Figure 1. Cellular and network mechanisms of pathological HFOs.

A: HFOs are generated by synchronous action potential firing of principal cells. An individual cycle of an oscillation is a population spike. The frequency of the oscillation is determined by the frequency of the cellular firing – so called ‘pure‘ HFOs. B: Fast ripples, i.e. HFOs with a frequency of up to 600 Hz can be generated, if the cells fire action potentials at the same frequency. Physiological mechanisms underlying the genesis of action potentials limit the rate of cellular firing. Therefore, this mechanism is least probable. C: Out-of-phase firing between two neuronal populations can result in a doubling of the frequency of the extracellularly recorded ‘emergent’ type of HFOs. In this scenario, the out-of-phase firing is due to cell loss. D: Asymmetric excitatory input or polychronicity due to various lengths of axons can result in functional clustering and out-of-phase firing. E: Morphological changes, axonal growth and sprouting may result in functional clustering due to the presence of hub neurons. F: Asynchronous firing within an active neuronal population may result in random co-incidental firing and the occurrence of fast ripples.