OBJECTIVE Spectral 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. METHODS PAC 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. CONCLUSIONS Our 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. SIGNIFICANCE The 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.

中文翻译：

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脑内脑电图谱调和揭示癫痫患者发作期的两种相位-幅度耦合

目的从两个临床相关方面分析发作活动的频谱谐波，(1) 作为产生“虚假”相位-幅度耦合 (PAC) 的混杂因素，可能导致关于潜在发作机制的错误结论，以及 (2) PAC 的好坏与癫痫病学家进行的癫痫发作区 (SOZ) 分类相对应。方法 回顾性研究了在 7 名药物耐药局灶性癫痫患者癫痫发作期间在脑内脑电图 (iEEG) 记录中观察到的 PAC 模式。引入时间锁定指数 (TLI) 测量以量化与癫痫发作期间 PAC 出现相关的频带之间的和谐程度。结果（1）在使用宏电极的 iEEG 记录中，在癫痫发作动力学期间谐波和非谐波 PAC 模式共存。(2) 谐波 PAC 模式是构成癫痫样活动的周期性非正弦波形的紧急特性。(3) TLI 度量允许区分非谐波 PAC 模式，该模式以前通过癫痫传播的阵发性去极化移位机制与发作核心相关联。结论我们的结果表明，发作活动的频谱和谐性在癫痫学家为定义 SOZ 进行的 iEEG 记录的视觉分析中起着相关作用，并且应该考虑它以正确解释发作机制。