Systems and methods for determining optimal temporal patterns of neural stimulation are disclosed. According to an aspect, a method includes selecting a temporal pattern for neural stimulation. The method also includes determining a mutation type for altering a pattern of pulses of the temporal pattern. The method also includes identifying a location within the pattern of pulses of the temporal pattern to alter based on the determined mutation type. The method further includes altering the pattern of pulses of the temporal pattern based on the identified location and mutation type for application of the altered temporal pattern to a subject.