Neuromelanin MRI: A Tool for Non-invasive Investigation of Dopaminergic Abnormalities in Adolescent Substance Use

Substance use disorders affect several million people in the United States every year, create significant economic burden, and cause tremendous suffering at the person, family, and societal levels. This proposal aims to investigate the dynamic interplay between pediatric substance use (a risk factor for substance use disorders) and rate of neuromelanin accumulation (a proxy for dopamine function) for the first time. Thus, this research seeks to identify a brain mechanism (dopamine function) that could be targeted in youth by future treatments in order to prevent onset of substance use disorders.

The goals of this study require a prospective imaging design that relies on the naturally-occurring adolescent substance use (e.g., differences in timing and amount of substance use is treated as quasi-experimental). Importantly, the investigators will begin data collection in a cohort on the cusp of entering a high-risk period of substance use initiation and conclude data collection after 36-months to capture substance use escalation. An intermediate 18-month follow-up NM-MRI scan is needed to help clarify the magnitude of early changes in NM accumulation. Thus, this is a longitudinal, observational study.

Of note, the use of the Monetary Incentive Delay fMRI task at baseline, 18-month, and 36-month follow-ups fulfills the NIH criteria of a basic experimental studies involving humans (BESH). Thus, this study as a whole qualifies as a clinical trial based on the determination:

1. The study involves humans
2. The participants are prospectively assigned to an intervention, which in this case means that the subject will be assigned to complete the Monetary Incentive Delay fMRI task while lying in the MRI scanner.
3. The study is designed to evaluate the effect of the intervention on participants, which in this case means that the investigators will evaluate the effect of the Monetary Incentive Delay task on brain activation in participants.
4. The effect being evaluated is a health-related biomedical or behavioral outcome, which in this case means fMRI brain activation between win and loss conditions, as well as between phases of anticipation and consummation/outcome.

In brief, use of this fMRI task is a single arm, non-masked, non-randomized, basic science intervention. This does not match any of the NIH-defined clinical trials phases (n/a). The fMRI data (brain activation) is the primary outcome measure of the BESH intervention, but is a tertiary outcome in the context of this longitudinal study. The task is utilized for its short-lived, reversible, and benign effects (e.g., brief changes in brain activation).