Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life

Abstract

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Keywords: EMA; SUD; Stroop; inhibition; resting state; white matter.

FIGURE 1

Mixed model procedure from the raw data. Legend: During a typical day of EMA assessment, participants had to report if they used anysubstance and their primary substance (for the SUD sample) 5 times and had to complete theStroop mobile testing twice. The week of assessment hence results in 35‐time point assessmentsof substance use and 14 assessments of inhibition functioning that can be lagged in time topredict the next time point's assessments (Time t+1) from the immediately preceding time pointassessments (Time t). By treating each time point as a repetition, we modeled the prediction offuture use (at time t+1) by the current Stroop performance (at time t) while controlling fromprevious use (at time t). FA values within each cluster were then entered as a moderator of theStroop / use link. To do so the Stroop scores at each time point is multiplied by FA values ofeach cluster, resulting in an interaction term FA value * Stroop for each time t. This interactionterm is entered as predictor of subsequent use (at time t +1) while correcting for previous use(at time t). This is similar to a moderation analysis where FA values (indicated by the red arrow)modified the strength of the prediction between inhibition and use (indicated by the blackarrow).

FIGURE 2

Voxels in which fractional anisotropy (FA) values are significantly linked to shorter mean Stroop times, indicating better performances, in the substance use disorder (SUD) group. Legend: Results of the GLM whole brain analysis using the function randomize from FSL toevaluate the link between FA values in participant's skeletons and their mean Stroop Timeduring the week. Significant voxels are highlighted in orange and negatively linked to theStroop Time, indicating that higher FA values is linked to better inhibition performance.

FIGURE 3

(A–C) Association between use of substance at time t + 1 for any (A) and primary substance (B) and fractional anisotropy (FA) values within left anterior corona radiata and corpus callosum and right anterior corona radiata and corpus callosum (C) for shorter, mean, and longer Stroop time centred around the week at time t. Legend: Illustration of the probability of use associated with FA value in our clusters dependingon Stroop Time performance at time t: shorter time compared to the rest of the week (‐1 standarddeviation) indicating better performance in red, habitual mean time for the week in blue andlonger time compared to the rest of the week (+1 standard deviation) indicating worstperformance in green. S.d.: standard deviation (centered about each individual's mean across the week).