–behavior relationships were examined.

Results: Cannabis users exhibited significantly thinner cortex bilaterally within the STG (left: d = − 0.280, p = 0.001; right: d = − 0.241, p = 0.003), AG (bilateral d ≈ − 0.26, p < 0.002), SMG (left: d = − 0.309, p < 0.001; right: d = − 0.239, p = 0.003), and right HG (d = − 0.272, p = 0.001). Cannabis users also demonstrated steeper delay discounting (AUC-200: d = − 0.145, p = 0.063 (trend); AUC-40K: d = − 0.140, p = 0.073 (trend)). Across groups, greater right HG thickness was associated with increased delay tolerance (r = 0.097–0.101, p < 0.02).

Conclusions: Cannabis use was associated with cortical thinning throughout bilateral auditory–temporoparietal association cortices and with increased preference for immediate rewards. Within cannabis users, older age was associated with accelerated right BanksSTS and right SMG thinning, and older cannabis users exhibited accelerated thinning in right SMG and right BanksSTS, suggesting cumulative vulnerability in multisensory integration cortex. Given the established involvement of these regions in auditory hallucinations and psychosis, these findings suggest that cannabis-related alterations in neural systems supporting auditory processing, multisensory integration, and predictive inference may contribute to vulnerability for hallucination-proneness. The observed association between Heschl's gyrus morphology and impulsive decision-making further raises the possibility that structural abnormalities within auditory networks are linked to broader disturbances in salience attribution and reward-guided behavior relevant to psychosis risk.