A tunable local field potentials computer simulator to assess minimal requirements for phase-amplitude cross-frequency-coupling estimation

The quantitative study of cross-frequency coupling (CFC) is a relevant issue in neuroscience. In local field potentials (LFPs), measured either in the cortex or in the hippocampus, how gamma-oscillation amplitude is modulated by changes in theta-rhythms-phase is thought to be important in memory formation. Several methods were proposed to quantify CFC, but reported evidence suggests that experimental parameters affect the results. Therefore, a simulation tool to support the determination of minimal requirements for CFC estimation in order to obtain reliable results is particularly useful. An approach to generate computer-simulated signals having CFC intensity, sweep duration, signal-to-noise ratio (SNR), and multiphasic-coupling tunable by the user has been developed. Its utility has been proved by a study evaluating minimal sweep duration and SNR required for reliable theta-gamma CFC estimation from signals simulating LFP measured in the mouse hippocampus. A MATLAB (R) software was made available to facilitate methodology reproducibility. The analysis of the synthetic LFPs created by the simulator shows how the minimal sweep duration for achieving accurate theta-gamma CFC estimates increases as SNR decreases and the number of CFC levels to discriminate increases. In particular, a sufficient reliability in discriminating five different predetermined CFC levels is reached with 35-s sweep with SNR = 20, while SNR = 5 requires at least 140-s sweep.