Paediatric obesity and metabolic syndrome associations with cognition and the brain in youth: Current evidence and future directions

Abstract

Obesity and components of the metabolic syndrome (MetS) are associated with differences in brain structure and function and in general and food-related cognition in adults. Here, we review evidence for similar phenomena in children and adolescents, with a focus on the implications of extant research for possible underlying mechanisms and potential interventions for obesity and MetS in youth. Current evidence is limited by a relative reliance on small cross-sectional studies. However, we find that youth with obesity and MetS or MetS components show differences in brain structure, including alterations in grey matter volume and cortical thickness across brain regions subserving reward, cognitive control and other functions, as well as in white matter integrity and volume. Children with obesity and MetS components also show some evidence for hyperresponsivity of food reward regions and hyporesponsivity of cognitive control circuits during food-related tasks, altered brain responses to food tastes, and altered resting-state connectivity including between cognitive control and reward processing networks. Potential mechanisms for these findings include neuroinflammation, impaired vascular reactivity, and effects of diet and obesity on myelination and dopamine function. Future observational research using longitudinal measures, improved sampling strategies and study designs, and rigorous statistical methods, promises to further illuminate dynamic relationships and causal mechanisms. Intervention studies targeted at modifiable biological and behavioural factors associated with paediatric obesity and MetS can further inform mechanisms, as well as test whether brain and behaviour can be altered for beneficial outcomes.

Keywords: Diffusion Tensor Imaging (DTI); Magnetic Resonance Imaging (MRI); brain function; brain structure; food motivation; food reward; functional MRI (fMRI); glucose; inhibitory control; insulin; neuroimaging; type 2 diabetes.

FIGURE 1

Schematic showing relationships of paediatric obesity and metabolic syndrome with cognitive function and brain structure and function. Grey font/lines represent potential mechanisms. Relationships depicted are not universal but have been reported across multiple studies.

FIGURE 2

Brain imaging methods commonly used to investigate effects of paediatric obesity and metabolic syndrome. Grey matter volume (GMV) and white matter volume (WMV) can be measured using T1 weighted (T1W) structural MRI; white matter integrity can be estimated by fractional anisotropy (FA) and mean diffusivity (MD) derived from Diffusion Tensor Imaging (DTI); neural activation to food cues and food tastes can be assessed using Blood Oxygen Level Dependent (BOLD) responses assessed via functional MRI (fMRI); functional connectivity of brain regions can be assessed using resting state fMRI.

FIGURE 3

Brain regions implicated in food reward, cognitive control and homeostatic regulation demonstrating functional and structural differences in paediatric obesity and metabolic syndrome. ACC, anterior cingulate cortex; Amyg, amygdala; dlPFC, dorsolateral prefrontal cortex; FO, frontal operculum; Hipp, hippocampus; Hyp, hypothalamus; Ins, insula; IFG, inferior frontal gyrus; NAcc, nucleus accumbens; OFC, orbitofrontal cortex; RO, rolandic operculum; vmPFC, ventromedial prefrontal cortex. Regions showing functional as well as structural differences are preferentially represented. [Correction added on 9 June 2023, after first online publication: Figure 3 has been corrected in this version.]