This experiment tested the hypothesis that exercise would improve executive function. Sedentary, overweight 7- to 11-year-old children (N = 171, 56% girls, 61% Black, M ± SD age = 9.3 ± 1.0 years, body mass index [BMI] = 26 ± 4.6 kg/m², BMI z-score = 2.1 ± 0.4) were randomized to 13 ± 1.6 weeks of an exercise program (20 or 40 min/day), or a control condition. Blinded, standardized psychological evaluations (Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III) assessed cognition and academic achievement. Functional MRI measured brain activity during executive function tasks. Intent to treat analysis revealed dose-response benefits of exercise on executive function and mathematics achievement. Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity attributable to exercise was also observed. Consistent with results obtained in older adults, a specific improvement on executive function and brain activation changes attributable to exercise were observed. The cognitive and achievement results add evidence of dose-response and extend experimental evidence into childhood. This study provides information on an educational outcome. Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic, physical activity may prove to be a simple, important method of enhancing aspects of children's mental functioning that are central to cognitive development. This information may persuade educators to implement vigorous physical activity.

Adipose tissue is a known source of proinflammatory cytokines in obese humans and animal models, including thedb/dbmouse, in which obesity arises as a result of leptin receptor insensitivity. Inflammatory cytokines induce cognitive deficits across numerous conditions, but no studies have determined whether obesity-induced inflammation mediates synaptic dysfunction. To address this question, we used a treadmill training paradigm in which mice were exposed to daily training sessions or an immobile belt, with motivation achieved by delivery of compressed air on noncompliance. Treadmill training prevented hippocampal microgliosis, abolished expression of microglial activation markers, and also blocked the functional sensitization observed in isolated cells afterex vivoexposure to lipopolysaccharide. Reduced microglial reactivity with exercise was associated with reinstatement of hippocampus-dependent memory, reversal of deficits in long-term potentiation, and normalization of hippocampal dendritic spine density. Because treadmill training evokes broad responses not limited to the immune system, we next assessed whether directly manipulating adiposity through lipectomy and fat transplantation influences inflammation, cognition, and synaptic plasticity. Lipectomy prevents and fat transplantation promotes systemic and central inflammation, with associated alterations in cognitive and synaptic function. Levels of interleukin 1β (IL1β) emerged as a correlate of adiposity and cognitive impairment across both the treadmill and lipectomy studies, so we manipulated hippocampal IL1 signaling using intrahippocampal delivery of IL1 receptor antagonist (IL1ra). Intrahippocampal IL1ra prevented synaptic dysfunction, proinflammatory priming, and cognitive impairment. This pattern supports a central role for IL1-mediated neuroinflammation as a mechanism for cognitive deficits in obesity and diabetes.

Child obesity and overweight are epidemic in US children.¹ A third of elementary school–aged children are overweight or obese.² Childhood obesity is associated with a number of adverse conditions formerly thought to occur only in adults, including type 2 diabetes and atherosclerosis.^3-7 Overweight, minority race/ethnicity, and family history of diabetes are risk factors for type 2 diabetes in youth.⁸

Objective: Children who are less fit reportedly have lower performance on tests of cognitive control and differences in brain function. This study examined the effect of an exercise intervention on brain function during two cognitive control tasks in overweight children.Design and Methods: Participants included 43 unfit, overweight (BMI ≥ 85th percentile) children 8‐ to 11‐years old (91% Black), who were randomly divided into either an aerobic exercise (n = 24) or attention control group (n = 19). Each group was offered a separate instructor‐led after‐school program every school day for 8 months. Before and after the program, all children performed two cognitive control tasks during functional magnetic resonance imaging (fMRI): antisaccade and flanker.Results: Compared to the control group, the exercise group decreased activation in several regions supporting antisaccade performance, including precentral gyrus and posterior parietal cortex, and increased activation in several regions supporting flanker performance, including anterior cingulate and superior frontal gyrus.Conclusions: Exercise may differentially impact these two task conditions, or the paradigms in which cognitive control tasks were presented may be sensitive to distinct types of brain activation that show different effects of exercise. In sum, exercise appears to alter efficiency or flexible modulation of neural circuitry supporting cognitive control in overweight children.