S003329172100252Xjra 1143..1150

Background. People who tend to impulsively choose smaller, sooner rewards over larger, later rewards are at increased risk for addiction and psychiatric disorders. A neurobiological measure of the tendency to overvalue immediate gratification could facilitate the study of individuals who are susceptible to these mental disorders. The objective of this research was to develop a cortical assay of impulsive choice for immediate rewards. Methods. A cortex-based assay of impulsive choice was developed using 1105 healthy adults from the Human Connectome Project, and then cross-validated in two independent samples of adults with elevated rates of psychiatric disorders. Results. Study 1: Cortical delay discounting (C-DD) was developed using a multivariate additive model of gray matter thickness across both hemispheres. Higher C-DD corresponded to thinner cortex and greater impulsive choice for immediate rewards. It also predicted cannabis use beyond established risk factors for drug use, including familial substance use, childhood conduct problems, personality traits, and cognitive functioning. Study 2: C-DD replicated the association with delay discounting performance from study 1. Structural equation modeling showed C-DD covaried with symptoms of externalizing, but not internalizing disorders. Study 3: C-DD positively predicted future delay discounting behavior (6–34 months later). Conclusions. Across three studies, a cortical assay of impulsive choice evidenced consistent associations with drug use and delay discounting task performance. It was also uniquely associated with psychiatric disorders that share impulsivity as a core feature. Together, findings support the utility of C-DD as a neurobiological assay of impulsive decision-making and a possible biomarker of externalizing disorders. It is generally accepted that larger rewards are more desirable than smaller ones, and rewards that are immediately available are preferable to those that are delayed in time. However, everyday decisions are rarely so clean-cut and often require individuals to choose between pursuing rewards that are highly valued, but whose benefit is not immediately evident (e.g. avoiding illness during a pandemic), v. those that are immediately available but less valuable in the long run (e.g. drinking at a bar with friends). Across species and reward types, delay discounting paradigms have proven to be robust measures of the tendency to impulsively choose immediate rewards, a decision-making style with strong predictive validity for explaining addictive behaviors and psychiatric disorders (Amlung, Vedelago, Acker, Balodis, & MacKillop, 2017; Amlung et al., 2019; Bickel et al., 2019; Yoon et al., 2007). Discounting paradigms are used to estimate the rate at which an individual devalues rewards as a function of time (i.e. delaydiscounting rate or k value) (Odum, 2011a). Individuals with addiction show particularly steep discounting rates (Amlung et al., 2017), as do those with externalizing spectrum disorders, characterized by chronic drug and alcohol use, impulsivity, and antisocial behavior (Bobova, Finn, Rickert, & Lucas, 2009; Finn, Gunn, & Gerst, 2015). Efforts to identify biomarkers of delay discounting have focused on cortical regions that regulate impulsive urges and evaluate future outcomes, and limbic/paralimbic structures that value reinforcers (McClure, Laibson, Loewenstein, & Cohen, 2004; Noda et al., 2020). In terms of structural abnormalities, steeper discounting has been associated with decreased cortical thickness and/or gray matter volume in several regions of the prefrontal cortex (Barry, Koeppel, & Ho, 2020; Bernhardt et al., 2014; Bjork, Momenan, & Hommer, 2009), as well as the cingulate (Bernhardt et al., 2014; Cho et al., 2013) and putamen (Cho et al., 2013; Dombrovski et al., 2012). The largest published study of adults to date (N = 1038) found that delay discounting increased as gray matter volume decreased in 20 discrete regions across the cortex, and total cortical (but not total subcortical) gray matter volume was inversely related to delay discounting (Owens et al., 2017). Based on these findings, it is clear that the tendency to discount future rewards is not limited to a small subset of cortical regions, but rather evidences widespread associations across the cortex. The broad spectrum of regions that have been associated with delay discounting suggests a cortical assay of impulsive choice that incorporates many regions is needed to represent the cognitive neural underpinnings of this complex decision-making process. To test the utility of such a measure, we created a cortical delay discounting (C-DD) assay using a multivariate additive model of gray matter thickness across 148 brain regions. Although subcortical regions likely play a role in impulsive choice, we focused on cortical thickness based on the findings of Owens et al. (2017), which is the largest structural study of delay discounting to date. We did not consider functional activation or connectivity in creation of C-DD, because we were interested in developing a neurobiological metric of impulsive choice with relatively stable trait-like properties that could be easily implemented by researchers using widely available neuroimaging scans. As cortical thickness tends to have greater temporal stability and reliability than functional neuroimaging measures (e.g. Han et al. 2006; Noble et al. 2017), and T1-weighted anatomical scans are collected in all magnetic resonance imaging (MRI) research studies and routinely collected clinically, we focused exclusively on cortical thickness as our neurobiological metric. We hypothesized that this cortical assay would reliably relate to known correlates of impulsive choice, specifically drug use, delay discounting rate, and externalizing disorder symptoms. To avoid the confounds that arise in highly impulsive samples (e.g. the effects of long-term substance use on cortical thickness), we used a large healthy sample to develop the cortical assay and then cross-validated it in two independent samples with elevated rates of psychiatric disorders.