Effects of lisdexamfetamine on cognitive control and reward response in adolescents and young adults with ADHD:  neural and clinical outcomes

Principal Investigator:  Julie Schweitzer, Ph.D.

The goal of this project is to identify the effect of a commonly used stimulant (lisdexamfetamine; LDX) in adolescents and young adults with ADHD. This is a developmental period associated with high-risk taking activity in typical development, but particularly in individuals with ADHD. Everyday challenges in risk-taking for this population include issues that have the potential for long-term consequences including poor academic functioning, reckless automobile driving, substance abuse and unprotected sex. The cognitive control neural system likely mediates the ability to monitor and control behaviors associated with these actions. The effects of pharmacological intervention on the neural processes of cognitive control that mediate these behaviors, particularly in this developmental period, are unknown. Similarly the effects of stimulants to treat ADHD on the neural processes underlying self-control associated with this developmental period are unknown. We will use a delay discounting paradigm to quantify the neural and cognitive changes in self-control associated with LDX and placebo. Delay discounting paradigms measure decision-making between sooner, smaller rewards versus larger, more delayed rewards and provide a quantitative measure of self-control. We will investigate how the cognitive control and reward/self-control mechanisms, interact.  We will use a combination of behavioral and neuroimaging measures in an 8-week, randomized, double-blind, placebo-controlled, parallel-groups titrated optimal dose trial of LDX oral once daily.

Developmental changes in neural processes underlying impulsivity and ADHD

Principal Investigator:  Julie Schweitzer, Ph.D.

Problems with self-control are of major public health relevance as they are associated with physical and mental health, substance abuse and academic success impacting both individuals and society. The development of self-control is a critical step toward successful independence in young adulthood. Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder associated with elevated problems with self-control. We hypothesize that poor self-control in ADHD leads to their impaired academic achievement and poor high school graduation rates. An improved understanding of the developmental trajectory of self-control will lead to more focused and successful intervention programs.

Despite the public health importance of self-control, no studies have directly tested how the underlying mechanisms that determine self-control develop. It is hypothesized that a balance between cognitive control and reward response processes determine degree of self-control functioning. This project will characterize for the first time how cognitive control and reward-related neural functioning during adolescence and early adulthood independently contribute to self-control in both healthy development and ADHD. We will assess how changes in brain development occur in a two system model of self-control, which includes cognitive control (dorsolateral prefrontal cortex) and reward processing (ventral striatum) systems, and how the systems relate to broader impairments associated with ADHD. An additional goal is to assess if brain activity associated with self-control can serve as a biomarker for predicting academic performance. At the conclusion of these studies we will be able to identify age-related specific targets and recommendations for improving self-control.

This study is a collaborative effort by ADHD and functional imaging cognitive control researchers Julie Schweitzer and Catherine Fassbender at the UC Davis MIND Institute; Amanda Guyer at UC Davis with expertise in reward and emotional systems in neurodevelopment; Jamal Abedi at UC Davis with proficiency in measuring academic outcomes; and from Stanford University Samuel McClure, developer of the two-system model of self-control in neuro-economics, and Wouter van den Bos with experience in the development of social and reward based decision-making. Stephen Hinshaw at UC Berkeley brings to the contribution experience in ADHD, diagnostic issues, longitudinal research methods, measurement of academic issues in ADHD and general outcome research methods associated with the disorder. The geographic proximity of these collaborators from northern California will help to facilitate this collaboration.