Background: Phase-amplitude coupling (PAC) is widely used to quantify interactions between neural oscillations across timescales and is often interpreted as reflecting temporally meaningful coordination between slow and fast neural activity. New method: Combining empirical EEG data with mathematical analysis, we tested whether modulation index (MI)-based PAC distinguishes opposite temporal organisations of cross-frequency coupling by inverting the phase of the low-frequency oscillation by 180 degrees. Results: MI remained unchanged after phase inversion, whereas preferred phase rotated by exactly 180 degrees. Thus, opposite temporal organisations of cross-frequency coupling yielded identical MI values. Comparison with existing methods: Unlike preferred phase and the full phase-binned amplitude profile, MI quantifies the strength of phase-dependent amplitude modulation but does not retain information about temporal polarity or phase direction. Conclusions: Modulation index-based PAC does not encode temporal polarity and therefore cannot, on its own, support inferences about temporal alignment, phase polarity, or directionality. Studies seeking mechanistic interpretation of temporal organisation should complement MI with phase-sensitive measures.
Keshavarzi, M.
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