Neurometabolic network (NMetNet) for functional neurological disorder in children and adolescents

Functional neurological disorder (FND) in children and adolescents is a biopsychosocially complex condition characterized by a wide range of neurological symptoms. Using magnetic resonance spectroscopy to study neurometabolites has become an important approach to studying the mechanisms of FND. Unlike previous studies focusing on concentration-level analysis, this study examines conditional dependencies between six neurometabolites: N-acetyl aspartate, creatine, glutathione, choline, myo-inositol, and glutamate. Conditional dependence implies that two neurometabolites have joint variability that is not mediated by other neurometabolites.

A Bayesian graphical lasso approach was used to estimate neurometabolites' conditional dependencies in three regions of interest: the anterior default mode network (aDMN), supplementary motor area (SMA), and posterior default mode network (pDMN). We introduce the term neurometabolic network (NMetNet) to describe these conditional dependencies.

Children and adolescents with FND (vs. healthy controls) showed a loss of conditional dependencies related to creatine and glutathione between the aDMN and SMA/pDMN. Glutathione is the primary antioxidant in the brain. Creatine plays a key role in maintaining bioenergetics and also acts as an antioxidant.

These findings suggest that FND is characterized by dysregulated bioenergetics and increased vulnerability to oxidative stress. Understanding NMetNet in FND offers novel insights into the disorder's neurobiology, with implications for therapeutic interventions to restore energy homeostasis and oxidative balance.