Phase-amplitude Coupling and Neuroglial Networks of the Brain: Big Role for a Small Cell

Epilepsy affects over 45 million people worldwide and while treatment options exist, antiepileptic drugs don't work in up to 50% of the cases; furthermore, poorly-treated epilepsy may cause complications such as sudden unexpected death in epilepsy (SUDEP) and status epilepticus. Brain rhythms can characterize both normal and pathologic brain states and the coupling between these rhythms, namely between low frequency oscillations (LFOs,Ph.D

Low-to-High Cross-Frequency Coupling in the Electrical Rhythms as Biomarker for Hyperexcitable Neuro-Glial Networks of the Brain

Objective: One of the features used in the study of hyperexcitablility are high frequency oscillations (HFOs, >80Hz). HFOs have been reported in the electrical rhythms of the brain's neuro-glial networks under physiological and pathological conditions. Cross-frequency coupling (CFC) of HFOs with low frequency rhythms was used to identify pathologic HFOs (pHFOs) (i) in the epileptogenic zones of epileptic patients, and (ii) as a biomarker for the severity of seizure-like events in genetically modified rodent models. We describe a model to replicate reported CFC features extracted from recorded local field potentials (LFPs) representing network properties. Methods: This study deals with a 4-unit neuro-glial cellular network model where each unit incorporates pyramidal cells, interneurons and astrocytes. Three different pathways of hyperexcitability generation - Na+-K+ ATPase pump, glial potassium clearance, and potassium afterhyperpolarization channel - were used to generate LFPs. Changes in excitability, average spontaneous electrical discharge (SED) duration and CFC were then measured and analyzed. Results: Each parameter caused an increase in network excitability and the consequent lengthening of the SED duration. Short SEDs showed CFC between HFOs and theta oscillations (4-8 Hz), but in longer SEDs the low frequency changed to the delta range (1-4 Hz). Conclusion: Longer duration SEDs exhibit CFC features similar to those reported by our team. Significance: (i) Identifying the exponential relationship between network excitability and SED durations, (ii) highlighting the importance of glia in hyperexcitability (as they relate to extracellular potassium), and (iii) elucidation of the biophysical basis for CFC coupling features