Dysfunctional Ephaptic Interactions May Play a Role in Major Depressive Disorder

Dysfunction in ephaptic entrainment may contribute to the pathophysiology of Major Depressive Disorder (MDD) by affecting the dynamics of neuronal activity. In this study, we tested this hypothesis using multiscale entropy (MSE) analysis, which quantifies the complexity inherent in time series data. Our investigation involved the analysis of electroencephalographic (EEG) data acquired from patients with Major Depressive Disorder (MDD), alongside simulated neural network data with and without the inclusion of ephaptic effects. The results revealed changes in brain signal complexity associated with the disorder, suggesting an impact of the ephapticity function on the dysregulation of neural dynamics in depression.We analyzed the dynamics of the small-world network using the Ephaptic Quadratic Integrate-and-Fire (QIF-E) neuronal model with ephapticity modulation. We modified the network topology and neuronal parameters based on empirical data related to depression. The entropy approach allowed us to quantify the irregularity and unpredictability of simulated neuronal signals at various time scales and compare them with real EEG results. Our simulated results suggest that the neural network without ephapticity presented statistical similarity in terms of entropy with the brain networks of individuals with MDD, as observed in the EEG signals. Specifically, we observed an increase in the mean entropy and a reduction in the dispersion of this mean compared to the CG (or ephaptic simulated group). Analysis reveals a predisposition among neural networks within the MG to converge upon a less adaptable terminal state, even in demonstrably higher variability and complexity within individual EEG time series. This comparative analysis aimed to evaluate the role of ephaptic coupling malfunction in the brain dynamics associated with MDD and shed light on the function of ephaptic coupling in the regulation and promotion of multiple brain dynamic states in quasi-equilibrium in healthy individuals.