Neural Correlates of Rewarded Response Inhibition in Youth at Risk for Problematic Alcohol Use

Abstract

Risk for substance use disorder (SUD) is associated with poor response inhibition and heightened reward sensitivity. During adolescence, incentives improve performance on response inhibition tasks and increase recruitment of cortical control areas (Geier et al., 2010) associated with SUD (Chung et al., 2011). However, it is unknown whether incentives moderate the relationship between response inhibition and trait-level psychopathology and personality features of substance use risk. We examined these associations in the current project using a rewarded antisaccade (AS) task (Geier et al., 2010) in youth at risk for substance use. Participants were 116 adolescents and young adults (ages 12–21) from the University of Pittsburgh site of the National Consortium on Adolescent Neurodevelopment and Alcohol [NCANDA] study, with neuroimaging data collected at baseline and 1 year follow up visits. Building upon previous work using this task in normative developmental samples (Geier et al., 2010) and adolescents with SUD (Chung et al., 2011), we examined both trial-wise BOLD responses and those associated with individual task-epochs (cue presentation, response preparation, and response) and associated them with multiple substance use risk factors (externalizing and internalizing psychopathology, family history of substance use, and trait impulsivity). Results showed that externalizing psychopathology and high levels of trait impulsivity (positive urgency, SUPPS-P) were associated with general decreases in antisaccade performance. Accompanying this main effect of poor performance, positive urgency was associated with reduced recruitment of the frontal eye fields (FEF) and inferior frontal gyrus (IFG) in both a priori regions of interest and at the voxelwise level. Consistent with previous work, monetary incentive improved antisaccade behavioral performance and was associated with increased activation in the striatum and cortical control areas. However, incentives did not moderate the association between response inhibition behavioral performance and any trait-level psychopathology and personality factor of substance use risk. Reward interactions were observed for BOLD responses at the task-epoch level, however, they were inconsistent across substance use risk types. The results from this study may suggest poor response inhibition and heightened reward sensitivity are not overlapping neurocognitive features of substance use risk. Alternatively, more subtle, common longitudinal processes might jointly explain reward sensitivity and response inhibition deficits in substance use risk.

Neurocognitive development of inhibitory control and substance use vulnerability

“…We found that greater externalizing scores were associated with poorer correct response rate in the antisaccade task. This result is consistent with our previous findings within a subset of the current sample (Tervo-Clemmens et al, 2017), and supports theories relating disinhibitory phenotypes of substance use risk with poor response inhibition (Iacono et al, 2008;Young et al, 2009). We further sought to investigate how the relationship between inhibitory control limitations and substance use risk changes developmentally.…”

“…To this end, it has been suggested that diverging developmental trajectories of inhibitory control and other higher-order cognitive functions may increase vulnerability to problematic substance use (Casey et al, 2008, Steinberg, 2005, by way of early substance use experimentation (Johnston et al, 2018) and individual differences in psychiatric symptoms (Paus et al, 2008) that frequently co-occur with problematic substance use (Kreuger et al, 2002;Hussong et al, 2011). Supporting this perspective, recent work from our group has demonstrated that substance use risk factors, specifically externalizing psychopathology and impulsivity, are associated with poor inhibitory control and cortical activation differences among adolescents during an antisaccade task (Tervo-Clemmens, et al, 2017). However, it remains unclear whether certain periods of development are more sensitive to inhibitory control limitations associated with substance use vulnerability and if at-risk youth follow different trajectories of neurocognitive development.…”

“…Problematic substance use was defined at baseline using an established scoring protocol from the Customary Drinking and Drug Use Record (CDDR; Brown et al, 1998), where substance use was coded categorically and indicated whether participants exceeded age-specific National Institute on Alcohol Abuse and Alcoholism (NIAAA) guidelines for risky drinking (Exceeds Threshold Drinking; ETD; n = 29). This variable was selected for primary analysis to match our work with this sample using baseline and one-year follow-up data (Tervo-Clemmens et al, 2017). Furthermore, problematic substance use beyond this baseline characterization was uncommon in the final behavioral sample (weekly binge drinking: n = 17, weekly marijuana use n = 14; see Supplementary Methods for details), reflecting the isolation of substance use risk and relatively minimal levels of problematic substance use at this stage of the Pittsburgh NCANDA sample.…”

“…Participants completed a rewarded antisaccade task during fMRI acquisition initially described by Geier et al (2010; Figure 2) and reported in prior work from our group on an earlier portion of this sample (Tervo-Clemmens et al, 2017). Briefly, each trial consisted of cue, preparation, and response epochs lasting 1.5s each.…”

“…Preprocessing of fMRI data followed the same procedures as other recent task-based fMRI from our group (Paulsen, et al, 2015;Simmonds et al, 2018;Tervo-Clemmens et al, 2017). This included the removal of motion and noise artifacts (Analysis of Functional Neuroimages, AFNI; 3dDespike; Cox, 1996), non-linear registration of functional data to a standardized structural brain (3 mm, MNI-152 template; 2009c), slice timing and motion correction (mcflirt; Jenkinson et al, 2002).…”