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bioRxivNeurosciencePreprint

An interpretable connectivity-based decoding model for classification of chronic marijuana use

Kaustubh R. KulkarniiD, Matthew SchaferiD, Laura A. BerneriD, Vincenzo G. FioreiD, Matthew HefliniD, Kent E. HutchisoniD, Vince D. CalhouniD, Francesca Mapua FilbeyiD, Gaurav Shankar PandeyiD, Daniela SchilleriD, Xiaosi GuiD

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Abstract

BackgroundPsychiatric neuroimaging typically proceeds with one of two approaches: encoding models, which aim to model neural mechanisms, or decoding models, which aim to predict behavioral or clinical characteristics from brain imaging data. In this study, we seek to combine these aims by developing interpretable decoding models that offer both accurate prediction and novel neural insights. We demonstrate the effectiveness of this combined approach in a case study of chronic marijuana use. MethodsChronic marijuana (MJ) users (n=195) and non-using healthy controls (n=128) completed a cue-elicited craving task during functional magnetic resonance imaging. Linear machine learning methods were used to classify individuals into chronic MJ users and non-users based on task-evoked, whole-brain functional connectivity. We then used graph theoretic analyses to identify predictive functional connectivities among brain regions that contributed most substantially to the classification of chronic marijuana use. ResultsWe obtained high (~80% out-of-sample) accuracy across four different classification models, demonstrating that task-evoked, whole-brain functional connectivity can successfully differentiate chronic marijuana users from non-users. Subsequent network analyses revealed key predictive regions (e.g., anterior cingulate cortex, dorsolateral prefrontal cortex, and precuneus) that are often implicated in neuroimaging studies of substance use disorders, as well as some key exceptions. We also identified a core set of networks of brain regions that contributed to successful classification, comprised of many of the same predictive regions. ConclusionsOur dual aims of accurate prediction and interpretability were successful, producing a predictive model that also provides interpretability at the neural level. This novel approach may complement other predictive-exploratory approaches for a more complete understanding of neural mechanisms in drug use and other neuropsychiatric disorders.

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Ayaka Kato, Kaustubh R. Kulkarni, Nikash R Das+4 more·bioRxiv·Oct 24, 2025