br Conclusions br Conflicts of interest br Acknowledgment br

Conclusions
Conflicts of interest
Acknowledgment
Introduction Sensitivity to reward and inhibitory control play important roles in the development and maintenance of substance use behavior (Dawe et al., 2004; Koob and Volkow, 2010). Much less is known about brain-based indicators of reward sensitivity and inhibitory control in relation to substance use treatment outcome. Research with treatment-seeking adult substance users suggests that pre-treatment regional order MG 149 activity in response to fMRI tasks assessing cognitive control is associated with substance use treatment outcomes (Brewer et al., 2008; Kober et al., 2014). This pilot study of adolescents recruited from substance use treatment examined the extent to which regional brain activation associated with inhibitory control in a reward cue antisaccade (AS) fMRI task (Geier et al., 2010; Chung et al., 2011), administered during or shortly after treatment completion, was correlated with 6-month treatment outcome. In research with substance dependent adults, two fMRI studies found that greater pre-treatment brain activation related to cognitive control, particularly in prefrontal regions, was associated with less substance use over follow-up (Brewer et al., 2008; Kober et al., 2014). Specifically, among cocaine dependent adults, greater pre-treatment regional brain activity during a Stroop color-word interference task in prefrontal regions, including the anterior cingulate and ventrolateral prefrontal cortex, was associated with less cocaine use during treatment (Brewer et al., 2008). Behavioral Stroop response, however, was not associated with cocaine use during treatment (Brewer et al., 2008). Further, among cannabis dependent males, greater pre-treatment Stroop-related activity in dorsal anterior cingulate cortex was associated with less cannabis use during treatment; and greater pre-treatment activation in prefrontal regions, such as ventrolateral prefrontal cortex, was associated with lower rates of cannabis use over 1-year follow-up (Kober et al., 2014). These studies of adult substance users suggest an inverse association between pre-treatment regional activation related to cognitive control and substance use outcomes over follow-up, and that task-related regional activation, relative to behavioral response, may be more strongly related to treatment outcome. A sensitive marker of cognitive control of behavior and executive functioning is provided by antisaccade (AS) performance (Hutton and Ettinger, 2006). Performing an AS requires stopping a prepotent eye movement toward a salient stimulus in favor of a voluntary movement to the opposite spatial location (Hallett, 1978; Munoz and Everling, 2004). Advantages of using AS to assay cognitive control include its well-characterized neural circuitry, and the ability to isolate activity related to response preparation, which is critical to effective response inhibition (Everling et al., 1998, 2000; Luna et al., 2008). Processes supporting AS have a protracted development into adolescence, with the ability to consistently execute AS continuing to mature into young adulthood (Luna et al., 2008). In particular, when executing AS, adolescents, compared to adults, tend to rely more on less mature regions such as dorsolateral prefrontal cortex, relative to regions associated with inhibitory control such as the cortical eye fields (Luna et al., 2001). Research indicates that youth at high, relative to low, risk for substance involvement showed poorer AS performance (Habeych et al., 2006), and less activation of brain regions supporting AS (McNamee et al., 2008). These findings suggest possible deficits or delayed maturation in neural circuitry supporting AS among high risk youth, and the sensitivity of AS as a measure of cognitive control. A distributed network of fronto-subcortical-parietal regions subserves AS, including, for example, the frontal eye field (FEF), supplementary eye field (SEF), dorsolateral and ventrolateral prefrontal cortex (dlPFC and vlPFC), posterior parietal cortex, anterior cingulate cortex, basal ganglia, thalamus, and superior colliculus (Munoz and Everling, 2004; Luna et al., 2004; Jamadar et al., 2013).