Network control theory and substance use disorder

Computational psychiatry allows us to get closer to uncovering the neural bases of mental health disorders and, eventually, novel interventions to treat them. A particularly powerful tool has emerged in this realm - Network Control Theory (NCT) - which takes engineering principles and applies them to enable quantification of brain dynamics. Specifically, NCT allows mapping of the amount of control energy needed by individuals’ brains to transition between recurring states of activation, called transition energy (TE). Current neurodevelopmental models posit vulnerability to SUD in youth is due to an overreactive reward system and reduced inhibitory control. Having a family history of SUD is a particularly strong risk factor, yet few studies have explored its impact on brain function and structure prior to substance exposure. Herein, we utilized NCT to quantify sex-specific differences in brain activity dynamics in youth with and without a family history of SUD, drawn from a large cohort of substance-naïve youth from the Adolescent Brain Cognitive Development Study (N=1894, 1018 female, aged 9-11). Our findings reveal that a family history of SUD is associated with alterations in the brain's dynamics wherein: i) independent of sex, certain regions' transition energies are higher in those with a family history of SUD and ii) there exist sex-specific differences in SUD family history groups at multiple levels of transition energy (global, network, and regional). Family history-by-sex effects reveal that energetic demand is increased in females with a family history of SUD and decreased in males with a family history of SUD, compared to their same-sex counterparts with no SUD family history. Specifically, we localize these effects to higher energetic demands of the default mode network in females with a family history of SUD and lower energetic demands of attention networks in males with a family history of SUD. These results suggest a family history of SUD may increase reward saliency in males (easier time “stepping on the gas") and decrease efficiency of top-down inhibitory control in females (harder time “stepping on the brakes”). This work could be used to inform personalized intervention strategies that may target differing cognitive mechanisms that predispose individuals to the development of SUD.