Study of Cognition and Control in Youths

The goal of this research proposes to take a developmental neuroimaging approach to
elucidating brain mechanisms that lead to distinct forms of impulsivity in youth with
externalizing disorders, including attention-deficit/hyperactivity disorder (ADHD),
oppositional defiant disorder (ODD), and conduct disorder (CD). Roughly 12-15% of youth
suffer from at least one of these disorders (many of them have more than one) and they go on
to experience serious adverse outcomes over the course of their lifetimes including increased
rates of substance abuse, violence and criminality, maladjustment, and suicide. The absence
of a biological, and in particular a neurodevelopmental, understanding of the pathophysiology
of distinct kinds of impulsivity has been a major barrier to improving clinical care for
impulsive youth; it has hindered efforts at building better nosology, earlier and more
reliable diagnosis, and more effective treatments.

The NIMH Research Domain Criteria (RDoC) Initiative encourages clinical scientists to no
longer think in terms of single categorical diagnoses (whose boundaries may in fact be drawn
incorrectly), but rather to identify disorder-spanning constructs. Inspired by the RDoC
Initiative, our research aims to delineate the neural mechanisms of distinct forms of
impulsivity in youth from a transdiagnostic perspective that spans the three main
externalizing disorders, ADHD, CD, and ODD, as well as across subtypes of these disorders
(e.g., ADHD inattentive, hyperactive/impulsive, and combined types). More specifically, the
study aims to develop a new class of imaging-based biomarkers for specific forms of
impulsivity—markers that are rooted in aberrant brain maturation patterns.

Developing neuroimaging markers of impulsivity could have a number of important clinical
impacts. For example, these markers could provide a basis for more objective diagnosis,
facilitate earlier diagnosis, catalyze the development of new treatments, and help to guide
the selection of treatments.

For this study, 270 youth subjects will be recruited, 135 with at least one externalizing
disorder and 135 matched controls, between the ages of 6-18 . All participants will receive
the following: 1) a comprehensive clinical/neurological assessment to quantify impulsivity
symptoms; and 2) an fMRI session (structural, diffusion tensor imaging, resting, and task).
Three cohorts are recruited: childhood (6-9 years; n=90), early adolescence (10-13 years;
n=90), and middle adolescence (14-18; n=90).

The main aim of the study is to use imaging results to generate normative maturational curves
for each component in the brain's regulatory control architecture using a multi-level linear
mixed effects model. Multivariate models that predict types of impulsivity based on component
expression will then be constructed.

Inclusion Criteria:

- The healthy control group will be made up of approximately 135 subjects between the
ages of 6-18 at the start of the study who meet no diagnostic criteria for any
externalizing disorders.

- The externalizing group will be made up of approximately 135 subjects between the ages
of 6-18 at the start of the study who meet the diagnostic criteria for at least one
externalizing disorder (ADHD, ODD, CD, etc)

Exclusion Criteria:

- IQ below 80

- History of significant head injury (e.g. loss of consciousness greater than 5 minutes,
report of skull fracture or cerebral hemorrhage, or hospitalization)

- Presence of any significant medical or neurological condition that might impact
activity in the neural circuits of interest or that might increase risk of
participation for the subject (e.g. seizure disorder or mass lesions)

- Contraindications to MRI (e.g. metal objects in body, claustrophobia)

- Abnormal vision after correction