Studying the response of a climate system to perturbations has practical significance. Standard methods in computing the trajectory-wise deviation caused by perturbations may suffer from the chaotic nature that makes the model error dominate the true response after a short lead time. Statistical response, which computes the return described by the statistics, provides a systematic way of reaching robust outcomes with an appropriate quantification of the uncertainty and extreme events. In this paper, information theory is applied to compute the statistical response and find the most sensitive perturbation direction of different El Ni\~no-Southern Oscillation (ENSO) events to initial value and model parameter perturbations. Depending on the initial phase and the time horizon, different state variables contribute to the most sensitive perturbation direction. While initial perturbations in sea surface temperature (SST) and thermocline depth usually lead to the most significant response of SST at short- and long-range, respectively, initial adjustment of the zonal advection can be crucial to trigger strong statistical responses at medium-range around 5 to 7 months, especially at the transient phases between El Ni\~no and La Ni\~na. It is also shown that the response in the variance triggered by external random forcing perturbations, such as the wind bursts, often dominates the mean response, making the resulting most sensitive direction very different from the trajectory-wise methods. Finally, despite the strong non-Gaussian climatology distributions, using Gaussian approximations in the information theory is efficient and accurate for computing the statistical response, allowing the method to be applied to sophisticated operational systems.
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