There is a growing focus on links between obesity Ledipasvir (GS 5885) and cognitive decline in adulthood including Alzheimer��s disease. inflammatory cytokines and obesity-associated gut hormones have been associated with learning memory and general cognitive function. To date examination of obesity-associated biology with brain function has primarily occurred in animal models. The few studies examining such biologically-mediated pathways in adult humans have corroborated the animal data Ledipasvir (GS 5885) but this body of work has gone relatively unrecognized by the pediatric literature. Despite the fact that differences in these biomarkers have been found in association with obesity in children the possibility that obesity-related biology could affect brain development in children has not been actively considered. We review obesity-associated biomarkers that have shown associations with neurocognitive skills specifically executive functioning skills which have far-reaching implications for child development. Understanding such gut-brain associations early in the lifespan may yield unique intervention implications. Executive Functioning Skills Involve Multiple Brain Areas and Develop in Early Childhood Executive functioning (EF) skills are a set of cognitive processes that enable conscious and subconscious control of attention and effort. As such the executive system can shape multiple cognitive and behavioral outcomes across the lifespan ranging from specific academic skills (1) to intelligence quotient (IQ) scores (2) and overall school achievement (3). Central EF skills include working memory problem solving set-shifting inhibitory control flexible thinking and planning. Such skills emerge rapidly during the early childhood years and continue to develop throughout later childhood and into adolescence (4). Moreso than simply academic knowledge EF skills are vital for preparing children to be successful in school (5 6 The prefrontal cortex (PFC) has traditionally been viewed as the ��seat�� of EF as this region of the brain is centrally involved in the high-level top-down control of impulses that are generated from elsewhere in the brain (e.g. the limbic system which is typically considered more emotionally reactive). It is increasingly recognized however that there are multiple areas of the brain involved in EF (e.g. dorsolateral PFC anterior cingulate cortex orbitofrontal cortex medial PFC) and that each of these brain regions have extensive functional connections to other regions of the brain (subcortical areas and brain stem) which govern the automatic processes that also shape an Ledipasvir (GS 5885) individual��s EF profile. Although some of the brain regions associated with specific EF skills are beginning to be mapped the nature of the executive control system is that multiple brain areas play a role in the process and there is ongoing Ledipasvir (GS Rabbit Polyclonal to CAMK5. 5885) communication among these regions. Children’s brains undergo extensive change and development during the first years of life with continued maturation of the cortical regions responsible for top-down control of cognitive and behavioral processes continuing into adolescence (7). Importantly not only brain structures but also neural organization and functional connectivity among brain regions change and develop over this time. As obesity tends to have its onset during early childhood when rapid brain development is occurring this means that children are exposed to the potential effects of obesity-related biology during developmentally-sensitive periods wherein brain-behavior connections are being established and begin to shape subsequent long-term cognitive outcomes. Thus considering how the biological changes associated with obesity may affect the organization of the developing brain is vital. The focus of this review is on how obesity-specific biology may adversely affect multiple regions of the brain that shape the range of EF skills that are in turn critical for successful child development across domains. Although such effects may operate through multiple pathways we focus here on gut-hormone- and adipose-tissue- mediated pathways. We do not include a review of the literature regarding diabetes and its associated biology with cognitive functioning because it remains relatively uncommon in children even in adolescents (8). Obesity May Affect Executive Functioning.