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

IEEE Trans Biomed Eng. 2018 Jul;65(7):1504-1515. doi: 10.1109/TBME.2017.2757878. Epub 2017 Sep 28.

Abstract

Objective: One of the features used in the study of hyperexcitablility is high-frequency oscillations (HFOs, >80 Hz). HFOs have been reported in the electrical rhythms of the brain's neuroglial networks under physiological and pathological conditions. Cross-frequency coupling (CFC) of HFOs with low-frequency rhythms was used to identify pathologic HFOs in the epileptogenic zones of epileptic patients and 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 four-unit neuroglial cellular network model where each unit incorporates pyramidal cells, interneurons, and astrocytes. Three different pathways of hyperexcitability generation-Na - 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: First, Identifying the exponential relationship between network excitability and SED durations; second, highlighting the importance of glia in hyperexcitability (as they relate to extracellular potassium); and third, elucidation of the biophysical basis for CFC coupling features.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / cytology*
  • Brain / physiology
  • CA3 Region, Hippocampal / physiology
  • Humans
  • Membrane Potentials / physiology
  • Models, Neurological*
  • Neuroglia / cytology*
  • Neuroglia / physiology*
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Synapses

Substances

  • Sodium-Potassium-Exchanging ATPase

Grants and funding