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.

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.

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).

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.

Research has demonstrated that chronic stress exposure early in development can lead to detrimental alterations in the orbitofrontal cortex (OFC)–amygdala circuit. However, the majority of this research uses functional neuroimaging methods, and thus the extent to which childhood trauma corresponds to morphometric alterations in this limbic-cortical network has not yet been investigated. This study had two primary objectives: (i) to test whether anatomical associations between OFC–amygdala differed between adults as a function of exposure to chronic childhood assaultive trauma and (ii) to test how these environment-by-neurobiological effects relate to pathological personality traits.

Participants were 137 ethnically diverse adults (48.1% female) recruited from the community who completed a clinical diagnostic interview, a self-report measure of pathological personality traits, and anatomical MRI scans.

Findings revealed that childhood trauma moderated bilateral OFC–amygdala volumetric associations. Specifically, adults with childhood trauma exposure showed a positive association between medial OFC volume and amygdalar volume, whereas adults with no childhood exposure showed the negative OFC–amygdala structural association observed in prior research with healthy samples. Examination of the translational relevance of trauma-related alterations in OFC–amygdala volumetric associations for disordered personality traits revealed that trauma exposure moderated the association of OFC volume with antagonistic and disinhibited phenotypes, traits characteristic of Cluster B personality disorders.

The OFC–amygdala circuit is a potential anatomical pathway through which early traumatic experiences perpetuate emotional dysregulation into adulthood and confer risk for personality pathology. Results provide novel evidence of divergent neuroanatomical pathways to similar personality phenotypes depending on early trauma exposure.

Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes associated with genomic vulnerability for externalizing disorders.

One-hundred fifty-five White, non-Hispanic veterans were genotyped using a genome-wide array and underwent resting-state functional magnetic resonance imaging. Genetic susceptibility was assessed using an independently developed polygenic score (PS) for externalizing, and functional neural networks were identified using graph theory based network analysis. Tasks of inhibitory control and psychiatric diagnosis (alcohol/substance use disorders) were used to measure externalizing phenotypes.

A polygenic externalizing disorder score (PS) predicted connectivity in a brain circuit (10 nodes, nine links) centered on left amygdala that included several cortical [bilateral inferior frontal gyrus (IFG) pars triangularis, left rostral anterior cingulate cortex (rACC)] and subcortical (bilateral amygdala, hippocampus, and striatum) regions. Directional analyses revealed that bilateral amygdala influenced left prefrontal cortex (IFG) in participants scoring higher on the externalizing PS, whereas the opposite direction of influence was observed for those scoring lower on the PS. Polygenic variation was also associated with higher Participation Coefficient for bilateral amygdala and left rACC, suggesting that genes related to externalizing modulated the extent to which these nodes functioned as communication hubs.

Findings suggest that externalizing polygenic risk is associated with disrupted connectivity in a neural network implicated in emotion regulation, impulse control, and reinforcement learning. Results provide evidence that this network represents a genetically associated neurobiological vulnerability for externalizing disorders.