The Neuroeconomics of Behavioral Therapies for Adolescent Substance Abuse

Little is known about the role of adolescent neurodevelopment in adolescent substance abuse
treatment outcomes. The development and evaluation of adolescent substance abuse treatments
rarely includes consideration of varying cognitive capacities and their neural
representations as determinants of individual variation in treatment response. This proposed
R21 project would address this gap by identifying associations among decision making,
task-related neural processing, and treatment outcome among adolescents participating/have
participated in two randomized clinical trials for adolescent substance abuse. Increasing our
understanding of neural processes that underlie decision making in adolescent marijuana and
alcohol users would inform the development of future intervention and prevention efforts.

This complementary project draws subjects from two studies investigating
contingency-management (CM) based treatments "Behavioral Treatment of Adolescent Marijuana
Abuse" (DA015186), and "Family Based Contingency Management for Adolescent Alcohol Abuse"
(AA016917). Both trials compare a unique CM intervention that involves an abstinence-based
reinforcement program to a standard, state of the art cognitive behavioral intervention.
Analyses would be performed separately for the two samples, with hypotheses tested first
using the Marijuana sample, and assessed for replication/specificity using the Alcohol
sample. The proposed project would explore novel neurobiological predictors of response to CM
interventions.

Adolescents recruited into the Marijuana Trial (n=69; 23 per treatment arm) and the Alcohol
Trial (n=54; 27 per treatment arm) during the period of this R21 project would participate in
a single neuroimaging session as soon after the intake session as possible, within 7 to 30
days. During the neuroimaging session, adolescents would make intertemporal choice decisions
in a Delay Discounting task regarding gains of $100 and $1,000. Preliminary data from the
Marijuana trial demonstrates significant association between performance on this behavioral
delay discounting task and abstinence achieved during treatment over and above the
significant effect of treatment condition. The investigators seek to understand the neural
processes that underlie performance on this laboratory task, and the degree to which
variation in these neural processes relates to and predicts adolescent substance abuse
treatment outcomes. The conceptual framework for the proposed project is based on the
neuroeconomics of addiction in general, and the competing neural systems hypothesis in
particular (Bechara, 2005a; Bickel, et al., 2007; Daw, et al., 2005; Jentsch & Taylor, 1999).
This behavioral choice hypothesis postulates a biased competition between an "impulsive" (or
''reflexive") neural system (including the striatum, amygdala, ventral pallidum, and related
structures) and the "executive" (or "reflective") neural system (including the prefrontal
cortex) in understanding patterns of suboptimal decision making among substance-dependent
individuals. An overarching hypothesis is that differing responses to distinct treatment
approaches (CM vs. CBT) are partially determined by the pattern of activation or functional
connectivity within and across these competing neural systems. These project hypotheses would
be tested by the following specific aims:

Primary Aims:

- Determine the degree to which performance on a laboratory delay discounting task
correlates with activity in impulsive and/or executive neural systems.

- Determine the degree to which performance on a laboratory delay discounting task and
neural processing predict adolescent substance abuse treatment outcome over and above
the effects of treatment condition.

Secondary Aim:

- Explore interactions between response to CM and delay discounting-related neural
processing.

In summary, this proposed exploratory/developmental project would importantly contribute to
the understanding of the role of neural processing in adolescent substance-abuse treatment
processes and outcome. Specifically, this study has the potential to reveal relations among
decision making, neural processing, and treatment outcomes, including the role of patterns of
neural activation on response to contingency management among adolescent substance abusers.
Results will have implications for future research on adolescent neurodevelopment and
adolescent substance abuse treatment. The potential to use neuroscience findings to better
understand and improve treatment outcomes in substance-abusing adolescents will have strong
public health impact.

Inclusion Criteria:

- Participants must be 12 to 18 years old and have a parent/guardian who can
participate.

- Youth must meet either of the following inclusion criteria:

1. Report using marijuana during the previous 30 days or provide a
marijuana-positive urine test, plus meet criteria for Cannabis Abuse or
Dependence OR

2. Meet Diagnostic Statistical Manual (DSM) criteria for Alcohol Abuse or dependence
or have had one binge episode, specified by ≥5 drinks in one day, in the past 90
days and report alcohol use in the past 30 days.

Exclusion Criteria:

- Contraindications to MRI including ferromagnetic implants or claustrophobia

- Meeting DSM criteria for dependence on illicit drugs other than marijuana or alcohol
(use/abuse of other drugs will not be excluded)

- Exhibit active psychosis, have severe medical or psychiatric illness limiting
participation

- Are pregnant or breast-feeding.