Brain networks underlying vulnerability and resilience to drug addiction

Significance

Resting-state functional connectivity provides novel insight into variations in neural networks associated with addiction to stimulant drugs in individuals with and without a family history of addiction, and both with and without personal drug use. An increased risk for addiction, either because of drug use or genetic/psychosocial vulnerability, is associated with hypoconnectivity in frontostriatal networks, which may weaken goal-directed decision-making. Resilience against addiction development, by contrast, is characterized by hyperconnectivity in two corticostriatal pathways, possibly reflecting compensatory responses in networks associated with regulatory control over habitual behaviors. It is thus conceivable that defying the risk of developing stimulant drug addiction requires increased efforts to control behavior—a hypothesis that may open up new pathways for therapeutic and preventative strategies.

Abstract

Regular drug use can lead to addiction, but not everyone who takes drugs makes this transition. How exactly drugs of abuse interact with individual vulnerability is not fully understood, nor is it clear how individuals defy the risks associated with drugs or addiction vulnerability. We used resting-state functional MRI (fMRI) in 162 participants to characterize risk- and resilience-related changes in corticostriatal functional circuits in individuals exposed to stimulant drugs both with and without clinically diagnosed drug addiction, siblings of addicted individuals, and control volunteers. The likelihood of developing addiction, whether due to familial vulnerability or drug use, was associated with significant hypoconnectivity in orbitofrontal and ventromedial prefrontal cortical-striatal circuits—pathways critically implicated in goal-directed decision-making. By contrast, resilience against a diagnosis of substance use disorder was associated with hyperconnectivity in two networks involving 1) the lateral prefrontal cortex and medial caudate nucleus and 2) the supplementary motor area, superior medial frontal cortex, and putamen—brain circuits respectively implicated in top-down inhibitory control and the regulation of habits. These findings point toward a predisposing vulnerability in the causation of addiction, related to impaired goal-directed actions, as well as countervailing resilience systems implicated in behavioral regulation, and may inform novel strategies for therapeutic and preventative interventions.