Altered hippocampal effective connectivity predicts BMI and food approach behavior in children with obesity

Objective The vicious circle model of obesity proposes that the hippocampus plays a crucial role in food reward processing and obesity. However, few studies focused on whether and how pediatric obesity influences the potential direction of information exchange between hippocampus and key regions, as well as whether these alterations in neural interaction could predict future BMI and eating behaviors. Methods In this longitudinal study, a total of 39 children with overweight/obesity and 51 children with normal weight, aged 8 to 12, underwent resting-state fMRI. One year later, we conducted follow-up assessments of eating behaviors and BMI. Resting-state functional connectivity (FC) and spectral dynamic casual modeling technique were used to examine altered functional and effective connectivity (EC) of the hippocampus in children with overweight/obesity. Linear support vector regression, a machine learning method, was employed to investigate whether hippocampal connections at baseline could predict future BMI and eating behaviors. Results Compared to controls, children with overweight/obesity displayed abnormal bidirectional inhibitory effects between the right hippocampus and left postcentral gyrus (PoCG), namely, stronger inhibitory EC from the hippocampus to PoCG but weaker inhibitory EC from the PoCG to hippocampus, which further predicted BMI and food approach behavior one year later. Conclusion These findings suggest that imbalanced information exchange in the appetitive reward circuitry between the hippocampus to somatosensory cortex may be a sensitive neurobiomarker for childhood obesity and future food approach behavior, which expands the vicious circle model of obesity by revealing the crucial role of hippocampal undirectional and directional connections in childhood obesity. This study is essential for developing effective intervention strategies and for reducing long-term health-care costs associated with obesity.