Activation of Functional Brain Networks in Children With Psychogenic Non-epileptic Seizures

Abstract

Objectives: Psychogenic non-epileptic seizures (PNES) have been hypothesized to emerge in the context of neural networks instability. To explore this hypothesis in children, we applied a graph theory approach to examine connectivity in neural networks in the resting-state EEG in 35 children with PNES, 31 children with other functional neurological symptoms (but no PNES), and 75 healthy controls. Methods: The networks were extracted from Laplacian-transformed time series by a coherence connectivity estimation method. Results: Children with PNES (vs. controls) showed widespread changes in network metrics: increased global efficiency (gamma and beta bands), increased local efficiency (gamma band), and increased modularity (gamma and alpha bands). Compared to controls, they also had higher levels of autonomic arousal (e.g., lower heart variability); more anxiety, depression, and stress on the Depression Anxiety and Stress Scales; and more adverse childhood experiences on the Early Life Stress Questionnaire. Increases in network metrics correlated with arousal. Children with other functional neurological symptoms (but no PNES) showed scattered and less pronounced changes in network metrics. Conclusion: The results indicate that children with PNES present with increased activation of neural networks coupled with increased physiological arousal. While this shift in functional organization may confer a short-term adaptive advantage-one that facilitates neural communication and the child's capacity to respond self-protectively in the face of stressful life events-it may also have a significant biological cost. It may predispose the child's neural networks to periods of instability-presenting clinically as PNES-when the neural networks are faced with perturbations in energy flow or with additional demands.

Clinical Correlation Advised: Measuring Functional Connectivity in PNES

“…Moreover, they found that children with other functional neurological symptoms (but no PNES) showed scattered and less pronounced changes in network metrics. Radmanesh and colleagues 10 also observed that increases in some of the functional network metrics were correlated with increased arousal in children with PNES.…”

“…In their recent resting-state EEG study, Radmanesh and colleagues 10 used graph theory to examine neural network function in children with PNES, children with other functional neurological symptoms (but no PNES), and healthy controls. Graph theory is a relatively new tool that has been widely applied to characterize human brain network architecture.…”

“…It provides quantitative measurements for each node to depict integrated nature of local brain activity and to describe the global properties of brain networks. Radmanesh and colleagues 10 found that children with PNES showed widespread changes in network metrics compared to controls: increased global efficiency, local efficiency, and modularity in several frequency bands (ie, alpha, beta, and gamma). Moreover, they found that children with other functional neurological symptoms (but no PNES) showed scattered and less pronounced changes in network metrics.…”

Changing the culture of care for children and adolescents with functional neurological disorder

“…For example, the emerging picture from neuroscience research is that FND is a neuropsychiatric (mind–body) condition that involves complex interactions between brain, mind, body, and context—the lived experience of the child and the family. FND reflects the activation of brain regions that underpin salience detection, arousal, pain, and emotional states [3] , [5] , [54] , [55] . These regions, collectively referred to as the brain’s stress system or emotion-processing regions, are commonly activated in the context of stress (the psychological-arousal component of FND).…”

“…These regions, collectively referred to as the brain’s stress system or emotion-processing regions, are commonly activated in the context of stress (the psychological-arousal component of FND). And because these emotion-processing regions are over-active and over-dominant, they over-connect with motor- and sensory-processing regions and disrupt motor and sensory function (the physical, motor-sensory component of FND) [3] , [5] , [54] , [55] . Given that FND thus involves both psychological and physical components, treatment needs to address both dimensions.…”