He, C; Fan, D; Wang, W; Wang, Q; Baier, G; (2025) Network dynamics mechanisms underlying the instigation and propagation of cortical spreading depression. Neurocomputing , 649 , Article 130733. 10.1016/j.neucom.2025.130733.

Text NetworkDynamics in CSD HeFan2024.pdf - Accepted Version Access restricted to UCL open access staff until 25 June 2026. Download (49MB)

Abstract

Cortical spreading depression (CSD) waves are widely recognized as the pathophysiological mechanism underlying migraine aura. Modeling the macroscopic phenomenological characteristics of CSD wave propagation is challenging due to the inability to capture biophysical features, while microscopic studies based on excitatory–inhibitory (E/I) neuron pairs struggle to link effectively with wave propagation behaviors. In order to couple the electrical activity of micro neurons with the macroscopic propagation behavior of the cortex, we adopt a network perspective and constructed a dual-layer ring network model. Within this unified framework, we identify four factors influencing CSD instigation and propagation: (i) the type and number of pathological neurons, (ii) the extracellular potassium concentration, (iii) the ratio of excitatory to inhibitory connections within the cortical network, and (iv) the architecture of network connectivity incorporating both short and long-range connections. Model results indicate counterintuitively that the number of initially pathological neurons does not significantly correlate with CSD propagation duration. The extracellular potassium concentration required for CSD instigation within the network is lower than that for single neurons, suggesting that coexisting cluster discharges alongside CSD may contribute to the comorbidity of epilepsy and migraine. An excessive imbalance in the E/I ratio can induce global re-entrant and retracting phenomena of CSD, whereas a higher proportion of long-range connections within the network can effectively reduce the probability of such occurrences. These findings suggest that designing intervention strategies that comprehensively consider these influential factors can effectively decrease the instigation probability of CSD or enhance the stability of brain networks during CSD propagation.

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