Toward Addiction Prediction: An Overview of Cross-Validated Predictive Modeling Findings and Considerations for Future Neuroimaging Research.

Substance use is a leading cause of disability and death worldwide. Despite the existence of evidence-based treatments, clinical outcomes are highly variable across individuals, and relapse rates following treatment remain high. Within this context, methods to identify individuals at particular risk for unsuccessful treatment (i.e., limited within-treatment abstinence), or for relapse following treatment, are needed to improve outcomes. Cumulatively, the literature generally supports the hypothesis that individual differences in brain function and structure are linked to differences in treatment outcomes, although anatomical loci and directions of associations have differed across studies. However, this work has almost entirely used methods that may overfit the data, leading to inflated effect size estimates and reduced likelihood of reproducibility in novel clinical samples. In contrast, cross-validated predictive modeling (i.e., machine learning) approaches are designed to overcome limitations of traditional approaches by focusing on individual differences and generalization to novel subjects (i.e., cross-validation), thereby increasing the likelihood of replication and potential translation to novel clinical settings. Here, we review recent studies using these approaches to generate brain-behavior models of treatment outcomes in addictions and provide recommendations for further work using these methods.