Identifying the role of (dis)inhibition in the vicious cycle of substance use through ecological momentary assessment and resting-state fMRI

Abstract

Functional inhibition is known to improve treatment outcomes in substance use disorder (SUD), potentially through craving management enabled by underlying cerebral integrity. Whereas treatment is challenged by a multitude of substances that patients often use, no study has yet unraveled if inhibition and related cerebral integrity could prevent relapse from multiples substances, that is, one's primary drug of choice and secondary ones. Individuals with primary alcohol, cannabis, or tobacco use disorders completed intensive Ecological Momentary Assessment (EMA) coupled with resting-state functional MRI (rs-fMRI) to characterize the extent to which inhibition and cerebral substrates interact with craving and use of primary and any substances. Participants were 64 patients with SUD and 35 healthy controls who completed one week EMA using Smartphones to report 5 times daily their craving intensity and substance use and to complete Stroop inhibition testing twice daily. Subsamples of 40 patients with SUD and 34 control individuals underwent rs-fMRI. Mixed Model Analysis revealed that reported use of any substance by SUD individuals predicted later use of any and primary substance, whereas use of the primary substance only predicted higher use of that same substances. Craving and inhibition level independently predicted later use but did not significantly interact. Preserved inhibition performance additionally influenced use indirectly by mediating the link between subsequent uses and by being linked to rs-fMRI connectivity strength in fronto-frontal and cerebello-occipital connections. As hypothesized, preserved inhibition performance, reinforced by the integrity of inhibitory neurofunctional substrates, may partake in breaking an unhealthy substance use pattern for a primary substance but may not generalize to non-target substances or to craving management.

Fig. 1. Typical day of EMA assessments and illustration of potential direct vs indirect effect of inhibition on use.

Usual “wake” and “sleep” times were selected by each participant to ensure that they would be able to answer each signal. Signals occurred randomly within 5-time intervals periods and could concern craving and substance use only or could be followed by a Stroop test. Craving was assessed on a scale from 1 to 7, and Substance use was coded in a dichotomous manner (“Yes” or “No”) for the primary substance and for any substance. Stroop refers to the timed ink color naming of an incongruent color-related word (i.e., blue written in yellow ink), with longer time completion indicating a poorer inhibition performance. All variables can be used to predict the same-time assessment level or next-time assessment level (i.e., lagged in time) of another measure. This prediction can test direct effect as indicated by the continuous arrow or indirect effect, such as moderation, as indicated by the dotted arrow.

Fig. 2. Rs connections linked to mean stroop time and amount of substance use during the week.

Cereb Cerebellum, Occ. Occipital, Par. Parietal, Mid. Middle, Sup. Superior, Inf. Inferior, Orb. Orbital, R Right. Regression analyses were conducted between the individual connectomes and mean Stroop times from each participant while controlling for age and correcting for false discovery rate (FDR) with alpha level of 0.05. Resulting connections are highlighted in the above figure and colored depending on their association with Stroop times, positively (highlighted in green) or negatively (highlighted in red). The strength of connectivity within these connections were entered in a correlation matrix along with the number of any or primary substance use occasions. Significant correlations with use are highlighted by the node colored in red (positive correlation) and blue (for negative correlation).