The performance of tasks that involve strong cognitive contr

The performance of tasks that involve strong cognitive control over behavior, such as AS, can be improved with the use of reward or incentive (Hardin et al., 2007; Geier et al., 2010). Adolescents, relative to adults, tend to be especially sensitive to the motivational effects of incentive on AS performance (Padmanabhan et al., 2011). In the context of reward cues, adolescents tend to show increased activity in striatal regions, whereas adults show greater activation in OFC (Padmanabhan et al., 2011), suggesting that adolescent behavior may be particularly influenced by bottom-up reward processing (striatum) in combination with a relatively immature OFC which supports executive processing of reward cues (Geier, 2013). Modulation of response inhibition by reward cues has been examined using an fMRI reward cue AS task in healthy adolescents (Geier and Luna, 2009; Geier et al., 2010; Padmanabhan et al., 2011), and youth with substance use disorder (SUD) (Chung et al., 2011). When SUD youth were compared with matched controls using the reward cue AS task, monetary incentive improved AS performance among SUD youth (Chung et al., 2011). Further, when preparing to execute AS (“preparation” phase) in reward trials, SUD youth, compared to controls, showed greater activation in prefrontal and oculomotor control areas associated with effective inhibitory control. The brain-based mechanisms by which incentives improve AS are thought to involve activation of regions involved in reward processing (e.g., ventral striatum [VS]), which in turn may enhance activity in regions associated with motor control (e.g., frontal eye fields) and executive function (e.g., prefrontal cortex) that support AS (Geier, 2013; Geier and Luna, 2009; Harsay et al., 2011). As a measure of cognitive control, successful AS behavior and greater activation of cognitive control regions supporting AS would be expected to be associated with better substance use treatment outcome. Regional EAI045 activation supporting AS, however, may be more strongly related to treatment outcome than AS behavioral performance, as found in a study using a Stroop task in treated adults (Brewer et al., 2008). Further, the use of an incentive (reward cue) to motivate cognitive control and to improve AS performance through greater regional activation supporting AS suggests that regional activation and AS performance during reward (versus neutral) trials will be more strongly associated with better treatment outcome. That is, an optimized or motivated level of inhibitory control may be an important indicator of lower substance use severity over follow-up among adolescents in substance use treatment. This pilot study examined response to an fMRI reward cue AS task administered during or shortly after treatment completion as a correlate of 6-month outcomes in adolescent substance users. We predicted, based on the adult literature (e.g., Brewer et al., 2008), that regional brain activation associated with response inhibition would be more strongly associated with treatment outcome than AS behavioral performance. In addition, we hypothesized that when preparing to execute an AS (preparation phase), greater activation in regions involved in cognitive (e.g., dlPFC, vlPFC) and oculomotor (e.g., FEF, SEF) control which support AS would be associated with lower severity of substance involvement at 6-month follow-up. We also predicted that the association between regional activation and treatment outcome would be stronger for reward, relative to neutral, trials because reward cues may motivate and optimize effective cognitive control in adolescents. Study results could help to identify neurobiological mechanisms that are associated with substance use treatment outcomes in youth.
Materials and methods
Results
Discussion Results from this preliminary study support hypotheses that, when preparing to execute an AS, specifically during the reward cue condition, activation in regions associated with cognitive and oculomotor control was inversely correlated with marijuana symptom count at 6-month follow-up. Findings highlight the role of incentives (“reward cue”) in enhancing or motivating optimal levels of task-related activation to support effective inhibitory control, and indicate that this optimized level of activation during a cognitive control task was associated with fewer marijuana-related problems among treated adolescents over follow-up. Notably, youth with more marijuana symptoms over follow-up tended to show deactivation during the reward condition in ROIs that were associated with treatment outcome. The absence of an association between AS behavioral performance and treatment outcome is consistent with a study of treatment-seeking adults (Brewer et al., 2008), and suggests the potential utility of a brain-based, relative to behavioral, indicator in relation to treatment outcome.