Spectral harmonicity distinguishes two types of ictal phase-amplitude cross frequency couplings in patients candidate to epilepsy surgery

ObjectiveSpectral harmonicity of the ictal activity was analyzed regarding two clinically relevant aspects, (1) as a confounding factor producing spurious phase-amplitude couplings (PAC) which may lead to wrong conclusions about the underlying ictal mechanisms, and (2) its role in how good PAC is in correspondence to the seizure onset zone (SOZ) classification performed by the epileptologists. MethodsPAC patterns observed in intracerebral electroencephalography (iEEG) recordings were retrospectively studied during seizures of seven patients with pharmacoresistant focal epilepsy. The time locked index (TLI) measure was introduced to quantify the degree of harmonicity between frequency bands associated to the emergence of PAC during epileptic seizures. Results(1) Harmonic and non harmonic PAC patterns coexist during the seizure dynamics in iEEG recordings with macroelectrodes. (2) Harmonic PAC patterns are an emergent property of the periodic non sinusoidal waveform constituting the epileptiform activity. (3) The TLI metric allows to distinguish the non harmonic PAC pattern, which has been previously associated with the ictal core through the paroxysmal depolarizing shifts mechanism of seizure propagation. ConclusionsOur results suggest that the spectral harmonicity of the ictal activity plays a relevant role in the visual analysis of the iEEG recordings performed by the epileptologists to define the SOZ, and that it should be considered for the proper interpretation of ictal mechanisms. SignificanceThe proposed harmonicity analysis can be used to improve the delineation of the SOZ by reliably identifying non harmonic PAC patterns emerging from fully recruited cortical and subcortical areas. HighlightsO_LIHarmonic and non harmonic phase-amplitude couplings coexist in epileptiform local field potentials. C_LIO_LIThe time locked index quantitatively differentiates harmonic and non harmonic ictal PAC patterns. C_LIO_LISpectral harmonicity plays a relevant role in the interpretation of underlying ictal mechanisms. C_LI