Obesity risk shows individual variation such that some children are more likely than
others to gain excess weight. One potential reason is that, due to genetic and
environmental factors, individuals vary in appetitive behaviors that drive food intake
and weight. However, the neurodevelopmental mechanisms underpinning variation in appetite
and weight, and effects of risk and protective factors on those outcomes, are not
understood. Preliminary data from RESONANCE, the investigators large MRI cohort, suggests
obesity risk factors such as maternal pre-pregnancy obesity and obesity-associated
genetic variants are associated with not just heightened parent-reported child appetite
and adiposity, but with altered patterns of brain structure development from infancy
through early childhood. However the relevance of these findings to appetitive behaviors
and development of obesity in middle childhood is unknown. This is important because
obesity rates and metabolic complications increase through development, adiposity and
eating habits measured in later childhood track into adulthood, and obesity is harder to
treat later in development, making middle childhood a key stage for capturing outcomes
with relevance for lifetime metabolic health. Further, although functional magnetic
resonance imaging (MRI) studies have identified altered patterns of activation in brain
appetite circuits in association with pediatric obesity and early risk factors for
obesity, the predictors of altered functioning of brain appetite circuits in middle
childhood are unknown. Identifying the patterns of brain development that predict
obesity-promoting behaviors and brain functioning in middle childhood is essential to
understand the neural mechanisms by which early obesity risk factors drive excess intake
and obesity, and may help pinpoint neurobehavioral targets for early obesity prevention.
Finally, although preclinical research and MRI studies of children under 9 years of age
support that hypothalamic gliosis, a cellular inflammatory response, plays a role in
obesity pathogenesis, it is unclear whether it occurs or impacts appetite in earlier
life. For the proposed study, RESONATE, the investigators will address the above research
gaps by extending the RESONANCE study to administer meal tests, behavioral and functional
magnetic resonance imaging (fMRI) tasks assessing food and non-food reward and cognitive
control, and weight/ adiposity measures in middle childhood, and examining hypothalamic
gliosis, in a sub-sample of RESONANCE children. By combining this data with extant MRI
data and extant or newly-collected data on obesity risk and protective factors, the
investigators will test a multi-faceted hypothesis that prenatal, genetic and postnatal
factors lead to differential early development of brain appetite circuits, which in turn
gives rise to variation in appetitive behaviors and behaviors involving reward processing
and cognitive control as well as altered function of brain appetite circuits, that act to
influence the development of obesity into middle childhood. The investigator's long-term
goal is to lay foundations for developmentally-appropriate, neurobehaviorally-informed
interventions to address child obesity.