Value-based decision-making network functional connectivity correlates with substance use and delay discounting behaviour among young adults

Abstract

Substance use disorders are characterized by reduced control over the quantity and frequency of psychoactive substance use and impairments in social and occupational functioning. They are associated with poor treatment compliance and high rates of relapse. Identification of neural susceptibility biomarkers that index risk for developing a substance use disorder can facilitate earlier identification and treatment. Here, we aimed to identify the neurobiological correlates of substance use frequency and severity amongst a sample of 1,200 (652 females) participants aged 22–37 years from the Human Connectome Project. Substance use behaviour across eight classes (alcohol, tobacco, marijuana, sedatives, hallucinogens, cocaine, stimulants, opiates) was measured using the Semi-Structured Assessment for the Genetics of Alcoholism. We explored the latent organization of substance use behaviour using a combination of exploratory structural equation modelling, latent class analysis, and factor mixture modelling to reveal a unidimensional continuum of substance use behaviour. Participants could be rank ordered along a unitary severity spectrum encompassing frequency of use of all eight substance classes, with factor score estimates generated to represent each participant’s substance use severity. Factor score estimates and delay discounting scores were compared with functional connectivity in 650 participants with imaging data using the Network-based Statistic. This neuroimaging cohort excludes participants aged 31 and over. We identified brain regions and connections correlated with impulsive decision-making and poly-substance use, with the medial orbitofrontal, lateral prefrontal and posterior parietal cortices emerging as key hubs. Functional connectivity of these networks could serve as susceptibility biomarkers for substance use disorders, informing earlier identification and treatment.