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 the 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 excess weight (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 and spectral dynamic casual modeling (spDCM) 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 further investigate whether these sensitive hippocampal connections at baseline could predict future BMI and eating behaviors. Results: Compared to controls, children with excess weight displayed abnormal bidirectional inhibitory effects between the right hippocampus and left postcentral gyrus (PoCG), that is, stronger inhibitory hippocampus-*PoCG EC but weaker inhibitory PoCG-*hippocampus EC, which further predicted BMI and food approach behavior one year later. Conclusion: These findings point to a particularly important role of abnormal information exchange between the hippocampus and somatosensory cortex in pediatric obesity and future food approach behavior, which provide novel insights into the neural hierarchical mechanisms underlying childhood obesity and further expand the spDCM model of adult obesity by identifying the directionality of abnormal influences between crucial circuits associated with appetitive regulation.