Abstract
ObjectivesPsychogenic 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.MethodsThe networks were extracted from Laplacian-transformed time series by a coherence connectivity estimation method.ResultsChildren 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.ConclusionThe 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.
Highlights
Functional neurological disorder (FND) involves disturbances of motor and sensory function not explained by other neurological disease
Differences between the psychogenic non-epileptic seizures (PNES) and FND-other group were found on two parameters
The PNES group showed increased global efficiency compared to healthy controls for a range of medium densities in the gamma and beta bands
Summary
Functional neurological disorder (FND) involves disturbances of motor and sensory function not explained by other neurological disease. Children (including adolescents) with FND present with diverse symptoms, often in combination, including loss of motor function (e.g., leg or arm paresis or weakness), loss of sensory functions (e.g., blindness, deafness, or loss of feeling in the limbs), positive movements (e.g., tremor, dystonia, or gait abnormalities), or psychogenic non-epileptic seizures (PNES). The working hypothesis from these studies is that FND symptoms emerge when stress—physical or emotional—triggers excessive activation of the brain stress systems (regions processing salience, arousal, and emotional states), which, in turn, disrupts motor- and sensory-processing regions (Blakemore et al, 2016; Kozlowska, 2017; Pick et al, 2018; Diez et al, 2020). PNES, which are paroxysmal, have been hypothesized to emerge in the context of neural network instability (Knyazeva et al, 2011; Barzegaran et al, 2012, 2016; Szaflarski and LaFrance, 2018). Potential mechanisms include a temporary disruption in neural networks, thereby compromising the horizontal and vertical integration of brain function and causing a disconnect between cortical and subcortical systems (Barzegaran et al, 2016; Kozlowska et al, 2018a), and alternatively, a time-limited increase in functional connectivity between limbic and motor regions that enables “upstream control and modulation of motor activity” (p. 213) (Li et al, 2015b; Szaflarski and LaFrance, 2018)
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