Brain Activation and Satiety in Children: Functional Magnetic Resonance Imaging

The high prevalence of childhood obesity in the U.S. demands a better understanding of
factors that drive weight gain and influence the outcome of pediatric obesity interventions.
This project investigates the hypothesis that, as in adults, a subset of obese children
experience a diminished satiety response to food consumption, and that these children are
more resistant to gold standard family-based behavioral treatment (FBT) for obesity. FBT is
targeted almost exclusively toward parents; however, there is evidence that obesity
development and response to intervention may depend on additional factors such as individual
internal satiety perception and variability in the function of brain centers associated with
impulsivity and reward. The proposed research uses functional magnetic resonance imaging
(fMRI) to characterize brain function related to satiety and examines fMRI along with
behavioral, cognitive, and hormonal testing to fully examine potential mediators of
children's experience of satiety and response to FBT. The approach is based on evidence that
failure to attenuate the reward value of palatable foods after eating can be a manifestation
of a blunted central satiety response that is reliably detected using fMRI. Key objectives
will be to determine if differences in the central satiety response exist between obese and
non-obese children, and, among obese children, if the strength of the central satiety
response is associated with impulsivity and/or the success of obesity treatment. The central
hypothesis is that, in obese children, a blunted central nervous system satiety response
impairs the success of obesity interventions. To achieve study objectives, brain activation
by high-calorie visual food cues before and after food consumption will be measured by fMRI.
Participants will be obese and non-obese children aged 9-11 years. The 49 obese children will
be evaluated before and after they participate in a 6-month evidence-based FBT intervention.
Their pre-intervention fMRI will be compared to those of 20 non-obese controls to test for a
blunted central satiety response (Aim 1). The relationship of impulsivity to satiety
responses and food intake will be determined in obese children (Aim 2). The longitudinal
component tests whether central satiety responses prior to treatment predict treatment
outcomes (Aim 3A) and whether changes in central satiety responses during treatment predict
maintenance of reduced weight 6 and 12 months after treatment cessation (Aim 3B). Behavioral,
cognitive, and hormonal measures will be examined as potential mediating or confounding
factors contributing to fMRI responses. The proposed research is guided by an integrated,
transdisciplinary team with expertise in pediatric and adult neuroimaging, appetite
regulation, and family-based childhood obesity treatment. This research will provide new
insights into the neurobiological basis of child obesity and the relevance of neurobiological
factors to treatment success. The long-term objective is to translate these findings to
improve obesity interventions cost-effectively and sustain better long-term results.

During years 1-3, obese children will be enrolled into intervention groups of 9-11 families
with staggered start dates by 3-6 months. Years 1-4 includes enrollment, intervention,
longitudinal follow-up, and data collection for obese children. Control children will
primarily be recruited during years 2-3 to facilitate matching. FMRI scans are processed on a
rolling basis as studies are completed. In years 3 and 4 hormonal assays will be performed.
Final data analyses will be completed in year 4.

Inclusion Criteria:

- 9-11 years of age

- Male or female

- Ability and willingness to participate in study visits including fMRI scans and blood
draws;

- ability to provide informed written consent and assent;

- BMI z-score for lean control children 15th to 84.9th perc. for age and sex,

- BMI z-score for obese children BMI z-score >90th perc. for age and sex;

- Additional inclusion criteria for obese children: One overweight parent (BMI >25
kg/m2); willingness of 1 parent (does not have to be the obese parent) to engage in
family-based weight control treatment.

Exclusion Criteria:

- History of acute or chronic serious medical conditions;

- known diabetes mellitus or recent (6 mo.) history of anemia;

- presence of any implanted metal or metal devices, including ferro-metallic surgical
clips or braces;

- claustrophobia;

- documented cognitive disorder, disruptive behavior, inability to participate in group
sessions;

- current use of medications known to alter appetite, body weight, or brain response
(e.g. anti-seizure medications, glucocorticoids, medications for attention deficit
disorder);

- food intolerance or vegetarianism.